Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic Analyses and Prediction of Human Drug Side Effect Associated Proteins from the Perspective of Protein Evolution

Identification of various factors involved in adverse drug reactions in target proteins to develop therapeutic drugs with minimal/no side effect is very important. In this context, we have performed a comparative evolutionary rate analyses between the genes exhibiting drug side-effect(s) (SET) and genes showing no side effect (NSET) with an aim to increase the prediction accuracy of SET/NSET proteins using evolutionary rate determinants. We found that SET proteins are more conserved than the NSET proteins. The rates of evolution between SET and NSET protein primarily depend upon their noncomplex (protein complex association number = 0) forming nature, phylogenetic age, multifunctionality, membrane localization, and transmembrane helix content irrespective of their essentiality, total druggability (total number of drugs/target), m-RNA expression level, and tissue expression breadth. We also introduced two novel terms—killer druggability (number of drugs with killing side effect(s)/target), essential druggability (number of drugs targeting essential proteins/target) to explain the evolutionary rate variation between SET and NSET proteins. Interestingly, we noticed that SET proteins are younger than NSET proteins and multifunctional younger SET proteins are candidates of acquiring killing side effects. We provide evidence that higher killer druggability, multifunctionality, and transmembrane helices support the conservation of SET proteins over NSET proteins in spite of their recent origin. By employing all these entities, our Support Vector Machine model predicts human SET/NSET proteins to a high degree of accuracy (∼86%).
Why Thought Experiments Do Not Transcend Empiricism

Thought experiments are ordinary argumentation disguised in a vivid pictorial or narrative form. This account of their nature will allow me to show that empiricism has nothing to fear from thought experiments. They perform no epistemic magic. In so far as they tell us about the world, thought experiments draw upon what we already know of it, either explicitly or tacitly; they then transform that knowledge by disguised argumentation. They can do nothing more epistemically than can argumentation. I defend my account of thought experiments in Section 3 by urging that the epistemic reach of thought experiments turns out to coincide with that of argumentation and that this coincidence is best explained by the simple view that thought experiments just are arguments. Thought experiments can err-a fact to be displayed by the thought experiment - anti thought experiment pairs of Section 2. Nonetheless thought experiments can be used reliably and, I urge in Section 4. , this is only possible if they are governed by some very generalized logic. I will suggest on evolutionary considerations that their logics are most likely the familiar logics of induction and deduction, recovering the view that thought experiment is argumentation. Finally in Section 5 I defend this argument based epistemology of thought experiments against competing accounts. I suggest that these other accounts can offer a viable epistemology only insofar as they already incorporate the notion that thought experimentation is governed by a logic, possibly of very generalized form.
Encoding the ` p Ball from Limited Measurements

We address the problem of encoding signals which are sparse, i.e. signals that are concentrated on a set of small support. Mathematically, such signals are modeled as elements in the `p ball for some p ≤ 1. We describe a strategy for encoding elements of the `p ball which is universal in that 1) the encoding procedure is completely generic, and does not depend on p (the sparsity of the signal), and 2) it achieves near-optimal minimax performance simultaneously for all p < 1. What makes our coding procedure unique is that it requires only a limited number of nonadaptive measurements of the underlying sparse signal; we show that near-optimal performance can be obtained with a number of measurements that is roughly proportional to the number of bits used by the encoder. We end by briefly discussing these results in the context of image compression.
The Relationships between Organizational Justice, Organizational Citizenship Behavior and Job Satisfaction

Job satisfaction is the most researched concept studied in industrial and organizational psychology since researches had found it to be related to factors that are important in creating a better organization. Hence the first objective of this study was to examine the relationship between organizational justice and organizational citizenship behavior with job satisfaction among secondary school teachers in Selangor, Malaysia. Secondly, it identified effects of the dimensions of organizational justice and organizational citizenship on job satisfaction. Finally this study looked at the moderating effect of organizational citizenship behavior on the relationship between job satisfaction and organizational justice. The psychometric measurement tools used for data collection were: Organization Justice Scale (OJS), Organizational Citizenship Behavior (OCB) and Minnesota Satisfaction Questionnaire (MSQ). Data collected were analyzed using Pearson correlation and multiple regressions. Results showed significant relationships between organizational justice and job satisfaction, organizational citizenship behavior and job satisfaction. Organizational justice was found to have a positive significant relationship with job satisfaction where organizational citizenship behavior acts as a moderator between the two variables.
Local distributed algorithms for multi-robot systems

