Search results for: variant calling

Authors: Bellinda R. Chinowawa

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As part of a wider strategy to stifle civil society, Governments routinely resort to judicial harassment through the use of civil and criminal to impugn the integrity of human rights defenders and that of perceived political opponents. This phenomenon is rife in militarised or autocratic regimes where there is no tolerance for dissenting voices. Zimbabwe, ostensibly a presidential republic founded on the values of transparency, equality, freedom, is characterised by brutal suppression of perceived political opponents and those who assert their basic human rights. This is done through a wide range of tactics including unlawful arrests and detention, torture and other cruel, inhuman degrading treatment and enforced disappearances. Professionals including, journalists and doctors are similarly not spared from state attack. For human rights defenders, the most widely used tool of repression is that of judicial harassment where the judicial system is used to persecute them. This can include the levying of criminal charges, civil lawsuits and unnecessary administrative proceedings. Charges preferred against range from petty offences such as criminal nuisance to more serious charges of terrorism and subverting a constitutional government. Additionally, government sponsored individuals and organisations file strategic lawsuits with pecuniary implications order to intimidate and silence critics and engender self-censorship. Some HRDs are convicted and sentenced to prison terms, despite not being criminals in a true sense. While others are acquitted judicial harassment diverts energy and resources away from their human rights work. Through a consideration of statistical data reported by human rights organisations and face to face interviews with a cross section of human rights defenders, the article will map the incidence of judicial harassment in Zimbabwe. The article will consider the multi-level sociological and contextual factors which influence the Government of Zimbabwe to have easy recourse to criminal law and the debilitating effect of these actions on HRDs. These factors include the breakdown of the rule of law resulting in state capture of the judiciary, the proven efficacy of judicial harassment from colonial times to date, and the lack of an adequate redress mechanism at international level. By mapping the use of the judiciary as a tool of repression, from the inception of modern day Zimbabwe to date, it is hoped that HRDs will realise that they are part of a greater community of activists throughout the ages and should emboldened in the realisation that it is an age old tactic used by fallen regimes which should not deter them from calling for accountability.

Keywords: autocratic regime, colonial legacy, judicial harassment, human rights defenders

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Authors: Eisha Vienna M. Fernandez, Cristan Q. Cabanilla, Hiyasmin Lim, John Donnie A. Ramos

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Allergy is a multifactorial disease affecting a significant proportion of the population. It is developed through the interaction of allergens and the presence of certain polymorphisms in various susceptibility genes. In this study, the correlation of the 105A/C single nucleotide polymorphism (SNP) of the IL-18 gene and house dust mite-specific IgE among Filipino allergic and non-allergic population was investigated. Atopic status was defined by serum total IgE concentration of ≥100 IU/mL, while house dust mite allergy was defined by specific IgE value ≥ +1SD of IgE of nonatopic participants. Two hundred twenty match-paired Filipino cases and controls aged 6-60 were the subjects of this investigation. The level of total IgE and Specific IgE were measured using Enzyme-Linked Immunosorbent Assay (ELISA) while Polymerase Chain Reaction – Restriction Fragment Length Polymorphism (PCR-RFLP) analysis was used in the SNP detection. Sensitization profiles of the allergic patients revealed that 97.3% were sensitized to Blomia tropicalis, 40.0% to Dermatophagoides farinae, and 29.1% to Dermatophagoides pteronyssinus. Multiple sensitization to HDMs was also observed among the 47.27% of the atopic participants. Any of the allergy classes of the atopic triad were exhibited by the cases (allergic asthma: 48.18%; allergic rhinitis: 62.73%; atopic dermatitis: 19.09%), and two or all of these atopic states are concurrently occurring in 26.36% of the cases. A greater proportion of the atopic participants with allergic asthma and allergic rhinitis were sensitized to D. farinae, and D. pteronyssinus, while more of those with atopic dermatitis were sensitized to D. pteronyssinus than D. farinae. Results show that there is overrepresentation of the allele “A” of the 105A/C IL-18 gene SNP in both cases and control groups of the population. The genotype that predominate the population is the heterozygous “AC”, followed by the homozygous wild “AA”, and the homozygous variant “CC” being the least. The study confirmed a positive association between serum specific IgE against B. tropicalis and D. pteronyssinus and the allele “C” (Bt P=0.021, Dp P=0.027) and “AC” (Bt P=0.003, Dp P=0.026) genotype. Findings also revealed that the genotypes “AA” (OR:1.217; 95% CI: 0.701-2.113) and “CC” (OR, 3.5; 95% CI: 0.727-16.849) increase the risk of developing allergy. This indicates that the 105A/C IL-18 gene SNP is a candidate genetic marker for HDM allergy among Filipino patients.

Keywords: house dust mite allergy, interleukin-18 (IL-18), single nucleotide polymorphism,

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Authors: Quentin Lobbe, David Chavalarias, Alexandre Delanoe

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The ICT revolution has given birth to an unprecedented world of digital traces and has impacted a wide number of knowledge-driven domains such as science, education or policy making. Nowadays, we are daily fueled by unlimited flows of articles, blogs, messages, tweets, etc. The internet itself can thus be considered as an unsteady hyper-textual environment where websites emerge and expand every day. But there are structures inside knowledge. A given text can always be studied in relation to others or in light of a specific socio-cultural context. By way of their textual traces, human beings are calling each other out: hypertext citations, retweets, vocabulary similarity, etc. We are in fact the architects of a giant web of elements of knowledge whose structures and shapes convey their own information. The global shapes of these digital traces represent a source of collective knowledge and the question of their visualization remains an opened challenge. How can we explore, browse and interact with such shapes? In order to navigate across these growing constellations of words and texts, interdisciplinary innovations are emerging at the crossroad between fields of social and computational sciences. In particular, complex systems approaches make it now possible to reconstruct the hidden structures of textual knowledge by means of multi-scale objects of research such as semantic maps and phylomemies. The phylomemy reconstruction is a generic method related to the co-word analysis framework. Phylomemies aim to reveal the temporal dynamics of large corpora of textual contents by performing inter-temporal matching on extracted knowledge domains in order to identify their conceptual lineages. This study aims to address the question of visualizing the global shapes of online political discussions related to the French presidential and legislative elections of 2017. We aim to build phylomemies on top of a dedicated collection of thousands of French political tweets enriched with archived contemporary news web articles. Our goal is to reconstruct the temporal evolution of online debates fueled by each political community during the elections. To that end, we want to introduce an iterative data exploration methodology implemented and tested within the free software Gargantext. There we combine synchronic and diachronic axis of visualization to reveal the dynamics of our corpora of tweets and web pages as well as their inner syntagmatic and paradigmatic relationships. In doing so, we aim to provide researchers with innovative methodological means to explore online semantic landscapes in a collaborative and reflective way.

