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Authors: Andrea Zielke-Nadkarni

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Pain management is a question of quality of life and an indicator for nursing quality. Chronic pain which is predominant in oncology and palliative nursing situations is perceived today as a multifactorial, individual emotional experience with specific characteristics including the sociocultural dimension when dealing with migrant patients. This dimension of chronic pain is of major importance in professional nursing of migrant patients in hospices or palliative care units. Objectives of the study are: 1. To find out more about the sociocultural views on pain and nursing care, on customs and nursing practices connected with pain of both Turkish Muslim and German Christian women, 2. To improve individual and family oriented nursing practice with view to sociocultural needs of patients in severe pain in palliative care. In a qualitative-explorative comparative study 4 groups of women, Turkish Muslims immigrants (4 from the first generation, 5 from the second generation) and German Christian women of two generations (5 of each age group) of the same age groups as the Turkish women and with similar educational backgrounds were interviewed (semistructured ethnographic interviews using Spradley, 1979) on their perceptions and experiences of pain and nursing care within their families. For both target groups the presentation will demonstrate the following results in detail: Utterance of pain as well as “private” and “public” pain vary within different societies and cultures. Permitted forms of pain utterance are learned in childhood and determine attitudes and expectations in adulthood. Language, especially when metaphors and symbols are used, plays a major role for misunderstandings. The sociocultural context of illness may include specific beliefs that are important to the patients and yet seem more than far-fetched from a biomedical perspective. Pain can be an influential factor in family relationships where respect or hierarchies do not allow the direct utterance of individual needs. Specific resources are often, although not exclusively, linked to religious convictions and are significantly helpful in reducing pain. The discussion will evaluate the results of the study with view to the relevant literature and present nursing interventions and instruments beyond medication that are helpful when dealing with patients from various socio-cultural backgrounds in painful end-oflife situations.

Keywords: pain management, migrants, sociocultural context, palliative care

Procedia PDF Downloads 363

Authors: Milda Nainyte, Viktoras Masevicius

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Biological methylation is a methyl group transfer from S-adenosyl-L-methionine (AdoMet) onto N-, C-, O- or S-nucleophiles in DNA, RNA, proteins or small biomolecules. The reaction is catalyzed by enzymes called AdoMet-dependent methyltransferases (MTases), which represent more than 3 % of the proteins in the cell. As a general mechanism, the methyl group from AdoMet replaces a hydrogen atom of nucleophilic center producing methylated DNA and S-adenosyl-L-homocysteine (AdoHcy). Recently, DNA methyltransferases have been used for the sequence-specific, covalent labeling of biopolymers. Two types of MTase catalyzed labeling of biopolymers are known, referred as two-step and one-step. During two-step labeling, an alkylating fragment is transferred onto DNA in a sequence-specific manner and then the reporter group, such as biotin, is attached for selective visualization using suitable chemistries of coupling. This approach of labeling is quite difficult and the chemical hitching does not always proceed at 100 %, but in the second step the variety of reporter groups can be selected and that gives the flexibility for this labeling method. In the one-step labeling, AdoMet analog is designed with the reporter group already attached to the functional group. Thus, the one-step labeling method would be more comfortable tool for labeling of biopolymers in order to prevent additional chemical reactions and selection of reaction conditions. Also, time costs would be reduced. However, effective AdoMet analog appropriate for one-step labeling of biopolymers and containing cleavable bond, required for reduction of PCR interferation, is still not known. To expand the practical utility of this important enzymatic reaction, cofactors with activated sulfonium-bound side-chains have been produced and can serve as surrogate cofactors for a variety of wild-type and mutant DNA and RNA MTases enabling covalent attachment of these chains to their target sites in DNA, RNA or proteins (the approach named methyltransferase-directed Transfer of Activated Groups, mTAG). Compounds containing hex-2-yn-1-yl moiety has proved to be efficient alkylating agents for labeling of DNA. Herein we describe synthetic procedures for the preparation of N-biotinoyl-N’-(pent-4-ynoyl)cystamine starting from the coupling of cystamine with pentynoic acid and finally attaching the biotin as a reporter group. The synthesis of the first AdoMet based cofactor containing a cleavable reporter group and appropriate for one-step labeling was developed.

Keywords: adoMet analogs, DNA alkylation, cofactor, methyltransferases

Procedia PDF Downloads 195

Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

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Authors: Bharti Jain, Rajeev Jain, Abuzar Kabir, Torki Zughaibi, Shweta Sharma

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Drug-facilitated crimes (DFCs) entail the use of a single drug or a mixture of drugs to render a victim unable. Traditionally, biological samples have been gathered from victims and conducted analysis to establish evidence of drug administration. Nevertheless, the rapid metabolism of various drugs and delays in analysis can impede the identification of such substances. For this, the present article describes a rapid, sustainable, highly efficient and miniaturized protocol for the identification and quantification of three sedative-hypnotic drugs, namely diazepam, chlordiazepoxide and ketamine in alcoholic beverages and complex food samples (cream of biscuit, flavored milk, juice, cake, tea, sweets and chocolate). The methodology involves utilizing fabric phase sorptive extraction (FPSE) to extract diazepam (DZ), chlordiazepoxide (CDP), and ketamine (KET). Subsequently, the extracted samples are subjected to analysis using gas chromatography-mass spectrometry (GC-MS). Several parameters, including the type of membrane, pH, agitation time and speed, ionic strength, sample volume, elution volume and time, and type of elution solvent, were screened and thoroughly optimized. Sol-gel Carbowax 20M (CW-20M) has demonstrated the most effective extraction efficiency for the target analytes among all evaluated membranes. Under optimal conditions, the method displayed linearity within the range of 0.3–10 µg mL–¹ (or µg g–¹), exhibiting a coefficient of determination (R2) ranging from 0.996–0.999. The limits of detection (LODs) and limits of quantification (LOQs) for liquid samples range between 0.020-0.069 µg mL-¹ and 0.066-0.22 µg mL-¹, respectively. Correspondingly, the LODs for solid samples ranged from 0.056-0.090 µg g-¹, while the LOQs ranged from 0.18-0.29 µg g-¹. Notably, the method showcased better precision, with repeatability and reproducibility both below 5% and 10%, respectively. Furthermore, the FPSE-GC-MS method proved effective in determining diazepam (DZ) in forensic food samples connected to drug-facilitated crimes (DFCs). Additionally, the proposed method underwent evaluation for its whiteness using the RGB12 algorithm.

