Search results for: cerebral extracellular migration

Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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Authors: Kiranmay Sarma

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Recent decades have witnessed rapid increase in urbanization, for which, rural-urban migration is stated to be the principal reason. Urban growth throughout the world has already outstripped the capacities of most of the cities to provide basic amenities to the citizens, including clean drinking water and consequently, they are struggling to get fresh and clean water to meet water demands. Delhi, the capital of India, is one of the rapid fast growing metropolitan cities of the country. As a result, there has been large influx of population during the last few decades and pressure exerted to the limited available water resources, mainly on groundwater. Considering this important aspect, the present research has been designed to study the effects of urbanization on the green cover and groundwater and their relationships of Delhi. For the purpose, four different land uses of the study area have been considered, viz., protected forest area, trees outside forest, maintained park and settlement area. Samples for groundwater and vegetation were collected seasonally in post-monsoon (October), winter (February) and summer (June) at each study site for two years during 2012 and 2014. The results were integrated into GIS platform. The spatial distribution of groundwater showed that the concentration of most of the ions is decreasing from northern to southern parts of Delhi, thus groundwater shows an improving trend from north to south. The depth was found to be improving from south to north Delhi, i.e., opposite to the water quality. The study concludes the groundwater properties in Delhi vary spatially with depending on the types of land cover.

Keywords: groundwater, urbanization, GIS, green cover, Delhi

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Authors: Archil Undilashvili, Ketevan Stvilia, Dustin Gilbreath, Giorgi Dzneladze, Gordon Charchward

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Introduction: In recent years, diverse types of wheelchairs, both local production and imported, have been made available on the Georgian market for wheelchair users. Some types of wheelchairs are sold together with a service package, while the others, including the State Program, Supported locally-produced ones, don’t provide adjustment and maintenance service packages to users. Within the USAID Physical Rehabilitation Project in Georgia, a study was conducted to assess the impact of the wheelchair service provision in line with the WHO guidelines on the health and overall satisfaction of wheelchair users in Georgia. Methodology: A cross-sectional survey was conducted in May 2021. A structured questionnaire was used for telephone interviews that, along with socio-demographic characteristics, included questions for assessment of accessibility, availability, timeliness, cost and quality of wheelchair services received. Out of 1060 individuals listed in the census of wheelchair users, 752 were available for interview, with an actual response rate of 73.4%. 552 wheelchair users (31%) or their caregivers (69%) agreed to participate in the survey. In addition to using descriptive statistics, the study used multivariate matching of wheelchair users who received wheelchair services and who did not (control group). In addition, to evaluate satisfaction with service provision, respondents were asked to assess services. Findings: The majority (67%) of wheelchair users included in the survey were male. The average age of participants was 43. The three most frequently named reasons for using a wheelchair were cerebral palsy (29%), followed by stroke (18%), and amputation (12%). Users have had their current chair for four years on average. Overall, 60% of respondents reported that they were assessed before providing a wheelchair, but only half of them reported that their preferences and needs were considered. Only 13% of respondents had services in line with WHO guidelines and only 22% of wheelchair users had training when they received their current chair. 16% of participants said they had follow-up services, and 41% received adjustment services after receiving the chair. A slight majority (56%) of participants were satisfied with the quality of service provision and the service provision overall. Similarly, 55% were satisfied with the accessibility of service provision. A slightly larger majority (61%) were satisfied with the timeliness of service provision. The matching analysis suggests that users that received services in line with WHO guidelines were more satisfied with their chairs (the difference 17 point/0-100 scale) and they were four percentage points less likely to have health problems attributed to the chair. The regression analysis provides a similar finding of a 21 point increase in satisfaction attributable to services. Conclusion: The provision of wheelchair services in line with WHO guidelines and with follow-up services is likely to have a positive impact on the daily lives of wheelchair users in Georgia. Wheelchair services should be institutionalized as a standard component of wheelchair provision in Georgia.

Keywords: physical rehabilitation, wheelchair users, persons with disabilities, wheelchair production

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Authors: G. V. Manzane, S. J. Modise

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Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

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Authors: Mohammad H. Taheri, David J. Brown, Nasser Sherkat

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Engagement is one of the most important factors in determining successful outcomes and deep learning in students. Existing approaches to detect student engagement involve periodic human observations that are subject to inter-rater reliability. Our solution uses real-time multimodal multisensor data labeled by objective performance outcomes to infer the engagement of students. The study involves four students with a combined diagnosis of cerebral palsy and a learning disability who took part in a 3-month trial over 59 sessions. Multimodal multisensor data were collected while they participated in a continuous performance test. Eye gaze, electroencephalogram, body pose, and interaction data were used to create a model of student engagement through objective labeling from the continuous performance test outcomes. In order to achieve this, a type of continuous performance test is introduced, the Seek-X type. Nine features were extracted including high-level handpicked compound features. Using leave-one-out cross-validation, a series of different machine learning approaches were evaluated. Overall, the random forest classification approach achieved the best classification results. Using random forest, 93.3% classification for engagement and 42.9% accuracy for disengagement were achieved. We compared these results to outcomes from different models: AdaBoost, decision tree, k-Nearest Neighbor, naïve Bayes, neural network, and support vector machine. We showed that using a multisensor approach achieved higher accuracy than using features from any reduced set of sensors. We found that using high-level handpicked features can improve the classification accuracy in every sensor mode. Our approach is robust to both sensor fallout and occlusions. The single most important sensor feature to the classification of engagement and distraction was shown to be eye gaze. It has been shown that we can accurately predict the level of engagement of students with learning disabilities in a real-time approach that is not subject to inter-rater reliability, human observation or reliant on a single mode of sensor input. This will help teachers design interventions for a heterogeneous group of students, where teachers cannot possibly attend to each of their individual needs. Our approach can be used to identify those with the greatest learning challenges so that all students are supported to reach their full potential.