Keywords: online political debate, French election, hyper-text, phylomemy

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Authors: Waseem Makai

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The term ‘political Islam’ now seem to have gained the centre stage in every discourse pertaining to Islamic legitimacy and compatibility in modern civilisations. A never ceasing tradition of the philosophy of caliphate that has kept overriding the options of any alternate political institution in the Muslim world still permeates a huge faction of believers. Fully accustomed with the proliferation of changes and developments in individual, social and natural dispositions of the world, Islamic theologians retaliated to this flux through both conventional and modernist approaches. The so-called conventional approach was quintessential of the interpretations put forth by Syed Maududi, with new comprehensive, academic and powerful vigour, as never seen before. He generated the avant-garde scholarship which would bear testimony to his statements, made to uphold the political institution of Islam as supreme and noble. However, it was not his trait to challenge the established views but to codify them in such a bracket which a man of the 20th century would find captivating to his heart and satisfactory to his rationale. The delicate microcosms like selection of a caliph, implementation of Islamic commandments (Sharia), interest free banking sectors, imposing tax (Jazyah) on non-believers, waging the holy crusade (Jihad) for the expansion of Islamic boundaries, stoning for committing adulteration and capital punishment for apostates were all there in his scholarship which he spent whole of his life defending in the best possible manner. What and where did he went wrong with all this, was supposedly to be notified later, by his once been disciple, Javed Ahmad Ghamidi. Ghamidi is being accused of struggling between Scylla and Charybdis as he tries to remain steadfast to his basic Islamic tenets while modernising their interpretations to bring them in harmony with the Western ideals of democracy and liberty. His blatant acknowledgement of putting democracy at a high pedestal, calling the implementation of Sharia a non-mandatory task and denial to bracket people in the categories of Zimmi and Kaafir fully vindicates his stance against conventional narratives like that of Syed Maududi. Ghamidi goes to the extent of attributing current forms of radicalism and extremism, as exemplified in the operations of organisations like ISIS in Iraq and Syria and Tehreek-e-Taliban in Pakistan, to such a version of political Islam as upheld not only by Syed Maududi but by other prominent theologians like Ibn-Timyah, Syed Qutub and Dr. Israr Ahmad also. Ghamidi is wretched, in a way that his allegedly insubstantial claims gained him enough hostilities to leave his homeland when two of his close allies were brutally murdered. Syed Maududi and Javed Ghamidi, both stand poles apart in their understanding of Islam and its political domain. Who has the appropriate methodology, scholarship and execution in his mode of comprehension, is an intriguing task, worth carrying out in detail.

Keywords: caliphate, democracy, ghamidi, maududi

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Authors: Ivana Prochazkova

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Cognitive linguistics offers biblical scholarship a specific methodological tool for analysis and interpretation of metaphorical expressions. Its methodology makes it possible to study processes involved in constructing the meaning of individual metaphorical expressions and whole conceptual metaphors; to analyze their function in the text; to follow the semantic development of concepts and conceptual domains, and to trace semantic changes and their motivation. The legal language in the Hebrew canon is extremely specific and formalized. Especially in the preambles to the collections of laws in the Pentateuch, more general considerations of the motif of keeping and breaking the law are encountered. This is also true in the psalms and wisdom literature. Legal theory and the philosophy of law deal with these motifs today. Metaphors play an important role in texts that reflect on more general issues. The purpose of this conference contribution is to write all over the central metaphorical concept, conceptual metaphor ךרד תורה (TORAH/LAW IS A JOURNEY), its function in the Torah and principal trends of the further development in the Prophets and the Writings. The conceptual metaphor תורה ךרד (TORAH/LAW IS A JOURNEY) constitutes a coherent system in conjunction with other metaphors that include e.g., conceptual metaphors נחה תורה (TORAH/LAW LEADS); its variant רעה תורה (TORAH IS A SHEPHERD/GUIDE); מקור תורה (TORAH/LAW IS A FOUNTAIN/A SOURCE OF LIFE). Some conceptual metaphors are well known, and their using are conventional (עשׁר תורה TORAH/LAW IS RICHES, שׂשׂון תורה TORAH/LAW IS DELIGHT, דבשׁ תורה TORAH/LAW IS HONEY, שׁמשׁ תורה TORAH/LAW IS SUN ). But some conceptual metaphors are by its occurrence innovative and unique (e.g., שׁריון תורה TORAH /LAW IS BODY ARMOR, כובע תורה TORAH /LAW IS A HELMET, בגד תורה TORAH/LAW IS A GARMENT, etc.). There will be given examples. Conceptual metaphors will be described by means of some 'metaphorical vehicles,' which are Hebrew expressions in the source domain that are repeatedly used in metaphorical conceptualizations of the target domain(s). Conceptual metaphors will be further described by means of 'generic narrative structures,' which are the particular aspects of a conceptual metaphor that emerge during the metaphorical structuring of concepts. They are the units of the metaphorical vehicles – the Hebrew expressions in the source domain – that structure concepts in much the same way that the conceptual metaphor in the target domain does. And finally, they will be described by means of the network of correspondences that exist between metaphorical vehicles – or generic metaphorical structures – and the Hebrew expressions in the target domain.

Keywords: cognitive theology, conceptual metaphor in the Old Testament, conceptual metaphors of the Torah, conceptual domain of law, righteousness, and justice

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

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

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

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Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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Authors: Bingqing Chen

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The Opium War unlocked the gate of China. Since then, modern western culture has been imported strongly and spread throughout this Asian country. The monologue of traditional Chinese culture in the past has been replaced by the hustle and bustle of multiculturalism. In the field of music, starting from school music, China, a country without the concept of composition, was deeply influenced by western culture and professional music composition, and entered the era of professional music composition. Recognizing the importance of national culture, a group of insightful artists began to try to add ‘China’ to musical composition. However, due to the special historical origin of Chinese professional musical composition and the three times of cultural nihilism in China, professional musical composition at this time failed to interpret the deep language structure of local culture within Chinese traditional culture, but only regarded Chinese traditional music as a ‘melody material library.’ At this time, the cross-cultural composition still takes Western music as its ‘norm,’ while our own music culture only exists as the sound of the contrast of Western music. However, after reading scores extensively, watching video performances, and interviewing several active composers, we found that at least in the past 30 years, China has created some works that can be called intercultural music. In these kinds of music, composers put Chinese and Western, traditional and modern in an almost equal position to have a dialogue based on their deep understanding and respect for the two cultures. This kind of music connects two music worlds, and links the two cultural and ideological worlds behind it, and communicates and grows together. This paper chose the works of three composers with different educational backgrounds, and pay attention to how composers can make a dialogue at the organizational structure level of their works. Based on the strategies adopted by composers in structuring their works, this paper expounds on how the composer's music procedure shows intercultural in terms of whole sound effects and cultural symbols. By actively participating in this intercultural practice, composers resorting to various musical and extra-musical procedures to arrive at the so-called ‘innovation within tradition.’ Through the dialogue, we can activate the space of creative thinking and explore the potential contained in culture. This interdisciplinary research promotes the rethinking of the possibility of innovation in contemporary Chinese intercultural music composition, spanning the fields of sound studies, dialogue theory, cultural research, music theory, and so on. Recently, China is calling for actively promoting 'the construction of Chinese music canonization,’ expecting to form a particular music style to show national-cultural identity. In the era of globalization, it is possible to form a brand-new Chinese music style through intercultural composition, but it is a question about talents, and the key lies in how composers do it. There is no recipe for the formation of the Chinese music style, only the composers constantly trying and tries to solve problems in their works.