The field of swarm robotics focuses on controlling large populations of simple robots to accomplish tasks more effectively than what is possible using a single robot. This thesis develops distributed algorithms tailored for multi-robot systems with large populations. Specifically we focus on local distributed algorithms since their performance depends primarily on local parameters on the system and are guaranteed to scale with the number of robots in the system. The first part of this thesis considers and solves the problem of finding a trajectory for each robot which is guaranteed to preserve the connectivity of the communication graph, and when feasible it also guarantees the robots advanced towards a goal defined by an arbitrary motion planner. We also describe how to extend our proposed approach to preserve the k-connectivity of a communication graph. Finally, we show how our connectivity-preserving algorithm can be combined with standard averaging procedures to yield a provably correct flocking algorithm. The second part of this thesis considers and solves the problem of having each robot localize an arbitrary subset of robots in a multi-robot system relying only on sensors at each robot that measure the angle, relative to the orientation of each robot, towards neighboring robots in the communication graph. We propose a distributed localization algorithm that computes the relative orientations and relative positions, up to scale, of an arbitrary subset of robots. For the case when the robots move in between rounds we show how to use odometry information to allow each robot to compute the relative positions complete with scale, of an arbitrary subset of robots. Finally we describe how to use the our localization algorithm to design a variety of multi-robot tasks. Thesis Supervisor: Nancy Lynch Title: Professor of Electrical Engineering and Computer Science
3 β-Hydroxysteroid-Δ 24 Reductase (DHCR24) Protects Neuronal Cells from Apoptotic Cell Death Induced by Endoplasmic Reticulum (ER) Stress

3β-Hydroxysteroid-Δ24 reductase (DHCR24) is an endoplasmic reticulum (ER)-localized multifunctional enzyme that possesses anti-apoptotic and cholesterol-synthesizing activities. Accumulating evidence suggests that ER stress is involved in the pathogenesis of neurodegenerative disease. In this study, we investigated whether DHCR24 may function as a neuroprotective protein under ER stress. Neuroblastoma N2A cells were infected with adenovirus expressing myc-tagged DHCR24 (Ad-DHCR24) or lacZ (Ad-lacZ, serving as a control) and subjected to ER-stress, induced with Tunicamycin (TM). Cells infected with Ad-DHCR24-myc were resistant to TM-induced apoptosis, and showed weaker level of caspase-12 activity. These cells also exhibited lower levels of Bip and CHOP proteins than Ad-LacZ-infected cells. Moreover, a stronger and rapid activation of PERK, and a prolonged activation of JNK and p38 were observed in Ad-LacZ–infected cells. The generation of intracellular reactive oxygen species from ER stress was also diminished by the overexpression of DHCR24. Additionally, intracellular cholesterol level was also elevated in the Ad-DHCR24-infected cells, accompanied by a well-organized formation of caveolae (cholesterol-rich microdomain) on the plasma membrane, and improved colocalization of caveolin-1 and insulin-like growth factor 1 receptor. These results demonstrated for the first time that DHCR24 could protect neuronal cells from apoptosis induced by ER stress.
The Thin Woman

The Thin Woman provides an in-depth discussion of anorexia nervosa from a feminist social psychological standpoint. Medicine, psychiatry and psychology have all presented us with particular ways of understanding eating disorders, yet the notion of 'anorexia' as a medical condition limits our understanding of anorexia and the extent to which we can explore it as a socially, discursively produced problem. Based on original research using historical and contemporary literature on anorexia nervosa, and a series of interviews with women diagnosed as anorexic, The Thin Woman offers new insights into the problem. It will prove useful both to those with an interest in eating disorders and gender, and to those interested in the new developments in feminist post-structuralist theory and discourse analytic research in psychology.
Hemolysis Via the Lectin Pathway as C4 and C2 in Complement-Dependent Requirement for the Alternative Pathway as Well