Keywords: drug facilitated crime, fabric phase sorptive extraction, food forensics, white analytical chemistry

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Authors: Dalicia Bouallouche, Jean-Baptiste Vioix, Stéphane Millot, Eric Busvelle

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When researchers or logistics software developers deal with vehicle routing optimization, they mainly focus on minimizing the total travelled distance or the total time spent in the tours by the trucks, and maximizing the number of visited customers. They assume that the upstream real data given to carry the optimization of a transporter tours is free from errors, like customers’ real constraints, customers’ addresses and their GPS-coordinates. However, in real transporter situations, upstream data is often of bad quality because of address geocoding errors and the irrelevance of received addresses from the EDI (Electronic Data Interchange). In fact, geocoders are not exempt from errors and could give impertinent GPS-coordinates. Also, even with a good geocoding, an inaccurate address can lead to a bad geocoding. For instance, when the geocoder has trouble with geocoding an address, it returns those of the center of the city. As well, an obvious geocoding issue is that the mappings used by the geocoders are not regularly updated. Thus, new buildings could not exist on maps until the next update. Even so, trying to optimize tours with impertinent customers GPS-coordinates, which are the most important and basic input data to take into account for solving a vehicle routing problem, is not really useful and will lead to a bad and incoherent solution tours because the locations of the customers used for the optimization are very different from their real positions. Our work is supported by a logistics software editor Tedies and a transport company Upsilon. We work with Upsilon's truck routes data to carry our experiments. In fact, these trucks are equipped with TOMTOM GPSs that continuously save their tours data (positions, speeds, tachograph-information, etc.). We, then, retrieve these data to extract the real truck routes to work with. The aim of this work is to use the experience of the driver and the feedback of the real truck tours to validate GPS-coordinates of well geocoded addresses, and bring a correction to the badly geocoded addresses. Thereby, when a vehicle makes its tour, for each visited customer, the vehicle might have trouble with finding this customer’s address at most once. In other words, the vehicle would be wrong at most once for each customer’s address. Our method significantly improves the quality of the geocoding. Hence, we achieve to automatically correct an average of 70% of GPS-coordinates of a tour addresses. The rest of the GPS-coordinates are corrected in a manual way by giving the user indications to help him to correct them. This study shows the importance of taking into account the feedback of the trucks to gradually correct address geocoding errors. Indeed, the accuracy of customer’s address and its GPS-coordinates play a major role in tours optimization. Unfortunately, address writing errors are very frequent. This feedback is naturally and usually taken into account by transporters (by asking drivers, calling customers…), to learn about their tours and bring corrections to the upcoming tours. Hence, we develop a method to do a big part of that automatically.

Keywords: driver experience feedback, geocoding correction, real truck tours

Procedia PDF Downloads 674

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Jonathan Sohn

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Deep neural networks (DNNs) have shown state-of-the-art performance for many applications, including computer vision, natural language processing, and speech recognition. Recently, adversarial attacks have been studied in the context of deep neural networks, which aim to alter the results of deep neural networks by modifying the inputs slightly. For example, an adversarial attack on a DNN used for object detection can cause the DNN to miss certain objects. As a result, the reliability of DNNs is undermined by their lack of robustness against adversarial attacks, raising concerns about their use in safety-critical applications such as autonomous driving. In this paper, we focus on studying the adversarial attacks and defenses on DNNs for image classification. There are two types of adversarial attacks studied which are fast gradient sign method (FGSM) attack and projected gradient descent (PGD) attack. A DNN forms decision boundaries that separate the input images into different categories. The adversarial attack slightly alters the image to move over the decision boundary, causing the DNN to misclassify the image. FGSM attack obtains the gradient with respect to the image and updates the image once based on the gradients to cross the decision boundary. PGD attack, instead of taking one big step, repeatedly modifies the input image with multiple small steps. There is also another type of attack called the target attack. This adversarial attack is designed to make the machine classify an image to a class chosen by the attacker. We can defend against adversarial attacks by incorporating adversarial examples in training. Specifically, instead of training the neural network with clean examples, we can explicitly let the neural network learn from the adversarial examples. In our experiments, the digit recognition accuracy on the MNIST dataset drops from 97.81% to 39.50% and 34.01% when the DNN is attacked by FGSM and PGD attacks, respectively. If we utilize FGSM training as a defense method, the classification accuracy greatly improves from 39.50% to 92.31% for FGSM attacks and from 34.01% to 75.63% for PGD attacks. To further improve the classification accuracy under adversarial attacks, we can also use a stronger PGD training method. PGD training improves the accuracy by 2.7% under FGSM attacks and 18.4% under PGD attacks over FGSM training. It is worth mentioning that both FGSM and PGD training do not affect the accuracy of clean images. In summary, we find that PGD attacks can greatly degrade the performance of DNNs, and PGD training is a very effective way to defend against such attacks. PGD attacks and defence are overall significantly more effective than FGSM methods.

Keywords: deep neural network, adversarial attack, adversarial defense, adversarial machine learning

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Authors: Rafał Szmajser, Katarzyna Świetla, Mariusz Andrzejewski

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Robotic process automation (RPA) is a technology of repeatable business processes performed using computer programs, robots that simulate the work of a human being. This approach assumes replacing an existing employee with the use of dedicated software (software robots) to support activities, primarily repeated and uncomplicated, characterized by a low number of exceptions. RPA application is widespread in modern business services, particularly in the areas of Finance, Accounting and Human Resources Management. By utilizing this technology, the effectiveness of operations increases while reducing workload, minimizing possible errors in the process, and as a result, bringing measurable decrease in the cost of providing services. Regardless of how the use of modern information technology is assessed, there are also some doubts as to whether we should replace human activities in the implementation of the automation in business processes. After the initial awe for the new technological concept, a reflection arises: to what extent does the implementation of RPA increase the efficiency of operations or is there a Business Case for implementing it? If the business case is beneficial, in which business processes is the greatest potential for RPA? A closer look at these issues was provided by in this research during which the respondents’ view of the perceived advantages resulting from the use of robotization and automation in financial and accounting processes was verified. As a result of an online survey addressed to over 500 respondents from international companies, 162 complete answers were returned from the most important types of organizations in the modern business services industry, i.e. Business or IT Process Outsourcing (BPO/ITO), Shared Service Centers (SSC), Consulting/Advisory and their customers. Answers were provided by representatives of the positions in their organizations: Members of the Board, Directors, Managers and Experts/Specialists. The structure of the survey allowed the respondents to supplement the survey with additional comments and observations. The results formed the basis for the creation of a business case calculating tangible benefits associated with the implementation of automation in the selected financial processes. The results of the statistical analyses carried out with regard to revenue growth confirmed the correctness of the hypothesis that there is a correlation between job position and the perception of the impact of RPA implementation on individual benefits. Second hypothesis (H2) that: There is a relationship between the kind of company in the business services industry and the reception of the impact of RPA on individual benefits was thus not confirmed. Based results of survey authors performed simulation of business case for implementation of RPA in selected Finance and Accounting Processes. Calculated payback period was diametrically different ranging from 2 months for the Account Payables process with 75% savings and in the extreme case for the process Taxes implementation and maintenance costs exceed the savings resulting from the use of the robot.