Keywords: dialogism, intercultural music, national-cultural identity, organization/structure, sound

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Authors: Katerina Antoniou

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When examining conflicts around the world, it is evident that the majority of intractable conflicts are steeped in identity. Identity seems to be not only a causal variable for conflict, but also a catalytic parameter for the process of reconciliation that follows ceasefire. This paper focuses on the process of identity securitization that occurs between rival groups of heterogeneous collective identities – ethnic, national or religious – as well as on the relationship between identity securitization and the ability of the groups involved to reconcile. Are securitized identities obstacles to the process of reconciliation, able to hinder any prospects of peace? If the level to which an identity is securitized is catalytic to a conflict’s discourse and settlement, then which factors act as indicators of identity de-securitization? The level of an in-group’s identity securitization can be estimated through a number of indicators, one of which is narrative. The stories, views and stances each in-group adopts in relation to its history of conflict and relation with their rival out-group can clarify whether that specific in-group feels victimized and threatened or safe and ready to reconcile. Accordingly, this study discusses identity securitization through narrative in relation to intractable conflicts. Are there conflicts around the world that, despite having been identified as intractable, stagnated or insoluble, show signs of identity de-securitization through narrative? This inquiry uses the case of the Cyprus conflict and its partitioned societies to present official narratives from the two communities and assess whether these narratives have transformed, indicating a less securitized in-group identity for the Greek and Turkish Cypriots. Specifically, the study compares the official historical overviews presented by each community’s Ministry of Foreign Affairs website and discusses the extent to which the two official narratives present a securitized collective identity. In addition, the study will observe whether official stances by the two communities – as adopted by community leaders – have transformed to depict less securitization over time. Additionally, the leaders’ reflection of popular opinion is evaluated through recent opinion polls from each community. Cyprus is currently experiencing renewed optimism for reunification, with the leaders of its two communities engaging in rigorous negotiations, and with rumors calling for a potential referendum for reunification to be taking place even as early as within 2016. Although leaders’ have shown a shift in their rhetoric and have moved away from narratives of victimization, this is not the case for the official narratives used by their respective ministries of foreign affairs. The study’s findings explore whether this narrative inconsistency proves that Cyprus is transitioning towards reunification, or whether the leaders are risking sending a securitized population to the polls to reject a potential reunification. More broadly, this study suggests that in the event that intractable conflicts might be moving towards viable peace, in-group narratives--official narratives in particular--can act as indicators of the extent to which rival entities have managed to reconcile.

Keywords: conflict, identity, narrative, reconciliation

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Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

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Introduction: Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) in steel was above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. Materials and Methods: The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) was used cytogenetic analysis of peripheral blood lymphocytes, gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistical analysis was used the Mann-Whitney U-test. Results: The mean Cr level in exposed group was 0.095 mmol/l (0.019 min-max 0.504). No value does exceed the average normal value. The average value Cr in urine was 7.9 mmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs 0.80% and CSA-type 0.96% vs 0.90%). In the number of total CA was observed statistical difference between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44%<1.82%<2.13%). There was observed a statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups (1.22% vs. 0.59%, P<0.05). Discussion and conclusions: The work place is usually higher source of exposure to harmful factors. Workers need consistently and checked frequently health control. In assessing the risk of adverse effects of metals is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: genotoxicity, chromium, stainless steels, welders

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Authors: Federica Marangio

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This study looks at the triangle of knowledge: research-education-innovation as growth engine of an inclusive and sustainable society, where the research is the strategic process which allows the acquisition of knowledge, innovation appraises the knowledge acquired and the education is the enabling factor of the human capital to create entrepreneurial capital. Where does Italy and China stand in the global geography of innovation? Europe is calling on a smart, inclusive and sustainable growth through a specializing process that looks at the social and economic challenges, able to understand the characteristics of specific geographic areas. It is easily questionable why it is not as simple as it looks to come up with entrepreneurial ideas in all the geographic areas. Seen that the technology plus the human capital should be the means through which is possible to innovate and contribute to the boost of innovation culture, then the young educated people can be seen as the society changing agents and it becomes clear the importance of investigating the skills and competencies that lead to innovation. By starting innovation-based activities, other countries on an international level, are able now to be part of an healthy innovative ecosystem which is the result of a strong growth policy which enables innovation. Analyzing the geography of the innovation on a global scale, comes to light that the innovative entrepreneurship is the process which portrays the competitiveness of the regions in the knowledge-based economy as strategic process able to match intellectual capital and market opportunities. The level of innovative entrepreneurship is not only the result of the endogenous growth ability of the enterprises, but also by significant relations with other enterprises, universities, other centers of education and institutions. To obtain more innovative entrepreneurship is necessary to stimulate more synergy between all these territory actors in order to create, access and value existing and new knowledge ready to be disseminate. This study focuses on individual’s lived experience and the researcher believed that she can’t understand the human actions without understanding the meaning that they attribute to their thoughts, feelings, beliefs and so given she needed to understand the deeper perspectives captured through face-to face interaction. A case study approach will contribute to the betterment of knowledge in this field. This case study will represent a picture of the innovative ecosystem and the entrepreneurial mindset as a key ingredient of endogenous growth and a must for sustainable local and regional development and social cohesion. The case study will be realized analyzing two Chinese companies. A structured set of questions will be asked in order to gain details on what generated success or failure in the different situations with the past and at the moment of the research. Everything will be recorded not to lose important information during the transcription phase. While this work is not geared toward testing a priori hypotheses, it is nevertheless useful to examine whether the projects undertaken by the companies, were stimulated by enabling factors that, as result, enhanced or hampered the local innovation culture.

Keywords: Entrepreneurship, education, geography of innovation, education.

