Search results for: human transmembrane transporters binding propensity

Authors: Ana Luiza Casasanta Garcia, Maria Del Carmen Cortizo

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From the classic contractualist and early declarations of modern rights, discussions on policies for the protection and promotion of human rights were highlighted in an attempt to ensure the realization of human dignity and its values, which are (re) negotiated according to the needs evidenced in each historical and contextual moment. Aiming at guaranteeing human rights to Brazilian citizens, created in 2009 and updated in 2010, the Third National Human Rights Program (PNDH III) in force highlights guidelines and recommendations to guarantee human rights, among them, to guarantee the rights of women in Brazil. Based on this document, this article aims to locate historically and culturally the understanding of human rights related to the rights of women in Brazilian territory, from the analysis of the guiding axes of women's rights of the PNDH III. In methodological terms, the qualitative approach and documentary research were used to analyze the data according to the critical discourse analysis. As a result, it has been found that the process of building and maintaining the guarantee of women's human rights needs a reformulation that also shows a social revolution. This is justified by the fact that even with the provision in the PNDH III that, in order to guarantee the rights of women, it is necessary, for example, to adapt the Penal Code to the decriminalization of abortion and the professionalization of prostitution, these points are still very controversial and are not put into practice by the State. Finally, the importance of the critique of politics and the current system of production of understandings in favor of this social transformation is emphasized.

Keywords: human rights of women, social transformation, national human rights program III, public politics

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Authors: Uche A. Nnawulezi

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This study evolved from the need to look at and evaluate the difficulties in the domestication of International Laws and Human Rights Laws in Nigeria. Essentially, the paper-based its examination on documentary evidence and depended much on secondary sources, for example, textbooks, journals, articles, periodicals and research reports emanating from suggestions of international law experts, jurists and human rights lawyers on the development challenges in domesticating international laws and human rights laws in Nigeria. These data were analyzed by the application of content analysis and careful observation of the current municipal laws which has posed great challenges in the domestication of International laws. This paper might follow the historical backdrop of the practices in the use of International law in Nigeria and should likewise consider the challenges inherent in these practices. The paper suggests that a sustainable domestication of International Laws and its application in Nigerian courts will ensure a better enforcement of human rights within the domestic jurisdiction.

Keywords: international law, human rights, domestication, challenges

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Authors: Tooba Sabir, Namra Sabir, Mohammad Amjad Sabir

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The human-environment relationship has been projected since the beginning of literary tradition i.e. pastoral tradition, however, the interest of critics, writers and poets, in this view, has been developed, since the last couple of decades because of the increasing scope of environmental studies and growing environmental issues. One such novel, that projects human-environment relationship, is ‘The Alchemist.’ It is Paulo Coelho’s one of the most read novels. It holds a central theme that the universe conspires to help a person achieve his destiny, projecting anthropocentrism and human domination by centralizing human and devaluing the intrinsic worth of ecosystem. However, ecocritical analysis of the text reveals that the novel contains, at several instances, ecocentrism as well e.g. ‘everything on earth is being continuously transformed because earth is alive.’ This portrays ecosphere as living and dynamic entity rather than a mere instrument for human to achieve his destiny. The idea that the universe shares the same language projects unity of nature showing the relationship between human and non-human aspects of the environment as one being and not separate or superior to one another. It depicts human as a part of the environment and not the lord of the world. Therefore, it can be concluded that the novel oscillates between both the ecocentric and the anthropocentric phenomena. It is not suggested, however, that one phenomenon should be valued over the other but that the complexities of both the phenomena should be recognized, acknowledged and valued in order to encourage the interactions between literature and environment.

Keywords: anthropocentrism, ecocentrism, ecocritical analysis, human-environment relationship

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Authors: Aidan Battison, Neliswa Mama

