Search results for: human retinal endothelial cells (hrecs)
Commenced in January 2007
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Edition: International
Paper Count: 10747

Search results for: human retinal endothelial cells (hrecs)

7237 Systematic Identification and Quantification of Substrate Specificity Determinants in Human Protein Kinases

Authors: Manuel A. Alonso-Tarajano, Roberto Mosca, Patrick Aloy

Abstract:

Protein kinases participate in a myriad of cellular processes of major biomedical interest. The in vivo substrate specificity of these enzymes is a process determined by several factors, and despite several years of research on the topic, is still far from being totally understood. In the present work, we have quantified the contributions to the kinase substrate specificity of i) the phosphorylation sites and their surrounding residues in the sequence and of ii) the association of kinases to adaptor or scaffold proteins. We have used position-specific scoring matrices (PSSMs), to represent the stretches of sequences phosphorylated by 93 families of kinases. We have found negative correlations between the number of sequences from which a PSSM is generated and the statistical significance and the performance of that PSSM. Using a subset of 22 statistically significant PSSMs, we have identified specificity determinant residues (SDRs) for 86% of the corresponding kinase families. Our results suggest that different SDRs can function as positive or negative elements of substrate recognition by the different families of kinases. Additionally, we have found that human proteins with known function as adaptors or scaffolds (kAS) tend to interact with a significantly large fraction of the substrates of the kinases to which they associate. Based on this characteristic we have identified a set of 279 potential adaptors/scaffolds (pAS) for human kinases, which is enriched in Pfam domains and functional terms tightly related to the proposed function. Moreover, our results show that for 74.6% of the kinase– pAS association found, the pAS colocalize with the substrates of the kinases they are associated to. Finally, we have found evidence suggesting that the association of kinases to adaptors and scaffolds, may contribute significantly to diminish the in vivo substrate crossed- specificity of protein kinases. In general, our results indicate the relevance of several SDRs for both the positive and negative selection of phosphorylation sites by kinase families and also suggest that the association of kinases to pAS proteins may be an important factor for the localization of the enzymes with their set of substrates.

Keywords: kinase, phosphorylation, substrate specificity, adaptors, scaffolds, cellular colocalization

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7236 A Report of 5-Months-Old Baby with Balanced Chromosomal Rearrangements along with Phenotypic Abnormalities

Authors: Mohit Kumar, Beklashwar Salona, Shiv Murti, Mukesh Singh

Abstract:

We report here a case of five-months old male baby, born as second child of non-consanguineous parents with no considerable history of genetic abnormality which was referred to our cytogenetic laboratory for chromosomal analysis. Physical dysmorphic facial features including mongoloid face, cleft palate, simian crease, and developmental delay were observed. We present this case with unique balanced autosomal translocation of t(3;10)(p21;p13). The risk of phenotypic abnormalities based on de novo balanced translocation was estimated to be 7%. The association of balanced chromosomal rearrangement with Down syndrome features such as multiple congenital anomalies, facial dysmorphism and congenital heart anomalies are very rare in a 5-months old male child. Trisomy-21 is not uncommon in chromosomal abnormality with the birth defect and balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion (RSA). Two ml heparinized peripheral blood cells cultured in RPMI-1640 for 72 hours supplemented with 20% fetal bovine serum, phytohemagglutinin (PHA), and antibiotics were used for chromosomal analysis. A total 30 metaphases images were captured using Olympus-BX51 microscope and analyzed using Bio-view karyotyping software through GTG-banding (G bands by trypsin and Giemsa) according to International System for Human Cytogenetic Nomenclature 2016. The results showed balanced translocation between short arm of chromosome # 3 and short arm of chromosome # 10. The karyotype of the child was found to be 46,XY,t(3;10)(p21; p13). Chromosomal abnormalities are one of the major causes of birth defect in new born babies. Also, balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion. The index case presented with dysmorphic facial features and had a balanced translocation 46,XY,t(3;10)(p21;p13). This translocation with break points at (p21; p13) has not been reported in the literature in a child with facial dysmorphism. To the best of our knowledge, this is the first report of novel balanced translocation t(3;10) with break points in a child with dysmorphic features. We found balanced chromosomal translocation instead of any trisomy or unbalanced aberrations along with some phenotypic abnormalities. Therefore, we suggest that such novel balanced translocation with abnormal phenotype should be reported in order to enable the pathologist, pediatrician, and gynecologist to have a better insight into the intricacies of chromosomal abnormalities and their associated phenotypic features. We hypothesized that dysmorphic features as seen in this case may be the result of change in the pattern of genes located at the breakpoint area in balanced translocations or may be due to deletion or mutation of genes located on the p-arm of chromosome # 3 and p-arm of chromosome # 10.

Keywords: balanced translocation, karyotyping, phenotypic abnormalities, facial dimorphisms

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7235 Feasibility of Leukemia Cancer Treatment (K562) by Atmospheric Pressure Plasma Jet

Authors: Mashayekh Amir Shahriar, Akhlaghi Morteza, Rajaee Hajar, Khani Mohammad Reza, Shokri Babak

Abstract:

A new and novel approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper a pin-to-hole plasma jet suitable for biological applications is investigated, characterized and the possibility and feasibility of cancer cell treatment is evaluated. The characterization includes power consumption via Lissajous method, thermal behavior of plasma using Infra-red camera as a novel method, Optical Emission Spectroscopy (OES) to determine the species that are generated. Treatment of leukemia cancer cells is also implemented and MTT assay is used to evaluate viability.