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Authors: Fru Vitalis Akuma, Jenna Koenen

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The science education community is increasingly calling for learning experiences that mirror the work of scientists. Although inquiry-based science education is aligned with these calls, the implementation of this strategy is a complex and daunting task for many teachers. Thus, policymakers and researchers have noted the need for continued teacher Professional Development (PD) in the enactment of inquiry-based science education, coupled with effective ways of reaching the goals of teacher PD. This is a complex problem for which educational design research is suitable. The purpose at this stage of our design research is to develop a generic PD framework that is valid as the blueprint of a PD program for supporting science teachers in relation to inquiry-based curriculum units. The seven components of the framework are the goal, learning theory, strategy, phases, support, motivation, and an instructional model. Based on a systematic review of the literature on effective (science) teacher PD, coupled with developer screening, we have generated a design principle per component of the PD framework. For example, as per the associated design principle, the goal of the framework is to provide science teachers with experiences in authentic inquiry, coupled with enhancing their competencies linked to the adoption, customization and design; then the classroom implementation and the revision of inquiry-based curriculum units. The seven design principles have allowed us to synthesize the PD framework, which, coupled with the design principles, are the preliminary outcomes of the current research. We are in the process of evaluating the content and construct validity of the framework, based on nine one-on-one interviews with experts in inquiry-based classroom and teacher learning. To this end, we have developed an interview protocol with the input of eight such experts in South Africa and Germany. Using the protocol, the expert appraisal of the PD framework will involve three experts from Germany, South Africa, and Cameroon, respectively. These countries, where we originate and/or work, provide a variety of inquiry-based science education contexts, making the countries suitable in the evaluation of the generic PD framework. Based on the evaluation, we will revise the framework and its seven design principles to arrive at the final outcomes of the current research. While the final content and construct a valid version of the framework will serve as an example of the needed ways through which effective inquiry-based science teacher PD may be achieved, the final design principles will be useful to researchers when transforming the framework for use in any specific educational context. For example, in our further research, we will transform the framework to one that is practical and effective in supporting inquiry-based practical work in resource-constrained physical sciences classrooms in South Africa. Researchers in other educational contexts may similarly consider the final framework and design principles in their work. Thus, our final outcomes will inform practice and research around the support of teachers to increase the incorporation of learning experiences that mirror the work of scientists in a worldwide manner.

Keywords: design principles, educational design research, evaluation, inquiry-based science education, professional development framework

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Authors: Dragana R. Stamenov, Simonida S. Djuric, Timea Hajnal Jafari

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Plant growth promoting rhizobacteria (PGPR) are a heterogeneous group of bacteria that can be found in the rhizosphere, at root surfaces and in association with roots, enhancing the growth of the plant either directly and/or indirectly. Increased crop productivity associated with the presence of PGPR has been observed in a broad range of plant species, such as raspberry, chickpeas, legumes, cucumber, eggplant, pea, pepper, radish, tobacco, tomato, lettuce, carrot, corn, cotton, millet, bean, cocoa, etc. However, until now there has not been much research about influences of the PGPR on the growth and yield of onion. Onion (Allium cepa L.), of the Liliaceae family, is a species of great economic importance, widely cultivated all over the world. The aim of this research was to examine the influence of plant growth promoting bacteria Pseudomonas sp. Dragana, Pseudomonas sp. Kiš, Bacillus subtillis and Azotobacter sp. on the seed germination and early growth of onion (Allium cepa). PGPR Azotobacter sp., Bacillus subtilis, Pseudomonas sp. Dragana, Pseudomonas sp. Kiš, from the collection of the Faculty of Agriculture, Novi Sad, Serbia, were used as inoculants. The number of cells in 1 ml of the inoculum was 10⁸ CFU/ml. The control variant was not inoculated. The effect of PGPR on seed germination and hypocotyls length of Allium cepa was evaluated in controlled conditions, on filter paper in the dark at 22°C, while effect on the plant length and mass in semicontrol conditions, in 10 l volume vegetative pots. Seed treated with fungicide and untreated seed were used. After seven days the percentage of germination was determined. After seven and fourteen days hypocotil length was measured. Fourteen days after germination, length and mass of plants were measured. Application of Pseudomonas sp. Dragana and Kiš and Bacillus subtillis had a negative effect on onion seed germination, while the use of Azotobacter sp. gave positive results. On average, application of all investigated inoculants had a positive effect on the measured parameters of plant growth. Azotobacter sp. had the greatest effect on the hypocotyls length, length and mass of the plant. In average, better results were achieved with untreated seeds in compare with treated. Results of this study have shown that PGPR can be used in the production of onion.

Keywords: germination, length, mass, microorganisms, onion

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Authors: Saima Ali, Liaqat Ali, Nasir Orakzai

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Background: Hydronephrosis is the most common abnormal finding in the urinary tract on prenatal screening with Ultrasonography. The prenatal hydronephrosis is a diagnostic dilemma in differentiating between obstructive variant versus physiologic hydronephrosis. The assessment and prompt diagnosis of prenatal hydronephrosis is important because of the fact that untreated obstructive hydronephrosis usually leads to recurrent UTI, Urosepsis, deterioration of renal functions, non-functioning kidneys, and even end-stage renal disease. Objectives: To determine the etiology and outcome of postnatal treatment of children with prenatal hydronephrosis in two teaching hospitals of Khyber Pakhtunkhwa (KPK) Methods: It is a multicentric descriptive study that was conducted in department of Paediatrics in Kuwait teaching hospital Peshawar and Department of Urology in Institute of Kidney Diseases Hayatabad Medical Complex Peshawar from January 2008 till December 2010. Total numbers of 64 neonates were included in the study with the mean follow-up of 14.5 months. All the diagnostic data in prenatal, postnatal data, and operative and non-operative data were collected on structured Proforma and was analyzed on SPSS version 17. Results: Out of 64 patients, 39 (60.9 %) were male while 25 were female. 52 patients had unilateral while 12 patients had bilateral hydronephrosis. Based upon prenatal USG in term of AP diameter, 37 (57 %) patients had mild hydronephrosis (5-10 mm AP diameter), 14 patients had moderate hydronephrosis (10-15 mm AP diameter) while 13 patients had gross hydronephrosis (More than 15mm). Regarding etiology, 44(76 %) patients were labeled as physiologic hydronephrosis, 11 patients (9.3%) with PUJ obstruction, 5 patients with Vesicoureteric reflux (VUR) and 4 patients with posterior urethral valves. Surgery was performed in total of 15 (23.4%) patients that included open Pyeloplasty in 11 patients, Vesicostomy followed by posterior valve fulguration in 4 patients. All the patients of VUR treated medically. The severity in the grade of prenatal hydronephrosis is significantly associated with the need for definitive urological surgery p < 0.005. Ancillary procedures like percutaneous nephrostomy (PCN) were inserted 7 patients. Conclusions: Prenatal hydronephrosis is a common ailment associated with significant morbidity. Physiological Hydronephrosis and VUR can be successfully treated with medical treatment. However obstructive PUJ obstructions and posterior urethral valves require surgical correction with a good success rate.

