Miracle-dz/UniFAR-FTUs huggingface dataset:
Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling.
Modeling Loss-Propagation in the Global Supply Network: The Dynamic Agent-Based Model Acclimate

World markets are highly interlinked and local economies extensively rely on global supply and value chains. Consequently, local production disruptions, for instance caused by extreme weather events, are likely to induce indirect losses along supply chains with potentially global repercussions. These complex loss dynamics represent a challenge for comprehensive disaster risk assessments. Here, we introduce the numerical agent-based model acclimate designed to analyze the cascading of economic losses in the global supply network. Using national sectors as agents, we apply the model to study the global propagation of losses induced by stylized disasters. We find that indirect losses can become comparable in size to direct ones, but can be efficiently mitigated by warehousing and idle capacities. Consequently, a comprehensive risk assessment cannot focus solely on first-tier suppliers, but has to take the whole supply chain into account. To render the supply network climate-proof, national adaptation policies have to be complemented by international adaptation efforts. In that regard, our model can be employed to assess reasonable leverage points and to identify dynamic bottlenecks inaccessible to static analyses.
Trends in medication use among US adults with diabetes mellitus: glycemic control at the expense of controlling cardiovascular risk factors.

S uccessful reduction of cardiovascular disease (CVD) risk among people with diabetes mellitus is increasingly reliant on combination pharmacotherapy targeting its major risk factors, especially hypertension and high cholesterol level. The impact of tight hyperglycemia control on CVD and mortality risk is currently unclear, but its control is a major part of comprehensive diabetes care and is also increasingly attained through combination therapy. We sought to examine the competing treatment priorities for US adults with diabetes by analyzing the use of antidiabetes, antihypertensive, and statin medications over time from the populationbased National Health and Nutrition Examination Survey (NHANES) between 1999 and 2006.
Behavioral Log Analysis with Statistical Guarantees

Scalability is a major challenge for existing behavioral log analysis algorithms, which extract finite-state automaton models or temporal properties from logs generated by running systems. In this paper we present statistical log analysis, which addresses scalability using statistical tools. The key to our approach is to consider behavioral log analysis as a statistical experiment.Rather than analyzing the entire log, we suggest to analyze only a sample of traces from the log and, most importantly, provide means to compute statistical guarantees for the correctness of the analysis result.We present the theoretical foundations of our approach and describe two example applications, to the classic k-Tails algorithm and to the recently presented BEAR algorithm.Finally, based on experiments with logs generated from real-world models and with real-world logs provided to us by our industrial partners, we present extensive evidence for the need for scalable log analysis and for the effectiveness of statistical log analysis.
Corticotropin-Releasing Hormone Receptor 1 Gene Variants in Irritable Bowel Syndrome

Background Corticotropin-releasing hormone (CRH) acts mainly via the CRH receptor 1 (CRH-R1) and plays a crucial role in the stress-induced pathophysiology of irritable bowel syndrome (IBS). Several studies have demonstrated that variants of the CRH-R1 gene carry a potential risk for depression, but evidence for an association between CRH-R1 genotypes and IBS is lacking. We tested the hypothesis that genetic polymorphisms and haplotypes of CRH-R1 moderate the IBS phenotype and negative emotion in IBS patients. Methods A total of 103 patients with IBS and 142 healthy controls participated in the study. Three single-nucleotide polymorphisms of the CRH-R1 gene (rs7209436, rs242924, and rs110402) were genotyped. Subjects' emotional states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-rating Depression Scale. Results The TT genotype of rs7209436 (P = 0.01) and rs242924 (P = 0.02) was significantly more common in patients with IBS than in controls. Total sample analysis showed significant association between bowel pattern (normal, diarrhea, constipation, or mixed symptoms) and the T allele of rs7209436 (P = 0.008), T allele of rs242924 (P = 0.019), A allele of rs110402 (P = 0.047), and TAT haplocopies (P = 0.048). Negative emotion was not associated with the examined CRH-R1 SNPs. Conclusion These findings suggest that genetic polymorphisms and the CRH-R1 haplotypes moderate IBS and related bowel patterns. There was no clear association between CRH-R1 genotypes and negative emotion accompanying IBS. Further studies on the CRH system are therefore warranted.
Restarting anticoagulation in prosthetic heart valve patients after intracranial haemorrhage: a 2‐year follow‐up