Keywords: Atmospheric Pressure Plasma Jet (APPJ), Plasma Medicine, Cancer cell treatment, leukemia, Optical Emission

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7234 The Internal View of the Mu'min: Natural Law Theories in Islam

Authors: Gianni Izzo

Abstract:

The relation of Islam to its legal precepts, reflected in the various jurisprudential 'schools of thought' (madhahib), is one expressed in a version of 'positivism' (fiqh) providing the primary theory for deducing Qurʾan rulings and those from the narrations (hadith) of the Prophet Muhammad. Scholars of Islam, including Patricia Crone (2004) and others chronicled by Anver Emon (2005), deny the influence of natural law theories as extra-scriptural indices of revelation’s content. This paper seeks to dispute these claims by reference to historical and canonical examples within Shiʿa legal thought that emphasize the salient roles of ‘aql (reason), fitrah (primordial human nature), and lutf (divine grace). These three holistic features, congenital to every human, and theophanically reflected in nature make up a mode of moral intelligibility antecedent to prophetic revelation. The debate between the 'traditionalist' Akhbaris and 'rationalist' Usulis over the nature of deriving legal edicts in Islam is well-covered academic ground. Instead, an attempt is made to define and detail the built-in assumptions of natural law revealed in the jurisprudential summa of Imami Shiʿism, whether of either dominant school, that undergird its legal prescriptions and methods of deduction.

Keywords: Islam, fiqh, natural law, legal positivism, aql

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7233 Medium Design and Optimization for High Β-Galactosidase Producing Microbial Strains from Dairy Waste through Fermentation

Authors: Ashish Shukla, K. P. Mishra, Pushplata Tripathi

Abstract:

This paper investigates the production and optimization of β-galactosidase enzyme using synthetic medium by isolated wild strains (S1, S2) mutated strains (M1, M2) through SSF and SmF. Among the different cell disintegration methods used, the highest specific activity was obtained when the cells were permeabilized using isoamyl alcohol. Wet lab experiments were performed to investigate the effects of carbon and nitrogen substrates present in Vogel’s medium on β-galactosidase enzyme activity using S1, S2, and M1, M2 strains through SSF. SmF experiments were performed for effects of carbon and nitrogen sources in YLK2Mg medium on β-galactosidase enzyme activity using S1, S2 and M1, M2 strains. Effect of pH on β-galactosidase enzyme production was also done using S1, S2, and M1, M2 strains. Results were found to be very appreciable in all the cases.

Keywords: β-galactosidase, cell disintegration, permeabilized, SSF, SmF

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7232 Effect of Hypoxia on AOX2 Expression in Chlamydomonas reinhardtii

Authors: Maria Ostroukhova, Zhanneta Zalutskaya, Elena Ermilova

Abstract:

The alternative oxidase (AOX) mediates cyanide-resistant respiration, which bypasses proton-pumping complexes III and IV of the cytochrome pathway to directly transfer electrons from reduced ubiquinone to molecular oxygen. In Chlamydomonas reinhardtii, AOX is a monomeric protein that is encoded by two genes of discrete subfamilies, AOX1 and AOX2. Although AOX has been proposed to play essential roles in stress tolerance of organisms, the role of subfamily AOX2 is largely unknown. In C. reinhardtii, AOX2 was initially identified as one of constitutively low expressed genes. Like other photosynthetic organisms C. reinhardtii cells frequently experience periods of hypoxia. To examine AOX2 transcriptional regulation and role of AOX2 in hypoxia adaptation, real-time PCR analysis and artificial microRNA method were employed. Two experimental approaches have been used to induce the anoxic conditions: dark-anaerobic and light-anaerobic conditions. C. reinhardtii cells exposed to the oxygen deprivation have shown increased AOX2 mRNA levels. By contrast, AOX1 was not an anoxia-responsive gene. In C. reinhardtii, a subset of genes is regulated by transcription factor CRR1 in anaerobic conditions. Notable, the AOX2 promoter region contains the potential motif for CRR1 binding. Therefore, the role of CRR1 in the control of AOX2 transcription was tested. The CRR1-underexpressing strains, that were generated and characterized in this work, exhibited low levels of AOX2 transcripts under anoxic conditions. However, the transformants still slightly induced AOX2 gene expression in the darkness. These confirmed our suggestions that darkness is a regulatory stimulus for AOX genes in C. reinhardtii. Thus, other factors must contribute to AOX2 promoter activity under dark-anoxic conditions. Moreover, knock-down of CRR1 caused a complete reduction of AOX2 expression under light-anoxic conditions. These results indicate that (1) CRR1 is required for AOX2 expression during hypoxia, and (2) AOX2 gene is regulated by CRR1 together with yet-unknown regulatory factor(s). In addition, the AOX2-underexpressing strains were generated. The analysis of amiRNA-AOX2 strains suggested a role of this alternative oxidase in hypoxia adaptation of the alga. In conclusion, the results reported here show that C. reinhardtii AOX2 gene is stress inducible. CRR1 transcriptional factor is involved in the regulation of the AOX2 gene expression in the absence of oxygen. Moreover, AOX2 but not AOX1 functions under oxygen deprivation. This work was supported by Russian Science Foundation (research grant № 16-14-10004).