Keywords: prenatal hydronephrosis, Pelviureteric Junction (PUJ) Obstruction, vesicoureteric reflux, posterior urethral valve, renography

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Sidrah Ahmed

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The river and lakes flows are modeled mathematically by shallow water equations that are depth-averaged Reynolds Averaged Navier-Stokes equations under Boussinesq approximation. The temperature stratification dynamics influence the water quality and mixing characteristics. It is mainly due to the atmospheric conditions including air temperature, wind velocity, and radiative forcing. The experimental observations are commonly taken along vertical scales and are not sufficient to estimate small turbulence effects of temperature variations induced characteristics of shallow flows. Wind shear stress over the water surface influence flow patterns, heat fluxes and thermodynamics of water bodies as well. Hence it is crucial to couple temperature gradients with shallow water model to estimate the atmospheric effects on flow patterns. The Ripa system has been introduced to study ocean currents as a variant of shallow water equations with addition of temperature variations within the flow. Ripa model is a hyperbolic system of partial differential equations because all the eigenvalues of the system’s Jacobian matrix are real and distinct. The time steps of a numerical scheme are estimated with the eigenvalues of the system. The solution to Riemann problem of the Ripa model is composed of shocks, contact and rarefaction waves. Solving Ripa model with Riemann initial data with the central schemes is difficult due to the eigen structure of the system.This works presents the comparison of four different finite difference schemes for the numerical solution of Riemann problem for Ripa model. These schemes include Lax-Friedrichs, Lax-Wendroff, MacCormack scheme and a higher order finite difference scheme with WENO method. The numerical flux functions in both dimensions are approximated according to these methods. The temporal accuracy is achieved by employing TVD Runge Kutta method. The numerical tests are presented to examine the accuracy and robustness of the applied methods. It is revealed that Lax-Freidrichs scheme produces results with oscillations while Lax-Wendroff and higher order difference scheme produce quite better results.

Keywords: finite difference schemes, Riemann problem, shallow water equations, temperature gradients

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Authors: Joana Beyer

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Background: Alzheimer’s disease (AD) is the predominant cause of dementia, characterized by progressive cognitive decline. Posterior cortical atrophy (PCA) is a less common variant of AD, primarily affecting younger individuals and presenting with visual, visuospatial, and visuoperceptual deficits, often leading to delayed diagnosis due to its atypical presentation. Case Presentation: We report the case of a 58-year-old woman referred to psychiatric services with a two-year history of progressive visuospatial decline, mild memory difficulties, and language impairments, notably anomia. Despite undergoing cataract and squint surgeries, her visual symptoms persisted, impacting her professional life as a music educator. The neuropsychological evaluation revealed profound visuoperceptual and visuospatial disturbances, with neuroimaging supporting a diagnosis of PCA. Treatment with Donepezil showed symptom improvement, highlighting the challenges and importance of early intervention and managing this atypical form of AD. Methods: The diagnostic process involved comprehensive physical, neuropsychological assessments, and neuroimaging, including MRI and F18 FDG PET CT, which demonstrated severe bilateral posterior cortical involvement. The case underscores the utility of these modalities in diagnosing PCA. Results: The initiation of Donepezil, an acetylcholinesterase inhibitor, resulted in symptom improvement, emphasizing the potential for AD treatments to benefit PCA patients. However, challenges in management, including treatment side effects and the necessity of multidisciplinary care, are discussed. Conclusion: This case highlights PCA's diagnostic challenges due to its atypical presentation and the broader implications for managing younger patients with early-onset dementia. It underscores the necessity for early recognition, comprehensive assessment, and tailored management strategies, including both pharmacological and non-pharmacological interventions, to improve patients' quality of life. Additionally, the case illustrates the need for expanding community memory services to accommodate younger patients with atypical forms of dementia, advocating for a more inclusive approach to dementia care.

Keywords: Alzheimer’s disease, posterior cortical atrophy, dementia, diagnosis, management, donepezil, early-onset dementia

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Authors: Mamunur Rashid, Jialin Yan

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The current years have witnessed a rapid evolution and integration of artificial intelligence (AI) in various fields, prominently influencing the education industry. Acknowledging this transformative wave, AI tools like ChatGPT and Grammarly have undeniably introduced perspectives and skills, enriching the educational experiences of higher education students. The prevalence of AI utilization in higher education also drives an increasing number of researchers' attention in various dimensions. Departments, offices, and professors in universities also designed and released a set of policies and guidelines on using AI effectively. In regard to this, the study targets exploring and analyzing graduate students' perspectives regarding AI guidelines set by teachers. A mixed-methods study will be mainly conducted in this study, employing in-depth interviews and focus groups to investigate and collect students' perspectives. Relevant materials, such as syllabi and course instructions, will also be analyzed through the documentary analysis to facilitate understanding of the study. Surveys will also be used for data collection and students' background statistics. The integration of both interviews and surveys will provide a comprehensive array of student perspectives across various academic disciplines. The study is anchored in the theoretical framework of self-determination theory (SDT), which emphasizes and explains the students' perspective under the AI guidelines through three core needs: autonomy, competence, and relatedness. This framework is instrumental in understanding how AI guidelines influence students' intrinsic motivation and sense of empowerment in their learning environments. Through qualitative analysis, the study reveals a sense of confusion and uncertainty among students regarding the appropriate application and ethical considerations of AI tools, indicating potential challenges in meeting their needs for competence and autonomy. The quantitative data further elucidates these findings, highlighting a significant communication gap between students and educators in the formulation and implementation of AI guidelines. The critical findings of this study mainly come from two aspects: First, the majority of graduate students are uncertain and confused about relevant AI guidelines given by teachers. Second, this study also demonstrates that the design and effectiveness of course materials, such as the syllabi and instructions, also need to adapt in regard to AI policies. It indicates that certain of the existing guidelines provided by teachers lack consideration of students' perspectives, leading to a misalignment with students' needs for autonomy, competence, and relatedness. More emphasize and efforts need to be dedicated to both teacher and student training on AI policies and ethical considerations. To conclude, in this study, graduate students' perspectives on teacher-provided AI guidelines are explored and reflected upon, calling for additional training and strategies to improve how these guidelines can be better disseminated for their effective integration and adoption. Although AI guidelines provided by teachers may be helpful and provide new insights for students, educational institutions should take a more anchoring role to foster a motivating, empowering, and student-centered learning environment. The study also provides some relevant recommendations, including guidance for students on the ethical use of AI and AI policy training for teachers in higher education.