35 patients with oral anticoagulant (OAC) related intracranial or intraspinal haemorrhage were studied to determine treatment received, outcome and rate of recurrent bleeding and thromboembolism after restarting OAC. All patients underwent active anticoagulant reversal and in 14 patients with prosthetic heart valves (PHV) the INR remained below 2.0 for 0–19 d (median 7) with no thromboembolic events. 10 patients received heparin, although a therapeutic level was rarely achieved. 13 patients with PHV were restarted on OAC and followed for a median 23.5 months. One patient had recurrent intracranial bleeding. 3/13 patients had cerebral embolic events despite anticoagulation. We conclude that in PHV patients temporary cessation of OAC is safe and the risk of recurrent bleeding after restarting OAC is low.
The Relationship between Lutein and Zeaxanthin Status and Body Fat

The objective of this project was to investigate the relationships between total and regional distribution of body fat and tissue lutein (L) and zeaxanthin (Z) status. Healthy men and women (N = 100; average age: 22.5 year, average BMI: 23.4 kg/m2) were evaluated. Total body and regional fat mass were assessed by dual-energy X-ray absorptiometry (Hologic Delphi A). Serum LZ was measured using reverse phase high-performance liquid chromatography, and retinal LZ (referred to as macular pigment optical density; MPOD) was measured using heterochromatic flicker photometry. Body fat percentage (total and regional) was inversely related to MPOD (p < 0.01) but no significant relationship was found for serum LZ. Higher body fat percentage, even within relatively healthy limits, is associated with lower tissue LZ status. The results indicate that adiposity may affect the nutritional state of the retina. Such links may be one of the reasons that obesity promotes age-related degenerative conditions of the retina.
Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration.

BACKGROUND Recent recognition of its broad pathophysiological importance has triggered an increased interest in 25-hydroxyvitamin D [25(OH)D]. By consequence, throughput in 25(OH)D testing has become an issue for clinical laboratories, and several automated assays for measurement of 25(OH)D are now available. The aim of this study was to test the accuracy and robustness of these assays by comparing their results to those of an isotope dilution/online solid-phase extraction liquid chromatography/tandem mass spectrometry (ID-XLC-MS/MS) method. We put specific focus on the influence of vitamin D-binding protein (DBP) by using samples with various concentrations of DBP. METHODS We used 5 automated assays (Architect, Centaur, iSYS, Liaison, and Elecsys), 1 RIA (Diasorin) preceded by extraction, and an ID-XLC-MS/MS method to measure 25(OH)D concentrations in plasma samples of 51 healthy individuals, 52 pregnant women, 50 hemodialysis patients, and 50 intensive care patients. Using ELISA, we also measured DBP concentrations in these samples. RESULTS Most of the examined 25(OH)D assays showed significant deviations in 25(OH)D concentrations from those of the ID-XLC-MS/MS method. As expected, DBP concentrations were higher in samples of pregnant women and lower in samples of IC patients compared to healthy controls. In 4 of the 5 fully automated 25(OH)D assays, we observed an inverse relationship between DBP concentrations and deviations from the ID-XLC-MS/MS results. CONCLUSIONS 25(OH)D measurements performed with most immunoassays suffer from inaccuracies that are DBP concentration dependent. Therefore, when interpreting results of 25(OH)D measurements, careful consideration of the measurement method is necessary.
Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50

ABSTRACT Retromer and the associated actin-polymerizing WASH complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's-disease-causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH complex and also with the uncharacterized protein ankyrin-repeat-domain-containing protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a new and essential component of the SNX27–retromer–WASH super complex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome-to-cell-surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASH-complex components. Mass-spectrometry-based quantification of the cell surface proteome of ANKRD50-depleted cells identified amino acid transporters of the SLC1A family, among them SLC1A4, as additional cargo molecules that depend on ANKRD50 and retromer for their endocytic recycling. Mechanistically, we show that ANKRD50 simultaneously engages multiple parts of the SNX27–retromer–WASH complex machinery in a direct and co-operative interaction network that is needed to efficiently recycle the nutrient transporters GLUT1 (also known as SLC2A1) and SLC1A4, and potentially many other surface proteins. Highlighted Article: Here, we investigate the function of the completely uncharacterized protein ANKRD50 showing that it is involved in recycling of cell surface proteins through multiple interactions with the retromer complex.
Drift Analysis and Evolutionary Algorithms Revisited