Keywords: alternative oxidase 2, artificial microRNA approach, chlamydomonas reinhardtii, hypoxia

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7231 Mapping Context, Roles, and Relations for Adjudicating Robot Ethics

Authors: Adam J. Bowen

Abstract:

Abstract— Should robots have rights or legal protections. Often debates concerning whether robots and AI should be afforded rights focus on conditions of personhood and the possibility of future advanced forms of AI satisfying particular intrinsic cognitive and moral attributes of rights-holding persons. Such discussions raise compelling questions about machine consciousness, autonomy, and value alignment with human interests. Although these are important theoretical concerns, especially from a future design perspective, they provide limited guidance for addressing the moral and legal standing of current and near-term AI that operate well below the cognitive and moral agency of human persons. Robots and AI are already being pressed into service in a wide range of roles, especially in healthcare and biomedical contexts. The design and large-scale implementation of robots in the context of core societal institutions like healthcare systems continues to rapidly develop. For example, we bring them into our homes, hospitals, and other care facilities to assist in care for the sick, disabled, elderly, children, or otherwise vulnerable persons. We enlist surgical robotic systems in precision tasks, albeit still human-in-the-loop technology controlled by surgeons. We also entrust them with social roles involving companionship and even assisting in intimate caregiving tasks (e.g., bathing, feeding, turning, medicine administration, monitoring, transporting). There have been advances to enable severely disabled persons to use robots to feed themselves or pilot robot avatars to work in service industries. As the applications for near-term AI increase and the roles of robots in restructuring our biomedical practices expand, we face pressing questions about the normative implications of human-robot interactions and collaborations in our collective worldmaking, as well as the moral and legal status of robots. This paper argues that robots operating in public and private spaces be afforded some protections as either moral patients or legal agents to establish prohibitions on robot abuse, misuse, and mistreatment. We already implement robots and embed them in our practices and institutions, which generates a host of human-to-machine and machine-to-machine relationships. As we interact with machines, whether in service contexts, medical assistance, or home health companions, these robots are first encountered in relationship to us and our respective roles in the encounter (e.g., surgeon, physical or occupational therapist, recipient of care, patient’s family, healthcare professional, stakeholder). This proposal aims to outline a framework for establishing limiting factors and determining the extent of moral or legal protections for robots. In doing so, it advocates for a relational approach that emphasizes the priority of mapping the complex contextually sensitive roles played and the relations in which humans and robots stand to guide policy determinations by relevant institutions and authorities. The relational approach must also be technically informed by the intended uses of the biomedical technologies in question, Design History Files, extensive risk assessments and hazard analyses, as well as use case social impact assessments.

Keywords: biomedical robots, robot ethics, robot laws, human-robot interaction

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7230 Reviewing the Relation of Language and Minorities' Rights

Authors: Mohsen Davarzani, Ehsan Lame, Mohammad Taghi Hassan Zadeh

Abstract:

Language is considered as a powerful and outstanding feature of ethnicity. However, humiliating and prohibiting using human language is one the most heinous and brutal acts in the form of racism. In other words, racism can be a product of physiological humiliations and discrimination, such as skin color, and can also be resulted from ethnic humiliation and discrimination such as language, customs and so on. Ethnic and racial discrimination is one of the main problems of the world that minorities and occasionally the majority have suffered from. Nowadays, few states can be found in which all individuals and its citizens are of the same race and ethnicity, culture and language. In these countries, referred to as the multinational states, (eg, Iran, Switzerland, India, etc.), there are the communities and groups which have their own linguistic, cultural and historical characteristics. Characteristics of human rights issues, diversity of issues and plurality of meanings indicate that they appear in various aspects. The states are obliged to respect, as per national and international obligations, the rights of all citizens from different angles, especially different groups that require special attention in order of the particular aspects such as ethnicity, religious and political minorities, children, women, workers, unions and in case the states are in breach of any of these items, they are faced with challenges in local, regional or international fields.

Keywords: law, language, minorities, ethnicity

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7229 Omni-Relay (OR) Scheme-Aided LTE-A Communication Systems

Authors: Hassan Mahasneh, Abu Sesay

Abstract:

We propose the use of relay terminals at the cell edge of an LTE-based cellar system. Each relay terminal is equipped with an omni-directional antenna. We refer to this scheme as the Omni-Relay (OR) scheme. The OR scheme coordinates the inter-cell interference (ICI) stemming from adjacent cells and increases the desired signal level at cell-edge regions. To validate the performance of the OR scheme, we derive the average signal-to-interference plus noise ratio (SINR) and the average capacity and compare it with the conventional universal frequency reuse factor (UFRF). The results show that the proposed OR scheme provides higher average SINR and average capacity compared to the UFRF due to the assistance of the distributed relay nodes.