Keywords: higher education policy, graduate students’ perspectives, higher education teacher, AI guidelines, AI in education

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

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

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

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Authors: Kinnsley Travis, Camerron M. Crowder

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Mapk8ip3 (Mitogen-Activated Protein Kinase 8 Interacting Protein 3) is a gene that codes for the JIP3 protein, which is a part of the JIP scaffolding protein family. This protein is involved in axonal vesicle transport, elongation and regeneration. Variants in the Mapk8ip3 gene are associated with a rare-genetic condition that results in a neurodevelopmental disorder that can cause a range of phenotypes including global developmental delay and intellectual disability. Currently, there are 18 known individuals diagnosed to have sequenced confirmed Mapk8ip3 genetic disorders. This project focuses on examining the impact of a subset of missense patient variants on the Jip3 protein function by overexpressing the mRNA of these variants in a zebrafish knockout model for Jip3. Plasmids containing cDNA with individual missense variants were reverse transcribed, purified, and injected into single-cell zebrafish embryos (Wild Type, Jip3 -/+, and Jip3 -/-). At 6-days post mRNA microinjection, morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Morphologically, we compared the size and shape of the zebrafish during their development over a 5-day period. Total locomotive activity was assessed using the Microtracker assay and patterns of movement over time were examined using the DanioVision assay. Lastly, we used confocal microscopy to examine sensory axons for swelling and shortened length, which are phenotypes observed in the loss-of-function knockout Jip3 zebrafish model. Using these assays during embryonic development, we determined the impact of various missense variants on Jip3 protein function, compared to knockout and wild-type zebrafish embryo models. Variants in the gene Mapk8ip3 cause rare-neurodevelopmental disorders due to an essential role in axonal vesicle transport, elongation and regeneration. A subset of missense variants was examined by overexpressing the mRNA of these variants in a Jip3 knock-out zebrafish. Morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Using these assays, the spectrum of disorders can be phenotypically determined and the impact of variant location can be compared to knockout and wild-type zebrafish embryo models.

Keywords: rare disease, neurodevelopmental disorders, mrna overexpression, zebrafish research

Procedia PDF Downloads 87

Authors: H. Akhloufi, M. Hulscher, J. M. Prins, I. H. Van Der Sijs, D. Melles, A. Verbon

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Background: A timely switch from intravenous to oral antibiotic therapy has many advantages, such as reduced incidence of IV-line related infections, a decreased hospital length of stay and less workload for healthcare professionals with equivalent patient safety. Additionally, numerous studies have demonstrated significant decreases in costs of a timely intravenous to oral antibiotic therapy switch, while maintaining efficacy and safety. However, a considerable variation in iv to oral antibiotic switch therapy criteria has been described in literature. Here, we report the development of a set of iv to oral switch criteria that are generally applicable in all hospitals. Material/methods: A RAND-modified Delphi procedure, which was composed of 3 rounds, was used. This Delphi procedure is a widely used structured process to develop consensus using multiple rounds of questionnaires within a qualified panel of selected experts. The international expert panel was multidisciplinary and composed out of clinical microbiologists, infectious disease consultants and clinical pharmacists. This panel of 19 experts appraised 6 major intravenous to oral antibiotic switch therapy criteria and operationalized these criteria using 41 measurable conditions extracted from the literature. The procedure to select a concise set of iv to oral switch criteria included 2 questionnaire rounds and a face-to-face meeting. Results: The procedure resulted in the selection of 16 measurable conditions, which operationalize 6 major intravenous to oral antibiotic switch therapy criteria. The following 6 major switch therapy criteria were selected: (1) Vital signs should be good or improving when bad. (2) Signs and symptoms related to the infection have to be resolved or improved. (3) The gastrointestinal tract has to be intact and functioning. (4) The oral route should not be compromised. (5) Absence of contra-indicated infections. (6) An oral variant of the antibiotic with good bioavailability has to exist. Conclusions: This systematic stepwise method which combined evidence and expert opinion resulted in a feasible set of 6 major intravenous to oral antibiotic switch therapy criteria operationalized by 16 measurable conditions. This set of early antibiotic iv to oral switch criteria can be used in daily practice in all adult hospital patients. Future use in audits and as rules in computer assisted decision support systems will lead to improvement of antimicrobial steward ship programs.

Keywords: antibiotic resistance, antibiotic stewardship, intravenous to oral, switch therapy

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Authors: M. V. Shivaani, P. K. Jain, Surendra S. Yadav

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Worldwide regulators, practitioners and researchers view risk-disclosure as one of the most important steps that will promote corporate accountability and transparency. Recognizing this growing significance of risk disclosures, the paper first develops a risk disclosure index. Covering 69 risk items/themes, this index is developed by employing thematic content analysis and encompasses three attributes of disclosure: namely, nature (qualitative or quantitative), time horizon (backward-looking or forward-looking) and tone (no impact, positive impact or negative impact). As the focus of study is on substantive rather than symbolic disclosure, content analysis has been carried out manually. The study is based on non-financial companies of Nifty500 index and covers a ten year period from April 1, 2005 to March 31, 2015, thus yielding 3,872 annual reports for analysis. The analysis reveals that (on an average) only about 14% of risk items (i.e. about 10 out 69 risk items studied) are being disclosed by Indian companies. Risk items that are frequently disclosed are mostly macroeconomic in nature and their disclosures tend to be qualitative, forward-looking and conveying both positive and negative aspects of the concerned risk. The second objective of the paper is to gauge the factors that affect the level of disclosures in annual reports. Given the panel nature of data, and possible endogeneity amongst variables, Diff-GMM regression has been applied. The results indicate that age and size of firms have a significant positive impact on disclosure quality, whereas growth rate does not have a significant impact. Further, post-recession period (2009-2015) has witnessed significant improvement in quality of disclosures. In terms of corporate governance variables, board size, board independence, CEO duality, presence of CRO and constitution of risk management committee appear to be significant factors in determining the quality of risk disclosures. It is noteworthy that the study contributes to literature by putting forth a variant to existing disclosure indices that not only captures the quantity but also the quality of disclosures (in terms of semantic attributes). Also, the study is a first of its kind attempt in a prominent emerging market i.e. India. Therefore, this study is expected to facilitate regulators in mandating and regulating risk disclosures and companies in their endeavor to reduce information asymmetry.

Keywords: risk disclosure, voluntary disclosures, corporate governance, Diff-GMM

Procedia PDF Downloads 136

Authors: Ljiljana Stojković, Manja Zec, Maja Zivkovic, Maja Bundalo, Marija Glibetić, Dragan Alavantić, Aleksandra Stankovic

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Cardiovascular disease (CVD) is associated with alterations in DNA methylation, the latter modulated by dietary polyphenols. The present pilot study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to investigate the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes, in subjects (n=34, age of 41.1±6.6 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation, such as folate intake levels, MTHFR C677T gene variant, as well as the anthropometric and metabolic parameters, modulated the LINE-1 methylation levels upon consumption of polyphenol-rich Aronia juice. The experimental analysis of LINE-1 methylation was done by the MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Folate intake was assessed by processing the data from the food frequency questionnaire and repeated 24-hour dietary recalls. Serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using the Statistica software package. In women, after vs. before the treatment period, a significant decrease in LINE-1 methylation levels was observed (97.54±1.50% vs. 98.39±0.86%, respectively; P=0.01). The change (after vs. before treatment) in LINE-1 methylation correlated directly with MTHFR 677T allele presence, average daily folate intake and the change in serum low-density lipoprotein cholesterol, while inversely with the change in serum triacylglycerols (R=0.72, R2=0.52, adjusted R2=0.36, P=0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich Aronia juice consumption achieved through the modifications of DNA methylation pattern in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of DNA methylation may become targets for new approaches in the prevention and treatment of CVD.