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Environmental pollution by ionic species has been identified as one of the biggest challenges to the sustainable development of communities. The widespread use of organic and inorganic chemical products and the release of toxic chemical species from industrial waste have resulted in a need for advanced monitoring technologies for environment protection, remediation and restoration. Some of the disadvantages of conventional sensing methods include expensive instrumentation, well-controlled experimental conditions, time-consuming procedures and sometimes complicated sample preparation. On the contrary, the development of fluorescent chemosensors for biological and environmental detection of metal ions has attracted a great deal of attention due to their simplicity, high selectivity, eidetic recognition, rapid response and real-life monitoring. Coumarin derivatives S1 and S2 (Scheme 1) containing 1,2,3-triazole moieties at position -3- have been designed and synthesized from azide and alkyne derivatives by CuAAC “click” reactions for the detection of metal ions. These compounds displayed a strong preference for Fe3+ ions with complexation resulting in fluorescent quenching through photo-induced electron transfer (PET) by the “sphere of action” static quenching model. The tested metal ions included Cd2+, Pb2+, Ag+, Na+, Ca2+, Cr3+, Fe3+, Al3+, Cd2+, Ba2+, Cu2+, Co2+, Hg2+, Zn2+ and Ni2+. The detection limits of S1 and S2 were determined to be 4.1 and 5.1 uM, respectively. Compound S1 displayed the greatest selectivity towards Fe3+ in the presence of competing for metal cations. S1 could also be used for the detection of Fe3+ in a mixture of CH3CN/H¬2¬O. Binding stoichiometry between S1 and Fe3+ was determined by using both Jobs-plot and Benesi-Hildebrand analysis. The binding was shown to occur in a 1:1 ratio between the sensor and a metal cation. Reversibility studies between S1 and Fe3+ were conducted by using EDTA. The binding site of Fe3+ to S1 was determined by using 13 C NMR and Molecular Modelling studies. Complexation was suggested to occur between the lone-pair of electrons from the coumarin-carbonyl and the triazole-carbon double bond.

Keywords: chemosensor, "click" chemistry, coumarin, fluorescence, static quenching, triazole

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Authors: Hamza Javar Magnier, Robin Curtis

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There have been rapid advances in the upstream processing of protein therapeutics, which has shifted the bottleneck to downstream purification and formulation. Finding liquid formulations with shelf lives of up to two years is increasingly difficult for some of the newer therapeutics, which have been engineered for activity, but their formulations are often viscous, can phase separate, and have a high propensity for irreversible aggregation1. We explore means to develop improved predictive ability from a better understanding of how protein-protein interactions on formulation conditions (pH, ionic strength, buffer type, presence of excipients) and how these impact upon the initial steps in protein self-association and aggregation. In this work, we study the initial steps in the aggregation pathways using a minimal protein model based on square-well potentials and discontinuous molecular dynamics. The effect of model parameters, including range of interaction, stiffness, chain length, and chain sequence, implies that protein models fold according to various pathways. By reducing the range of interactions, the folding- and collapse- transition come together, and follow a single-step folding pathway from the denatured to the native state2. After parameterizing the model interaction-parameters, we developed an understanding of low-temperature conformational properties and fluctuations, and the correlation to the folding transition of proteins in isolation. The model fluctuations increase with temperature. We observe a low-temperature point, below which large fluctuations are frozen out. This implies that fluctuations at low-temperature can be correlated to the folding transition at the melting temperature. Because proteins “breath” at low temperatures, defining a native-state as a single structure with conserved contacts and a fixed three-dimensional structure is misleading. Rather, we introduce a new definition of a native-state ensemble based on our understanding of the core conservation, which takes into account the native fluctuations at low temperatures. This approach permits the study of a large range of length and time scales needed to link the molecular interactions to the macroscopically observed behaviour. In addition, these models studied are parameterized by fitting to experimentally observed protein-protein interactions characterized in terms of osmotic second virial coefficients.

Keywords: protein folding, native-ensemble, conformational fluctuation, aggregation

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Authors: Timothy Fwa Yerima

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This paper evaluates the development of human rights jurisprudence in Africa by the ECOWAS Court of Justice. It traces that though ECOWAS was not established with the aim of promoting and protecting human rights as the African Court of Human and Peoples’ Rights, no doubt, the 1991 ECOWAS Court Protocol and the 1993 ECOWAS Revised Treaty give the ECOWAS Court its human rights mandate. The paper, however, points out that despite the availability of these two Laws, the ECOWAS Court had difficulty in its human rights mandate, in view of the twin problems of lack of access to the Court by private parties and personal jurisdiction of the Court to entertain cases filed by private parties. The paper considers the 2005 Supplementary Protocol, not only as an effective legal framework in West African Sub-Region that tackles these problems in human rights cases but also a strong foundation upon which the Court has been developing human rights jurisprudence in Africa through the interpretation and application of this Law and other sources of Law of the Court. After a thorough analysis of some principles laid down by the ECOWAS Court so far, the paper observes that human rights jurisprudence in Africa is growing rapidly; depicting that though the ECOWAS Court initially had difficulty in its human rights mandate, today it has a bright and visionary landing. The paper concludes that West African Sub-Region will witness a more effective performance of the ECOWAS Court if some of its challenges are tackled.