Keywords: automation, outsourcing, business process automation, process automation, robotic process automation, RPA, RPA business case, RPA benefits

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Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

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Authors: Tomasz Borowski, Dawid Sołoducha, Agata Markowska-Szczupak, Aneta Wesołowska, Marian Kordas, Rafał Rakoczy

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Essential oils (EOs) are fragrant volatile oils obtained from plants. These are used for cooking (for flavor and aroma), cleaning, beauty (e.g., rosemary essential oil is used to promote hair growth), health (e.g. thyme essential oil cures arthritis, normalizes blood pressure, reduces stress on the heart, cures chest infection and cough) and in the food industry as preservatives and antioxidants. Rosemary and thyme essential oils are considered the most eminent herbs based on their history and medicinal properties. They possess a wide range of activity against different types of bacteria and fungi compared with the other oils in both in vitro and in vivo studies. However, traditional uses of EOs are limited due to rosemary and thyme oils in high concentrations can be toxic. In light of the accessible data, the following hypothesis was put forward: Low frequency rotating magnetic field (RMF) increases the antimicrobial potential of EOs. The aim of this work was to investigate the antimicrobial activity of commercial Salvia Rosmarinus L. and Thymus vulgaris L. essential oil from Polish company Avicenna-Oil under Rotating Magnetic Field (RMF) at f = 25 Hz. The self-constructed reactor (MAP) was applied for this study. The chemical composition of oils was determined by gas chromatography coupled with mass spectrometry (GC-MS). Model bacteria Escherichia coli K12 (ATCC 25922) was used. Minimum inhibitory concentrations (MIC) against E. coli were determined for the essential oils. Tested oils in very small concentrations were prepared (from 1 to 3 drops of essential oils per 3 mL working suspensions). From the results of disc diffusion assay and MIC tests, it can be concluded that thyme oil had the highest antibacterial activity against E. coli. Moreover, the study indicates the exposition to the RMF, as compared to the unexposed controls causing an increase in the efficacy of antibacterial properties of tested oils. The extended radiation exposure to RMF at the frequency f= 25 Hz beyond 160 minutes resulted in a significant increase in antibacterial potential against E. coli. Bacteria were killed within 40 minutes in thyme oil in lower tested concentration (1 drop of essential oils per 3 mL working suspension). Rapid decrease (>3 log) of bacteria number was observed with rosemary oil within 100 minutes (in concentration 3 drops of essential oils per 3 mL working suspension). Thus, a method for improving the antimicrobial performance of essential oil in low concentrations was developed. However, it still remains to be investigated how bacteria get killed by the EOs treated by an electromagnetic field. The possible mechanisms relies on alteration in the permeability of ionic channels in ionic channels in the bacterial cell walls that transport in the cells was proposed. For further studies, it is proposed to examine other types of essential oils and other antibiotic-resistant bacteria (ARB), which are causing a serious concern throughout the world.

Keywords: rotating magnetic field, rosemary, thyme, essential oils, Escherichia coli

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Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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Authors: Hana Hanaee-Ahvaz, Monika Cserjan-Puschmann, Christopher Tauer, Gerald Striedner

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Incorporation of noncanonical amino acids (ncAA) into proteins has become an interesting topic as proteins featured with ncAAs offer a wide range of different applications. Nowadays, technologies and systems exist that allow for the site-specific introduction of ncAAs in vivo, but the efficient production of proteins modified this way is still a big challenge. This is especially true for 'hard-to-express' proteins where low yields are encountered even with the native sequence. In this study, site-specific incorporation of azido-ethoxy-carbonyl-Lysin (azk) into an anti-tumor-necrosis-factor-α-Fab (FTN2) was investigated. According to well-established parameters, possible site positions for ncAA incorporation were determined, and corresponding FTN2 genes were constructed. Each of the modified FTN2 variants has one amber codon for azk incorporated either in its heavy or light chain. The expression level for all variants produced was determined by ELISA, and all azk variants could be produced with a satisfactory yield in the range of 50-70% of the original FTN2 variant. In terms of expression yield, neither the azk incorporation position nor the subunit modified (heavy or light chain) had a significant effect. We confirmed correct protein processing and azk incorporation by mass spectrometry analysis, and antigen-antibody interaction was determined by surface plasmon resonance analysis. The next step is to characterize the effect of azk incorporation on protein stability and aggregation tendency via differential scanning calorimetry and light scattering, respectively. In summary, the incorporation of ncAA into our Fab candidate FTN2 worked better than expected. The quantities produced allowed a detailed characterization of the variants in terms of their properties, and we can now turn our attention to potential applications. By using click chemistry, we can equip the Fabs with additional functionalities and make them suitable for a wide range of applications. We will now use this option in a first approach and develop an assay that will allow us to follow the degradation of the recombinant target protein in vivo. Special focus will be laid on the proteolytic activity in the periplasm and how it is influenced by cultivation/induction conditions.

Keywords: degradation, FTN2, hard-to-express protein, non-canonical amino acids

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Authors: I. Wiemann, N. Weiß, E. Schlücker, M. Wensing, A. Kölpin

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Chemical storage of hydrogen by liquid organic hydrogen carriers (LOHC) is a very promising alternative to compression or cryogenics. These carriers have high energy density and allow at the same time efficient and safe storage of hydrogen under ambient conditions and without leakage losses. Another benefit of LOHC is the possibility to transport it using already available infrastructure for transport of fossil fuels. Efficient use of LOHC is related to a precise process control, which requires a number of sensors in order to measure all relevant process parameters, for example, to measure the level of hydrogen loading of the carrier. The degree of loading is relevant for the energy content of the storage carrier and represents simultaneously the modification in chemical structure of the carrier molecules. This variation can be detected in different physical properties like viscosity, permittivity or density. Thereby, each degree of loading corresponds to different viscosity values. Conventional measurements currently use invasive viscosity measurements or near-line measurements to obtain quantitative information. Avoiding invasive measurements has several severe advantages. Efforts are currently taken to provide a precise, non-invasive measurement method with equal or higher precision of the obtained results. This study investigates a method for determination of the viscosity of LOHC. Since the viscosity can retroactively derived from the degree of loading, permittivity is a target parameter as it is a suitable for determining the hydrogenation degree. This research analyses the influence of common physical properties on permittivity. The permittivity measurement system is based on a cavity resonator, an electromagnetic resonant structure, whose resonation frequency depends on its dimensions as well as the permittivity of the medium inside. For known resonator dimensions, the resonation frequency directly characterizes the permittivity. In order to determine the dependency of the permittivity on temperature and flow velocity, an experimental setup with heating device and flow test bench was designed. By varying temperature in the range of 293,15 K -393,15 K and flow velocity up to 140 mm/s, corresponding changes in the resonation frequency were measured in the hundredths of the GHz range.

