Search results for: side channel

Authors: Przemysław Adamczyk, Mirosław Wyczesany, Aleksandra Domagalik, Artur Daren, Kamil Cepuch, Piotr Błądziński, Tadeusz Marek, Andrzej Cechnicki

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The present study aimed at evaluation of neural correlates of humor comprehension impairments observed in schizophrenia. To investigate the nature of this deficit in schizophrenia and to localize cortical areas involved in humor processing we used functional magnetic resonance imaging (fMRI). The study included chronic schizophrenia outpatients (SCH; n=20), and sex, age and education level matched healthy controls (n=20). The task consisted of 60 stories (setup) of which 20 had funny, 20 nonsensical and 20 neutral (not funny) punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible (yes/no) and how funny it was (1-9 Likert-type scale). fMRI was performed on a 3T scanner (Magnetom Skyra, Siemens) using 32-channel head coil. Three contrasts in accordance with the three stages of humor processing were analyzed in both groups: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution; funny vs neutral - elaboration. Additionally, parametric modulation analysis was performed using both subjective ratings separately in order to further differentiate the areas involved in incongruity resolution processing. Statistical analysis for behavioral data used U Mann-Whitney test and Bonferroni’s correction, fMRI data analysis utilized whole-brain voxel-wise t-tests with 10-voxel extent threshold and with Family Wise Error (FWE) correction at alpha = 0.05, or uncorrected at alpha = 0.001. Between group comparisons revealed that the SCH subjects had attenuated activation in: the right superior temporal gyrus in case of irresolvable incongruity processing of nonsensical puns (nonsensical > neutral); the left medial frontal gyrus in case of incongruity resolution processing of funny puns (funny > nonsensical) and the interhemispheric ACC in case of elaboration of funny puns (funny > neutral). Additionally, the SCH group revealed weaker activation during funniness ratings in the left ventro-medial prefrontal cortex, the medial frontal gyrus, the angular and the supramarginal gyrus, and the right temporal pole. In comprehension ratings the SCH group showed suppressed activity in the left superior and medial frontal gyri. Interestingly, these differences were accompanied by protraction of time in both types of rating responses in the SCH group, a lower level of comprehension for funny punchlines and a higher funniness for absurd punchlines. Presented results indicate that, in comparison to healthy controls, schizophrenia is characterized by difficulties in humor processing revealed by longer reaction times, impairments of understanding jokes and finding nonsensical punchlines more funny. This is accompanied by attenuated brain activations, especially in the left fronto-parietal and the right temporal cortices. Disturbances of the humor processing seem to be impaired at the all three stages of the humor comprehension process, from incongruity detection, through its resolution to elaboration. The neural correlates revealed diminished neural activity of the schizophrenia brain, as compared with the control group. The study was supported by the National Science Centre, Poland (grant no 2014/13/B/HS6/03091).

Keywords: communication skills, functional magnetic resonance imaging, humor, schizophrenia

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Authors: C. Bateira, J. Fernandes, A. Costa

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The Douro Demarked Region (DDR) is a production Porto wine region. On the NE of Portugal, the strong incision of the Douro valley developed very steep slopes, organized with agriculture terraces, have experienced an intense and deep transformation in order to implement the mechanization of the work. The old terrace system, based on stone vertical wall support structure, replaced by terraces with earth embankments experienced a huge terrace instability. This terrace instability has important economic and financial consequences on the agriculture enterprises. This paper presents and develops cartographic tools to access the embankment instability and identify the area prone to instability. The priority on this evaluation is related to the use of physically based mathematical models and develop a validation process based on an inventory of the past embankment instability. We used the shallow landslide stability model (SHALSTAB) based on physical parameters such us cohesion (c’), friction angle(ф), hydraulic conductivity, soil depth, soil specific weight (ϱ), slope angle (α) and contributing areas by Multiple Flow Direction Method (MFD). A terraced area can be analysed by this models unless we have very detailed information representative of the terrain morphology. The slope angle and the contributing areas depend on that. We can achieve that propose using digital elevation models (DEM) with great resolution (pixel with 40cm side), resulting from a set of photographs taken by a flight at 100m high with pixel resolution of 12cm. The slope angle results from this DEM. In the other hand, the MFD contributing area models the internal flow and is an important element to define the spatial variation of the soil saturation. That internal flow is based on the DEM. That is supported by the statement that the interflow, although not coincident with the superficial flow, have important similitude with it. Electrical resistivity monitoring values which related with the MFD contributing areas build from a DEM of 1m resolution and revealed a consistent correlation. That analysis, performed on the area, showed a good correlation with R2 of 0,72 and 0,76 at 1,5m and 2m depth, respectively. Considering that, a DEM with 1m resolution was the base to model the real internal flow. Thus, we assumed that the contributing area of 1m resolution modelled by MFD is representative of the internal flow of the area. In order to solve this problem we used a set of generalized DEMs to build the contributing areas used in the SHALSTAB. Those DEMs, with several resolutions (1m and 5m), were built from a set of photographs with 50cm resolution taken by a flight with 5km high. Using this maps combination, we modelled several final maps of terrace instability and performed a validation process with the contingency matrix. The best final instability map resembles the slope map from a DEM of 40cm resolution and a MFD map from a DEM of 1m resolution with a True Positive Rate (TPR) of 0,97, a False Positive Rate of 0,47, Accuracy (ACC) of 0,53, Precision (PVC) of 0,0004 and a TPR/FPR ratio of 2,06.

Keywords: agricultural terraces, cartography, landslides, SHALSTAB, vineyards

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Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

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Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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Authors: Vinod Kumar Tewari, Mazhar Husain, Hari Kishan Das Gupta

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Background: Primary or secondary brain death is also accompanied with vasospasm of the perforators other than tissue disruption & further exaggerates the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT) and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO) is produced by Nitric oxide Synthetase (NOS) in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT). Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC) at presynaptic membrane. The affinity of haem exhibits > 10,000-fold excess for NO than Oxygen (THE 10,000 FOLD EFFECT). In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP) releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane) thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS) at the adventitial side (outer border) on which sodium nitroprusside (SNP) acts; causing release of Nitric Oxide (NO) which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. Objective: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP) in cases of brain death in which: 1. Retrograde transmission = assessed by the hyperacute timings of reversal 2. The arteriolar perforator vasodilatation caused by NO and the maintenance of reversal of brain death reversal. Methods: 35 year old male, who became brain death after head injury and has not shown any signs of improvement after every maneuver for 6 hours, a single superfusion done by SNP via transoptic canal route for quadrigeminal cistern and cisternal puncture for IV ventricular with SNP done. Results: He showed spontaneous respiration (7 bouts) with TCD studies showing start of pulsations of various branches of common carotid arteries. Conclusions: In future we can give this SNP via transoptic canal route and in IV ventricle before declaring the body to be utilized for transplantations or dead or in broader way we can say that in near future it is possible to revert back from brain death or we have to modify our criterion.

Keywords: brain death, intrathecal sodium nitroprusside, TCD studies, perforators, vasodilatations, retrograde transmission, 10, 000 fold effect

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Authors: Probuddha Mukhopadhyay

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The infiltration of key elements to the civil structure is foraying its way to reclaim, what is its own. The reclamation of lives and spaces, once challenged, becomes a consistent process of ingress, disguised as parallels to the moving city, disperses into discourses often unheard of and conveniently forgotten. In this age of 'hyper'-urbanization, there are solutions suggested to a plethora of issues faced by citizens, in improving their standards of living. Problems are ancillary to proposals that emerge out of the underlying disorders of the townscape. These interventions result in the formulation of urban policies, to consolidate and optimize, to regularize and to streamline resources. Policy and practice are processes where the politics in policies define the way in which urban solutions are prescribed. Social constraints, that formulate the various cycles of order and disorders within the urban realm, are the stigmas for such interventions. There is often a direct relation of policy to place, no matter how people-centric it may seem to be projected. How we live our lives depends on where we live our lives - a relative statement for urban problems, varies from city to city. Communal compositions, welfare, crisis, socio-economic balance, need for management are the generic roots for urban policy formulation. However, in reality, the gentry administering its environmentalism is the criterion, that shapes and defines the values and expanse of such policies. In relation to the psycho-spatial characteristic of urban spheres with respect to the other side of this game, there have been instances, where the associational values have been reshaped by interests. The public domain reclaimed for exclusivity, thus creating fortified neighborhoods. Here, the citizen cumulative is often drifted by proposals that would over time deplete such landscapes of the city. It is the organized rebellion that in turn formulates further inward looking enclaves of latent aggression. In recent times, it has been observed that the unbalanced division of power and the implied processes of regulating the weak, stem the rebellion who respond in kits and parts. This is a phenomenon that mimics the guerilla warfare tactics, in order to have systems straightened out, either by manipulations or by force. This is the form of the city determined by the various forms insinuated by the state of city wide decisions. This study is an attempt at understanding the way in which development is interpreted by the state and the civil society and the role that community driven processes undertake to reinstate their claims to the city. This is a charter of consolidated patterns of negotiations that tend to counter policies. The research encompasses a study of various contested settlements in two cities of India- Mumbai and Kolkata, tackling dissent through spatial order. The study has been carried out to identify systems - formal and informal, catering to the most challenged interests of the people with respect to their habitat, a model to counter the top-down authoritative framework challenging the legitimacy of such settlements.