Keywords: access, African human rights, ECOWAS court of justice, jurisprudence, personal jurisdiction

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Authors: S. J. Higgs, E. Van Eck, K. Heynis, S. H. Broadberry

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Engagement with non-human animals is a rapidly-growing field of study within the animal science and social science sectors, with human-interactions occurring in many forms; interactions, encounters and animal-assisted therapy. To our knowledge, there has been a wide array of research published on domestic and livestock human-animal interactions, however, there appear to be fewer publications relating to zoo animals and the effect these interactions have on the animal, human and establishment. The aim of this study was to identify if there were any perceivable benefits from the human-animal interaction for the cheetah, the human and the establishment. Behaviour data were collected before, during and after the interaction on the behaviour of the cheetah and the human participants to highlight any trends with nine interactions conducted. All 35 participants were asked to fill in a questionnaire prior to the interaction and immediately after to ascertain if their perceptions changed following an interaction with the cheetah. An online questionnaire was also distributed for three months to gain an understanding of the perceptions of human-animal interactions from members of the public, gaining 229 responses. Both questionnaires contained qualitative and quantitative questions to allow for specific definitive answers to be analysed, but also expansion on the participants perceived perception of human-animal interactions. In conclusion, it was found that participants’ perceptions of human-animal interactions saw a positive change, with 64% of participants altering their opinion and viewing the interaction as beneficial for the cheetah (reduction in stress assumed behaviours) following participation in a 15-minute interaction. However, it was noted that many participants felt the interaction lacked educational values and therefore this is an area in which zoological establishments can work to further improve upon. The results highlighted many positive benefits for the human, animal and establishment, however, the study does indicate further areas for research in order to promote positive perceptions of human-animal interactions and to further increase the welfare of the animal during these interactions, with recommendations to create and regulate legislation.

Keywords: Acinonyx jubatus, encounters, human-animal interactions, perceptions, zoological establishments

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Authors: Fausto Morais

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Artificial intelligence has been widely used in law. Programs are able to classify suits, to identify decision-making patterns, to predict outcomes, and to formalize legal arguments as well. In Brazil, the artificial intelligence victor has been classifying cases to supreme court’s standards. When those programs act doing those tasks, they simulate some kind of legal decision and legal arguments, raising doubts about how artificial intelligence can be integrated into legal reasoning. Taking this into account, the following three issues are identified; the problem of hypernormatization, the argument of legal anthropocentrism, and the artificial legal principles. Hypernormatization can be seen in the Brazilian legal context in the Supreme Court’s usage of the Victor program. This program generated efficiency and consistency. On the other hand, there is a feasible risk of over standardizing factual and normative legal features. Then legal clerks and programmers should work together to develop an adequate way to model legal language into computational code. If this is possible, intelligent programs may enact legal decisions in easy cases automatically cases, and, in this picture, the legal anthropocentrism argument takes place. Such an argument argues that just humans beings should enact legal decisions. This is so because human beings have a conscience, free will, and self unity. In spite of that, it is possible to argue against the anthropocentrism argument and to show how intelligent programs may work overcoming human beings' problems like misleading cognition, emotions, and lack of memory. In this way, intelligent machines could be able to pass legal decisions automatically by classification, as Victor in Brazil does, because they are binding by legal patterns and should not deviate from them. Notwithstanding, artificial intelligent programs can be helpful beyond easy cases. In hard cases, they are able to identify legal standards and legal arguments by using machine learning. For that, a dataset of legal decisions regarding a particular matter must be available, which is a reality in Brazilian Judiciary. Doing such procedure, artificial intelligent programs can support a human decision in hard cases, providing legal standards and arguments based on empirical evidence. Those legal features claim an argumentative weight in legal reasoning and should serve as references for judges when they must decide to maintain or overcome a legal standard.

Keywords: artificial intelligence, artificial legal principles, hypernormatization, legal anthropocentrism argument, legal reasoning

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Authors: Alhaji Khuzaima Mohammed Osman, Zaeem Sheikh Abdul Wadudi Haruna

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This article aims to explore the crucial link between counter-terrorism efforts and the preservation of human security. As acts of terrorism continue to pose significant threats to societies worldwide, it is imperative to develop effective strategies that mitigate risks while safeguarding the rights and well-being of individuals. This paper discusses key aspects of counter-terrorism and human security, emphasizing the need for a comprehensive approach that integrates intelligence, prevention, response, and resilience-building measures. By highlighting successful case studies and lessons learned, this article provides valuable insights for policymakers, law enforcement agencies, and practitioners in their quest to address terrorism and foster human security.