Keywords: affective computing in education, affect detection, continuous performance test, engagement, flow, HCI, interaction, learning disabilities, machine learning, multimodal, multisensor, physiological sensors, student engagement

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Authors: Teklebrhan Kidane

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The aim of this study is to investigate the species diversity and relative abundance of migratory waterbirds in Abijata Lake, an Important Bird Area and potential Ramsar site located in the Central Rift Valley of Ethiopia. The study was carried out, using line transect method along the shoreline and open area of the Lake. The data was analyzed with different diversity indices; t-Test and descriptive statistics. Thirty-two migratory waterbird species grouped into twelve families consisting of globally threatened birds were identified and recorded. Family Scolopacidae (12 species) had the highest number of species. The lowest number of species was observed under the families Ciconidae, Accipitridae, Laridae and Falconidae with one species each. The recorded bird species comprised 19 Palearctic, 5 Intra-African, 2 local migrants as well as 6 resident Palearctic migratory waterbird species. The dry season had higher species diversity (H'=1.01) compared to the wet season (H'=0.76). The highest and lowest diversity of migratory waterbirds were recorded during January (H'= 1.28) and June (H'= 0.52), respectively. However, the highest evenness (E) of bird species was recorded during wet season (E=0.21) and lower during the dry season (E=0.09). The computed seasonal effect reveals that there is significant effect of seasons on species diversity (t=2.80, P < 0.05), but the effect of seasons on individuals of migratory bird species was not significant (t=1.42, P > 0.05). Even though Lake Abijata is the sanctuary of several migratory waterbirds, anthropogenic activities are rigorously threatening their survival. Therefore, it needs an urgent conservation concern.

Keywords: migration, important bird area, species diversity, wetland birds

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Authors: Soroush Hooshyar, Mohamadali Masoudian, Natalie Germann

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Many soft materials such as polymer solutions can develop localized bands with different shear rates, which are known as shear bands. Using the generalized bracket approach of nonequilibrium thermodynamics, we recently developed a new two-fluid model to study shear banding for semi-dilute polymer solutions. The two-fluid approach is an appropriate means for describing diffusion processes such as Fickian diffusion and stress-induced migration. In this approach, it is assumed that the local gradients in concentration and, if accounted for, also stress generate a nontrivial velocity difference between the components. Since the differential velocity is treated as a state variable in our model, the implementation of the boundary conditions arising from the derivative diffusive terms is straightforward. Our model is a good candidate for benchmark simulations because of its simplicity. We analyzed its behavior in cylindrical Couette flow, a rectilinear channel flow, and a 4:1 planar contraction flow. The latter problem was solved using the OpenFOAM finite volume package and the impact of shear banding on the lip and salient vortices was investigated. For the other smooth geometries, we employed a standard Chebyshev pseudospectral collocation method. The results showed that the steady-state solution is unique with respect to initial conditions, deformation history, and the value of the diffusivity constant. However, smaller the value of the diffusivity constant is, the more time it takes to reach the steady state.

Keywords: nonequilibrium thermodynamics, planar contraction, polymer solutions, shear banding, two-fluid approach

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Authors: Swadhin Mondal

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While safe drinking water is an effective defense against the infection of water borne diseases, a large number of populations suffering from these diseases do not have access to safe drinking water due inadequacy of supply. Private entrepreneurs entered this sector and made bottled drinking water available by supplying various kinds of bottled water. In this study we found that the bottled drinking water industry has experienced a spectacular growth over the past two decades and it has a huge growth potential because of rising demand for safe drinking. High profit margin (217 %) is the main attraction to the entrepreneur to invest in this industry. Health awareness, lack of safe drinking water facilities, rising income, urbanization, migration and rising trend in tourism industries are the major influencing factors of demand for bottled drinking water (BDW). This industry also partially fulfills the demand for drinking water. More than 2 percent of household’s demands were met by this industry and many more households (additional 4 percent) coping with BDW during water crisis. Poor households spend around 4 percent of their total monthly household’s consumption expenditure on BDW which may have an adverse impact on household because households could have spent this for purchasing other goods. Like other developed counties, a large section of Indian households are shifting from their traditional sources of water to BDW. However, there are some concerns about the quality of BDW. Many cases, BDW contains chemical toxins at more than permissible level that can be harmful for health. Hence, there is an urgent need for appropriate intervention to regulate price, reduce potential harm and improve the quality of water provided by this industry.