Keywords: urban design, insurgence, tactical urbanism, urban governance, civil society, state

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Authors: Shomaila Sadaf, Margarethe Olbertz-Siitonen

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This study looks at identity and othering in discourses around sensitive issues in social media. More specifically, the study explores the multimodal resources and narratives through which the other is formed, and identities are ascribed in online spaces. As an integral part of social life, media spaces have become an important site for negotiating and ascribing identities. In line with recent research, identity is seen hereas constructions of belonging which go hand in hand with processes of in- and out-group formations that in some cases may lead to othering. Previous findings underline that identities are neither fixed nor limited but rather contextual, intersectional, and interactively achieved. The goal of this study is to explore and develop an understanding of how people co-construct the ‘other’ and ascribe certain identities in social media using multiple modes. In the beginning of the year 2018, the British government decided to include relationships, sexual orientation, and sex education into the curriculum of state funded primary schools. However, the addition of information related to LGBTQ+in the curriculum has been met with resistance, particularly from religious parents.For example, the British Muslim community has voiced their concerns and protested against the actions taken by the British government. YouTube has been used by news companies to air video stories covering the protest and narratives of the protestors along with the position ofschool officials. The analysis centers on a YouTube video dealing with the protest ofa local group of parents against the addition of information about LGBTQ+ in the curriculum in the UK. The video was posted in 2019. By the time of this study, the videos had approximately 169,000 views andaround 6000 comments. In deference to multimodal nature of YouTube videos, this study utilizes multimodal discourse analysis as a method of choice. The study is still ongoing and therefore has not yet yielded any final results. However, the initial analysis indicates a hierarchy of ascribing identities in the data. Drawing on multimodal resources, the media works with social categorizations throughout the documentary, presenting and classifying involved conflicting parties in the light of their own visible and audible identifications. The protesters can be seen to construct a strong group identity as Muslim parents (e.g., clothing and reference to shared values). While the video appears to be designed as a documentary that puts forward facts, the media does not seem to succeed in taking a neutral position consistently throughout the video. At times, the use of images, soundsand language contributes to the formation of “us” vs. “them”, where the audience is implicitly encouraged to pick a side. Only towards the end of the documentary this problematic opposition is addressed and critically reflected through an expert interview that is – interestingly – visually located outside the previously presented ‘battlefield’. This study contributes to the growing understanding of the discursive construction of the ‘other’ in social media. Videos available online are a rich source for examining how the different social actors ascribe multiple identities and form the other.

Keywords: identity, multimodal discourse analysis, othering, youtube

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Authors: Yollande Sènan Djivoh, Dominique de Jaeger

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Background: Abdominal exercises are commonly practised nowadays. Specific techniques of abdominal muscles strengthening like hypopressive exercises have recently emerged and their practice is encouraged against the practice of Curl-up especially in postpartum. The acute and the training effects of these exercises did not allow to advise one exercise to the detriment of another. However, physiotherapists remain reluctant to perform Curl-up with postpartum women because of its potential harmful effect on the pelvic floor. Design: This study was a randomized control trial registered under the number PACTR202110679363984. Objective: to observe the training effect of two experimental protocols (Curl-up versus Drawing-in+Diaphragmatic aspiration) on the abdominal wall (interrecti distance, rectus and transversus abdominis thickness, abdominal strength) in Beninese postpartum women. Pelvic floor function (tone, endurance, urinary incontinence) will be assessed to evaluate potential side effects of exercises on the pelvic floor. Method: Postpartum women diagnosed with diastasis recti were randomly assigned to one of three groups (Curl-up, Drawingin+Diaphragmatic aspiration and control). Abdominal and pelvic floor parameters were assessed before and at the end of the 6-week protocol. The interrecti distance and the abdominal muscles thickness were assessed by ultrasound and abdominal strength by dynamometer. Pelvic floor tone and strength were assessed with Biofeedback and urinary incontinence was quantified by pad test. To compare the results between the three groups and the two measurements, a two-way Anova test with repeated measures was used (p<0.05). When interaction was significant, a posthoc using Student t test, with Bonferroni correction, was used to compare the three groups regarding the difference (end value minus initial value). To complete these results, a paired Student t test was used to compare in each group the initial and end values. Results: Fifty-eight women participated in this study, divided in three groups with similar characteristics regarding their age (29±5 years), parity (2±1 children), BMI (26±4 kg/m2 ), time since the last birth (10±2 weeks), weight of their baby at birth (330±50 grams). Time effect and interaction were significant (p<0.001) for all abdominal parameters. Experimental groups improved more than control group. Curl-up group improved more (p=0.001) than Drawing-in+Diaphragmatic aspiration group regarding the interrecti distance (9.3±4.2 mm versus 6.6±4.6 mm) and abdominal strength (20.4±16.4 Newton versus 11.4±12.8 Newton). Drawingin+Diaphragmatic aspiration group improved (0.8±0.7 mm) more than Curl-up group (0.5±0.7 mm) regarding the transversus abdominis thickness (p=0.001). Only Curl-up group improved (p<0.001) the rectus abdominis thickness (1.5±1.2 mm). For pelvic floor parameters, both experimental groups improved (p=0.01) except for tone which improved (p=0.03) only in Drawing-in+Diaphragmatic aspiration group from 19.9±4.1 cmH2O to 22.2±4.5 cmH2O. Conclusion: Curl-up was more efficient to improve abdominal function than Drawingin+Diaphragmatic aspiration. However, these exercises are complementary. None of them degraded the pelvic floor, but Drawing-in+Diaphragmatic aspiration improved further the pelvic floor function. Clinical implications: Curl-up, Drawing-in and Diaphragmatic aspiration can be used for the management of abdominal function in postpartum women. Exercises must be chosen considering the specific needs of each woman’s abdominal and pelvic floor function.

Keywords: curl-up, drawing-in, diaphragmatic aspiration, hypopressive exercise, postpartum women

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Authors: Ananya Mukhopadhyay, Priyanka Mazumdar, Tithi Banerjee, Alono Thorie

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Outcrop-based facies analysis of the Proterozoic rock successions in the Simla Basin, Lesser Himalaya was combined with the application of sequence stratigraphy to delineate the stages of wave-tide dominated fluvio-marine depositional system development. On this basis, a vertical profile depositional model has been developed. Based on lateral and vertical facies transitions, twenty lithofacies have been delineated from the lower-middle-upper part of the Simla Group, which are categorized into four major facies (FA1, FA2, FA3 and FA4) belts. FA1 documented from the Basantpur Formation (lower part of the Simla Group) indicates evolution of a distally steepened carbonate ramp deposits) highly influenced by sea level fluctuations, where outer, mid and inner ramp sub environments were identified. This transition from inner-mid to outer ramp is marked by a distinct slope break that has been widely cited as an example of a distally steepened ramp. The Basantpur carbonate ramp represents two different systems tracts: TST and HST which developed at different stages of sea level fluctuations. FA2 manifested from the Kunihar Formation (uncorformably overlying the Basantpur Formation) indicates deposition in a rimmed shelf (rich in microbial activity) sub-environment and bears the signature of an HST. FA3 delineated from the Chhaosa Formation (unconformably overlying the Kunihar mixed siliciclastic carbonates, middle part of the Simla Group) provides an excellent example of tide- and wave influenced deltaic deposit (FA3) which is characterized by wave dominated shorefacies deposit in the lower part, sharply overlain by fluvio-tidal channel and/or estuarine bay successions in the middle part followed by a tide dominated muddy tidal flat in the upper part. Despite large-scale progradation, the Chhaosa deltaic deposits are volumetrically dominated by transgressive estuarine deposits. The transgressive deposits are overlain by highstand units which are characterized by muddy tidal flat deposit. The Sanjauli Formation (upper part of the Simla Basin) records a major marine regression leading to the shifting of the shoreline basinward thereby resulting in fluvial incision on the top of the Chhaosa deltaic succession. The development of a braided fluvial system (FA4) with prominent fluvial incision is marked by presence of conglomerate-sandstone facies associations. Prominent fluvial incision on top of the delta deposits indicates the presence of sub-aerial TYPE 1 unconformity. The fluvial deposits mark the closure of sedimentation in the Simla basin that evolved during high frequency periods of coastal progradation and retrogradation. Each of the depositional cycles represents shoreline regression followed by transgression which is bounded by flooding surfaces and further followed by regression. The proposed depositional model in the present work deals with lateral facies variation due to shift in shore line along with fluctuations in accommodation space on a wave-tide influenced depositional system owing to fluctuations of sea level. This model will probably find its applicability in similar depositional setups.