Keywords: human security, risk mitigation, terrorist activities, civil liberties

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Authors: Varinder Singh

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The primitive man had not known anything like human rights. In the later centuries of human progress with the development of scientific and technological knowledge, the growth of population and the tremendous changes in the human environment, the laws of nature that maintained the Eco-balance crumbled. The race for better and comfortable life landed mankind in a vicious circle. It created environmental imbalance, unplanned and uneven development, breakdown of self-sustaining village economy, mushrooming of shanty towns and slums, widening the chasm between the rich and the poor, over-exploitation of natural resources, desertification of arable lands, pollution of different kinds, heating up of earth and depletion of ozone layer. Modem International Life has been deeply marked and transformed by current endeavors to meet the needs and fulfill the requirements of protection of human person and of the environment. Such endeavors have been encouraged by the widespread recognition that protection of human being and the environment reflects common superior values and constitutes a common concern of mankind. The parallel evolutions of human rights protection and environmental protection disclose some close affinities. There was the occurrence of process of internationalization of both human rights protection and environmental protection, the former beginning with the 1948 Universal Declaration of Human Rights, the latter with the 1972 Stockholm Declaration on the Human Environment.It is now well established that it is the basic human right of every individual to live in a pollution free environment with full human dignity. The judiciary has so far pronounced a number of judgments in this regard. The Supreme Court in view of various laws relating to environment protection and the constitutional provision has held that right to pollution free environment. Article-21 is the heart of the fundamental rights and has received expanded meanings from time to time.

Keywords: human rights, law, environment, polluter

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Authors: Fatemeh Jalalvand

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The critical human rights problems such as extreme poverty, hunger, inequalities and gender discrimination need to be addressed by powerful and influential actors in the world. In today’s globalization, corporations have become one of the potent agents in the society. They are capable of generating economic growth, reducing poverty, and increasing the well-being of individuals, thereby contributing to the betterment of a broad spectrum of human rights. However, the discussion on how business can contribute to human rights has primarily focused on not violating them (reactive approach) rather than improving the conditions and solving the problems of human rights (proactive approach). In particular, the role of corporate social responsibility (CSR) in bringing proactivity of business in human rights has gained less attention. This paper develops a conceptual framework to examine the role of different categories of CSR, including discretionary, ethical, legal, instrumental and political CSR in encouraging the proactive contribution of corporations to the betterment of human rights. The five propositions, related to the conceptual framework, outline the relationships between five categories of CSR and proactivity of corporations in human rights. The findings indicate that discretionary CSR with voluntary nature might not be able to motivate any contribution of business in human rights. Moreover, ethical CSR and legal CSR might lead to reactive strategies of business toward human rights. Meanwhile, the economic incentives behind the notion of instrumental CSR could result in partial proactive engagement of corporations in human rights. Finally, the internal motives as profit and power besides the external duties might lead to the highest level of proactivity of corporations in human rights under the context of political CSR. The model developed offers a map for business to adopt proactive human rights strategies more systematically maintaining key profit-drivers like power and profit. In sum, instrumental and political categories of CSR might lead corporations to improve the conditions of human rights proactively.

Keywords: CSR, human rights, proactive approach, reactive approach

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Authors: Santiago Martínez Hernández

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The establishment of the European Union signified the culmination of the supra-national power addressing economic, political, legal and humanitarian matters within and above a national territory. Human rights have taken a protagonist role as one of the pressing concerns that the EU addresses, and one of the most critical problems is that of human trafficking. This multi-billion dollar criminal business represents $31.6 per year made out of 2.5 million trafficked persons worldwide, making it one of the most crucial human rights problems in the world to address. The EU has developed strategies to tackle this issue through supra-national governance, however, how have they fared? What is the impact of its development on the issue? This paper will address the direct and indirect impact of the formation of the European Union as a supranational political and economic entity on the illicit industry of human trafficking in Europe. It attempts to analyse first, the situation of human trafficking in Europe, as an attempt to understand its importance in the region, addressing its root causes and the role of the states addressed. Second, the paper will examine the impact of the EU on human breaking down its policy-making at a supranational level, the role of the economic integration of the region, and the change of migration patterns since its inception.