Keywords: drinking water, public health public failure, privatization, development, public policy

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Authors: Iliya Ibrahim Gimba

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The period between the late 18th and early 19th centuries was characterized by conflict of ethnic nationalities in the Benue valley region. This conflict was exacerbated by the introduction of the Fulani jihad that began in Hausa land into the Benue valley region. Fulani in this region launched the Jihad movement which pushed out some ethnic groups from their natural abode or ancestral home to live a nomad live until they could settle and established a stayed in a particular place. The Chamba were being displaced by the Fulani jihad that took place around Faro deo in about 1809. It was from there that most of the Chamba migrated out, some into the Cameroon republic, while others moved into the Benue valley region. Among those that entered into the Benue valley region are the Sama, Kola, Gayam etc, and could be found in Donga local Government area of Taraba state. Those Chamba clan that later on cameo into the Benue Valley are Pyeri, Kashimbila etc. The sudden movement of the Chamba or migrations into the Jukun territory co-in ceded with the period that the Jihad had already had a severe and consequential effect or impact on the Jukun territory cause by Yakubu Ibrahim of Bzuchi, and Buba Yero of Gombe, and Hamaruwa of Muri Emirate. This ne authorities in Kwararafa Kingdom cut the Jukun King out of contact with Borno and Hausa-land. This paper set to examine the chiefdom that the Chamba established right within the Jukun headquarters of Wukari. Sources to be used are published books, Journals, Archival materials, and M.A. Thesis to enable us know the impact of Chamba migrations on the Jukun territory and reactions of the Jukun’s to this new comers.

Keywords: Chamba people, encroachment, migration, ethnic nationalities

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Authors: Maria Florencia Ferrer, Saulo Fabiano Amancio-Vieira

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The use of the blockchain in the public sector is present today and no longer the future of disruptive institutional and technological models. There are still some cultural barriers and resistance to the proper use of its potential. This research aims to present the strengths and weaknesses of using a public-permitted and distributed network in the context of the public sector. Therefore, bibliographical/documentary research was conducted to raise the main aspects of the studied platform, focused on the use of the main demands of the public sector. The platform analyzed was LACChain, which is a global alliance composed of different actors in the blockchain environment, led by the Innovation Laboratory of the Inter-American Development Bank Group (IDB Lab) for the development of the blockchain ecosystem in Latin America and the Caribbean. LACChain provides blockchain infrastructure, which is a distributed ratio technology (DLT). The platform focuses on two main pillars: community and infrastructure. It is organized as a consortium for the management and administration of an infrastructure classified as public, following the ISO typologies (ISO / TC 307). It is, therefore, a network open to any participant who agrees with the established rules, which are limited to being identified and complying with the regulations. As benefits can be listed: public network (open to all), decentralized, low transaction cost, greater publicity of transactions, reduction of corruption in contracts / public acts, in addition to improving transparency for the population in general. It is also noteworthy that the platform is not based on cryptocurrency and is not anonymous; that is, it is possible to be regulated. It is concluded that the use of record platforms, such as LACChain, can contribute to greater security on the part of the public agent in the migration process of their informational applications.

Keywords: blockchain, LACChain, public sector, technological disruptions

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Authors: Malab Sana Balouch, Meenakshi Nayar

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Hemispatial Neglect is a common disorder primarily associated with right hemispheric stroke, in the acute phase of which it can occur up to 82% of the time. Such individuals fail to acknowledge or respond to people and objects in their left field of vision due to deficits in attention and awareness. Persistent hemispatial neglect significantly impedes post-stroke recovery, leading to longer hospital stays post-stroke, increased functional dependency, longer-term disability in ADLs and increased risk of falls. Recently, evidence has emerged for the use of dopamine agonist Rotigotine in neglect. The aim of our Quality Improvement Project (QIP) is to evaluate and better the current protocols and practice in assessment, documentation and management of neglect and rotigotine use at the Neurorehabilitation unit at Charing Cross Hospital (CNRU). In addition, it brings light to rotigotine use in the management of hemispatial neglect and paves the way for future research in the field. Our QIP was based in the CNRU. All patients admitted to the CNRU suffering from a right-sided stroke from 2nd of February 2018 to the 2nd of February 2021 were included in the project. Each patient’s multidisciplinary team report and hospital notes were searched for information, including bio-data, fulfilment of the inclusion criteria (having hemispatial neglect) and data related to rotigotine use. This includes whether or not the drug was administered, any contraindications to drug in patients that did not receive it, and any therapeutic benefits(subjective or objective improvement in neglect) in those that did receive the rotigotine. Data was simultaneously entered into excel sheet and further statistical analysis was done on SPSS 20.0. Out of 80 patients suffering from right sided strokes, 72.5% were infarcts and 27.5% were hemorrhagic strokes, with vast majority of both types of strokes were in the middle cerebral artery territory (MCA). A total of 31 (38.8%) of our patients were noted to have hemispatial neglect, with the highest number of cases being associated with MCA strokes. Almost half of our patients with MCA strokes suffered from neglect. Neglect was more common in male patients. Out of the 31 patients suffering from visuospatial neglect, only 16% actually received rotigotine and 80% of them were noted to have an objective improvement in their neglect tests and 20% revealed subjective improvement. After thoroughly going through neglect-associated documentation, the following recommendations/plans were put in place for the future. We plan to liaise with the occupational therapy team at our rehab unit to set a battery of tests that would be done on all patients presenting with neglect and recommend clear documentation of outcomes of each neglect screen under it. Also to create two proformas; one for the therapy team to aid in systematic documentation of neglect screens done prior to and after rotigotine administration and a second proforma for the medical team with clear documentation of rotigotine use, its benefits and any contraindications if not administered.