Keywords: proterozoic, carbonate ramp, tide dominated delta, braided fluvial system, TYPE 1 unconformity

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Authors: Kamal Tolani, Sandeep Kumar, Rohit Luthra, Ankit Dadhania, Krishnaprasad K., Ram Gupta, Deepa Joshi

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Background: Post-operative analgesia remains a clinical challenge, with central and peripheral sensitization playing a pivotal role in treatment-related complications and impaired quality of life. Centrally acting opioids offer poor risk benefit profile with increased intensity of gastrointestinal or central side effects and slow onset of clinical analgesia. The objective of this study was to assess the clinical feasibility of induction and maintenance therapy with Tapentadol Nasal Spray (NS) in moderate to severe acute post-operative pain. Methods: Phase III, randomized, active-controlled, non-inferiority clinical trial involving 294 cases who had undergone surgical procedures under general anesthesia or regional anesthesia. Post-surgery patients were randomized to receive either Tapentadol NS 45 mg or Tramadol 100mg IV as a bolus and subsequent 50 mg or 100 mg dose over 2-3 minutes. The frequency of administration of NS was at every 4-6 hours. At the end of 24 hrs, patients in the tramadol group who had a pain intensity score of ≥4 were switched to oral tramadol immediate release 100mg capsule until the pain intensity score reduced to <4. All patients who had achieved pain intensity ≤ 4 were shifted to a lower dose of either Tapentadol NS 22.5 mg or oral Tramadol immediate release 50mg capsule. The statistical analysis plan was envisaged as a non-inferiority trial involving comparison with Tramadol for Pain intensity difference at 60 minutes (PID60min), Sum of Pain intensity difference at 60 minutes (SPID60min), and Physician Global Assessment at 24 hrs (PGA24 hrs). Results: The per-protocol analyses involved 255 hospitalized cases undergoing surgical procedures. The median age of patients was 38.0 years. For the primary efficacy variables, Tapentadol NS was non-inferior to Inj/Oral Tramadol in relief of moderate to severe post-operative pain. On the basis of SPID60min, no clinically significant difference was observed between Tapentadol NS and Tramadol IV (1.73±2.24 vs. 1.64± 1.92, -0.09 [95% CI, -0.43, 0.60]). In the co-primary endpoint PGA24hrs, Tapentadol NS was non–inferior to Tramadol IV (2.12 ± 0.707 vs. 2.02 ±0.704, - 0.11[95% CI, -0.07, 0.28). However, on further assessment at 48hr, 72 hrs, and 120hrs, clinically superior pain relief was observed with the Tapentadol NS formulation that was statistically significant (p <0.05) at each of the time intervals. Secondary efficacy measures, including the onset of clinical analgesia and TOTPAR, showed non-inferiority to Tramadol. The safety profile and need for rescue medication were also similar in both the groups during the treatment period. The most common concomitant medications were anti-bacterial (98.3%). Conclusion: Tapentadol NS is a clinically feasible option for improved compliance as induction and maintenance therapy while offering a sustained and persistent patient response that is clinically meaningful in post-surgical settings.

Keywords: tapentadol nasal spray, acute pain, tramadol, post-operative pain

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Authors: Varun Joshi, M. S. Rawat

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The Indian Himalayan Region (IHR) is inherently fragile and susceptible to landslide hazard due to its extremely weak geology, highly rugged topography and heavy monsoonal rainfall. One of the most common hazards in the IHR is landslide, and this event is particularly frequent in Himalayan states of India i.e. Jammu & Kashmir, Himachal Pradesh, Uttarakhand, Sikkim, Manipur and Arunachal Pradesh. Landslides are mostly triggered by extreme rainfall events but the incidence increases during monsoon months (June to September). Natural slopes which are otherwise stable but they get destabilized due to anthropogenic activities like construction of various developmental activities and deforestation. These activities are required to fulfill the developmental needs and upliftment of societal status in the region. Landslides also trigger during major earthquakes and reported most observable and damaging phenomena. Studies indicate that the landslide phenomenon has increased many folds due to developmental activities in Himalayan region. Gradually increasing and devastating consequences of landslides turned into one of the most important hydro-geological hazards in Himalayan states especially in Uttarakhand and Sikkim states of India. The recent most catastrophic rainfall in June 2013 in Uttarakhand lead to colossal loss of life and property. The societal damage due to this incident is still to be recovered even after three years. Sikkim earthquake of September 2011 is witnessed for triggering of large number of coseismic landslides. The rescue and relief team faced huge problem in helping the trapped villagers in remote locations of the state due to road side blockade by landslides. The recent past incidences of landslides in Uttarakhand, as well as Sikkim states, created a new domain of research in terms of understanding the phenomena of landslide and management of disaster in such situation. Every year at many locations landslides trigger which force dwellers to either evacuate their dwelling or lose their life and property. The communication and transportation networks are also severely affected by landslides at several locations. Many times the drinking water supply disturbed and shortage of daily need household items reported during monsoon months. To minimize the severity of landslide in IHR requires in-depth research and developmental planning. For most of the areas in the present study, landslide hazard zonation is done on 1:50,000 scale. The land use planning maps on extensive basis are not available. Therefore, there is a need of large-scale landslide hazard zonation and land use planning maps. If the scientist conduct research on desired aspects and their outcome of research is utilized by the government in developmental planning then the incidents of landslide could be minimized, subsequent impact on society, life and property would be reduced. Along with the scientific research, there is another need of awareness generation in the region for stake holders and local dwellers to combat with the landslide hazard, if triggered in their location.

Keywords: coseismic, Indian Himalayan Region, landslide hazard zonation, Sikkim, societal, Uttarakhand

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Authors: Albert W. K. Tan

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This research consolidates a comprehensive array of publications from peer-reviewed journals, case studies, and seminar reports focused on reverse logistics and network design. By synthesizing this secondary knowledge, our objective is to identify and articulate key decision factors crucial to reverse logistics network design for e-commerce. Through this exploration, we aim to present a refined mathematical model that offers valuable insights for companies seeking to optimize their reverse logistics operations. The primary goal of this research endeavor is to develop a comprehensive framework tailored to advising organizations and companies on crafting effective networks for their reverse logistics operations, thereby facilitating the achievement of their organizational goals. This involves a thorough examination of various network configurations, weighing their advantages and disadvantages to ensure alignment with specific business objectives. The key objectives of this research include: (i) Identifying pivotal factors pertinent to network design decisions within the realm of reverse logistics across diverse supply chains. (ii) Formulating a structured framework designed to offer informed recommendations for sound network design decisions applicable to relevant industries and scenarios. (iii) Propose a mathematical model to optimize its reverse logistics network. A conceptual framework for designing a reverse logistics network has been developed through a combination of insights from the literature review and information gathered from company websites. This framework encompasses four key stages in the selection of reverse logistics operations modes: (1) Collection, (2) Sorting and testing, (3) Processing, and (4) Storage. Key factors to consider in reverse logistics network design: I) Centralized vs. decentralized processing: Centralized processing, a long-standing practice in reverse logistics, has recently gained greater attention from manufacturing companies. In this system, all products within the reverse logistics pipeline are brought to a central facility for sorting, processing, and subsequent shipment to their next destinations. Centralization offers the advantage of efficiently managing the reverse logistics flow, potentially leading to increased revenues from returned items. Moreover, it aids in determining the most appropriate reverse channel for handling returns. On the contrary, a decentralized system is more suitable when products are returned directly from consumers to retailers. In this scenario, individual sales outlets serve as gatekeepers for processing returns. Considerations encompass the product lifecycle, product value and cost, return volume, and the geographic distribution of returns. II) In-house vs. third-party logistics providers: The decision between insourcing and outsourcing in reverse logistics network design is pivotal. In insourcing, a company handles the entire reverse logistics process, including material reuse. In contrast, outsourcing involves third-party providers taking on various aspects of reverse logistics. Companies may choose outsourcing due to resource constraints or lack of expertise, with the extent of outsourcing varying based on factors such as personnel skills and cost considerations. Based on the conceptual framework, the authors have constructed a mathematical model that optimizes reverse logistics network design decisions. The model will consider key factors identified in the framework, such as transportation costs, facility capacities, and lead times. The authors have employed mixed LP to find the optimal solutions that minimize costs while meeting organizational objectives.