Keywords: human trafficking, human rights, European union, criminal business

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Authors: Ayyoub Jamali, Alena Kozlova

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The Russian invasion of Ukraine has tested the mettle of the international community, prompting not only States but also non-state actors to take deterrent action in response. Indeed, international sports organisations, namely FIFA and UEFA, have been rather successful in shifting the power dynamics by introducing a complete ban on the Russian national and club teams. This article aims to inquire into the human rights implications of such actions taken by international sports organisations. First, the article departs from an assessment of the legal status of FIFA and UEFA under international law and reflects on how a legal link could be established vis-à-vis their human rights obligations. Second, it examines the human rights aspects of the impugned measures by FIFA and UEFA on the part of the Russian athletes, further scrutinising them against the international human rights law principle of non-discrimination through a proportionality test. Last, it draws basic pathways for how possible human rights violations committed in the context of measures adopted by such organisations could be remedied, outlining the challenges of arbitration and litigation in Switzerland.

Keywords: FIFA, UEFA, FUR, ban, human rights, Russia, Ukraine, non-state actors

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Authors: Son Nguyen, Thanh Van, Ly Le

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Ca2+ - dependent calmodulin kinase IIa (CaMKIIa) has recently been found to associate with protein tau missorting and polymerization in Alzheimer’s Disease (AD). However, there has yet inhibitors targeting CaMKIIa to investigate the correlation between CaMKIIa activity and protein tau polymer formation. Combining virtual screening and our statistics in binding contribution scoring function (BCSF), we rationally identified potential compounds that bind to specific CaMKIIa active site and specificity-affinity distribution of the ligand within the active site. Using molecular dynamics simulation, we identified structural stability of CaMKIIa and potent inhibitors, and site-directed bonding, separating non-specific and specific molecular interaction features. Despite of variation in confirmation of simulation time, interactions of the potent inhibitors were found to be strongly associated with the unique chemical features extracted from molecular binding poses. In addition, competitive inhibitors within CaMKIIa showed an important molecular recognition pattern toward specific ligand features. Our approach combining virtual screening with BCSF may provide an universally applicable method for precise identification in the discovery of compounds.

Keywords: Alzheimer’s disease, Ca 2+ -dependent calmodulin kinase IIa, protein tau, molecular docking

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Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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Authors: A. T. Adetunji, F. B. Lewu, R. Mundembe

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Plants require nitrogen (N) to support desired production levels. Nitrogen is available to plants in the form of nitrate or ammonium, which are transported into the cell with the aid of various transport proteins. Ammonium transporters (AMTs) play a role in the uptake of ammonium, the form in which nitrogen is preferentially absorbed by plants. Solanum tuberosum AMT1 (StAMT1) was characterized using molecular biology and bioinformatics methods. Nucleotide database sequences were used to design AMT1-specific primers which were used to amplify the AMT1 internal regions. Nucleotide sequencing, alignment and phylogenetic analysis assigned StAMT1 to the AMT1 family. The deduced amino acid sequences showed that StAMT1 is 92%, 83% and 76% similar to Solanum lycopersicum LeAMT1.1, Lotus japonicus LjAMT1.1 and Solanum lycopersicum LeAMT1.2 respectively. StAMT1 fragments were shown to correspond to the 5th - 10th trans-membrane domains. Residue StAMT1 D15 is predicted to be essential for ammonium transport, while mutations of StAMT1 S76A may further enhance ammonium transport.

Keywords: ammonium transporter, bioinformatics, nitrogen, primers, Solanum tuberosum

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Authors: B. Arend, P. Sunnen, P. Caire

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In a single case study, we show how a conversation analysis (CA) approach can shed light onto the sequential unfolding of human-robot interaction. Relying on video data, we are able to show that CA allows us to investigate the respective turn-taking systems of humans and a NAO robot in their dialogical dynamics, thus pointing out relevant differences. Our fine grained video analysis points out occurring breakdowns and their overcoming, when humans and a NAO-robot engage in a multimodally uttered multi-party communication during a sports guessing game. Our findings suggest that interdisciplinary work opens up the opportunity to gain new insights into the challenging issues of human robot communication in order to provide resources for developing mechanisms that enable complex human-robot interaction (HRI).