Keywords: hemispatial Neglect, right hemispheric stroke, rotigotine, neglect, dopamine agonist

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Authors: Zawahir Siddique

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The paper explores the philosophical, spiritual, and mystical dimensions of the glorified journey of Hajira and Bilal. The black Ethiopian slave Hajira’s skirt was chosen to cover the first house of God on earth. Hajira was chosen by God as the embodiment of love and submission. The philosophy behind her migration with her child Ismail and wandering between Safa and Marwa in search of water that eventually gushed forth from the feet of Ismail and how God gifted Hajira, Ismail, and the entire humanity with Zamzam needs to be explored. Every year over two million pilgrims assemble and circumambulate around the Holy Kabah during Hajj, and every day, millions of Muslims pray, riveting their faith around Kabah. The significance and mysticism of the central figure of Hajira deserve due attention. Several eras later, the most blessed personality of humanity, Prophet Muhammad, elevated another Ethiopian Slave to the highest honor in the first Mosque of the Prophet of Islam in Medina. The purity of his heart and spiritually captivating voice of Bilal was preferred over his pre-Islamic social status. When the companions of the Prophet questioned the diction and pronunciation of 'SHEEN' by Bilal owing to his African origin, the Prophet immediately corrected them, justifying the purity of Bilal’s heart mattered more and hence Bilal’s 'SEEN' was heard as 'SHEEN' by God Almighty. The journey of Bilal to Islam and his pious and devoted contributions to Islam in the light of spirituality, mysticism, and social reforms are also explored further in this paper.

Keywords: philosophy, spirituality, mysticism, Hajira, Bilal

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Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki

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In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.

Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration

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Authors: A. Alzahrani, G. Arnold, W. Wang

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Background: Stroke commonly occurs in middle-aged and elderly populations, and the diagnosis of early stroke is still difficult. Patients who have suffered a stroke have different balance and gait patterns from healthy people. Advanced techniques of motion analysis have been routinely used in the clinical assessment of cerebral palsy. However, so far, little research has been done on the direct diagnosis of early stroke patients using motion analysis. Objectives: The aim of this study was to investigate whether patients with stroke have different balance and gait from healthy people and which biomechanical parameters could be used to predict and diagnose potential patients who are at a potential risk to stroke. Methods: Thirteen patients with stroke were recruited as subjects whose gait and balance was analysed. Twenty normal subjects at the matched age participated in this study as a control group. All subjects’ gait and balance were collected using Vicon Nexus® to obtain the gait parameters, kinetic, and kinematic parameters of the hip, knee, and ankle joints in three planes of both limbs. Participants stood on force platforms to perform a single leg balance test. Then, they were asked to walk along a 10 m walkway at their comfortable speed. Participants performed 6 trials of single-leg balance for each side and 10 trials of walking. From the recorded trials, three good ones were analysed using the Vicon Plug-in-Gait model to obtain gait parameters, e.g., walking speed, cadence, stride length, and joint parameters, e.g., joint angle, force, moments, etc. Result: The temporal-spatial variables of Stroke subjects were compared with the healthy subjects; it was found that there was a significant difference (p < 0.05) between the groups. The step length, speed, cadence were lower in stroke subjects as compared to the healthy groups. The stroke patients group showed significantly decreased in gait speed (mean and SD: 0.85 ± 0.33 m/s), cadence ( 96.71 ± 16.14 step/min), and step length (0.509 ± 017 m) in compared to healthy people group whereas the gait speed was 1.2 ± 0.11 m/s, cadence 112 ± 8.33 step/min, and step length 0.648 ± 0.43 m. Moreover, it was observed that patients with stroke have significant differences in the ankle, hip, and knee joints’ kinematics in the sagittal and coronal planes. Also, the result showed that there was a significant difference between groups in the single-leg balance test, e.g., maintaining single-leg stance time in the stroke patients showed shorter duration (5.97 ± 6.36 s) in compared to healthy people group (14.36 ± 10.20 s). Conclusion: Our result showed that there are significantly differences between stroke patients and healthy subjects in the various aspects of gait analysis and balance test, as a consequences of these findings some of the biomechanical parameters such as joints kinematics, gait parameters, and single-leg stance balance test could be used in clinical practice to predict and diagnose potential patients who are at a high risk of further stroke.

Keywords: gait analysis, kinetics, kinematics, single-leg stance, Stroke

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Authors: Chieh-Chung Tsou, Chun-Min Lo, Yeh-Shiu Chu

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Cell’s mechanical forces provide important physical cues in regulation of proper cellular functions, such as cell differentiation, proliferation and migration. It is believed that adhesive forces generated by cell-cell interaction are able to transmit to the interior of cell through filamentous cortical cytoskeleton. Prominent among other membrane receptors, Cadherins are prototypical adhesive molecules able to generate remarkable forces to regulate intercellular adhesion. However, the mechanistic steps of mechano-transduction in Cadherin-mediated adhesion remain very controversial. We are interested in understanding how Cadherin protein complexes enable force generation and transmission at cell-cell contact in the initial stage of intercellular adhesion. For providing a better control of time, space, and substrate stiffness, in this study, a combination of protein micropattern, micropipette manipulation, and traction force microscopy is used. Pair micropattern with different forms confines cell spreading area and the gaps in pairs varied from 2 to 8 microns are applied for monitoring the forces that cell pairs generated, measured by traction force microscopy. Moreover, cell clones obtained from epithelial cells undergone genome editing are used to score the importance for known components of Cadherin complexes in force generation. We believe that our results from this combinatory mechanobiological method will provide deep insights on understanding the biophysical principle governing mechano- transduction of Cadherin-mediated intercellular adhesion.