Keywords: Aronia melanocarpa, cardiovascular risk, LINE-1, methylation, peripheral blood leukocytes, polyphenol

Procedia PDF Downloads 169

Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

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Authors: Stephanie Chen, Mitja Echim, Christof Büskens

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To describe and propagate the behavior of a system mathematical models are formulated. Parameter identification is used to adapt the coefficients of the underlying laws of science. For complex systems this approach can be incomplete and hence imprecise and moreover too slow to be computed efficiently. Therefore, these models might be not applicable for the numerical optimization of real systems, since these techniques require numerous evaluations of the models. Moreover not all quantities necessary for the identification might be available and hence the system must be adapted manually. Therefore, an approach is described that generates models that overcome the before mentioned limitations by not focusing on physical laws, but on measured (sensor) data of real systems. The approach is more general since it generates models for every system detached from the scientific background. Additionally, this approach can be used in a more general sense, since it is able to automatically identify correlations in the data. The method can be classified as a multivariate data regression analysis. In contrast to many other data regression methods this variant is also able to identify correlations of products of variables and not only of single variables. This enables a far more precise and better representation of causal correlations. The basis and the explanation of this method come from an analytical background: the series expansion. Another advantage of this technique is the possibility of real-time adaptation of the generated models during operation. Herewith system changes due to aging, wear or perturbations from the environment can be taken into account, which is indispensable for realistic scenarios. Since these data driven models can be evaluated very efficiently and with high precision, they can be used in mathematical optimization algorithms that minimize a cost function, e.g. time, energy consumption, operational costs or a mixture of them, subject to additional constraints. The proposed method has successfully been tested in several complex applications and with strong industrial requirements. The generated models were able to simulate the given systems with an error in precision less than one percent. Moreover the automatic identification of the correlations was able to discover so far unknown relationships. To summarize the above mentioned approach is able to efficiently compute high precise and real-time-adaptive data-based models in different fields of industry. Combined with an effective mathematical optimization algorithm like WORHP (We Optimize Really Huge Problems) several complex systems can now be represented by a high precision model to be optimized within the user wishes. The proposed methods will be illustrated with different examples.

Keywords: adaptive modeling, automatic identification of correlations, data based modeling, optimization

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Authors: N. Balaban, A. Buernstein, F. Gelman, Z. Ronen

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Brominated flame retardants are widespread pollutants, and are known to be toxic, carcinogenic, endocrinic disrupting as well as recalcitrant. The industrial complex Neot Hovav, in the Northern Negev, Israel, is situated above a fractured chalk aquitard, which is polluted by a wide variety of halogenated organic compounds. Two of the abundant pollutants found in the site are Dibromoneopentyl-glycol (DBNPG) and tribromoneopentyl-alcohol (TBNPA). Due to the elusive nature of the groundwater flow, it is difficult to connect between the spatial changes in contaminant concentrations to degradation. In this study, we attempt to determine whether these compounds are biodegraded in the groundwater, and to gain a better understanding concerning the bacterial community in the groundwater. This was achieved through the application of compound-specific isotope analysis (CSIA) of carbon (13^C/12^C) and bromine (81^Br/79^Br), and new-generation MiSeq pyrosequencing. The sampled boreholes were distributed among three main areas of the industrial complex: around the production plant of TBNPA and DBNPG; along the Hovav Wadi (small ephemeral stream) which crosses and drains the industrial complex; and downstream to the industrial area. TBNPA and DBNPG are found in all three areas, with no clear connection to the proximity of the borehole to the production plant. Initial isotopic data of TBNPA from boreholes in the area surrounding the production plant, reveal no changes in the carbon and bromine isotopic values. When observing the microbial groundwater community, the dominant phylum is Proteobacteria. Known anaerobic dehalogenating bacteria such as Dehalococcoides from the Chloroflexi phylum have also been detected. A statistical comparison of the groundwater microbial diversity using a multi-variant ordination of non-metric multidimensional scaling (NMDS) reveals three main clusters in accordance to spatial location in the industrial complex: all the boreholes sampled adjacent to the production plant cluster together and separately from the Wadi Hovav boreholes cluster and the downstream to the industrial area borehole cluster. This work provides the basis for the development and implication of an isotopic fractionation based tool for assessing the biodegradation of brominated organic compounds in contaminated environments, and a novel attempt to characterize the spatial microbial diversity in the contaminated site.

Keywords: biodegradation, brominated flame retardants, groundwater, isotopic fractionation, microbial diversity

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Authors: Cecile Meier, Drago Diaz Aleman, Itahisa Perez Conesa, Jose Luis Saorin Perez, Jorge De La Torre Cantero

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In this work, two ways of creating small-sized metal sculptures are proposed: the first by means of microcasting and the second by electroforming from models printed in 3D using an FDM (Fused Deposition Modeling‎) printer or using a DLP (Digital Light Processing) printer. It is viable to replace the wax in the processes of the artistic foundry with 3D printed objects. In this technique, the digital models are manufactured with resin using a low-cost 3D FDM printer in polylactic acid (PLA). This material is used, because its properties make it a viable substitute to wax, within the processes of artistic casting with the technique of lost wax through Ceramic Shell casting. This technique consists of covering a sculpture of wax or in this case PLA with several layers of thermoresistant material. This material is heated to melt the PLA, obtaining an empty mold that is later filled with the molten metal. It is verified that the PLA models reduce the cost and time compared with the hand modeling of the wax. In addition, one can manufacture parts with 3D printing that are not possible to create with manual techniques. However, the sculptures created with this technique have a size limit. The problem is that when printed pieces with PLA are very small, they lose detail, and the laminar texture hides the shape of the piece. DLP type printer allows obtaining more detailed and smaller pieces than the FDM. Such small models are quite difficult and complex to melt using the lost wax technique of Ceramic Shell casting. But, as an alternative, there are microcasting and electroforming, which are specialized in creating small metal pieces such as jewelry ones. The microcasting is a variant of the lost wax that consists of introducing the model in a cylinder in which the refractory material is also poured. The molds are heated in an oven to melt the model and cook them. Finally, the metal is poured into the still hot cylinders that rotate in a machine at high speed to properly distribute all the metal. Because microcasting requires expensive material and machinery to melt a piece of metal, electroforming is an alternative for this process. The electroforming uses models in different materials; for this study, micro-sculptures printed in 3D are used. These are subjected to an electroforming bath that covers the pieces with a very thin layer of metal. This work will investigate the recommended size to use 3D printers, both with PLA and resin and first tests are being done to validate use the electroforming process of microsculptures, which are printed in resin using a DLP printer.