Keywords: liquid organic hydrogen carriers, measurement, permittivity, viscosity., temperature, flow process

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Authors: Ji Zhou, Jung Hee Seo, Rajat Mittal

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Fish move in groups for foraging, reproduction, predator protection, and hydrodynamic efficiency. Schooling's predator protection involves the "many eyes" theory, which increases predator detection probability in a group. Reduced visual signature in a group scales with school size, offering per-capita protection. The ‘confusion effect’ makes it hard for predators to target prey in a group. These benefits, however, all focus on vision-based sensing, overlooking sound-based detection. Fish, including predators, possess sophisticated sensory systems for pressure waves and underwater sound. The lateral line system detects acoustic waves, while otolith organs sense infrasound, and sharks use an auditory system for low-frequency sounds. Among sound generation mechanisms of fish, the mechanism of dipole sound relates to hydrodynamic pressure forces on the body surface of the fish and this pressure would be affected by group swimming. Thus, swimming within a group could affect this hydrodynamic noise signature of fish and possibly serve as an additional protection afforded by schooling, but none of the studies to date have explored this effect. BAUVs with fin-like propulsors could reduce acoustic noise without compromising performance, addressing issues of anthropogenic noise pollution in marine environments. Therefore, in this study, we used our in-house immersed-boundary method flow and acoustic solver, ViCar3D, to simulate fish schools consisting of four swimmers in the classic ‘diamond’ configuration and discussed the feasibility of yielding higher swimming efficiency and controlling far-field sound signature of the school. We examine the effects of the relative phase of fin flapping of the swimmers and the simulation results indicate that the phase of the fin flapping is a dominant factor in both thrust enhancement and the total sound radiated into the far-field by a group of swimmers. For fish in the “diamond” configuration, a suitable combination of the relative phase difference between pairs of leading fish and trailing fish can result in better swimming performance with significantly lower hydroacoustic noise.

Keywords: fish schooling, biopropulsion, hydrodynamics, hydroacoustics

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Authors: I. Rodionov, A. Semenov, E. Gosteva, O. Sokolova

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Currently, the venture capital becomes more and more advanced and effective source of the innovation project financing, connected with a high-risk level. In the developed countries, it plays a key role in transforming innovation projects into successful businesses and creating prosperity of the modern economy. Actually, in Russia there are many necessary preconditions for creation of the effective venture investment system: the network of the public institutes for innovation financing operates; there is a significant number of the small and medium-sized enterprises, capable to sell production with good market potential. However, the current system does not confirm the necessary level of efficiency in practice that can be substantially explained by the absence of the accurate plan of action to form the national venture model and by the lack of experience of successful venture deals with profitable exits in Russian economy. This paper studies the influence of various factors on the venture industry development by the example of the IT-sector in Russia. The choice of the sector is based on the fact, that this segment is the main driver of the venture capital market growth in Russia, and the necessary set of data exists. The size of investment of the second round is used as the dependent variable. To analyse the influence of the previous round such determinant as the volume of the previous (first) round investments is used. There is also used a dummy variable in regression to examine that the participation of an investor with high reputation and experience in the previous round can influence the size of the next investment round. The regression analysis of short-term interrelations between studied variables reveals prevailing influence of the volume of the first round investments on the venture investments volume of the second round. Because of the research, the participation of investors with first-class reputation has a small impact on an indicator of the value of investment of the second round. The expected positive dependence of the second round investments on the forecasted market growth rate now of the deal is also rejected. So, the most important determinant of the value of the second-round investment is the value of first–round investment, so it means that the most competitive on the Russian market are the start-up teams which can attract more money on the start, and the target market growth is not the factor of crucial importance.

Keywords: venture industry, venture investment, determinants of the venture sector development, IT-sector

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Authors: Merve Uzuner Sahin, Kumru D. Atalay, Berna Dengiz

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In today’s competitive market, there are many alternative products that can be used in similar manner and purpose. Therefore, the utility of the product is an important issue for the preferability of the brand. This utility could be measured in terms of its functionality, durability, reliability. These all are affected by the system capabilities. Reliability is an important system design criteria for the manufacturers to be able to have high availability. Availability is the probability that a system (or a component) is operating properly to its function at a specific point in time or a specific period of times. System availability provides valuable input to estimate the production rate for the company to realize the production plan. When considering only the corrective maintenance downtime of the system, mean time between failure (MTBF) and mean time to repair (MTTR) are used to obtain system availability. Also, the MTBF and MTTR values are important measures to improve system performance by adopting suitable maintenance strategies for reliability engineers and practitioners working in a system. Failure and repair time probability distributions of each component in the system should be known for the conventional availability analysis. However, generally, companies do not have statistics or quality control departments to store such a large amount of data. Real events or situations are defined deterministically instead of using stochastic data for the complete description of real systems. A fuzzy set is an alternative theory which is used to analyze the uncertainty and vagueness in real systems. The aim of this study is to present a novel approach to compute system availability using representation of MTBF and MTTR in fuzzy numbers. Based on the experience in the system, it is decided to choose 3 different spread of MTBF and MTTR such as 15%, 20% and 25% to obtain lower and upper limits of the fuzzy numbers. To the best of our knowledge, the proposed method is the first application that is used fuzzy MTBF and fuzzy MTTR for fuzzy system availability estimation. This method is easy to apply in any repairable production system by practitioners working in industry. It is provided that the reliability engineers/managers/practitioners could analyze the system performance in a more consistent and logical manner based on fuzzy availability. This paper presents a real case study of a repairable multi-stage production line in lead-acid battery production factory in Turkey. The following is focusing on the considered wet-charging battery process which has a higher production level than the other types of battery. In this system, system components could exist only in two states, working or failed, and it is assumed that when a component in the system fails, it becomes as good as new after repair. Instead of classical methods, using fuzzy set theory and obtaining intervals for these measures would be very useful for system managers, practitioners to analyze system qualifications to find better results for their working conditions. Thus, much more detailed information about system characteristics is obtained.

Keywords: availability analysis, battery production system, fuzzy sets, triangular fuzzy numbers (TFNs)

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Authors: Mai Sirhan, Arieh Sidess

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Asphaltic mixture is a heterogeneous material composed of three main components: aggregates; bitumen and air voids. The professional experience and scientific literature categorize asphaltic mixture as a viscoelastic material, whose behavior is determined by temperature and loading rate. Properties characterization of the asphaltic mixture used under the service conditions is done by compacting and testing cylindric asphalt samples in the laboratory. These samples must resemble in a high degree internal structure of the mixture achieved in service, and the mechanical characteristics of the compacted asphalt layer in the pavement. The laboratory samples are usually compacted in temperatures between 140 and 160 degrees Celsius. In this temperature range, the asphalt has a low degree of strength. The laboratory samples are compacted using the dynamic or vibrational compaction methods. In the compaction process, the aggregates tend to align themselves in certain directions that lead to anisotropic behavior of the asphaltic mixture. This issue has been studied in the Strategic Highway Research Program (SHRP) research, that recommended using the gyratory compactor based on the assumption that this method is the best in mimicking the compaction in the service. In Israel, the Netivei Israel company is considering adopting the Gyratory Method as a replacement for the Marshall method used today. Therefore, the compatibility of the Gyratory Method for the use with Israeli asphaltic mixtures should be investigated. In this research, we aimed to examine the impact of the compaction method used on the mechanical characteristics of the asphaltic mixtures and to evaluate the degree of anisotropy in relation to the compaction method. In order to carry out this research, samples have been compacted in the vibratory and gyratory compactors. These samples were cylindrically cored both vertically (compaction wise) and horizontally (perpendicular to compaction direction). These models were tested under dynamic modulus and permanent deformation tests. The comparable results of the tests proved that: (1) specimens compacted by the vibratory compactor had higher dynamic modulus values than the specimens compacted by the gyratory compactor (2) both vibratory and gyratory compacted specimens had anisotropic behavior, especially in high temperatures. Also, the degree of anisotropy is higher in specimens compacted by the gyratory method. (3) Specimens compacted by the vibratory method that were cored vertically had the highest resistance to rutting. On the other hand, specimens compacted by the vibratory method that were cored horizontally had the lowest resistance to rutting. Additionally (4) these differences between the different types of specimens rise mainly due to the different internal arrangement of aggregates resulting from the compaction method. (5) Based on the initial prediction of the performance of the flexible pavement containing an asphalt layer having characteristics based on the results achieved in this research. It can be concluded that there is a significant impact of the compaction method and the degree of anisotropy on the strains that develop in the pavement, and the resistance of the pavement to fatigue and rutting defects.