Keywords: human robot interaction, conversation analysis, dialogism, breakdown, museum

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Authors: Ashima Sharma

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Human Serum Albumin (HSA)- one of the most demanded therapeutic proteins with immense biotechnological applications- is a large multidomain protein containing 17 disulfide bonds. The current source of HSA is human blood plasma which is a limited and unsafe source. Thus, there exists an indispensable need to promote non-animal derived recombinant HSA (rHSA) production. Escherichia coli is one of the most convenient hosts which had contributed to the production of more than 30% of the FDA approved recombinant pharmaceuticals. It grows rapidly and reaches high cell density using inexpensive and simple substrates. E. coli derived recombinant products have more economic potential as fermentation processes are cheaper compared to the other expression hosts. The major bottleneck in exploiting E. coli as a host for a disulfide-rich multidomain protein is the formation of aggregates of overexpressed protein. The majority of the expressed HSA forms inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA from inclusion bodies is not preferred because it is difficult to obtain a large multidomain disulfide bond rich protein like rHSA in its functional native form. Purification is tedious, time-consuming, laborious and expensive. Because of such limitations, the E. coli host system was neglected for rHSA production for the past few decades despite its numerous advantages. In the present work, we have exploited the capabilities of E. coli as a host for the enhanced functional production of rHSA (~60% of the total expressed rHSA in the soluble fraction). Parameters like intracellular environment, temperature, induction type, duration of induction, cell lysis conditions etc. which play an important role in enhancing the level of production of the desired protein in its native form in vivo have been optimized. We have studied the effect of assistance of different types of exogenously employed chaperone systems on the functional expression of rHSA in the E. coli host system. Different aspects of cell growth parameters during the production of rHSA in presence and absence of molecular chaperones in E. coli have also been studied. Upon overcoming the difficulties to produce functional rHSA in E. coli, it has been possible to produce significant levels of functional protein through engineering the biological system of protein folding in the cell, the E. coli-derived rHSA has been purified to homogeneity. Its detailed physicochemical characterization has been performed by monitoring its conformational properties, secondary and tertiary structure elements, surface properties, ligand binding properties, stability issues etc. These parameters of the recombinant protein have been compared with the naturally occurring protein from the human source. The outcome of the comparison reveals that the recombinant protein resembles exactly the same as the natural one. Hence, we propose that the E. coli-derived rHSA is an ideal biosimilar for human blood plasma-derived serum albumin. Therefore, in the present study, we have introduced and promoted the E. coli- derived rHSA as an alternative to the preparation from a human source, pHSA.

Keywords: recombinant human serum albumin, Escherichia coli, biosimilar, chaperone assisted protein folding

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Authors: Neziha Jaouedi, Noureddine Boujnah, Mohamed Salim Bouhlel

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In the framework of human machine interaction systems enhancement, we focus throw this paper on human behavior analysis and action recognition. Human behavior is characterized by actions and reactions duality (movements, psychological modification, verbal and emotional expression). It’s worth noting that many information is hidden behind gesture, sudden motion points trajectories and speeds, many research works reconstructed an information retrieval issues. In our work we will focus on motion extraction, tracking and action recognition using wavelet network approaches. Our contribution uses an analysis of human subtraction by Gaussian Mixture Model (GMM) and body movement through trajectory models of motion constructed from kalman filter. These models allow to remove the noise using the extraction of the main motion features and constitute a stable base to identify the evolutions of human activity. Each modality is used to recognize a human action using wavelets of derived beta distributions approach. The proposed approach has been validated successfully on a subset of KTH and UCF sports database.

Keywords: feautures extraction, human action classifier, wavelet neural network, beta wavelet

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Authors: Owonikoko Abayomi Dele

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Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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Authors: Yin Cheung Lam

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In 1949, the ratification of the Geneva Conventions heralded the international community’s adoption of a new universal and non-discriminatory approach to human rights in situations of conflict. However, with the proliferation of international terrorism after the 9/11 attacks on the United States (U.S.), the international community’s uneven and contradictory implementations of international humanitarian law (IHL) questioned its agenda of universal human rights. Specifically, the derogation from IHL has never been so pronounced in the U.S. led ‘War on Terror’. While an extensive literature has ‘assessed the impact’ of the implementation of the Geneva Conventions, limited attention has been paid to interrogating the ways in which the Geneva Conventions and its resulting implementation have functioned to discursively reproduce certain understandings of human rights between states and non-state actors. Through a discursive analysis of the Geneva Conventions and the conceptualization of human rights in relation to terrorism, this thesis problematises the way in which the U.S. has understood and reproduced understandings of human rights. Using the U.S. ‘War on Terror’ as an example, it seeks to extend previous analyses of the U.S.’ practice of IHL through a qualitative discursive analysis of the human rights content that appears in the Geneva Conventions in addition to the speeches and policy documents on the ‘War on Terror’.