Keywords: sculptures, DLP 3D printer, microcasting, electroforming, fused deposition modeling

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Authors: Emiliano Matta

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Passive resonant vibration absorbers are among the most widely used dynamic control systems in civil engineering. They typically consist in a single-degree-of-freedom mechanical appendage of the main structure, tuned to one structural target mode through frequency and damping optimization. One classical scheme is the pendulum absorber, whose mass is constrained to move along a curved trajectory and is damped by viscous dashpots. Even though the principle is well known, the search for improved arrangements is still under way. In recent years this investigation inspired a type of bidirectional pendulum absorber (BPA), consisting of a mass constrained to move along an optimal three-dimensional (3D) concave surface. For such a BPA, the surface principal curvatures are designed to ensure a bidirectional tuning of the absorber to both principal modes of the main structure, while damping is produced either by horizontal viscous dashpots or by vertical friction dashpots, connecting the BPA to the main structure. In this paper, a variant of BPA is proposed, where damping originates from the variable tangential friction force which develops between the pendulum mass and the 3D surface as a result of a spatially-varying friction coefficient pattern. Namely, a friction coefficient is proposed that varies along the pendulum surface in proportion to the modulus of the 3D surface gradient. With such an assumption, the dissipative model of the absorber can be proven to be nonlinear homogeneous in the small displacement domain. The resulting homogeneous BPA (HBPA) has a fundamental advantage over conventional friction-type absorbers, because its equivalent damping ratio results independent on the amplitude of oscillations, and therefore its optimal performance does not depend on the excitation level. On the other hand, the HBPA is more compact than viscously damped BPAs because it does not need the installation of dampers. This paper presents the analytical model of the HBPA and an optimal methodology for its design. Numerical simulations of single- and multi-story building structures under wind and earthquake loads are presented to compare the HBPA with classical viscously damped BPAs. It is shown that the HBPA is a promising alternative to existing BPA types and that homogeneous tangential friction is an effective means to realize systems provided with amplitude-independent damping.

Keywords: amplitude-independent damping, homogeneous friction, pendulum nonlinear dynamics, structural control, vibration resonant absorbers

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Authors: Astrid Tannert, Anuradha Ramoji, Christina Ebert, Frederike Gladigau, Lorena Tuchscherr, Jürgen Popp, Ute Neugebauer

Abstract:

Staphylococcus aureus is a facultative intracellular pathogen, which by entering host cells may evade immunologic host response as well as antimicrobial treatment. In that way, S. aureus can cause persistent intracellular infections which are difficult to treat. Depending on the strain, S. aureus may persist at different intracellular locations like the phagolysosome. The first barrier invading pathogens from the blood stream that they have to cross are the endothelial cells lining the inner surface of blood and lymphatic vessels. Upon proceeding from an acute to a chronic infection, intracellular pathogens undergo certain biochemical and structural changes including a deceleration of metabolic processes to adopt for long-term intracellular survival and the development of a special phenotype designated as small colony variant. In this study, the endothelial cell line Ea.hy 926 was used as a model for acute and chronic S. aureus infection. To this end, Ea.hy 926 cells were cultured on QIAscout™ Microraft Arrays, a special graded cell culture substrate that contains around 12,000 microrafts of 200 µm edge length. After attachment to the substrate, the endothelial cells were infected with GFP-expressing S. aureus for 3 weeks. The acute infection and the development of persistent bacteria was followed by confocal laser scanning microscopy, scanning the whole Microraft Array for the presence and for detailed determination of the intracellular location of fluorescent intracellular bacteria every second day. After three weeks of infection representative microrafts containing infected cells, cells with protruded infections and cells that did never show any infection were isolated and fixed for Raman micro-spectroscopic investigation. For comparison, also microrafts with acute infection were isolated. The acquired Raman spectra are correlated with the fluorescence microscopic images to give hints about a) the molecular alterations in endothelial cells during acute and chronic infection compared to non-infected cells, and b) metabolic and structural changes within the pathogen when entering a mode of persistence within host cells. We thank Dr. Ruth Kläver from QIAGEN GmbH for her support regarding QIAscout technology. Financial support by the BMBF via the CSCC (FKZ 01EO1502) and from the DFG via the Jena Biophotonic and Imaging Laboratory (JBIL, FKZ PO 633/29-1, BA 1601/10-1) is highly acknowledged.

Keywords: correlative image analysis, intracellular infection, pathogen-host adaption, Raman micro-spectroscopy

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Authors: Bruno Biagianti, Angela Tseng, Kathy Wannaviroj, Allison Corlett, Megan DuBois, Kyu Lee, Suma Jacob

Abstract:

Background: ASD is characterized by pervasive Sensory Processing Abnormalities (SPA) and social cognitive deficits that persist throughout the course of the illness and have been linked to functional abnormalities in specific neural systems that underlie the perception, processing, and representation of sensory information. SPA and social cognitive deficits are associated with difficulties in interpersonal relationships, poor development of social skills, reduced social interactions and lower academic performance. Importantly, they can hamper the effects of established evidence-based psychological treatments—including PEERS (Program for the Education and Enrichment of Relationship Skills), a parent/caregiver-assisted, 16-weeks social skills intervention—which nonetheless requires a functional brain capable of assimilating and retaining information and skills. As a matter of fact, some adolescents benefit from PEERS more than others, calling for strategies to increase treatment response rates. Objective: We will present interim data on CICADAS (Care Improving Cognition for ADolescents on the Autism Spectrum)—a clinician-assisted, closed-loop technology mobile application for adolescents with ASD. Via ten mobile assessments, CICADAS captures data on sensory processing abnormalities and associated cognitive deficits. These data populate a machine learning algorithm that tailors the delivery of ten neuroplasticity-based social cognitive training (NB-SCT) exercises targeting sensory processing abnormalities. Methods: In collaboration with the Autism Spectrum and Neurodevelopmental Disorders Clinic at the University of Minnesota, we conducted a fully remote, three-arm, randomized crossover trial with adolescents with ASD to document the acceptability of CICADAS and evaluate its potential as a stand-alone treatment or as a treatment enhancer of PEERS. Twenty-four adolescents with ASD (ages 11-18) have been initially randomized to 16 weeks of PEERS + CICADAS (Arm A) vs. 16 weeks of PEERS + computer games vs. 16 weeks of CICADAS alone (Arm C). After 16 weeks, the full battery of assessments has been remotely administered. Results: We have evaluated the acceptability of CICADAS by examining adherence rates, engagement patterns, and exit survey data. We found that: 1) CICADAS is able to serve as a treatment enhancer for PEERS, inducing greater improvements in sensory processing, cognition, symptom reduction, social skills and behaviors, as well as the quality of life compared to computer games; 2) the concurrent delivery of PEERS and CICADAS induces greater improvements in study outcomes compared to CICADAS only. Conclusion: While preliminary, our results indicate that the individualized assessment and treatment approach designed in CICADAS seems effective in inducing adaptive long-term learning about social-emotional events. CICADAS-induced enhancement of processing and cognition facilitates the application of PEERS skills in the environment of adolescents with ASD, thus improving their real-world functioning.

Keywords: ASD, social skills, cognitive training, mobile app

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