Keywords: cadherin, intercellular adhesion, protein micropattern, traction force microscopy

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Authors: Muhammad Ihsan Andi Dagong, Cece Sumantri, Ronny Rachman Noor, Rachmat Herman, Mohamad Yamin

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Calpastatin involved in various physiological processes in the body such as the protein turnover, growth, fusion and mioblast migration. Thus, allegedly Calpastatin gene diversity (CAST) have an association with growth and potential use as candidate genes for growth trait. This study aims to identify the association between the genetic diversity of CAST gene with some growth properties such as body dimention (morphometric), body weight and daily weight gain in sheep. A total of 157 heads of Thin Tail Sheep (TTS) reared intensively for fattening purposes in the uniform environmental conditions. Overall sheep used were male, and maintained for 3 months. The parameters of growth properties were measured among others: body weight gain (ADG) (g/head / day), body weight (kg), body length (cm), chest circumference (cm), height (cm). All the sheep were genotyped by using PCR-SSCP (single strand conformational polymorphism) methods. CAST gene in locus fragment intron 5 - exon 6 were amplified with a predicted length of about 254 bp PCR products. Then the sheep were stratified based on their CAST genotypes. The result of this research showed that no association were found between the CAST gene variations with morphometric body weight, but there was a significant association with daily body weight gain (ADG) in sheep observed. CAST-23 and CAST-33 genotypes has higher average daily gain than other genotypes. CAST-23 and CAST-33 genotypes that carrying the CAST-2 and CAST-3 alleles potential to be used in the selection of the nature of the growth trait of the TTS sheep.

Keywords: body weight, calpastatin, genotype, growth trait, thin tail sheep

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Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

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Objective: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage. However, EPCs are depleted in AS and contribute to the enhanced cardiovascular risk. Statins have a protective effect in CAD and diabetes by enhancing the proliferation, migration and survival of EPCs. Therapeutic potential of augmenting EPCs to treat the heightened cardiovascular risk of AS has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population and inflammation in AS. Methods: 30 AS patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=15) and placebo (n=15) as an adjunct to existing stable anti-rheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures (BASDAI, BASFI, CRP and ESR), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) and lipids were measured at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin. At 6 months, BASDAI, BASFI, ESR, CRP, TNF-α, and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and BASDAI, CRP and IL-6 after rosuvastatin treatment. Conclusion: First study to show that rosuvastatin augments EPCs population in AS. This defines a novel mechanism of rosuvastatin treatment in AS: the augmentation of EPCs with improvement in proinflammatory cytokines and inflammatory disease activity. The augmentation of EPCs by rosuvastatin may provide a novel strategy to prevent cardiovascular events in AS.

Keywords: ankylosing spondylitis, Endothelial Progenitor Cells, inflammation, pro-inflammatory cytokines, rosuvastatin

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Authors: Andreas Aceranti, Simonetta Vernocchi, Elisabetta Aldrovandi, Marco Colorato, Carolina Ascrizzi

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Nowadays, especially due to an increasing flow of migration and uncontrolled globalisation, linguistic, cultural and religious differences can be a major obstacle for people belonging to different ethnic groups. Each group has its own traditional background, which, in addition to its positive aspects, also includes extremely unpleasant and dramatic situations: culture-related crimes. We analysed several cases belonging to this category of crime which is becoming more and more present in Europe, creating not only a strong social rift dictated by the misunderstanding between migrants and host populations but also by the isolation and ghettoisation of subjects classified as 'different'. Such social rejection, in fact, represents a great source of stress and frustration for those who seek to be part of the community and can generate phenomena of rebellion that result in violent acts. Similar situations must be addressed by the figure of the cultural-linguistic mediator who, thanks to his or her multidisciplinary knowledge, assumes the role of a 'bridge', thus helping the process of awareness and understanding within the social group through the use of various tools, including awareness-raising campaigns and interventions in both the school and social-health sectors. By analysing how the notions of culture and offense have evolved throughout history until they have merged into a single principle and, secondly, how the figure of the language mediator represents a fundamental role in the resolution of conflicts related to cultural diversity has helped us define the basis for new protocols in dealing with such crimes. Especially we have to define the directions of further investigations that we will carry out in the next months.