Keywords: the UFRF scheme, the OR scheme, ICI, relay terminals, SINR, spectral efficiency

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7228 The Potential Involvement of Platelet Indices in Insulin Resistance in Morbid Obese Children

Authors: Orkide Donma, Mustafa M. Donma

Abstract:

Association between insulin resistance (IR) and hematological parameters has long been a matter of interest. Within this context, body mass index (BMI), red blood cells, white blood cells and platelets were involved in this discussion. Parameters related to platelets associated with IR may be useful indicators for the identification of IR. Platelet indices such as mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) are being questioned for their possible association with IR. The aim of this study was to investigate the association between platelet (PLT) count as well as PLT indices and the surrogate indices used to determine IR in morbid obese (MO) children. A total of 167 children participated in the study. Three groups were constituted. The number of cases was 34, 97 and 36 children in the normal BMI, MO and metabolic syndrome (MetS) groups, respectively. Sex- and age-dependent BMI-based percentile tables prepared by World Health Organization were used for the definition of morbid obesity. MetS criteria were determined. BMI values, homeostatic model assessment for IR (HOMA-IR), alanine transaminase-to-aspartate transaminase ratio (ALT/AST) and diagnostic obesity notation model assessment laboratory (DONMA-lab) index values were computed. PLT count and indices were analyzed using automated hematology analyzer. Data were collected for statistical analysis using SPSS for Windows. Arithmetic mean and standard deviation were calculated. Mean values of PLT-related parameters in both control and study groups were compared by one-way ANOVA followed by Tukey post hoc tests to determine whether a significant difference exists among the groups. The correlation analyses between PLT as well as IR indices were performed. Statistically significant difference was accepted as p-value < 0.05. Increased values were detected for PLT (p < 0.01) and PCT (p > 0.05) in MO group compared to those observed in children with N-BMI. Significant increases for PLT (p < 0.01) and PCT (p < 0.05) were observed in MetS group in comparison with the values obtained in children with N-BMI (p < 0.01). Significantly lower MPV and PDW values were obtained in MO group compared to the control group (p < 0.01). HOMA-IR (p < 0.05), DONMA-lab index (p < 0.001) and ALT/AST (p < 0.001) values in MO and MetS groups were significantly increased compared to the N-BMI group. On the other hand, DONMA-lab index values also differed between MO and MetS groups (p < 0.001). In the MO group, PLT was negatively correlated with MPV and PDW values. These correlations were not observed in the N-BMI group. None of the IR indices exhibited a correlation with PLT and PLT indices in the N-BMI group. HOMA-IR showed significant correlations both with PLT and PCT in the MO group. All of the three IR indices were well-correlated with each other in all groups. These findings point out the missing link between IR and PLT activation. In conclusion, PLT and PCT may be related to IR in addition to their identities as hemostasis markers during morbid obesity. Our findings have suggested that DONMA-lab index appears as the best surrogate marker for IR due to its discriminative feature between morbid obesity and MetS.

Keywords: children, insulin resistance, metabolic syndrome, plateletcrit, platelet indices

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7227 Molecular Characterization of Arginine Sensing Response in Unravelling Host-Pathogen Interactions in Leishmania

Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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7226 Mathematical Modelling of Human Cardiovascular-Respiratory System Response to Exercise in Rwanda

Authors: Jean Marie Ntaganda, Froduald Minani, Wellars Banzi, Lydie Mpinganzima, Japhet Niyobuhungiro, Jean Bosco Gahutu, Vincent Dusabejambo, Immaculate Kambutse

Abstract:

In this paper, we present a nonlinear dynamic model for the interactive mechanism of the cardiovascular and respiratory system. The model is designed and analyzed for human during physical exercises. In order to verify the adequacy of the designed model, data collected in Rwanda are used for validation. We have simulated the impact of heart rate and alveolar ventilation as controls of cardiovascular and respiratory system respectively to steady state response of the main cardiovascular hemodynamic quantities i.e., systemic arterial and venous blood pressures, arterial oxygen partial pressure and arterial carbon dioxide partial pressure, to the stabilised values of controls. We used data collected in Rwanda for both male and female during physical activities. We obtained a good agreement with physiological data in the literature. The model may represent an important tool to improve the understanding of exercise physiology.

Keywords: exercise, cardiovascular/respiratory, hemodynamic quantities, numerical simulation, physical activity, sportsmen in Rwanda, system

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7225 Monoallelic and Biallelic Deletions of 13q14 in a Group of 36 CLL Patients Investigated by CGH Haematological Cancer and SNP Array (8x60K)

Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

Abstract:

Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

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7224 Effect of Chronic Exposure to Diazinon on Glucose Homeostasis and Oxidative Stress in Pancreas of Rats and the Potential Role of Mesna in Ameliorating This Effect

Authors: Azza El-Medany, Jamila El-Medany

Abstract:

Residential and agricultural pesticide use is widespread in the world. Their extensive and indiscriminative use, in addition with their ability to interact with biological systems other than their primary targets constitute a health hazards to both humans and animals. The toxic effects of pesticides include alterations in metabolism; there is a lack of knowledge that organophosphates can cause pancreatic toxicity. The primary goal of this work is to study the effects of chronic exposure to Diazinon an organophosphate used in agriculture on pancreatic tissues and evaluate the ameliorating effect of Mesna as antioxidant on the toxicity of Diazinon on pancreatic tissues.40 adult male rats, their weight ranged between 300-350 g. The rats were classified into three groups; control (10 rats) was received corn oil at a dose of 1 0 mg/kg/day by gavage once a day for 2 months. Diazinon (15 rats) was received Diazinon at a dose of 10 mg/kg/day dissolved in corn oil by gavage once a day for 2 months. Treated group (15 rats), were received Mesna 180mg/kg once a week by gavage 15 minutes before administration of Diazinon for 2 months. At the end of the experiment, animals were anesthetized, blood samples were taken by cardiac puncture for glucose and insulin assays and pancreas was removed and divided into 3 portions; first portion for histopathological study; second portion for ultrastructural study; third portion for biochemical study using Elisa Kits including determination of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), myeloperoxidase activity (MPO), interleukin 1β (IL-1β). A significant increase in the levels of MDA, TNF-α, MPO activity, IL-1β, serum glucose levels in the toxicated group with Diazinon were observed, while a significant reduction was noticed in GSH in serum insulin levels. After treatment with Mesna a significant reduction was observed in the previously mentioned parameters except that there was a significant rise in GSH in insulin levels. Histopathological and ultra-structural studies showed destruction in pancreatic tissues and β cells were the most affected cells among the injured islets as compared with the control group. The current study try to spot light about the effects of chronic exposure to pesticides on vital organs as pancreas also the role of oxidative stress that may be induced by them in evoking their toxicity. This study shows the role of antioxidant drugs in ameliorating or preventing the toxicity. This appears to be a promising approach that may be considered as a complementary treatment of pesticide toxicity.

Keywords: Diazinon, reduced glutathione, myeloperoxidase activity, tumor necrosis factor α, Mesna

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7223 Health Expenditure and Household Age Composition in India: Consequences for Health System Development

Authors: Milind Bharambe, Chander Shekhar

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India is a vast country with its 1.21 billion population at the dawn of new decade, which accounts for one sixth of the global human capital in the world today. It is well known that health expenditure in India is dominated by private spending. This is an unfortunate consequence of India’s development because of large positive externality associated with health spending, which make health a merit good. This paper has used data from NSSO and Indian Government’s spending on health as reported by Ministry of Health and Family Welfare. Understanding of the dynamism of age-structure of the population would greatly optimize the expenditure on health care services. A country with good public health indicators is bound to possess good human capital which is an asset to the economic growth and indicator of development status of country. The paper tries to present the linkages between the health expenditure incurred by different states at various levels of demographic transition levels and the efficiency in utilization of health expenditure. It also looks into the way in which allocative efficiency health services can be improved. Paper tries to explore the per capita spending on health and how the demographic transition taking place in different states of India affect the required quantity and quality of health services.

Keywords: age structure, demographic transition, health expenditure, morbidity

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7222 Analysis of Facial Expressions with Amazon Rekognition

Authors: Kashika P. H.

Abstract:

The development of computer vision systems has been greatly aided by the efficient and precise detection of images and videos. Although the ability to recognize and comprehend images is a strength of the human brain, employing technology to tackle this issue is exceedingly challenging. In the past few years, the use of Deep Learning algorithms to treat object detection has dramatically expanded. One of the key issues in the realm of image recognition is the recognition and detection of certain notable people from randomly acquired photographs. Face recognition uses a way to identify, assess, and compare faces for a variety of purposes, including user identification, user counting, and classification. With the aid of an accessible deep learning-based API, this article intends to recognize various faces of people and their facial descriptors more accurately. The purpose of this study is to locate suitable individuals and deliver accurate information about them by using the Amazon Rekognition system to identify a specific human from a vast image dataset. We have chosen the Amazon Rekognition system, which allows for more accurate face analysis, face comparison, and face search, to tackle this difficulty.

Keywords: Amazon rekognition, API, deep learning, computer vision, face detection, text detection

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7221 A Theragnostic Approach for Alzheimer’s Disease Focused on Phosphorylated Tau

Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

Abstract:

Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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7220 Autophagy in the Midgut Epithelium of Spodoptera exigua Hübner (Lepidoptera: Noctuidae) Larvae Exposed to Various Cadmium Concentration - 6-Generational Exposure

Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska

Abstract:

Autophagy is a form of cell remodeling in which an internalization of organelles into vacuoles that are called autophagosomes occur. Autophagosomes are the targets of lysosomes, thus causing digestion of cytoplasmic components. Eventually, it can lead to the death of the entire cell. However, in response to several stress factors, e.g., starvation, heavy metals (e.g., cadmium) autophagy can also act as a pro-survival factor, protecting the cell against its death. The main aim of our studies was to check if the process of autophagy, which could appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects. As a model animal, we chose the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), a well-known polyphagous pest of many vegetable crops. We analyzed specimens at final larval stage (5th larval stage), due to its hyperfagy, resulting in great amount of cadmium assimilate. The culture consisted of two strains: a control strain (K) fed a standard diet, and a cadmium strain (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for 146 generations, both strains. In addition, the control insects were transferred to the Cd supplemented diet (5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food, 44 mg Cd per kg of dry weight of food). Therefore, we obtained Cd1, Cd2, Cd3 and KCd experimental groups. Autophagy has been examined using transmission electron microscope. During this process, degenerated organelles were surrounded by a membranous phagophore and enclosed in an autophagosome. Eventually, after the autophagosome fused with a lysosome, an autolysosome was formed and the process of the digestion of organelles began. During the 1st year of the experiment, we analyzed specimens of 6 generations in all the lines. The intensity of autophagy depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the Ist, IInd, IIIrd, IVth, Vth and VIth generation the intensity of autophagy in the midguts from cadmium-exposed strains decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. The higher amount of cells with autophagy was observed in Cd1 and Cd2. However, it was still higher than the percentage of cells with autophagy in the same tissues of the insects from the control and multigenerational cadmium strain. This may indicate that during 6-generational exposure to various Cd concentration, a preserved tolerance to cadmium was not maintained. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.