Keywords: anisotropy, asphalt compaction, dynamic modulus, gyratory compactor, mechanical properties, permanent deformation, vibratory compactor

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Authors: Kasun U. G. Palihakkara

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Although vaccine coverage in Sri Lanka is close to 100%, with the widely spreading vaccine rejection trend reaching South Asian regions, it is essential to catch on whether Sri Lankans are being misinformed from the common misconceptions regarding vaccines. As the rates of target diseases decrease, parents become less accepting of even minor common adverse events. It is essential to preserve the integrity of immunization programs and protect public health by finding out the prevalence of anti-immunization trends. The primary objective of this study was to assess the immunization practices and prevalence of trends related to anti-immunization among urban community in Sri Lanka. A descriptive cross-sectional quantitative study on 323 participants using convenient sampling with 213 self-administered questionnaires. Additionally, 110 online questionnaires were distributed. 31% of the study population does not maintain immunization records for their children. While majority seek information regarding immunization from reliable sources such as the family physician or specialist pediatricians, 30% also refer to unreliable sources such as online communities for their opinion. 31% of study population had not vaccinated for Japanese encephalitis. 73% of the study population had encountered with side effects of vaccination such as fever & 47% believed that such side effects are rare. 52% of the population had hostile attitude regarding the administration of several doses multiple vaccines within a child’s first year. Diseases like polio had been successfully eradicated from Sri Lanka with the help of vigorous vaccination programs. However, majority of the study population believe that there’s no need to keep vaccinating the children for those eradicated diseases and exposing the child for adverse effects of such vaccines. Majority of the population were aware of the existing misconceptions regarding immunization. The most popular misconceptions about vaccines popular among the study population were the MMR (Measles, Mumps, and Rubella) vaccine being a possible cause leading to autism and bowel disease and children getting infected with the disease even after they get vaccinated, may be due to the inactivated vaccine. Disturbingly 22% of the study population believed that vaccines are useless in preventing diseases nowadays. These data obtained from the urban study population reveals that even though statistically Sri Lankan immunization coverage is 100%, there is a possibility of anti-vaccination trend arising in Sri Lanka due to the prevalence of various misconceptions and rumors related to it. Therefore these data recommend the need for thorough awareness among the mothers.

Keywords: anti-vaccination, immunization, infectious diseases, pediatric health

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Authors: Isabella B. Davidman

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Violence used against Jewish women in both the Eastern European pogroms and during the Nazi era was specifically gendered, targeting their female identity and dignity of womanhood. Not only did these acts of gendered violence dehumanize Jewish women, but they also hurt the Jewish community as a whole. The devastating sexual violence that women endured during the pogroms and the Nazi era caused profound trauma. Out of shame and fear, silence about women’s experiences of sexual abuse manifests in forms that words cannot translate. Women have turned to art and other means of storytelling to convey their female experiences in visual and non-verbal ways. Therefore, this paper aims to address the historical accounts of gendered violence against Jewish women during the pogroms and Nazi era, as well as art that reflects upon the female experience, in order to understand the emotional impact resulting from these events. To analyze the artwork, a feminist analysis was used to understand the intersection of gender with the other systems of inequality, such as systemic anti-semitism, in women’s lives; this ultimately explained the ways in which cultural productions undermine and reinforce the political and social oppression of women by exploring how art confronts the exploitation of women's bodies. By analyzing the art in the context of specific acts of violence, such as public rape, as a strategic weapon, we are able to understand women’s experiences and how these experiences, in turn, challenged their womanhood. Additionally, these atrocities, which often occurred in the public space, were dismissed and forgotten due to the social stigma of rape. In this sense, the experiences of women in pogroms and the Nazi era were both highly unacknowledged and forgotten. Therefore, the art that was produced during those time periods, as well as those after those events, gives voice to the profound silence on the narratives of Jewish women. Sexual violence is a weapon of war used to cause physical and psychological destruction, not only as a product of war. In both the early twentieth-century pogroms and the Holocaust, the sexual violence that Jewish women endured was fundamentally the same: the rape of Jewish women became a focal target in the theater of violence– women were not raped because they were women, but specifically, because they were Jewish women. Although the events of the pogroms and the Holocaust are in the past, the art that serves as testimony to the experience of Jewish women remains an everlasting reminder of the gendered violence that occurred. Even though covert expressions, such as an embroidered image of a bird eating an apple, the artwork gives voice to the many silenced victims of sexualized and gendered violence.

Keywords: gendered violence, holocaust, Nazi era, pogroms

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Authors: Brady Manescau, Ilyas Sellami, Khaled Chetehouna, Charles De Izarra, Rachid Nait-Said, Fati Zidani

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During a fire in an oil and gas refinery, several thermal accidents can occur and cause serious damage to people and environment. Among these accidents, the BLEVE (Boiling Liquid Expanding Vapor Explosion) is most observed and remains a major concern for risk decision-makers. It corresponds to a violent vaporization of explosive nature following the rupture of a vessel containing a liquid at a temperature significantly higher than its normal boiling point at atmospheric pressure. Their effects on the environment generally appear in three ways: blast overpressure, radiation from the fireball if the liquid involved is flammable and fragment hazards. In order to estimate the potential damage that would be caused by such an explosion, risk decision-makers often use quantitative risk analysis (QRA). This analysis is a rigorous and advanced approach that requires a reliable data in order to obtain a good estimate and control of risks. However, in most cases, the data used in QRA are obtained from the empirical correlations. These empirical correlations generally overestimate BLEVE effects because they are based on simplifications and do not take into account real parameters like the geometry effect. Considering that these risk analyses are based on an assessment of BLEVE effects on human life and plant equipment, more precise and reliable data should be provided. From this point of view, the CFD modeling of BLEVE effects appears as a solution to the empirical law limitations. In this context, the main objective is to develop a numerical tool in order to predict BLEVE thermal effects using the CFD code FDS version 6. Simulations are carried out with a mesh size of 1 m. The fireball source is modeled as a vertical release of hot fuel in a short time. The modeling of fireball dynamics is based on a single step combustion using an EDC model coupled with the default LES turbulence model. Fireball characteristics (diameter, height, heat flux and lifetime) issued from the large scale BAM experiment are used to demonstrate the ability of FDS to simulate the various steps of the BLEVE phenomenon from ignition up to total burnout. The influence of release parameters such as the injection rate and the radiative fraction on the fireball heat flux is also presented. Predictions are very encouraging and show good agreement in comparison with BAM experiment data. In addition, a numerical study is carried out on an operational propane accumulator in an Algerian gas processing plant of SONATRACH company located in the Hassi R’Mel Gas Field (the largest gas field in Algeria).