Keywords: cultural crimes, hatred crimes, immigration, cultural mediation

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Authors: Christina Klippel, Lucia Pezzi, Silvio Neto, Rafael Bertani, Priscila Mendes, Flavio Machado, Aline Szeliga, Maria Cosendey, Adilson Mariz, Raquel Santos, Lys Bendett, Pedro Velasco, Thalita Rolleigh, Bruna Bellote, Daria Coelho, Bruna Martins, Julia Almeida, Juliana Cerqueira

Abstract:

This project presents a framework for teaching intracranial pressure monitoring (ICP) concepts using a low-cost experimental model in a neurointensive care education program. Data concerning ICP monitoring contribute to the patient's clinical assessment and may dictate the course of action of a health team (nursing, medical staff) and influence decisions to determine the appropriate intervention. This study aims to present a safe method for teaching ICP monitoring to medical students in a Simulation Center. Methodology: Medical school teachers, along with students from the 4th year, built an experimental model for teaching ICP measurement. The model consists of a mannequin's head with a plastic bag inside simulating the cerebral ventricle and an inserted ventricular catheter connected to the ICP monitoring system. The bag simulating the ventricle can also be changed for others containing bloody or infected simulated cerebrospinal fluid. On the mannequin's ear, there is a blue point indicating the right place to set the "zero point" for accurate pressure reading. The educational program includes four steps: 1st - Students receive a script on ICP measurement for reading before training; 2nd - Students watch a video about the subject created in the Simulation Center demonstrating each step of the ICP monitoring and the proper care, such as: correct positioning of the patient, anatomical structures to establish the zero point for ICP measurement and a secure range of ICP; 3rd - Students train the procedure in the model. Teachers help students during training; 4th - Student assessment based on a checklist form. Feedback and correction of wrong actions. Results: Students expressed interest in learning ICP monitoring. Tests concerning the hit rate are still being performed. ICP's final results and video will be shown at the event. Conclusion: The study of intracranial pressure measurement based on an experimental model consists of an effective and controlled method of learning and research, more appropriate for teaching neurointensive care practices. Assessment based on a checklist form helps teachers keep track of student learning progress. This project offers medical students a safe method to develop intensive neurological monitoring skills for clinical assessment of patients with neurological disorders.

Keywords: neurology, intracranial pressure, medical education, simulation

Procedia PDF Downloads 149

Authors: Justyna Mroczkowska

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Social worker's ability to provide culturally sensitive assistance in child protection is taken for granted; given limited training opportunities and lack of clear guidance, practitioners report working with migrant families more demanding in comparison to working with native families. In this study, the author developed and factor analyzed the Norwegian Cultural Self-Efficacy Scale to describe the level of cultural capability among Norwegian child protection professionals. The study aimed to determine the main influencing factors to cultural efficacy and examine the relationship between self-efficacy and perceived difficulty in working with migrant families. The scale was administered to child protection workers in Norway (N=251), and the reliability of the scale measured by Cronbach's alpha coefficient was .904. The confirmatory factor analysis of social work cultural self-efficacy found support for four separate but correlated subscales: Assessment, Communication, Support Request, and Teamwork. Regression analyses found the experience in working with migrant families, training and support from external agencies, and colleague support to be significant predictors of cultural self-efficacy. Self-efficacy in assessment skills and self-efficacy in communication skills were moderately related to the perceived difficulty to work with migrant families. The findings conclude with previous research and highlight the need for both professional development programs and institutional resources to be provided to support the practitioner's preparation for multicultural practice in child protection.

Keywords: child protection, cultural self-efficacy, cultural competency, migration, resources

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Authors: E. Sahar

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Civic political knowledge is crucial for the stability of democratic countries. In the USA, Americans have poor knowledge about their constitution and their political systems. Some states such as Florida State suffers from a huge decline in civics comparing to the National Average. This study concerns with using new technologies such as augmented reality to engage students in learning civics in classrooms. This is a participatory study, which engage teachers in the process of designing augmented reality civic games. The researcher used survey to find out the materials that teachers struggle with while teaching civics. Four lessons were found the most difficult to teach for middle school students: SS7C1.1 Enlightenment thinkers, SS7C1.2 influencing documents, SS7C1.7-Weakness of the Articles of Confederation, and Forms and systems of governments. For the limited scope of this study, we focused on “Forms and Systems of governments’ as the main project. Augmented Reality is used to help students to engage in learning civics through building a game that is based on the pedagogy constructivism theory. The resulted project meets the educational requirements for civics, provide students with more knowledge in at stake issues such as migration and citizenship, and help them to build leadership skills while playing in groups. The augmented reality game is also designed to test the students learning for each stage. This study helps to generate insightful implications for the use of augmented reality by educators, researchers, instructional designers, and developers who are interested in integrating technology in teaching civics for students in middle school classrooms.

Keywords: augmented reality, games, civics teaching, Florida middle school

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Authors: Marcela De Oliveira, Marina P. Da Silva, Fernando C. G. Da Rocha, Jorge M. Santos, Jaime S. Cardoso, Paulo N. Lisboa-Filho