Keywords: reverse logistics, supply chain management, optimization, e-commerce

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Authors: Shao-Huang Wu, Ai-Yun Wu, Meng-Chen Wu, Chun-Liang Wu, Kai-Ping Shaw, Hsiao-Ting Chen

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Objective: To analyze the forensic autopsy data of known passengers and compare it with the National database of the autopsy report in 2017, and obtain the special patterned injuries, which can be used as the reference for the reconstruction of hit-and-run motor vehicle accidents. Methods: Analyze the items of the Motor Vehicle Accident Report, including Date of accident, Time occurred, Day, Acc. severity, Acc. Location, Acc. Class, Collision with Vehicle, Motorcyclists Codes, Safety equipment use, etc. Analyzed the items of the Autopsy Report included, including General Description, Clothing and Valuables, External Examination, Head and Neck Trauma, Trunk Trauma, Other Injuries, Internal Examination, Associated Items, Autopsy Determinations, etc. Materials: Case 1. The process of injury formation: the car was chased forward and collided with the scooter. The passenger wearing the helmet fell to the ground. The helmet crashed under the bottom of the sedan, and the bottom of the sedan was raised. Additionally, the sedan was hit on the left by the other sedan behind, resulting in the front sedan turning 180 degrees on the spot. The passenger’s head was rotated, and the cervical spine was fractured. Injuries: 1. Fracture of atlantoaxial joint 2. Fracture of the left clavicle, scapula, and proximal humerus 3. Fracture of the 1-10 left ribs and 2-7 right ribs with lung contusion and hemothorax 4. Fracture of the transverse process of 2-5 lumbar vertebras 5. Comminuted fracture of the right femur 6. Suspected subarachnoid space and subdural hemorrhage 7. Laceration of the spleen. Case 2. The process of injury formation: The motorcyclist wearing the helmet fell to the left by himself, and his chest was crushed by the car going straight. Only his upper body was under the car and the helmet finally fell off. Injuries: 1. Dislocation of atlantoaxial joint 2. Laceration on the left posterior occipital 3. Laceration on the left frontal 4. Laceration on the left side of the chin 5. Strip bruising on the anterior neck 6. Open rib fracture of the right chest wall 7. Comminuted fracture of both 1-12 ribs 8. Fracture of the sternum 9. Rupture of the left lung 10. Rupture of the left and right atria, heart tip and several large vessels 11. The aortic root is nearly transected 12. Severe rupture of the liver. Results: The common features of the two cases were the fracture or dislocation of the atlantoaxial joint and both helmets that were crashed. There were no atlantoaxial fractures or dislocations in 27 pedestrians (without wearing a helmet) versus motor vehicle accidents in 2017 the National database of an autopsy report, but there were two atlantoaxial fracture or dislocation cases in the database, both of which were cases of falling from height. Conclusion: The cervical spine fracture injury of the motorcyclist, who was wearing a helmet, is very likely to be a patterned injury caused by his/her fall and rollover under the sedan. It could provide a reference for forensic peers.

Keywords: patterned injuries, atlantoaxial fracture or dislocation, accident reconstruction, motorcycle accident with helmet, forensic autopsy data

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Fatih Ercin Guney, Hami Karagol

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Day by day, humanity's energy needs increase, to facilitate access to energy sources by energy importing countries is of great importance in terms of issues both in terms of economic security and political security. The geographical location of the oil exporting countries in the Middle East (Iran, Iraq, Kuwait, Libya, Saudi Arabia, United Arab Emirates, Qatar) today, it is observed that evaluated by emerging Arab Spring(from Tunisia to Egypt) and freedom battles(in Syria) with security issues arise sourced from terrorist activities(ISIS). Progresses related with limited natural resources, energy and it's transportation issues which worries the developing countries, the energy in the region is considered to how to transfer safely. North Region of the Black Sea , the beginning of the conflict in the regional nature formed between Russia and Ukraine (2010), followed by the relevant regions of the power transmission line (From Russia to Europe) the discovery is considered to be the east's hand began to strengthen in terms of both the economical and political sides. With the growing need for safe access to the west of the new energy transmission lines are followed by Turkey, re-interest is considered to be shifted to the Mediterranean and the Middle East by West. Also, Russia, Iran and China (three axis of east) are generally performing as carry out parallel policies about energy , economical side and security in both United Nations Security Council (Two of Five Permanent Members are Russia and China) and Shanghai Cooperation Organization. In addition, Eastern Mediterranean Region Tension are rapidly increasing about research new oil and natural gas sources by Israel, Egypt, Cyprus, Lebanon. This paper provides, new energy corridor(s) are needed to transfer sources (Oil&Natural Gas) by Europe from East to West. So The West needs either safe bridge country to transfer natural sources to Europe in region or is needed to discovery new natural sources in extraterritorial waters of Eastern Mediterranean Region. But in two opportunities are evaluated with secure transfer corridors form region to Europe in safely. Even if the natural sources can be discovered, they are considered to transfer in safe manner. This paper involved, Turkey’s importance as a leader country in region over both of political and safe energy transfer sides as bridge country between south and north of Turkey why natural sources shall be transferred over Turkey, Even if diplomatic issues-For Example; Cyprus membership in European Union, Turkey membership candidate duration, Israel-Cyprus- Egypt-Lebanon researches about new natural sources in Mediterranean - occurred. But politic balance in Middle-East is changing quickly because of lack of democratic governments in region. So it is evaluated that the alliance of natural sources researches may not be long-time relations due to share sources after discoveries. After evaluating over causes and reasons, aim to reach finding foresight about future of region for energy transfer periods in secure manner.

Keywords: Middle East, natural gas, oil, Turkey

Procedia PDF Downloads 278

Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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Authors: Meena Agrawal, Chaitanya P. Agrawal

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The power systems are transforming and becoming smarter with innovations in technologies to enable embark simultaneously upon the sustainable energy needs, rising environmental concerns, economic benefits and quality requirements. The advantages provided by inter-connection of renewable energy resources are becoming more viable and dependable with the smart controlling technologies. The limitation of most renewable resources have their diversity and intermittency causing problems in power quality, grid stability, reliability, security etc. is being cured by these efforts. A necessitate of optimal energy management by intelligent Micro-Grids at the distribution end of the power system has been accredited to accommodate sustainable renewable Distributed Energy Resources on large scale across the power grid. All over the world Smart Grids are emerging now as foremost concern infrastructure upgrade programs. The hardware setup includes NI cRIO 9022, Compact Reconfigurable Input Output microcontroller board connected to the PC on a LAN router with three hardware modules. The Real-Time Embedded Controller is reconfigurable controller device consisting of an embedded real-time processor controller for communication and processing, a reconfigurable chassis housing the user-programmable FPGA, Eight hot-swappable I/O modules, and graphical LabVIEW system design software. It has been employed for signal analysis, controls and acquisition and logging of the renewable sources with the LabVIEW Real-Time applications. The employed cRIO chassis controls the timing for the module and handles communication with the PC over the USB, Ethernet, or 802.11 Wi-Fi buses. It combines modular I/O, real-time processing, and NI LabVIEW programmable. In the presented setup, the Analog Input Module NI 9205 five channels have been used for input analog voltage signals from renewable energy sources and NI 9227 four channels have been used for input analog current signals of the renewable sources. For switching actions based on the programming logic developed in software, a module having Electromechanical Relays (single-pole single throw) with 4-Channels, electrically isolated and LED indicating the state of that channel have been used for isolating the renewable Sources on fault occurrence, which is decided by the logic in the program. The module for Ethernet based Data Acquisition Interface ENET 9163 Ethernet Carrier, which is connected on the LAN Router for data acquisition from a remote source over Ethernet also has the module NI 9229 installed. The LabVIEW platform has been employed for efficient data acquisition, monitoring and control. Control logic utilized in program for operation of the hardware switching Related to Fault Relays has been portrayed as a flowchart. A communication system has been successfully developed amongst the sources and loads connected on different computers using Hypertext transfer protocol, HTTP or Ethernet Local Stacked area Network TCP/IP protocol. There are two main I/O interfacing clients controlling the operation of the switching control of the renewable energy sources over internet or intranet. The paper presents experimental results of the briefed setup for intelligent control of the micro-grid for renewable energy sources, besides the control of Micro-Grid with data acquisition and control hardware based on a microcontroller with visual program developed in LabVIEW.