Mannan-binding lectin (MBL) is a C1q-like molecule opsonic for several micro-organisms. MBL can activate C4, C2, and later acting complement components in the presence of serine proteases similar to but distinct from C1r and C1s via the lectin pathway of complement activation. We report here that mannan-coated MBL-sensitized erythrocytes are lysed via the lectin pathway in human serum-Mg-EGTA. The surprising occurrence of MBL-initiated lysis in the absence of calcium contrasts with the calcium requirement for C1q-initiated activation of C4 and C2. C2 is required, and lysis is signiﬁcantly enhanced when indicator cells presensitized with C4 and then coated with mannan (EAC4-M) are used. The alternative pathway also is required, since lysis is lost when either factor D or factor B is removed and is restored upon reconstitution with the puriﬁed protein. Even though MBL is a C-type lectin, it is retained on mannan-coated erythrocytes in the absence of calcium. This contrasts with the absence of calcium-independent retention on mannan immobilized on polystyrene plates or beads, and helps explain the MBL-initiated hemolysis in Mg-EGTA. These investigations show that the alternative pathway as well as C4 and C2 of the classical pathway are required for complement-dependent hemolysis via the lectin pathway and provide a method for assay of lectin pathway-mediated complement activity in human serum that should be useful in unraveling the molecular interactions of this pathway. The Journal of Immunology, 1998, 160: 3006–3013.
Macroeconomics for a Modern Economy

The modern economy began to supplant the traditional economy in several nations in the latter half of the nineteenth century—and in many more in the latter half of the twentieth. A system where selfemployment and self-finance was typical gave way to a system of companies having various business freedoms and enabling institutions. This was the “great transformation” on which historians and sociologists, as well as business commentators, were to write volumes. The modern economy, where fully adopted, has indeed been transformative for nations 1 —but much less so for economics.
Antiviral Effect, Safety, and Pharmacokinetics of Five-Day Oral Administration of Deleobuvir (BI 207127), an Investigational Hepatitis C Virus RNA Polymerase Inhibitor, in Patients with Chronic Hepatitis C

ABSTRACT Deleobuvir (BI 207127) is an investigational oral nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B RNA polymerase. Antiviral activity, virology, pharmacokinetics, and safety were assessed in HCV genotype 1-infected patients receiving 5 days' deleobuvir monotherapy. In this double-blind phase 1b study, treatment-naive (TN; n = 15) and treatment-experienced (TE; n = 45) patients without cirrhosis received placebo or deleobuvir at 100, 200, 400, 800, or 1,200 mg every 8 h (q8h) for 5 days. Patients with cirrhosis (n = 13) received deleobuvir at 400 or 600 mg q8h for 5 days. Virologic analyses included NS5B genotyping and phenotyping of individual isolates. At day 5, patients without cirrhosis had dose-dependent median HCV RNA reductions of up to 3.8 log10 (with no placebo response); patients with cirrhosis had median HCV RNA reductions of approximately 3.0 log10. Three patients discontinued due to adverse events (AEs). The most common AEs were gastrointestinal, nervous system, and skin/cutaneous tissue disorders. Plasma exposure of deleobuvir was supraproportional at doses ≥ 400 mg q8h and approximately 2-fold higher in patients with cirrhosis than in patients without cirrhosis. No virologic breakthrough was observed. NS5B substitutions associated with deleobuvir resistance in vitro were detected in 9/59 patients; seven encoded P495 substitutions, including P495L, which conferred 120- to 310-fold-decreased sensitivity to deleobuvir. P495 variants did not persist in follow-up without selective drug pressure. Deleobuvir monotherapy was generally well tolerated and demonstrated dose-dependent antiviral activity against HCV genotype 1 over 5 days.
A carbon sensitive supply chain network problem with green procurement