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Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by neurodegeneration, inflammation, demyelination, and axonal loss. Magnetic resonance imaging (MRI), due to the richness in the information details provided, is the gold standard exam for diagnosis and follow-up of neurodegenerative diseases, such as MS. Brain atrophy, the gradual loss of brain volume, is quite extensive in multiple sclerosis, nearly 0.5-1.35% per year, far off the limits of normal aging. Thus, the brain volume quantification becomes an essential task for future analysis of the occurrence atrophy. The analysis of MRI has become a tedious and complex task for clinicians, who have to manually extract important information. This manual analysis is prone to errors and is time consuming due to various intra- and inter-operator variability. Nowadays, computerized methods for MRI segmentation have been extensively used to assist doctors in quantitative analyzes for disease diagnosis and monitoring. Thus, the purpose of this work was to evaluate the brain volume in MRI of MS patients. We used MRI scans with 30 slices of the five patients diagnosed with multiple sclerosis according to the McDonald criteria. The computational methods for the analysis of images were carried out in two steps: segmentation of the brain and brain volume quantification. The first image processing step was to perform brain extraction by skull stripping from the original image. In the skull stripper for MRI images of the brain, the algorithm registers a grayscale atlas image to the grayscale patient image. The associated brain mask is propagated using the registration transformation. Then this mask is eroded and used for a refined brain extraction based on level-sets (edge of the brain-skull border with dedicated expansion, curvature, and advection terms). In the second step, the brain volume quantification was performed by counting the voxels belonging to the segmentation mask and converted in cc. We observed an average brain volume of 1469.5 cc. We concluded that the automatic method applied in this work can be used for the brain extraction process and brain volume quantification in MRI. The development and use of computer programs can contribute to assist health professionals in the diagnosis and monitoring of patients with neurodegenerative diseases. In future works, we expect to implement more automated methods for the assessment of cerebral atrophy and brain lesions quantification, including machine-learning approaches. Acknowledgements: This work was supported by a grant from Brazilian agency Fundação de Amparo à Pesquisa do Estado de São Paulo (number 2019/16362-5).

Keywords: brain volume, magnetic resonance imaging, multiple sclerosis, skull stripper

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Authors: Imad M. Assali

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Recently, the world main problem is a global warming and climate change affecting both outdoor and indoor environments, especially the air quality (AQ) as a result of vast migration of people from rural areas to urban areas. Therefore, cities became more crowded and denser from an irregular population increase, along with increasing urbanization caused many problems for the environment such as increasing the land prices, changes in life style, and the new buildings are not adapted to the climate producing uncomfortable and unhealthy indoor building conditions. As interior environments are the places that create the most intimate relationship with the user. Consequently, the indoor environment quality (IEQ) for buildings became uncomfortable and unhealthy for its occupants. The symptoms commonly associated with poor indoor environment such as itchy, headache, fatigue, and respiratory complaints such as cough and congestion, etc. The symptoms tend to improve over time or even disappear when people are away from the building. Therefore, designing a healthy indoor environment to fulfill human needs is the main concern for architects and interior designer. However, this research explores how occupant expectations and environmental attitudes may influence occupant health and satisfaction within the context of the indoor environment. In doing so, it reviews and contributes to the methods and tools used to evaluate only the indoor environment quality (IEQ) components of building performance. Its main aim is to review the literature on indoor human comfort. This is followed by a review of previous papers published related to human comfort. Finally, this paper will provide possible approaches in design level of healthy buildings.

Keywords: sustainable building, indoor environment quality (IEQ), occupant's health, active system, sick building syndrome (SBS)

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Authors: Sourav Ray, Christoph Stein, Marcus Weber

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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.

Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation

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Authors: Yakubu Abdulai, Kenichi Matsui

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The agricultural industry has faced a variety of challenges in meeting the expanding income demand of the rural population. As a result, rural households must diversify their income sources to meet their income demand. Although income diversification strategies help rural households, it contributes to total household income, and the socio-demographic determinants are not known in the Upper East Region of Ghana. For these reasons, the purpose of this study was to determine the contribution of income diversification strategies to household income and the socio-demographic factors influencing it. We conducted a questionnaire survey among 360 rural households in the Upper East Region of Ghana. We asked about their socio-demographic information, their choice of income diversification strategies, and their remittances through rural-city migration. The questionnaire survey findings demonstrate that the main livelihood income source contributes 22%, and on-farm income diversification contributes the most to household total income (47%), followed by non-farm diversification income (16%) and off-farm diversification income (15%). Calculations from the income diversity index showed that the average income diversification strategy was 0.5 out of 1. The calculation of the income dependence index also showed that the average dependent on a particular source of income was 0.2 out of 1. All the respondents said household members temporarily migrate to contribute to household income through remittances. The results further reveal that their choice of income diversification is influenced by their age, educational background, experience, and farm size. The paper recommends the promotion of rural development policies that increase income-generating activities and educate rural households on how to increase returns from their investment.

Keywords: income diversification, poverty alleviation, rural households, upper east region

Procedia PDF Downloads 100

Authors: John Joseph S. Martis, Rohanchandra R. Gatty, Aaron Jose Fernandes, Rahul P. Nambiar

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Introduction: Surgery for breast cancer is either mastectomy or breast conservation surgery. The most commonly used incision for modified radical mastectomy is the transverse Stewart incision. But this incision may have the disadvantage of causing disparity between the closure lines of superior and inferior skin flaps in mastectomy and can cause overhanging of soft tissue below and behind the axilla. The curvizigzag incision, on principle, may help in this regard and can prevent scar migration beyond the anterior axillary line. This study aims to compare the two incisions in this regard. Methods: 100 patients with cancer of breast were included in the study after satisfying inclusion and exclusion criteria. They underwent surgery at Father Muller Medical College, Mangalore, India, between November 2019 to September 2021. The patients were divided into two groups. Group A patients were subjected to modified radical mastectomy with curvizigzag incision and group B patients with transverse Stewart incision. Results: Seroma on postoperative day1, day 2 was 0% in both the groups. Seroma on postoperative day 30 was present in 14% of patients in group B. 60% of patients in group B had sag of soft tissue below and behind the axilla, and none of the patients in group A had this problem. In 64% of the patients in group B, the incision crossed the anterior axillary fold, 64% of the patients in group B had tension in the incision site while approximation of the skin flaps. Conclusion: Curvizigzag incision is statistically better with lesser complications when compared to the transverse Stewart incision for modified radical mastectomy for carcinoma breast.