Keywords: data acquisition and control, LabVIEW, microcontroller cRIO, Smart Micro-Grid

Procedia PDF Downloads 300

Authors: A. Odoom, A. Salama, H. Ibrahim

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Hydrogen is a clean source of energy for power production and transportation. The main source of hydrogen in this research is biodiesel. Glycerol also called glycerine is a by-product of biodiesel production by transesterification of vegetable oils and methanol. This is a reliable and environmentally-friendly source of hydrogen production than fossil fuels. A typical composition of crude glycerol comprises of glycerol, water, organic and inorganic salts, soap, methanol and small amounts of glycerides. Crude glycerol has limited industrial application due to its low purity thus, the usage of crude glycerol can significantly enhance the sustainability and production of biodiesel. Reforming techniques is an approach for hydrogen production mainly Steam Reforming (SR), Autothermal Reforming (ATR) and Partial Oxidation Reforming (POR). SR produces high hydrogen conversions and yield but is highly endothermic whereas POR is exothermic. On the downside, PO yields lower hydrogen as well as large amount of side reactions. ATR which is a fusion of partial oxidation reforming and steam reforming is thermally neutral because net reactor heat duty is zero. It has relatively high hydrogen yield, selectivity as well as limits coke formation. The complex chemical processes that take place during the production phases makes it relatively difficult to construct a reliable and robust numerical model. Numerical model is a tool to mimic reality and provide insight into the influence of the parameters. In this work, we introduce a finite volume numerical study for an 'in-house' lab-scale experiment of ATR. Previous numerical studies on this process have considered either using Comsol or nodal finite difference analysis. Since Comsol is a commercial package which is not readily available everywhere and lab-scale experiment can be considered well mixed in the radial direction. One spatial dimension suffices to capture the essential feature of ATR, in this work, we consider developing our own numerical approach using MATLAB. A continuum fixed bed reactor is modelled using MATLAB with both pseudo homogeneous and heterogeneous models. The drawback of nodal finite difference formulation is that it is not locally conservative which means that materials and momenta can be generated inside the domain as an artifact of the discretization. Control volume, on the other hand, is locally conservative and suites very well problems where materials are generated and consumed inside the domain. In this work, species mass balance, Darcy’s equation and energy equations are solved using operator splitting technique. Therefore, diffusion-like terms are discretized implicitly while advection-like terms are discretized explicitly. An upwind scheme is adapted for the advection term to ensure accuracy and positivity. Comparisons with the experimental data show very good agreements which build confidence in our modeling approach. The models obtained were validated and optimized for better results.

Keywords: autothermal reforming, crude glycerol, hydrogen, numerical model

Procedia PDF Downloads 119

Authors: Mary Ghobrial, Sahar Wefky

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Marine macroalgae have proven to be rich source of bioactive compounds with biomedical potential, not only for human but also for veterinary medicine. Emergence of microbial disease in aquaculture industries implies serious loses. Usage of commercial antibiotics for fish disease treatment produces undesirable side effects. Marine organisms are a rich source of structurally novel biologically active metabolites. Competition for space and nutrients led to the evolution of antimicrobial defense strategies in the aquatic environment. The interest in marine organisms as a potential and promising source of pharmaceutical agents has increased in the last years. Many bioactive and pharmacologically active substances have been isolated from microalgae. Compounds with antibacterial, antifungal and antiviral activities have been also detected in green, brown and red algae. Selected species of marine benthic algae belonging to the Phaeophyta and Rhodophyta, collected from different coastal areas of Alexandria (Egypt), were investigated for their antibacterial and antifungal, activities. Macroalgae samples were collected during low tide from the Alexandria Mediterranean coast. Samples were air dried under shade at room temperature. The dry algae were ground, using electric mixer grinder. They were soaked in 10 ml of each of the solvents acetone, ethanol, methanol and hexane. Antimicrobial activity was evaluated using well-cut diffusion technique In vitro screening of organic solvent extracts from the marine macroalgae Laurencia pinnatifida, Pterocladia capillaceae, Stepopodium zonale, Halopteris scoparia and Sargassum hystrix, showed specific activity in inhibiting the growth of five virulent strains of bacteria pathogenic to fish Pseudomonas fluorescens, Aeromonas hydrophila, Vibrio anguillarum, V. tandara, Escherichia coli and two fungi Aspergillus flavus and A. niger. Results showed that, acetone and ethanol extracts of all test macroalgae exhibited antibacterial activity, while acetone extract of the brown Sargassum hystrix displayed the highest antifungal activity. The extracts of seaweeds inhibited bacteria more strongly than fungi and species of the Rhodophyta showed the greatest activity against the bacteria rather than fungi tested. The gas liquid chromatography coupled with mass spectrometry detection technique allows good qualitative and quantitative analysis of the fractionated extracts with high sensitivity to the smaller amounts of components. Results indicated that, the main common component in the acetone extracts of L. pinnatifida and P. capillacea is 4-hydroxy-4-methyl2-pentanone representing 64.38 and 58.60%. Thus, the extracts derived from the red macroalgae were more efficient than those obtained from the brown macroalgae in combating bacterial pathogens rather than pathogenic fungi. The most preferred species over all was the red Laurencia pinnatifida. In conclusion, the present study provides the potential of red and brown macroalgae extracts for development of anti-pathogenic agents for use in fish aquaculture.

Keywords: bacteria, fungi, extracts, solvents

Procedia PDF Downloads 412

Authors: Jing Zhang, Yvonne Reinwald, Nick Poulson, Alicia El Haj, Chung See, Mike Somekh, Melissa Mather

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Biomedical imaging of native tissue using light offers the potential to obtain excellent structural and functional information in a non-invasive manner with good temporal resolution. Image contrast can be derived from intrinsic absorption, fluorescence, or scatter, or through the use of extrinsic contrast. A major challenge in applying optical microscopy to in vivo tissue imaging is the effects of light attenuation which limits light penetration depth and achievable imaging resolution. Recently Selective Plane Illumination Microscopy (SPIM) has been used to map the 3D distribution of fluorophores dispersed in biological structures. In this approach, a focused sheet of light is used to illuminate the sample from the side to excite fluorophores within the sample of interest. Images are formed based on detection of fluorescence emission orthogonal to the illumination axis. By scanning the sample along the detection axis and acquiring a stack of images, 3D volumes can be obtained. The combination of rapid image acquisition speeds with the low photon dose to samples optical sectioning provides SPIM is an attractive approach for imaging biological samples in 3D. To date all implementations of SPIM rely on the use of fluorescence reporters be that endogenous or exogenous. This approach has the disadvantage that in the case of exogenous probes the specimens are altered from their native stage rendering them unsuitable for in vivo studies and in general fluorescence emission is weak and transient. Here we present for the first time to our knowledge a label-free implementation of SPIM that has downstream applications in the clinical setting. The experimental set up used in this work incorporates both label-free and fluorescent illumination arms in addition to a high specification camera that can be partitioned for simultaneous imaging of both fluorescent emission and scattered light from intrinsic sources of optical contrast in the sample being studied. This work first involved calibration of the imaging system and validation of the label-free method with well characterised fluorescent microbeads embedded in agarose gel. 3D constructs of mammalian cells cultured in agarose gel with varying cell concentrations were then imaged. A time course study to track cell proliferation in the 3D construct was also carried out and finally a native tissue sample was imaged. For each sample multiple images were obtained by scanning the sample along the axis of detection and 3D maps reconstructed. The results obtained validated label-free SPIM as a viable approach for imaging cells in a 3D gel construct and native tissue. This technique has the potential use in a near-patient environment that can provide results quickly and be implemented in an easy to use manner to provide more information with improved spatial resolution and depth penetration than current approaches.