Keywords: BLEVE effects, CFD, FDS, fireball, LES, QRA

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Authors: Dina Siniora, Jasia Baig

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During the past few decades, the healthcare system has undergone profound changes in their healthcare decision-making competencies and moral aptitudes due to the vast advancement in technology, clinical skills, and scientific knowledge. Healthcare decision-making deals with morally contentious dilemmas ranging from illness, life and death judgments that require sensitivity and awareness towards the patient’s preferences while taking into consideration medicine’s abilities and boundaries. As the ever-evolving field of medicine continues to become more scientifically and morally multifarious; physicians and the hospital administrators increasingly rely on ethics committees to resolve problems that arise in everyday patient care. The role and latitude of responsibilities of ethics committees which includes being dispute intermediaries, moral analysts, policy educators, counselors, advocates, and reviewers; suggest the importance and effectiveness of a fully integrated committee. Despite achievements on Integrated Ethics and progress in standards and competencies, there is an imminent necessity for further improvement in quality within ethics consultation services in areas of credentialing, professionalism and standards of quality, as well as the quality of healthcare throughout the system. These concerns can be resolved first by collecting data about particular quality gaps and comprehend the level to which ethics committees are consistent with newly published ASBH quality standards. Policymakers should pursue improvement strategies that target both academic bioethics community and major stakeholders at hospitals, who directly influence ethics committees. This broader approach oriented towards education and intervention outcome in conjunction with preventive ethics to address disparities in quality on a systematic level. Adopting tools for improving competencies and processes within ethics consultation by implementing a credentialing process, upholding normative significance for the ASBH core competencies, advocating for professional Code of Ethics, and further clarifying the internal structures will improve productivity, patient satisfaction, and institutional integrity. This cannot be systemically achieved without a written certification exam for HCEC practitioners, credentialing and privileging HCEC practitioners at the hospital level, and accrediting HCEC services at the institutional level.

Keywords: ethics consultation, hospital, medical ethics, quality

Procedia PDF Downloads 189

Authors: Jalil ur Rehman, Ramesh C, Tailor, Isa Khan, Jahanzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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The purpose of this analysis is to estimate secondary cancer risks after VMAT compared to other modalities of head and neck radiotherapy (IMRT, 3DCRT). Computer tomography (CT) scans of Radiological Physics Center (RPC) head and neck phantom were acquired with CT scanner and exported via DICOM to the treatment planning system (TPS). Treatment planning was done using four arc (182-178 and 180-184, clockwise and anticlockwise) for volumetric modulated arc therapy (VMAT) , Nine fields (200, 240, 280, 320,0,40,80,120 and 160), which has been commonly used at MD Anderson Cancer Center Houston for intensity modulated radiation therapy (IMRT) and four fields for three dimensional radiation therapy (3DCRT) were used. True beam linear accelerator of 6MV photon energy was used for dose delivery, and dose calculation was done with CC convolution algorithm with prescription dose of 6.6 Gy. Primary Target Volume (PTV) coverage, mean and maximal doses, DVHs and volumes receiving more than 2 Gy and 3.8 Gy of OARs were calculated and compared. Absolute point dose and planar dose were measured with thermoluminescent dosimeters (TLDs) and GafChromic EBT2 film, respectively. Quality Assurance of VMAT and IMRT were performed by using ArcCHECK method with gamma index criteria of 3%/3mm dose difference to distance to agreement (DD/DTA). PTV coverage was found 90.80 %, 95.80 % and 95.82 % for 3DCRT, IMRT and VMAT respectively. VMAT delivered the lowest maximal doses to esophagus (2.3 Gy), brain (4.0 Gy) and thyroid (2.3 Gy) compared to all other studied techniques. In comparison, maximal doses for 3DCRT were found higher than VMAT for all studied OARs. Whereas, IMRT delivered maximal higher doses 26%, 5% and 26% for esophagus, normal brain and thyroid, respectively, compared to VMAT. It was noted that esophagus volume receiving more than 2 Gy was 3.6 % for VMAT, 23.6 % for IMRT and up to 100 % for 3DCRT. Good agreement was observed between measured doses and those calculated with TPS. The averages relative standard errors (RSE) of three deliveries within eight TLD capsule locations were, 0.9%, 0.8% and 0.6% for 3DCRT, IMRT and VMAT, respectively. The gamma analysis for all plans met the ±5%/3 mm criteria (over 90% passed) and results of QA were greater than 98%. The calculations for maximal doses and volumes of OARs suggest that the estimated risk of secondary cancer induction after VMAT is considerably lower than IMRT and 3DCRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD

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Authors: O. Ekrami, P. Claes, S. Van Dongen

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Fluctuating asymmetry (FA) has been studied for many years as an indicator of developmental stability or ‘genetic quality’ based on the assumption that perfect symmetry is ideally the expected outcome for a bilateral organism. Further studies have also investigated the possible link between FA and attractiveness or levels of masculinity or femininity. These hypotheses have been mostly examined using 2D images, and the structure of interest is usually presented using a limited number of landmarks. Such methods have the downside of simplifying and reducing the dimensionality of the structure, which will in return increase the error of the analysis. In an attempt to reach more conclusive and accurate results, in this study we have used high-resolution 3D scans of human faces and have developed an algorithm to measure and localize FA, taking a spatially-dense approach. A symmetric spatially dense anthropometric mask with paired vertices is non-rigidly mapped on target faces using an Iterative Closest Point (ICP) registration algorithm. A set of 19 manually indicated landmarks were used to examine the precision of our mapping step. The protocol’s accuracy in measurement and localizing FA is assessed using simulated faces with known amounts of asymmetry added to them. The results of validation of our approach show that the algorithm is perfectly capable of locating and measuring FA in 3D simulated faces. With the use of such algorithm, the additional captured information on asymmetry can be used to improve the studies of FA as an indicator of fitness or attractiveness. This algorithm can especially be of great benefit in studies of high number of subjects due to its automated and time-efficient nature. Additionally, taking a spatially dense approach provides us with information about the locality of FA, which is impossible to obtain using conventional methods. It also enables us to analyze the asymmetry of a morphological structures in a multivariate manner; This can be achieved by using methods such as Principal Components Analysis (PCA) or Factor Analysis, which can be a step towards understanding the underlying processes of asymmetry. This method can also be used in combination with genome wide association studies to help unravel the genetic bases of FA. To conclude, we introduced an algorithm to study and analyze asymmetry in human faces, with the possibility of extending the application to other morphological structures, in an automated, accurate and multi-variate framework.