Keywords: autophagy, cell death, digestive system, ultrastructure

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7219 Identification of Toxic Metal Deposition in Food Cycle and Its Associated Public Health Risk

Authors: Masbubul Ishtiaque Ahmed

Abstract:

Food chain contamination by heavy metals has become a critical issue in recent years because of their potential accumulation in bio systems through contaminated water, soil and irrigation water. Industrial discharge, fertilizers, contaminated irrigation water, fossil fuels, sewage sludge and municipality wastes are the major sources of heavy metal contamination in soils and subsequent uptake by crops. The main objectives of this project were to determine the levels of minerals, trace elements and heavy metals in major foods and beverages consumed by the poor and non-poor households of Dhaka city and assess the dietary risk exposure to heavy metal and trace metal contamination and potential health implications as well as recommendations for action. Heavy metals are naturally occurring elements that have a high atomic weight and a density of at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, and carcinogenicity.

Keywords: food chain, determine the levels of minerals, trace elements, heavy metals, production and use, human exposure, toxicity, carcinogenicity

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7218 Synthesis and Characterization of High-Aspect-Ratio Hematite Nanostructures for Solar Water Splitting

Authors: Paula Quiterio, Arlete Apolinario, Celia T. Sousa, Joao Azevedo, Paula Dias, Adelio Mendes, Joao P. Araujo

Abstract:

Nowadays one of the mankind's greatest challenges has been the supply of low-cost and environmentally friendly energy sources as an alternative to non-renewable fossil fuels. Hydrogen has been considered a promising solution, representing a clean and low-cost fuel. It can be produced directly from clean and abundant resources, such as sunlight and water, using photoelectrochemical cells (PECs), in a process that mimics the nature´s photosynthesis. Hematite (alpha-Fe2O3) has attracted considerable attention as a promising photoanode for solar water splitting, due to its high chemical stability, nontoxicity, availability and low band gap (2.2 eV), which allows reaching a high thermodynamic solar-to-hydrogen efficiency of 16.8 %. However, the main drawbacks of hematite such as the short hole diffusion length and the poor conductivity that lead to high electron-hole recombination result in significant PEC efficiency losses. One strategy to overcome these limitations and to increase the PEC efficiency is to use 1D nanostructures, such as nanotubes (NTs) and nanowires (NWs), which present high aspect ratios and large surface areas providing direct pathways for electron transport up to the charge collector and minimizing the recombination losses. In particular, due to the ultrathin walls of the NTs, the holes can reach the surface faster than in other nanostructures, representing a key factor for the NTs photoresponse. In this work, we prepared hematite NWs and NTs, respectively by hydrothermal process and electrochemical anodization. For hematite NWs growing, we studied the effect of variable hydrothermal conditions, different annealing temperatures and time, and the use of Ti and Sn dopants on the morphology and PEC performance. The crystalline phase characterization by X-ray diffraction was crucial to distinguish the formation of hematite and other iron oxide phases, alongside its effect on the photoanodes conductivity and consequent PEC efficiency. The conductivity of the as-prepared NWs is very low, in the order of 10-5 S cm-1, but after doping and annealing optimization it increased by a factor of 105. A high photocurrent density of 1.02 mA cm-2 at 1.45 VRHE was obtained under simulated sunlight, which is a very promising value for this kind of hematite nanostructures. The stability of the photoelectrodes was also tested, presenting good stability after several J-V measurements over time. The NTs, synthesized by fast anodizations with potentials ranging from 20-100 V, presented a linear growth of the NTs pore walls, with very low thicknesses from 10 - 18 nm. These preliminary results are also very promising for the use of hematite photoelectrodes on PEC hydrogen applications.

Keywords: hematite, nanotubes, nanowires, photoelectrochemical cells

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7217 Effect of Perception on People’s Behavior in Public Space

Authors: Morteza Maleki

Abstract:

In the present study is that it tried to behave in the environment to be monitored and the respective roles of environment (assumed as a vessel) and human beings (assumed as occupants of this vessel) inevitably create effects which can be expressed as various behaviors on the part of human being. The mutual relationship between man and his environment is exhibited through perceptions, behaviors, subjective images, activities, etc. This study investigates the conceptual dimension in the form of the four components of readability, sense of place, identity, and Tenability (tenability) at the Ahmadabad Axis in Mashhad. The theoretical fundamentals and the data regarding the status quo were presented through the descriptive method and the proposed policies were derived through analyzing the available status quo information. The required data were gathered from library resources and documents related to the studied area as well as from instruments used in field methods such as questionnaires. Upon conducting the necessary investigation, the conceptual dimension within the design area was analyzed. The SWOT table was presented, and the results obtained for improving environmental perception were arranged in the form of policy-making tables and operational projects tables for improving the sense of place, creating imagery, and other investigated components.