Keywords: bioimaging, optics, selective plane illumination microscopy, tissue imaging

Procedia PDF Downloads 223

Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

Procedia PDF Downloads 233

Authors: Lucile Rapin, Cynthia El Hage, Rihab Gamaoun, Maria-Fernanda Arboleda, Erin Prosk

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Introduction: Sante Cannabis (SC), a Canadian group of clinics dedicated to medical cannabis, based in Montreal and in the province of Quebec, has served more than 8000 patients seeking cannabis-based treatment over the past five years. As randomized clinical trials with natural medical cannabis are scarce, real-world evidence offers the opportunity to fill research gaps between scientific evidence and clinical practice. Data on the use of medical cannabis products from SC patients were prospectively collected, leading to a large real-world database on the use of medical cannabis. The aim of this study was to report information on the profiles of both patients and prescribed medical cannabis products at SC clinics, and to assess the safety of medical cannabis among Canadian patients. Methods: This is an observational retrospective study of 1342 adult patients who were authorized with medical cannabis products between October 2017 and September 2019. Information regarding demographic characteristics, therapeutic indications for medical cannabis use, patterns in dosing and dosage form of medical cannabis and adverse effects over one-year follow-up (initial and 4 follow-up (FUP) visits) were collected. Results: 59% of SC patients were female, with a mean age of 56.7 (SD= 15.6, range= (19-97)). Cannabis products were authorized mainly for patients with a diagnosis of chronic pain (68.8% of patients), cancer (6.7%), neurological disorders (5.6%), and mood disorders (5.4 %). At initial visit, a large majority (70%) of patients were authorized exclusively medical cannabis products, 27% were authorized a combination of pharmaceutical cannabinoids and medical cannabis and 3% were prescribed only pharmaceutical cannabinoids. This pattern was recurrent over the one-year follow-up. Overall, oil was the preferred formulation (average over visits 72.5%) followed by a combination of oil and dry (average 19%), other routes of administration accounted for less than 4%. Patients were predominantly prescribed products with a balanced THC:CBD ratio (59%-75% across visits). 28% of patients reported at least one adverse effect (AE) at the 3-month follow-up visit and 12% at the six-month FUP visit. 84.8% of total AEs were mild and transient. No serious AE was reported. Overall, the most common side effects reported were dizziness (11.95% of total AEs), drowsiness (11.4%), dry mouth (5.5%), nausea (4.8%), headaches (4.6%), cough (4.4%), anxiety (4.1%) and euphoria (3.5%). Other adverse effects accounted for less than 3% of total AE. Conclusion: Our results confirm that the primary area of clinical use for medical cannabis is in pain management. Patients in this cohort are largely utilizing plant-based cannabis oil products with a balanced ratio of THC:CBD. Reported adverse effects were mild and included dizziness and drowsiness. This real-world data confirms the tolerable safety profile of medical cannabis and suggests medical indications not yet validated in controlled clinical trials. Such data offers an important opportunity for the investigation of the long-term effects of cannabinoid exposure in real-life conditions. Real-world evidence can be used to direct clinical trial research efforts on specific indications and dosing patterns for product development.

Keywords: medical cannabis, safety, real-world data, Canada

Procedia PDF Downloads 103

Authors: José Antonio Donaire Benito, Konstantina Zerva

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Historically, cities have been places where people from many nations and cultures have met and settled together, while population flows and density have had a significant impact on urban dynamics. Cities' high density of social, cultural, business offerings, everyday services, and other amenities not intended for tourists draw not only tourists but a wide range of city users as well. With the coordination of city rhythms and the porosity of the community, city users order and frame their urban experience. From one side, recent literature focuses on the shift in urban tourist experience from 'having' a holiday through 'doing' activities to 'becoming' a local by experiencing a part of daily life. On the other hand, there is a debate on the 'touristification of everyday life', where middle and upper class urban dwellers display attitudes and behaviors that are virtually undistinguishable from those of visitors. With the advent of globalization and technological advances, modern society has undergone a radical transformation that has altered mobility patterns within it, blurring the boundaries between tourism and everyday life, work and leisure, and "hosts" and "guests". Additionally, the presence of other 'temporary city' users, such as commuters, digital nomads, second home owners, and migrants, contributes to a more complex transformation of tourist cities. Moving away from this traditional clear distinction between 'hosts' and 'guests', which represents a more static view of tourism, and moving towards a more liquid narrative of mobility, academics on tourism development are embracing the New Mobilities Paradigm. The latter moves beyond the static structures of the modern world and focuses on the ways in which social entities are made up of people, machines, information, and images in a moving system. In light of this fluid interdependence between tourists and guests, a question arises as to whether overtourism, which is considered as the underlying cause of citizens' perception of a lower urban quality of life, is a fair representation of perceived mobility excessiveness, place consumption disruptiveness, and residents displacement. As a representative example of an overtourism narrative, Barcelona was chosen as a study area for this purpose, focusing on the incoming city users to reflect in depth the variety of people who contribute to mobility flows beyond those residents already have. Several statistical data have been analyzed to determine the number of national and international visitors to Barcelona at some point during the day in 2019. Specifically, tracking data gathered from mobile phone users within the city are combined with tourist surveys, urban mobility data, zenithal data capture, and information about the city's attractions. The paper shows that tourists are only a small part of the different incoming city users that daily enter Barcelona; excursionists, commuters, and metropolitans also contribute to a high mobility flow. Based on the diversity of incoming city users and their place consumption, it seems that the city's urban experience is more likely to be impacted by over-mobility tan over-tourism.

Keywords: city users, density, new mobilities paradigm, over-tourism.

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Authors: Morello Sara, Pederiva Sabina, Bianchi Manila, Martucci Francesca, Marchis Daniela, Decastelli Lucia

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Vegetables represent an integral part of a healthy diet due to their valuable nutritional properties and the growth in consumer demand in recent years is particularly remarkable for a diet rich in vitamins and micronutrients. However, plant-based products are involved in several food outbreaks connected to various sources of contamination and quite often, bacteria responsible for side effects showed high resistance to antibiotics. The abuse of antibiotics can be one of the main mechanisms responsible for increasing antibiotic resistance (AR). Plants grown for food use can be contaminated directly by spraying antibiotics on crops or indirectly by treatments with antibiotics due to the use of manure, which may contain both antibiotics and genes of antibiotic resistance (ARG). Antibiotic residues could represent a potential way of human health risk due to exposure through the consumption of plant-based foods. The presence of antibiotic-resistant bacteria might pose a particular risk to consumers. The present work aims to investigate through a multidisciplinary approach the occurrence of ARG by means of a biomolecular approach (PCR) and the prevalence of antibiotic residues using a multi residues LC-MS/MS method, both in different plant-based products. During the period from July 2020 to October 2021, a total of 74 plant samples (33 lettuces and 41 tomatoes) were collected from 57 farms located throughout the Piedmont area, and18 out of 74 samples (11 lettuces and 7 tomatoes) were selected to LC-MS/MS analyses. DNA extracted (ExtractME, Blirt, Poland) from plants used on crops and isolated bacteria were analyzed with 6 sets of end-point multiplex PCR (Qiagen, Germany) to detect the presence of resistance genes of the main antibiotic families, such as tet genes (tetracyclines), bla (β-lactams) and mcr (colistin). Simultaneous detection of 43 molecules of antibiotics belonging to 10 different classes (tetracyclines, sulphonamides, quinolones, penicillins, amphenicols, macrolides, pleuromotilines, lincosamides, diaminopyrimidines) was performed using Exion LC system AB SCIEX coupled to a triple quadrupole mass spectrometer QTRAP 5500 from AB SCIEX. The PCR assays showed the presence of ARG in 57% (n=42): tetB (4.8%; n=2), tetA (9.5%; n=4), tetE (2.4%; n=1), tetL (12%; n=5), tetM (26%; n=11), blaSHV (21.5%; n=9), blaTEM (4.8%; n =2) and blaCTX-M (19%; n=8). In none of the analyzed samples was the mcr gene responsible for colistin resistance detected. Results obtained from LC-MS/MS analyses showed that none of the tested antibiotics appear to exceed the LOQ (100 ppb). Data obtained confirmed the presence of bacterial populations containing antibiotic resistance determinants such as tet gene (tetracycline) and bla genes (beta-lactams), widely used in human medicine, which can join the food chain and represent a risk for consumers, especially with raw products. The presence of traces of antibiotic residues in vegetables, in concentration below the LOQ of the LC-MS/MS method applied, cannot be excluded. In conclusion, traces of antibiotic residues could be a health risk to the consumer due to potential involvement in the spread of AR. PCR represents a useful and effective approach to characterize and monitor AR carried by bacteria from the entire food chain.