Keywords: developmental stability, fluctuating asymmetry, morphometrics, 3D image processing

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Authors: Bahar Hazal Yalçınkaya, Bayram Yılmaz, Mustafa Özilgen

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Brain information transmission in the neuronal network occurs in the form of electrical signals. Neural work transmits information between the neurons or neurons and target cells by moving charged particles in a voltage field; a fraction of the energy utilized in this process is dissipated via entropy generation. Exergy loss and entropy generation models demonstrate the inefficiencies of the communication along the dendritic trees. In this study, neurons of 4 different animals were analyzed with one dimensional cable model with N=6 identical dendritic trees and M=3 order of symmetrical branching. Each branch symmetrically bifurcates in accordance with the 3/2 power law in an infinitely long cylinder with the usual core conductor assumptions, where membrane potential is conserved in the core conductor at all branching points. In the model, exergy loss and entropy generation rates are calculated for each branch of equivalent cylinders of electrotonic length (L) ranging from 0.1 to 1.5 for four different dendritic branches, input branch (BI), and sister branch (BS) and two cousin branches (BC-1 & BC-2). Thermodynamic analysis with the data coming from two different cat motoneuron studies show that in both experiments nearly the same amount of exergy is lost while generating nearly the same amount of entropy. Guinea pig vagal motoneuron loses twofold more exergy compared to the cat models and the squid exergy loss and entropy generation were nearly tenfold compared to the guinea pig vagal motoneuron model. Thermodynamic analysis show that the dissipated energy in the dendritic tress is directly proportional with the electrotonic length, exergy loss and entropy generation. Entropy generation and exergy loss show variability not only between the vertebrate and invertebrates but also within the same class. Concurrently, single action potential Na⁺ ion load, metabolic energy utilization and its thermodynamic aspect contributed for squid giant axon and mammalian motoneuron model. Energy demand is supplied to the neurons in the form of Adenosine triphosphate (ATP). Exergy destruction and entropy generation upon ATP hydrolysis are calculated. ATP utilization, exergy destruction and entropy generation showed differences in each model depending on the variations in the ion transport along the channels.

Keywords: ATP utilization, entropy generation, exergy loss, neuronal information transmittance

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Authors: Daniela E. Marin, Cornelia Braicu, Gina C. Pistol, Roxana Cojocneanu-Petric, Ioana Berindan Neagoe, Mihail A. Gras, Ionelia Taranu

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Aristolochic acid (AA) is a carcinogenic, mutagenic, and nephrotoxic compound commonly found in the Aristolochiaceae family of plants. AA is frequently associated with urothelial carcinoma of the upper urinary tract in human and animals and is considered as being responsible for Balkan Endemic Nephropathy. The pig provides a good animal model because the porcine urological system is very similar to that of humans, both in aspects of physiology and anatomy. MicroRNA (miRNA) are small non-coding RNAs that have an impact on a wide range of biological processes by regulating gene expression at post-transcriptional level. The objective of this study was to analyze the miRNA profiling in the kidneys of AA intoxicated swine. For this purpose, ten TOPIGS-40 crossbred weaned piglets, 4-week-old, male and females with an initial average body weight of 9.83 ± 0.5 kg were studied for 28 days. They were given ad libitum access to water and feed and randomly allotted to one of the following groups: control group (C) or aristolochic acid group (AA). They were fed a maize-soybean-meal-based diet contaminated or not with 0.25mgAA/kg. To profile miRNA in the kidneys of pigs, microarrays and bioinformatics approaches were applied to analyze the miRNA in the kidney of control and AA intoxicated pigs. After normalization, our results have shown that a total of 5 known miRNAs and 4 novel miRNAs had different profiling in the kidney of intoxicated animals versus control ones. Expression of miR-32-5p, miR-497-5p, miR-423-3p, miR-218-5p, miR-128-3p were up-regulated by 0.25mgAA/kg feed, while the expression of miR-9793-5p, miR-9835-3p, miR-9840-3p, miR-4334-5p was down-regulated. The microRNA profiling in kidney of intoxicated animals was associated with modified expression of target genes as: RICTOR, LASP1, SFRP2, DKK2, BMI1, RAF1, IGF1R, MAP2K1, WEE1, HDGF, BCL2, EIF4E etc, involved in cell division cycle, apoptosis, cell differentiation and cell migration, cell signaling, cancer etc. In conclusion, this study provides new data concerning the microRNA profiling in kidney after aristolochic acid intoxications with important implications for human and animal health.

Keywords: aristolochic acid, kidney, microRNA, swine

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Authors: Sylvie Michel, Emmanuelle Gagnou, Joanne Hamet

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New major ethical dilemmas are posed by artificial intelligence. This article identifies an existing gap between the ethical questions that AI/robotics researchers grapple with in their research practice and those identified by literature review. The objective is to understand which ethical dilemmas are identified or concern AI researchers in order to compare them with the existing literature. This will enable to conduct training and awareness initiatives for AI researchers, encouraging them to consider these questions during the development of AI. Qualitative analyses were conducted based on direct observation of an AI/Robotics research team focused on collaborative robotics over several months. Subsequently, semi-structured interviews were conducted with 16 members of the team. The entire process took place during the first semester of 2023. The observations were analyzed using an analytical framework, and the interviews were thematically analyzed using Nvivo software. While the literature identifies three primary ethical concerns regarding AI—transparency, bias, and responsibility—the results firstly demonstrate that AI researchers are primarily concerned with the publication and valorization of their work, with the initial ethical concerns revolving around this matter. Questions arise regarding the extent to which to "market" publications and the usefulness of some publications. Research ethics are a central consideration for these teams. Secondly, another result shows that the researchers studied adopt a consequentialist ethics (though not explicitly formulated as such). They ponder the consequences of their development in terms of safety (for humans in relation to Robots/AI), worker autonomy in relation to the robot, and the role of work in society (can robots take over jobs?). Lastly, results indicate that the ethical dilemmas highlighted in the literature (responsibility, transparency, bias) do not explicitly appear in AI/Robotics research. AI/robotics researchers raise specific and pragmatic ethical questions, primarily concerning publications initially and consequentialist considerations afterward. Results demonstrate that these concerns are distant from the existing literature. However, the dilemmas highlighted in the literature also deserve to be explicitly contemplated by researchers. This article proposes that the journals these researchers target should mandate ethical reflection for all presented works. Furthermore, results suggest offering awareness programs in the form of short educational sessions for researchers.