Keywords: public space, perception, environment, behavior

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7216 Biodegradation Ability of Polycyclic Aromatic Hydrocarbon (PAHs) Degrading Bacillus cereus Strain JMG-01 Isolated from PAHs Contaminated Soil

Authors: Momita Das, Sofia Banu, Jibon Kotoky

Abstract:

Environmental contamination of natural resources with persistent organic pollutants is of great world-wide apprehension. Polycyclic aromatic hydrocarbons (PAHs) are among the organic pollutants, released due to various anthropogenic activities. Due to their toxic, carcinogenic and mutagenic properties, PAHs are of environmental and human concern. Presently, bioremediation has evolved as the most promising biotechnology for cleanup of such contaminants because of its economical and less cost effectiveness. In the present study, distribution of 16 USEPA priority PAHs was determined in the soil samples collected from fifteen different sites of Guwahati City, the Gateway of the North East Region of India. The total concentrations of 16 PAHs (Σ16 PAHs) ranged from 42.7-742.3 µg/g. Higher concentration of total PAHs was found more in the Industrial areas compared to all the sites (742.3 µg/g and 628 µg/g). It is noted that among all the PAHs, Naphthalene, Acenaphthylene, Anthracene, Fluoranthene, Chrysene and Benzo(a)Pyrene were the most available and contain the higher concentration of all the PAHs. Since microbial activity has been deemed the most influential and significant cause of PAH removal; further, twenty-three bacteria were isolated from the most contaminated sites using the enrichment process. These strains were acclimatized to utilize naphthalene and anthracene, each at 100 µg/g concentration as sole carbon source. Among them, one Gram-positive strain (JMG-01) was selected, and biodegradation ability and initial catabolic genes of PAHs degradation were investigated. Based on 16S rDNA analysis, the isolate was identified as Bacillus cereus strain JMG-01. Topographic images obtained using Scanning Electron Microscope (SEM) and Atomic Force Microscope (AFM) at scheduled time intervals of 7, 14 and 21 days, determined the variation in cell morphology during the period of degradation. AFM and SEM micrograph of biomass showed high filamentous growth leading to aggregation of cells in the form of biofilm with reference to the incubation period. The percentage degradation analysis using gas chromatography and mass analyses (GC-MS) suggested that more than 95% of the PAHs degraded when the concentration was at 500 µg/g. Naphthalene, naphthalene-2-methy, benzaldehyde-4-propyl, 1, 2, benzene di-carboxylic acid and benzene acetic acid were the major metabolites produced after degradation. Moreover, PCR experiments with specific primers for catabolic genes, ndo B and Cat A suggested that JMG-01 possess genes for PAHs degradation. Thus, the study concludes that Bacillus cereus strain JMG-01 has efficient biodegrading ability and can trigger the clean-up of PAHs contaminated soil.

Keywords: AFM, Bacillus cereus strain JMG-01, degradation, polycyclic aromatic hydrocarbon, SEM

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7215 Functionalized Nanoparticles for Drug Delivery Applications

Authors: Temesgen Geremew

Abstract:

Functionalized nanoparticles have emerged as a revolutionary platform for drug delivery, offering significant advantages over traditional methods. By strategically modifying their surface properties, these nanoparticles can be designed to target specific tissues and cells, significantly reducing off-target effects and enhancing therapeutic efficacy. This targeted approach allows for lower drug doses, minimizing systemic exposure and potential side effects. Additionally, functionalization enables controlled release of the encapsulated drug, improving drug stability and reducing the frequency of administration, leading to improved patient compliance. This work explores the immense potential of functionalized nanoparticles in revolutionizing drug delivery, addressing limitations associated with conventional therapies and paving the way for personalized medicine with precise and targeted treatment strategies.

Keywords: nanoparticles, drug, nanomaterials, applications

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7214 Ecological Risk Aspects of Essential Trace Metals in Soil Derived From Gold Mining Region, South Africa

Authors: Lowanika Victor Tibane, David Mamba

Abstract:

Human body, animals, and plants depend on certain essential metals in permissible quantities for their survival. Excessive metal concentration may cause severe malfunctioning of the organisms and even fatal in extreme cases. Because of gold mining in the Witwatersrand basin in South Africa, enormous untreated mine dumps comprise elevated concentration of essential trace elements. Elevated quantities of trace metal have direct negative impact on the quality of soil for different land use types, reduce soil efficiency for plant growth, and affect the health human and animals. A total of 21 subsoil samples were examined using inductively coupled plasma optical emission spectrometry and X-ray fluorescence methods and the results elevated men concentration of Fe (36,433.39) > S (5,071.83) > Cu (1,717,28) > Mn (612.81) > Cr (74.52) > Zn (68.67) > Ni (40.44) > Co (9.63) > P (3.49) > Mo > (2.74), reported in mg/kg. Using various contamination indices, it was discovered that the sites surveyed are on average moderately contaminated with Co, Cr, Cu, Mn, Ni, S, and Zn. The ecological risk assessment revealed a low ecological risk for Cr, Ni and Zn, whereas Cu poses a very high ecological risk.