Keywords: plant-based products, ARG, PCR, antibiotic residues

Procedia PDF Downloads 55

Authors: Hongmei Wang, Ziyun Xiang, Ying liu, Li Yu, Dongsheng Yue

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Intro: The COVID-19 (Corona Virus Disease 2019) has greatly changed the global economic, political and financial ecology. The mutation of the coronavirus in the UK in December 2020 has brought new panic to the world. Deep learning was performed on Chest Computed tomography (CT) of COVID-19 and Influenza and describes their characteristics. The predominant features of COVID-19 pneumonia was ground-glass opacification, followed by consolidation. Lesion density: most lesions appear as ground-glass shadows, and some lesions coexist with solid lesions. Lesion distribution: the focus is mainly on the dorsal side of the periphery of the lung, with the lower lobe of the lungs as the focus, and it is often close to the pleura. Other features it has are grid-like shadows in ground glass lesions, thickening signs of diseased vessels, air bronchi signs and halo signs. The severe disease involves whole bilateral lungs, showing white lung signs, air bronchograms can be seen, and there can be a small amount of pleural effusion in the bilateral chest cavity. At the same time, this year's flu season could be near its peak after surging throughout the United States for months. Chest CT for Influenza infection is characterized by focal ground glass shadows in the lungs, with or without patchy consolidation, and bronchiole air bronchograms are visible in the concentration. There are patchy ground-glass shadows, consolidation, air bronchus signs, mosaic lung perfusion, etc. The lesions are mostly fused, which is prominent near the hilar and two lungs. Grid-like shadows and small patchy ground-glass shadows are visible. Deep neural networks have great potential in image analysis and diagnosis that traditional machine learning algorithms do not. Method: Aiming at the two major infectious diseases COVID-19 and influenza, which are currently circulating in the world, the chest CT of patients with two infectious diseases is classified and diagnosed using deep learning algorithms. The residual network is proposed to solve the problem of network degradation when there are too many hidden layers in a deep neural network (DNN). The proposed deep residual system (ResNet) is a milestone in the history of the Convolutional neural network (CNN) images, which solves the problem of difficult training of deep CNN models. Many visual tasks can get excellent results through fine-tuning ResNet. The pre-trained convolutional neural network ResNet is introduced as a feature extractor, eliminating the need to design complex models and time-consuming training. Fastai is based on Pytorch, packaging best practices for in-depth learning strategies, and finding the best way to handle diagnoses issues. Based on the one-cycle approach of the Fastai algorithm, the classification diagnosis of lung CT for two infectious diseases is realized, and a higher recognition rate is obtained. Results: A deep learning model was developed to efficiently identify the differences between COVID-19 and influenza using chest CT.

Keywords: COVID-19, Fastai, influenza, transfer network

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Authors: Ho-Ting Wu, Kai-Wei Ke, Bo-Yu Huang, Liang-Lin Yan, Chun-Ting Lin

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With the advances in advanced technology, wireless sensor network (WSN) has become one of the most promising candidates to implement the wireless industrial internet of things (IIOT) architecture. However, the legacy IEEE 802.15.4 based WSN technology such as Zigbee system cannot meet the stringent QoS requirement of low powered, real-time, and highly reliable transmission imposed by the IIOT environment. Recently, the IEEE society developed IEEE 802.15.4e Time Slotted Channel Hopping (TSCH) access mode to serve this purpose. Furthermore, the IETF 6TiSCH working group has proposed standards to integrate IEEE 802.15.4e with IPv6 protocol smoothly to form a complete protocol stack for IIOT. In this work, we develop key network technologies for IEEE 802.15.4e based wireless IIoT architecture, focusing on practical design and system implementation. We realize the OpenWSN-based wireless IIOT system. The system architecture is divided into three main parts: web server, network manager, and sensor nodes. The web server provides user interface, allowing the user to view the status of sensor nodes and instruct sensor nodes to follow commands via user-friendly browser. The network manager is responsible for the establishment, maintenance, and management of scheduling and topology information. It executes centralized scheduling algorithm, sends the scheduling table to each node, as well as manages the sensing tasks of each device. Sensor nodes complete the assigned tasks and sends the sensed data. Furthermore, to prevent scheduling error due to packet loss, a schedule inspection mechanism is implemented to verify the correctness of the schedule table. In addition, when network topology changes, the system will act to generate a new schedule table based on the changed topology for ensuring the proper operation of the system. To enhance the system performance of such system, we further propose dynamic bandwidth allocation and distributed scheduling mechanisms. The developed distributed scheduling mechanism enables each individual sensor node to build, maintain and manage the dedicated link bandwidth with its parent and children nodes based on locally observed information by exchanging the Add/Delete commands via two processes. The first process, termed as the schedule initialization process, allows each sensor node pair to identify the available idle slots to allocate the basic dedicated transmission bandwidth. The second process, termed as the schedule adjustment process, enables each sensor node pair to adjust their allocated bandwidth dynamically according to the measured traffic loading. Such technology can sufficiently satisfy the dynamic bandwidth requirement in the frequently changing environments. Last but not least, we propose a packet retransmission scheme to enhance the system performance of the centralized scheduling algorithm when the packet delivery rate (PDR) is low. We propose a multi-frame retransmission mechanism to allow every single network node to resend each packet for at least the predefined number of times. The multi frame architecture is built according to the number of layers of the network topology. Performance results via simulation reveal that such retransmission scheme is able to provide sufficient high transmission reliability while maintaining low packet transmission latency. Therefore, the QoS requirement of IIoT can be achieved.

Keywords: IEEE 802.15.4e, industrial internet of things (IIOT), scheduling mechanisms, wireless sensor networks (WSN)

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Authors: Robert Pečenko, Karin Tomažič, Igor Planinc, Sabina Huč, Tomaž Hozjan

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Timber is favourable structural material due to high strength to weight ratio, recycling possibilities, and green credentials. Despite being flammable material, it has relatively high fire resistance. Everyday engineering practice around the word is based on an outdated design of timber structures considering standard fire exposure, while modern principles of performance-based design enable use of advanced non-standard fire curves. In Europe, standard for fire design of timber structures EN 1995-1-2 (Eurocode 5) gives two methods, reduced material properties method and reduced cross-section method. In the latter, fire resistance of structural elements depends on the effective cross-section that is a residual cross-section of uncharred timber reduced additionally by so called zero strength layer. In case of standard fire exposure, Eurocode 5 gives a fixed value of zero strength layer, i.e. 7 mm, while for non-standard parametric fires no additional comments or recommendations for zero strength layer are given. Thus designers often implement adopted 7 mm rule also for parametric fire exposure. Since the latest scientific evidence suggests that proposed value of zero strength layer can be on unsafe side for standard fire exposure, its use in the case of a parametric fire is also highly questionable and more numerical and experimental research in this field is needed. Therefore, the purpose of the presented study is to use advanced calculation methods to investigate the thickness of zero strength layer and parametric charring rates used in effective cross-section method in case of parametric fire. Parametric studies are carried out on a simple solid timber beam that is exposed to a larger number of parametric fire curves Zero strength layer and charring rates are determined based on the numerical simulations which are performed by the recently developed advanced two step computational model. The first step comprises of hygro-thermal model which predicts the temperature, moisture and char depth development and takes into account different initial moisture states of timber. In the second step, the response of timber beam simultaneously exposed to mechanical and fire load is determined. The mechanical model is based on the Reissner’s kinematically exact beam model and accounts for the membrane, shear and flexural deformations of the beam. Further on, material non-linear and temperature dependent behaviour is considered. In the two step model, the char front temperature is, according to Eurocode 5, assumed to have a fixed temperature of around 300°C. Based on performed study and observations, improved levels of charring rates and new thickness of zero strength layer in case of parametric fires are determined. Thus, the reduced cross section method is substantially improved to offer practical recommendations for designing fire resistance of timber structures. Furthermore, correlations between zero strength layer thickness and key input parameters of the parametric fire curve (for instance, opening factor, fire load, etc.) are given, representing a guideline for a more detailed numerical and also experimental research in the future.