Keywords: breast cancer, curvizigzag incision, transverse Stewart incision, seroma, modified radical mastectomy

Procedia PDF Downloads 78

Authors: Shivani Jha, Klaus Baier, Rafiq Azzam, Ramakar Jha

Abstract:

In India, generally people migrate from rural area to the urban area for better infra-structural facilities, high standard of living, good job opportunities and advanced transport/communication availability. In fact, unplanned urban development due to migration of people causes seriou damage to the land use, water pollution and available water resources. In the present work, an attempt has been made to use satellite data of different years for urban change detection of Chennai metropolitan city along with pattern analysis to generate future scenario of urban development using buffer zoning in GIS environment. In the analysis, SRTM (30m) elevation data and IRS-1C satellite data for the years 1990, 2000, and 2014, are used. The flow accumulation, aspect, flow direction and slope maps developed using SRTM 30 m data are very useful for finding suitable urban locations for industrial setup and urban settlements. Normalized difference vegetation index (NDVI) and Principal Component Analysis (PCA) have been used in ERDAS imagine software for change detection in land use of Chennai metropolitan city. It has been observed that the urban area has increased exponentially in Chennai metropolitan city with significant decrease in agriculture and barren lands. However, the water bodies located in the study regions are protected and being used as freshwater for drinking purposes. Using buffer zone analysis in GIS environment, it has been observed that the development has taken place in south west direction significantly and will do so in future.

Keywords: urban change, satellite data, the Chennai metropolis, change detection

Procedia PDF Downloads 382

Authors: T. S. Almutairi, Paul May, Neil Allan

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The geometrical, electronic and magnetic properties of the neutral Mg center and MgN₃ cluster in diamond have been studied theoretically in detail by means of an HSE06 Hamiltonian that includes a fraction of the exact exchange term; this is important for a satisfactory picture of the electronic states of open-shell systems. Another batch of the calculations by GGA functionals have also been included for comparison, and these support the results from HSE06. The local perturbations in the lattice by introduced Mg defect are restricted in the first and second shell of atoms before eliminated. The formation energy calculated with HSE06 and GGA of single Mg agrees with the previous result. We found the triplet state with C₃ᵥ is the ground state of Mg center with energy lower than the singlet with C₂ᵥ by ~ 0.1 eV. The recent experimental ZPL (557.4 nm) of Mg center in diamond has been discussed in the view of present work. The analysis of the band-structure of the MgN₃ cluster confirms that the MgN₃ defect introduces a shallow donor level in the gap lying within the conduction band edge. This observation is supported by the EMM that produces n-type levels shallower than the P donor level. The formation energy of MgN₂ calculated from a 2NV defect (~ 3.6 eV) is a promising value from which to engineer MgN₃ defects inside the diamond. Ion-implantation followed by heating to about 1200-1600°C might induce migration of N related defects to the localized Mg center. Temperature control is needed for this process to restore the damage and ensure the mobilities of V and N, which demands a more precise experimental study.

Keywords: empirical marker method, generalised gradient approximation, Heyd–Scuseria–Ernzerhof screened hybrid functional, zero phono line

Procedia PDF Downloads 102

Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

Abstract:

Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: Wajid Rehman, Sirajul Haq, Bakhtiar Muhammad, Syed Fahad Hassan, Amin Badshah, Muhammad Waseem, Fazal Rahim, Obaid-Ur-Rahman Abid, Farzana Latif Ansari, Umer Rashid

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Five novel triorganotin (IV) compounds have been synthesized and characterized. The tin atom is penta-coordinated to assume trigonal-bipyramidal geometry. Using in silico derived parameters; the objective of our study is to design and synthesize promiscuous antibacterials potent enough to combat resistance. Among various synthesized organotin (IV) complexes, compound 5 was found as potent antibacterial agent against various bacterial strains. Further lead optimization of drug-like properties was evaluated through in silico predictions. Data mining and computational analysis were utilized to derive compound promiscuity phenomenon to avoid drug attrition rate in designing antibacterials. Xanthine oxidase and human glucose- 6-phosphatase were found as only true positive off-target hits by ChEMBL database and others utilizing similarity ensemble approach. Propensity towards a-3 receptor, human macrophage migration factor and thiazolidinedione were found as false positive off targets with E-value 1/4> 10^-4 for compound 1, 3, and 4. Further, displaying positive drug-drug interaction of compound 1 as uricosuric was validated by all databases and docked protein targets with sequence similarity and compositional matrix alignment via BLAST software. Promiscuity of the compound 5 was further confirmed by in silico binding to different antibacterial targets.

Keywords: antibacterial activity, drug promiscuity, ADMET prediction, metallo-pharmaceutical, antimicrobial resistance

Procedia PDF Downloads 486