Faced with growing concerns over the environmental impact of human activities and increasing regulatory pressure, companies are beginning to recognize the importance of greening their supply chains by minimizing carbon emissions of their activities. An original equipment manufacturer that is concerned with minimizing the environmental impact of its activities should choose its suppliers based on the trade off between costs and respective emissions. In this paper, we develop an MIP model for the carbon-sensitive supply chain that minimizes emissions throughout the supply chain by taking into consideration green procurement. A sensitivity analysis of our model and results on several small problems are included.
Optimal PMU placement in a distribution network considering network reconfiguration

Now-a-days, phasor measurement units (PMUs) are essential devices in the modern distribution system, especially, in the way towards smart grid. The PMUs should be installed suitably in the distribution network. The problem of optimal PMU placement for full observability is analyzed in the literature. Distribution network reconfiguration for loss reduction is also analyzed in the literature. This paper studies the placement problem of PMUs in distribution system considering the system reconfiguration. System reconfiguration is achieved using the ant colony optimization method to solve the minimum power losses problem. Greedy algorithm is used as an optimization tool to determine the minimal number of PMUs and their locations. The 33-bus distribution system is studied for optimal installation of PMUs with different distribution network topologies.
Stunted growth: An exploration into the failures of African-language newspapers, Imvo Zabantsundu in focus

Abstract Publishing newspapers in African languages has largely been a precarious business, as many disappear no sooner than they appear on the newsstands. Several factors may be responsible for this short life-span, including apathy towards indigenous languages in Africa, which results in low patronage in terms of copy sales and advertisement placement. Yet, a number of local language newspapers actually endured, only to finally disappear after a long time. A good example was Imvo Zabantsundu, a Xhosa-language newspaper that existed, although with some interruption, between 1884 and 1997. This research examines the problems of managing local language publications, with a particular focus on Imvo. It also examines the success stories of the isiZulu newspaper, Isolezwe; the isiZulu, isiXhosa and Sesotho editions of Bona magazine; as well as the Alaroye titles in Yorubaland, Nigeria.
Dietary self-care in type 2 diabetes and the role of negative emotions: a Rational Emotive Behaviour Therapy (REBT) perspective

This thesis conducted three studies to explore negative emotions associated with dietary self-care and the role of rational and irrational beliefs in people with type 2 diabetes, from the Rational Emotive Behaviour Therapy perspective. The first study employed the Interpretative Phenomenological Analysis approach to explore people's experiences of maintaining good dietary self-care and the role of negative emotions. Guilt, anger, frustration, and feeling irritated, annoyed and depressed were negative emotions resulting from poor dietary self-care and resulting in poor dietary self-care. In study two which employed quantitative methodology, beliefs related to negative emotions were used to develop and validate a diabetes-related food beliefs questionnaire. Rational and irrational food beliefs were held concurrently and associated with distress about dietary restrictions. Irrational food beliefs were also linked to people's dietary self-care activities and dietary self-efficacy. The third study used the experimental method to further test the behavioural and physiological effects of beliefs, using three categories of food pictures. Although rational beliefs were associated with positive emotions, beliefs did not affect electrocortical processing of food pictures. Guilt was associated with high calorie foods and a further distinction was made between the high calorie foods, with larger amplitudes recorded for high-fat savoury foods.
Quantitative and Qualitative Differences in Proatherogenic NKT Cells in Apolipoprotein E–Deficient Mice