Keywords: discursive analysis, human rights, non-state actors, war on terror

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Authors: Jiahe Liu, Hongyang Yu, Feng Qian, Miao Luo

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SMPL-X was a powerful parametric human body model that included male, neutral, and female models, with significant gender differences between these three models. During the process of 3D human body reconstruction, the correct selection of standard templates was crucial for obtaining accurate results. To address this issue, we developed an efficient gender classification algorithm to automatically select the appropriate template for 3D human body reconstruction. The key to this gender classification algorithm was the precise analysis of human body features. By using the SMPL-X model, the algorithm could detect and identify gender features of the human body, thereby determining which standard template should be used. The accuracy of this algorithm made the 3D reconstruction process more accurate and reliable, as it could adjust model parameters based on individual gender differences. SMPL-X and the related gender classification algorithm have brought important advancements to the field of 3D human body reconstruction. By accurately selecting standard templates, they have improved the accuracy of reconstruction and have broad potential in various application fields. These technologies continue to drive the development of the 3D reconstruction field, providing us with more realistic and accurate human body models.

Keywords: gender classification, joint detection, SMPL-X, 3D reconstruction

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Authors: Stephanie K. Douglas, Gordon R. Haley

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Organizations face increasing disruptions, changes, and uncertainties through the rapid shifts in the economy and business environment. A capacity for resilience is necessary for organizations to survive and thrive in such adverse conditions. Learning is an essential component of an organization's capability for building resilience. Strategic human resource management is a principal component of learning and organizational resilience. To achieve organizational resilience, human resource management strategies must support individual knowledge, skills, and ability development through organizational learning. This study aimed to contribute to the comprehensive knowledge of the relationship between strategic human resource management and organizational learning to build organizational resilience. The organizational learning dimensions of knowledge acquisition, knowledge distribution, knowledge interpretation, and organizational memory can be fostered through human resource management strategies and then aggregated to the organizational level to build resilience.

Keywords: human resource development, human resource management, organizational learning, organizational resilience

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Authors: Rawa Delshada, Sanaa G. Hamab, Rastee D. Koyeec

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Eighty patients with suspected ischemic heart disease were enrolled in the present study. They were classified into two groups: patients with positive exercise stress test results (n=40) and control group with negative exercise stress test results (n=40). Serum concentration of troponin I, Heart-type Fatty Acid Binding Protein (H-FABP) and Ischemia Modified Albumin (IMA) were measured one hour after performing stress test. Enzyme Linked Immunosorbent Assay was used to measure both troponin I, H-FABP levels, while IMA levels were measured by albumin cobalt binding test. There was no statistically significant difference in the mean concentration of troponin I between two groups (0.75±0.55ng/ml) for patients with positive test result vs. (0.71±0.55ng/ml) for negative test result group with P>0.05. Contrary to our expectation, mean IMA level was slightly higher among control group (70.88±39.76U/ml) compared to (62.7±51.9U/ml) in positive test result group, but still with no statistically significant difference (P>0.05). Median H-FABP level was also higher among negative exercise stress testing group compared the positive one (2ng/ml vs. 1.9ng/ml respectively), but failed to reach statistically significant difference (P>0.05). When quartiles model used to explore the possible association between each study biomarkers with the others; serum H-FABP level was lowest (1.7ng/ml) in highest quartile of IMA and lowest H-FABP (1.8ng/ml) in highest quartile of troponin I but with no statistically significant association (P>0.05). Myocardial ischemia, more likely occurred after exercise stress test, is not capable of causing troponin I release. Furthermore, an increase in H-FABP and IMA levels after stress test are not reflecting myocardial ischemia. Moreover, the combination of troponin I, H-FABP and IMA after measuring their post exercise levels does not improve the diagnostic utility of exercise stress test enormously.