Keywords: ethics, artificial intelligence, research, robotics

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Authors: Jeannette Anniés, Panagiotis Michalis, Chrysoula Papathanasiou, Selby Knudsen

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RiskPACC project aims to bring together researchers, practitioners, and first responders from nine European countries following a co-creation approach aiming to develop customised solutions to meet the needs of end-users. The co-creation workshops target to enhance the communication pathways between local civil protection authorities (CPAs) and citizens, in an effort to close the risk perception-action gap (RPAG). The participants in the workshops include a variety of stakeholders, as well as citizens, fostering the dialogue between the groups and supporting citizen participation in disaster risk management (DRM). The co-creation methodology in place implements co-design elements due to the integration of four ICT tools. Such ICT tools include web-based and mobile application technical solutions in different development stages, ranging from formulation and validation of concepts to pilot demonstrations. In total, seven different case studies are foreseen in RiskPACC. The workflow of the workshops is designed to be adaptive to every of the seven case study countries and their cultures’ particular needs. This work aims to provide an overview of the the preparation and the conduction of the workshops in which researchers and practitioners focused on mapping these different needs from the end users. The latter included first responders but also volunteers and citizens who actively participated in the co-creation workshops. The strategies to improve communication between CPAs and citizens themselves differ in the countries, and the modules of the co-creation methodology are adapted in response to such differences. Moreover, the project partners experienced how the structure of such workshops is perceived differently in the seven case studies. Therefore, the co-creation methodology itself is a design method underlying several iterations, which are eventually shaped by cross-cultural collaboration. For example, some case studies applied other modules according to the participatory group recruited. The participants were technical experts, teachers, citizens, first responders, or volunteers, among others. This work aspires to present the divergent approaches of the seven case studies implementing the co-creation methodology proposed, in response to different perceptions of the modules. An analysis of the adaptations and implications will also be provided to assess where the case studies’ objective of improving disaster resilience has been obtained.

Keywords: citizen participation, co-creation, disaster resilience, risk perception, ICT tools

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Authors: Ruchi Pathania, Ahmad Ahmad, Shireesh Srivastava

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Cyanobacteria is a promising microbe that can capture and convert atmospheric CO₂ and light into valuable industrial bio-products like biofuels, biodegradable plastics, etc. Among their most attractive traits are faster autotrophic growth, whole year cultivation using non-arable land, high photosynthetic activity, much greater biomass and productivity and easy for genetic manipulations. Cyanobacteria store carbon in the form of glycogen which can be hydrolyzed to release glucose and fermented to form bioethanol or other valuable products. Marine cyanobacterial species are especially attractive for countries with scarcity of freshwater. We recently identified a marine native cyanobacterium Synechococcus sp. BDU 130192 which has good growth rate and high level of polyglucans accumulation compared to Synechococcus PCC 7002. In this study, firstly we sequenced the whole genome and the sequences were annotated using the RAST server. Genome scale metabolic model (GSMM) was reconstructed through COBRA toolbox. GSMM is a computational representation of the metabolic reactions and metabolites of the target strain. GSMMs construction through the application of Flux Balance Analysis (FBA), which uses external nutrient uptake rates and estimate steady state intracellular and extracellular reaction fluxes, including maximization of cell growth. The model, which we have named isyn942, includes 942 reactions and 913 metabolites having 831 metabolic, 78 transport and 33 exchange reactions. The phylogenetic tree obtained by BLAST search revealed that the strain was a close relative of Synechococcus PCC 7002. The flux balance analysis (FBA) was applied on the model iSyn942 to predict the theoretical yields (mol product produced/mol CO₂ consumed) for native and non-native products like acetone, butanol, etc. under phototrophic condition by applying metabolic engineering strategies. The reported strain can be a viable strain for biotechnological applications, and the model will be helpful to researchers interested in understanding the metabolism as well as to design metabolic engineering strategies for enhanced production of various bioproducts.

Keywords: cyanobacteria, flux balance analysis, genome scale metabolic model, metabolic engineering

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Authors: Wei-Po Wu, Wen-Yu Liu, Wei−Ting Lin, Hen-Yu Lien

Abstract:

Introduction: Improving balance function for individuals after stroke is a crucial target in physiotherapy. Aquatic therapy which challenges individual’s postural control in an unstable fluid environment may be beneficial in enhancing balance functions. The purposes of the systematic review with meta-analyses were to validate the effects of aquatic therapy in improving balance functions for individuals with strokes in contrast to conventional physiotherapy. Method: Available studies were explored from three electronic databases: PubMed, Scopus, and Web of Science. During literature search, the published date of studies was not limited. The study design of the included studies should be randomized controlled trials (RCTs) and the studies should contain at least one outcome measurement of balance function. The PEDro scale was adopted to assess the quality of included studies, while the 'Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence' was used to evaluate the level of evidence. After the data extraction, studies with same outcome measures were pooled together for meta-analysis. Result: Ten studies with 282 participants were included in analyses. The research qualities of the studies were ranged from fair to good (4 to 8 points). Levels of evidence of the included studies were graded as level 2 and 3. Finally, scores of Berg Balance Scale (BBS), Eye closed force plate center of pressure velocity (anterior-posterior, medial-lateral axis) and Timed up and Go test were pooled and analyzed separately. The pooled results shown improvement in balance function (BBS mean difference (MD): 1.39 points; 95% confidence interval (CI): 0.05-2.29; p=0.002) (Eye closed force plate center of pressure velocity (anterior-posterior axis) MD: 1.39 mm/s; 95% confidence interval (CI): 0.93-1.86; p<0.001) (Eye closed force plate center of pressure velocity (medial-lateral) MD: 1.48 mm/s; 95% confidence interval (CI): 0.15-2.82; p=0.03) and mobility (MD: 0.9 seconds; 95% CI: 0.07-1.73; p=0.03) of stroke individuals after aquatic therapy compared to conventional therapy. Although there were significant differences between two treatment groups, the differences in improvement were relatively small. Conclusion: The aquatic therapy improved general balance function and mobility in the individuals with stroke better than conventional physiotherapy.

Keywords: aquatic therapy, balance function, meta-analysis, stroke, systematic review

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Authors: Tiago Sigal Linhares, Ana Amélia Nascimento da Silva Bones, Juliana Miola, McArthur Alexander Barrow, Airton Tetelbom Stein

Abstract:

Introduction: As a result of increased globalization and changing migration trends, it is expected that a significant portion of People Living with HIV/AIDS (PLWHA) will change their place of residence over time. In order to provide better health care, monitor the HIV epidemic and plan urban public health care and policies, there is a growing need to formulate a strategy for monitoring PLWHA care, location and migration patterns. The Porto Alegre District is characterized by a high prevalence of PLWHA and is considered one of the epicenters of HIV epidemic in Latin America. Objectives: The aim of this study is to create a digital and easily editable map in order to create a visual representation of the location of PLWHA and to monitor their migration within the city and the country in an effort to promote longitudinal care. Methods: This Experience Report used Google Maps Map Creator to generate an active digital map showing the location and changes in residence of 165 PLWHA who received care at two Primary Health Care (PHC) clinics, which attended an estimated population of five thousand patients, in downtown Porto Alegre over the last four years. Their current addresses were discovered in the unified Brazilian health care system digital records (e-SUS) and updated on the map. Results: A digital map with PLWHA current residence location was created. It was possible to demonstrate visually areas with a large concentration of PLWHA and the migration of the population within the city as wells as other cities, regions and states. Conclusions: An easily reproducible and free map could aid in PLWHA monitoring, urban public health planning, target interventions and situational diagnosis. Moreover, a visual representation of PLWHA location and migration could help bring more attention and investments to areas with geographic inequities or higher prevalence of PLWHA. It also enables notification of local PHC units of monitored patients inside their area, which are in clinical risk or with treatment abandonment through active case findings, improving the care of PLWHA.

Keywords: health care, medical public health, theoretical and conceptual innovations, urban public health

Procedia PDF Downloads 122