Keywords: essential trace elements, soil contamination, contamination indices, toxicity, descriptive statistics, ecological risk evaluation

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7213 Ternary Content Addressable Memory Cell with a Leakage Reduction Technique

Authors: Gagnesh Kumar, Nitin Gupta

Abstract:

Ternary Content Addressable Memory cells are mainly popular in network routers for packet forwarding and packet classification, but they are also useful in a variety of other applications that require high-speed table look-up. The main TCAM-design challenge is to decrease the power consumption associated with the large amount of parallel active circuitry, without compromising with speed or memory density. Furthermore, when the channel length decreases, leakage power becomes more significant, and it can even dominate dynamic power at lower technologies. In this paper, we propose a TCAM-design technique, called Virtual Power Supply technique that reduces the leakage by a substantial amount.

Keywords: match line (ML), search line (SL), ternary content addressable memory (TCAM), Leakage power (LP)

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7212 Intellectual Property Rights and Health Rights: A Feasible Reform Proposal to Facilitate Access to Drugs in Developing Countries

Authors: M. G. Cattaneo

Abstract:

The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: global health, global justice, patent law reform, access to drugs

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7211 An Efficient Hybrid Approach Based on Multi-Agent System and Emergence Method for the Integration of Systematic Preventive Maintenance Policies

Authors: Abdelhadi Adel, Kadri Ouahab

Abstract:

This paper proposes a hybrid algorithm for the integration of systematic preventive maintenance policies in hybrid flow shop scheduling to minimize makespan. We have implemented a problem-solving approach for optimizing the processing time, methods based on metaheuristics. The proposed approach is inspired by the behavior of the human body. This hybridization is between a multi-agent system and inspirations of the human body, especially genetics. The effectiveness of our approach has been demonstrated repeatedly in this paper. To solve such a complex problem, we proposed an approach which we have used advanced operators such as uniform crossover set and single point mutation. The proposed approach is applied to three preventive maintenance policies. These policies are intended to maximize the availability or to maintain a minimum level of reliability during the production chain. The results show that our algorithm outperforms existing algorithms. We assumed that the machines might be unavailable periodically during the production scheduling.

Keywords: multi-agent systems, emergence, genetic algorithm, makespan, systematic maintenance, scheduling, hybrid flow shop scheduling

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7210 Human Performance Evaluating of Advanced Cardiac Life Support Procedure Using Fault Tree and Bayesian Network

Authors: Shokoufeh Abrisham, Seyed Mahmoud Hossieni, Elham Pishbin

Abstract:

In this paper, a hybrid method based on the fault tree analysis (FTA) and Bayesian networks (BNs) are employed to evaluate the team performance quality of advanced cardiac life support (ACLS) procedures in emergency department. According to American Heart Association (AHA) guidelines, a category relying on staff action leading to clinical incidents and also some discussions with emergency medicine experts, a fault tree model for ACLS procedure is obtained based on the human performance. The obtained FTA model is converted into BNs, and some different scenarios are defined to demonstrate the efficiency and flexibility of the presented model of BNs. Also, a sensitivity analysis is conducted to indicate the effects of team leader presence and uncertainty knowledge of experts on the quality of ACLS. The proposed model based on BNs shows that how the results of risk analysis can be closed to reality comparing to the obtained results based on only FTA in medical procedures.

Keywords: advanced cardiac life support, fault tree analysis, Bayesian belief networks, numan performance, healthcare systems

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7209 Differential Expression Profile Analysis of DNA Repair Genes in Mycobacterium Leprae by qPCR

Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

Abstract:

Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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7208 Stress Evaluation at Lower Extremity during Walking with Unstable Shoe

Authors: Sangbaek Park, Seungju Lee, Soo-Won Chae

Abstract:

Unstable shoes are known to strengthen lower extremity muscles and improve gait ability and to change the user’s gait pattern. The change in gait pattern affects human body enormously because the walking is repetitive and steady locomotion in daily life. It is possible to estimate the joint motion including joint moment, force and inertia effect using kinematic and kinetic analysis. However, the change of internal stress at the articular cartilage has not been possible to estimate. The purpose of this research is to evaluate the internal stress of human body during gait with unstable shoes. In this study, FE analysis was combined with motion capture experiment to obtain the boundary condition and loading condition during walking. Motion capture experiments were performed with a participant during walking with normal shoes and with unstable shoes. Inverse kinematics and inverse kinetic analysis was performed with OpenSim. The joint angle and muscle forces were estimated as results of inverse kinematics and kinetics analysis. A detailed finite element (FE) lower extremity model was constructed. The joint coordinate system was added to the FE model and the joint coordinate system was coincided with OpenSim model’s coordinate system. Finally, the joint angles at each phase of gait were used to transform the FE model’s posture according to actual posture from motion capture. The FE model was transformed into the postures of three major phases (1st peak of ground reaction force, mid stance and 2nd peak of ground reaction force). The direction and magnitude of muscle force were estimated by OpenSim and were applied to the FE model’s attachment point of each muscle. Then FE analysis was performed to compare the stress at knee cartilage during gait with normal shoes and unstable shoes.

Keywords: finite element analysis, gait analysis, human model, motion capture

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