Keywords: cardiac biomarkers, ischemic heart disease, troponin I, ischemia modified albumin, heart-type fatty acid binding protein, exercise stress testing

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Authors: Lottie Lane

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It is habitually assumed and stated that the World Bank should engage and comply with international human rights standards. However, the basis for holding the Bank to such standards is unclear. Most advocates of the idea invoke aspects of international law to argue that the Bank has existing obligations to act in compliance with human rights standards. The Bank itself, however, does not appear to accept such arguments, despite having endorsed the importance of human rights for a considerable length of time. A substantial challenge is that under the current international human rights law framework, the World Bank is considered a non-state actor, and as such, has no direct human rights obligations. In the absence of clear legal duties for the Bank, it is necessary to look at the tools available beyond the international human rights framework to encourage the Bank to comply with human rights standards. This article critically examines several bases for arguing that the Bank should comply and engage with human rights through its policies and practices. Drawing on the Bank’s own ‘good governance’ approach as well as the United Nations’ ‘human rights-based-approach’ to development, a new basis is suggested. First, the relationship between the World Bank and human rights is examined. Three perspectives are considered: (1) the legal position – what the status of the World Bank is under international human rights law, and whether it can be said to have existing legal human rights obligations; (2) the Bank’s own official position – how the Bank envisages its relationship with and role in the protection of human rights; and (3) the relationship between the Bank’s policies and practices and human rights (including how its attitudes are reflected in its policies and how the Bank’s operations impact human rights enjoyment in practice). Here, the article focuses on two examples – the (revised) 2016 Environmental and Social Safeguard Policies and the 2012 case-study regarding Gambella, Ethiopia. Both examples are widely considered missed opportunities for the Bank to actively engage with human rights. The analysis shows that however much pressure is placed on the Bank to improve its human rights footprint, it is extremely reluctant to do so explicitly, and the legal bases available are insufficient for requiring concrete, ex ante action by the Bank. Instead, the Bank’s own ‘good governance’ approach to development – which it has been advocating since the 1990s – can be relied upon. ‘Good governance’ has been used and applied by many actors in many contexts, receiving numerous different definitions. This article argues that human rights protection can now be considered a crucial component of good governance, at least in the context of development. In doing so, the article explains the relationship and interdependence between the two concepts, and provides three rationales for the Bank to take a ‘human rights-based approach’ to good governance. Ultimately, this article seeks to look beyond international human rights law and take a governance approach to provide a convincing basis upon which to argue that the World Bank should comply with human rights standards.

Keywords: World Bank, international human rights law, good governance, human rights-based approach

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Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

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Authors: Yustina Trihoni Nalesti Dewi

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Gross violations of human rights consisting of crime against humanity, genocide and war crime, are serious international crimes. Prohibition such crimes have obtain to the level of international norms of jus cogens based on conventions and customary international law. Therefore, the duty of the state to punish the crimes is obligatory. The legal consequence of jus cogens is obligation erga omnes which are a matter of state responsibility. When a state is not willing or neglects to do so in its national law, it results in state responsibility to be imposed by international human rights and humanitarian law. This article reviews the concept of jus cogens and obligatio erga omnes that appear as two sides of the same coin. It also explains how international human rights and humanitarian law set down the duty of the state to punish gross violations of human rights.

Keywords: duty of states, gross violations of human rights, jus cogens, obligatio erga omnes

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Authors: Yrfet Shkreli

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To determine the content of human rights norms in national constitutions, international law - in the form of treaties, declarations and case law from international monitoring bodies, and comparative case law from other countries - is often discussed in the judgments of domestic courts. This paper explores the extent to which international law has influenced domestic human rights case law in Africa. The paper first explores how the human rights provisions of African constitutions came into being before turning to the role played by international law in the constitutional order of various African states and how treaties, declarations and findings of international monitoring bodies have been used in African countries to interpret and expand on constitutional human rights provisions.

Keywords: European Union, global governance, globalization, normative power

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Luna Shamieh

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Various players are part of the game in an asymmetric war, all making efforts to provide human security to their own adherents. Although a fragile state is not able to provide sufficient and comprehensive services, it still provides special services and security to the elite; the insurgents as well provide services and security to their associates. The humanitarian organisations, on the other hand, provide some fundamental elements of human security, but only in the regions, they are able to access when possible (if possible). The counterinsurgents (security forces of the state and intervention forces) operate within a narrow band defined by the vision of the responsibility to protect and the perspective of the resolution of the conflict through combat; hence, the possibility to provide human security is shaken at this end. This article examines how each player provides human security from the perspective of freedom from want in order to secure basic and strategic needs, freedom from fear through providing protection against all kinds of violence, and the freedom to live in dignity. It identifies a vicious cycle caused by the intervention of the different players causing a centrifugal force that may lead to disintegration of the nation under war.

Keywords: asymmetric war, counterinsurgency, fragile state, human security, insurgency

Procedia PDF Downloads 311