Keywords: advanced numerical modelling, parametric fire exposure, timber structures, zero strength layer

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Authors: Lesly Y Carmona-Sarabia, Luisa Barraza-Vergara, Vilmalí López-Mejías, Wandaliz Torres-García, Maribella Domenech-Garcia, Madeline Torres-Lugo

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Biosensors are used in many applications providing real-time monitoring to treat long-term conditions. Thus, understanding the physicochemical properties and biological side effects on the skin of polymers (e. g., poly(methyl methacrylate), PMMA) employed in the fabrication of wearable biosensors is crucial for the selection of manufacturing materials within this field. The PMMA (hydrophobic and thermoplastic polymer) is commonly employed as a coating material or substrate in the fabrication of wearable devices. The cytotoxicityof PMMA (including residual monomers or degradation products) on the skin, in terms of cells and tissue, is required to prevent possible adverse effects (cell death, skin reactions, sensitization) on human health. Within this work, accelerated aging of PMMA (Mw ~ 15000) through thermal and photochemical degradation was under-taken. The accelerated aging of PMMA was carried out by thermal (200°C, 1h) and photochemical degradation (UV-Vis, 8-15d) adapted employing ISO protocols (ISO-10993-12, ISO-4892-1:2016, ISO-877-1:2009, ISO-188: 2011). In addition, in vitro cytotoxicity evaluation of PMMA degradation products was performed using NIH3T3 fibroblast cells to assess the response of skin tissues (in terms of cell viability) exposed with polymers utilized to manufacture wearable biosensors, such as PMMA. The PMMA (Mw ~ 15000) before and after accelerated aging experiments was characterized by thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), powder X-ray diffractogram (PXRD), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) to determine and verify the successful degradation of this polymer under the specific conditions previously mention. The degradation products were characterized through nuclear magnetic resonance (NMR) to identify possible byproducts generated after the accelerated aging. Results demonstrated a percentage (%) weight loss between 1.5-2.2% (TGA thermographs) for PMMA after accelerated aging. The EDS elemental analysis reveals a 1.32 wt.% loss of carbon for PMMA after thermal degradation. These results might be associated with the amount (%) of PMMA degrade after the accelerated aging experiments. Furthermore, from the thermal degradation products was detected the presence of the monomer and methyl formate (low concentrations) and a low molecular weight radical (·COOCH3) in higher concentrations by NMR. In the photodegradation products, methyl formate was detected in higher concentrations. These results agree with the proposed thermal or photochemical degradation mechanisms found in the literature.1,2 Finally, significant cytotoxicity on the NIH3T3 cells was obtained for the thermal and photochemical degradation products. A decrease in cell viability by > 90% (stock solutions) was observed. It is proposed that the presence of byproducts (e.g. methyl formate or radicals such as ·COOCH₃) from the PMMA degradation might be responsible for the cytotoxicity observed in the NIH3T3 fibroblast cells. Additionally, experiments using skin models will be employed to compare with the NIH3T3 fibroblast cells model.

Keywords: biosensors, polymer, skin irritation, degradation products, cell viability

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Authors: Lara Bettinelli, Bernhard Glatz, Josef Fink

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Planning engineers and researchers use various calculation models with different levels of complexity, calculation efficiency and accuracy in dynamic calculations of railway bridges under high-speed traffic. When choosing a vehicle model to depict the dynamic loading on the bridge structure caused by passing high-speed trains, different goals are pursued: On the one hand, the selected vehicle models should allow the calculation of a bridge’s vibrations as realistic as possible. On the other hand, the computational efficiency and manageability of the models should be preferably high to enable a wide range of applications. The commonly adopted and straightforward vehicle model is the moving load model (MLM), which simplifies the train to a sequence of static axle loads moving at a constant speed over the structure. However, the MLM can significantly overestimate the structure vibrations, especially when resonance events occur. More complex vehicle models, which depict the train as a system of oscillating and coupled masses, can reproduce the interaction dynamics between the vehicle and the bridge superstructure to some extent and enable the calculation of more realistic bridge accelerations. At the same time, such multi-body models require significantly greater processing capacities and precise knowledge of various vehicle properties. The European standards allow for applying the so-called additional damping method when simple load models, such as the MLM, are used in dynamic calculations. An additional damping factor depending on the bridge span, which should take into account the vibration-reducing benefits of the vehicle-bridge interaction, is assigned to the supporting structure in the calculations. However, numerous studies show that when the current standard specifications are applied, the calculation results for the bridge accelerations are in many cases still too high compared to the measured bridge accelerations, while in other cases, they are not on the safe side. A proposal to calculate the additional damping based on extensive dynamic calculations for a parametric field of simply supported bridges with a ballasted track was developed to address this issue. In this contribution, several different approaches to determine the additional damping of the supporting structure considering the vehicle-bridge interaction when using the MLM are compared with one another. Besides the standard specifications, this includes the approach mentioned above and two additional recently published alternative formulations derived from analytical approaches. For a bridge catalogue of 65 existing bridges in Austria in steel, concrete or composite construction, calculations are carried out with the MLM for two different high-speed trains and the different approaches for additional damping. The results are compared with the calculation results obtained by applying a more sophisticated multi-body model of the trains used. The evaluation and comparison of the results allow assessing the benefits of different calculation concepts for the additional damping regarding their accuracy and possible applications. The evaluation shows that by applying one of the recently published redesigned additional damping methods, the calculation results can reflect the influence of the vehicle-bridge interaction on the design-relevant structural accelerations considerably more reliable than by using normative specifications.

Keywords: Additional Damping Method, Bridge Dynamics, High-Speed Railway Traffic, Vehicle-Bridge-Interaction

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Authors: E. Loffi Borghese

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In this comprehensive study, we delve into the intricate dynamics of the big tech oligopoly, focusing particularly on Apple as a case study. The core objective is to scrutinize the evolving relationship between a firm's commitment to positive social impact as its primary purpose and its resilience in the face of disruptive innovations within the big tech market. Our exploration begins with a theoretical framework, emphasizing the significance of distinguishing between corporate social responsibility and social impact as a primary purpose. Drawing on insights from Drumwright and Bartkus and Glassman, we underscore the transformative potential when a firm aligns its core business with a social mission, transcending mere side activities. Examining successful firms, such as Apple, we adopt Sinek's perspective on inspirational leadership and the "golden circle." This framework sheds light on why some organizations, like Apple, succeed in making positive social impact their primary purpose. Apple's early-stage life cycle is dissected, revealing a profound commitment to challenging the status quo and promoting simpler alternatives that resonate with its users' lives. The study then navigates through industry life cycles, drawing on Klepper's stages and Christensen's disruptive innovations. Apple's dominance in the big tech oligopoly is contrasted with companies like Harley Davidson and Polaroid, illustrating the consequences of failing to adapt to disruptive innovations. The data and methods employed encompass a qualitative approach, leveraging sources like ECB, Forbes, World in Data, and scientific articles. A secondary data analysis probes Apple's market evolution within the big tech oligopoly, emphasizing the shifts in market context and innovation trends that demand strategic adaptations. The subsequent sections scrutinize Apple's present innovation strategies, highlighting its diversified product portfolio and intensified focus on big data. We examine the implications of these shifts on Apple's capacity to maintain positive social impact as its primary purpose, pondering potential consequences on its brand perception. The study culminates in a reflection on the broader implications of the big tech oligopoly's dominance. It contemplates the diminishing competitiveness in the market and the potential sidelining of positive social impact as a competitive advantage. The expansion of tech firms into diverse sectors raises concerns about negative societal impacts, prompting a call for increased regulatory attention and awareness. In conclusion, this research serves as a catalyst for heightened awareness and discussion on the intricate interplay between firms' social impact goals, disruptive innovations, and the broader societal implications within the evolving landscape of the big tech oligopoly. Despite limitations, this study aims to stimulate further research, urging a conscious and responsible approach to shaping the future economic system.

Keywords: innovation trends, market dynamics, social impact, tech oligopoly

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 347