Background—Atherosclerosis is a disease marked by lipid accumulation and inflammation. Recently, atherosclerosis has gained recognition as an autoimmune-type syndrome characterized by increased activation of the innate and acquired immune systems. Natural killer T (NKT) cells have characteristics of both conventional T cells and NK cells and recognize glycolipid antigens presented in association with CD1d molecules on antigen-presenting cells. The capacity of NKT cells to respond to lipid antigens and modulate innate and acquired immunity suggests that they may play a role in atherogenesis. Methods and Results—We examined the role of NKT cells in atherogenesis and how the atherosclerotic environment affects the NKT cell population itself. The data show that CD1d-deficiency in male apolipoprotein E–deficient (apoE0) mice results in reduction in atherosclerosis, and treatment of apoE0 mice with α-galactosylceramide, a potent and specific NKT cell activator, results in a 2-fold increase in atherosclerosis. Interestingly, we demonstrate that α-galactosylceramide–induced interferon-γ responses and numbers of NKT cells in apoE0 mice show age-dependent qualitative and quantitative differences as compared with age-matched wild-type mice. Conclusions—Collectively, these findings reveal that hyperlipidemia and atherosclerosis have significant effects on NKT cell responses and that these cells are proatherogenic.
Network-based characterization of brain functional connectivity in Zen practitioners

In the last decade, a number of neuroimaging studies have investigated the neurophysiological effects associated with contemplative practices. Meditation-related changes in resting state functional connectivity (rsFC) have been previously reported, particularly in the default mode network, frontoparietal attentional circuits, saliency-related regions, and primary sensory cortices. We collected functional magnetic resonance imaging data from a sample of 12 experienced Zen meditators and 12 meditation-naïve matched controls during a basic attention-to-breathing protocol, together with behavioral performance outside the scanner on a set of computerized neuropsychological tests. We adopted a network system of 209 nodes, classified into nine functional modules, and a multi-stage approach to identify rsFC differences in meditators and controls. Between-group comparisons of modulewise FC, summarized by the first principal component of the relevant set of edges, revealed important connections of frontoparietal circuits with early visual and executive control areas. We also identified several group differences in positive and negative edgewise FC, often involving the visual, or frontoparietal regions. Multivariate pattern analysis of modulewise FC, using support vector machine (SVM), classified meditators, and controls with 79% accuracy and selected 10 modulewise connections that were jointly prominent in distinguishing meditators and controls; a similar SVM procedure based on the subjects’ scores on the neuropsychological battery yielded a slightly weaker accuracy (75%). Finally, we observed a good correlation between the across-subject variation in strength of modulewise connections among frontoparietal, executive, and visual circuits, on the one hand, and in the performance on a rapid visual information processing test of sustained attention, on the other. Taken together, these findings highlight the usefulness of employing network analysis techniques in investigating the neural correlates of contemplative practices.
UDP-Glucuronic Acid Binds First and the Aglycone Substrate Binds Second to Form a Ternary Complex in UGT1A9-Catalyzed Reactions, in Both the Presence and Absence of Bovine Serum Albumin

The presence of bovine serum albumin (BSA) largely modulates the enzyme kinetics parameters of the human UDP-glucuronosyltransferase (UGT) 1A9, increasing both the apparent aglycone substrate affinity of the enzyme and its limiting reaction velocity (Drug Metab Dispos 39:2117–2129, 2011). For a better understanding of the BSA effects and an examination of whether its presence changes the catalytic mechanism, we have studied the enzyme kinetics of 4-methylumbelliferone glucuronidation by UGT1A9 in the presence and absence of 0.1% BSA, using bisubstrate enzyme kinetic experiments, in both the forward and reverse directions, as well as product and dead-end inhibition. The combined results strongly suggest that the reaction mechanism of UGT1A9, and presumably other human UGTs as well, involves the formation of a compulsory-order ternary-complex, with UDP-α-d-glucuronic acid (UDPGA) as the first binding substrate. Based on the enzyme kinetic parameters measured for the forward and reverse reactions, the equilibrium constant of the overall reaction was calculated (Keq = 574) and the relative magnitudes of the reaction rate constants were elucidated. The inclusion of BSA in the bisubstrate kinetic experiments quantitatively changed the apparent enzyme kinetic parameters, presumably by removing internal inhibitors that bind to the binary enzyme-UDPGA (E-UDPGA) complex, as well as to the ternary E-UDPGA-aglycone complex. Nevertheless, the underlying compulsory-order ternary-complex mechanism with UDPGA binding first is the same in both the absence and presence of BSA. The results offer a novel understanding of UGT enzyme kinetic mechanism and BSA effects.