One of the easiest randomized greedy optimization algorithms is the following evolutionary algorithm which aims at maximizing a function f: {0,1}n → ℝ. The algorithm starts with a random search point ξ ∈ {0,1}n, and in each round it flips each bit of ξ with probability c/n independently at random, where c > 0 is a fixed constant. The thus created offspring ξ' replaces ξ if and only if f(ξ') ≥ f(ξ). The analysis of the runtime of this simple algorithm for monotone and for linear functions turned out to be highly non-trivial. In this paper we review known results and provide new and self-contained proofs of partly stronger results.
The child abusers : research and controversy

The child protection controversy media and professional response Types of abuse Within-family abusers rediscovering the psychiatric dimension Special problems in child protection abusers in 'sudden-infant-death' syndrome: 'Munchausen-by-proxy'syndrome: 'shaken-baby'syndrome Extra-family abusers the child sex abuser The extreme abuser who kills children? The victim-to-abuser cycle Societal abuser rediscovering the poverty dimension Professional iatrogenesis 'the helping hand strikes again' Search for an effective intervention Ethical debate and humanitarian manifesto References Index.
Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity

Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (Crocuta crocuta) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis.
The neural bases of autobiographical memory : how personal recollections interact with emotion and influence semantic memory

The main aim of the present thesis has to help improving our understanding of neural mechanisms underlying autobiographical memory (AbM), particularly how personal recollections interact with emotion and influence semantic memory Our first study investigated the neural correlates of spontaneous re-living of emotion during recollection of personal event cued with personally known faces. Our findings suggested that the use of highly self-relevant stimuli and the collection of data with no previous refreshment of the memory trace (i) influenced the right lateralisation of the activation in the medial temporal lobe (MTL), and (ii) involved increased activity in the cortical midline structures and subcortical circuits, known to sustain the self-generated emotion, even though no emotion was explicitly acknowledged. In our second study, the aforementioned nonverbal experiment was compared with a verbal one involving pre-scanning testing in order to clarify whether the lateralisation issue of the general network sustaining AbM retrieval. Our finding of a predominantly left-lateralized cerebral network in both experiments suggested that left-sided pattern of brain activations is associated with AbM retrieval per se in healthy subjects. The third experimental work of the present thesis focused on the influence of autobiographical significance on the semantic memory cerebral network. Our results provided functional neuroimaging evidence that autobiographically significant semantic knowledge relies on a pattern of brain activations different from that underlying ‘purely’ semantic knowledge, with the core difference being located at the MTL. The last study investigated the neuronanatomical representations of both autobiographical and semantic remote memory in two patients presenting with left temporal lobe epilepsy. (i) We provided functional neuroimaging evidence of the dissociation within remote memory (autobiographical vs semantic). (ii) Importantly, we documented dissociation within semantic memory for famous people according to the nature of material. Our last experimental work confirms the importance of combining neuropsychological and neuroimaging methods in appropriate patients in order to better understand human memory functions.
Interpreting Quality as Perceived by Trainee Interpreters

Abstract This paper discusses quality assessment of the performance of both professional and student interpreters working in various contexts, using a wide range of methods. It then focuses on self-evaluation by trainee simultaneous interpreters as examined in two empirical studies. The first project applied retrospective verbal protocols to investigate interpreting strategies used by 36 advanced student interpreters working in both directions, between Polish (A) and English (B). The results concerning self-evaluation, which are presented here, were a by-product of this first study, but they gave rise to questions that are further explored in the second project. Eighteen subjects at the same stage of training were asked to interpret a text from English into Polish and to evaluate their performance, linking it to the strategic processing they had applied. The results suggest a significant trend towards negative assessment, combined with most attention being devoted to faithfulness to the original message and to completeness. Issues of presentation (including monotonous intonation, hesitant voice and long pauses), on the other hand, were hardly ever mentioned.
The emerging field of nanodielectrics an annotated appreciation

The turmoil of activities that has surrounded nanotechnology in recent years continued to grow and outburst in several directions. This has reflected as well in the field of nanodielectrics where a great number of contributions resulted, a progress that the authors will comment. This annotated appreciation will be developed with a concentration on information, known facts and uncertainties with a zest of critique. Force is to conclude that the felt potentials remain to be demonstrated in the context of an improved profitability
Fulfill psychological contract promises to manage in-demand employees

Purpose – The purpose of this paper is to explore the impact of three components of the psychological contract (i.e. obligations, fulfillment and breach) and the individual characteristic negative affectivity (NA) onto three key outcomes, namely, job satisfaction, organizational identification and psychological distress. Design/methodology/approach – Questionnaires were completed by 222 Australian nurses and midwives from a medium-sized metropolitan Australian hospital. The response rate for the study was 39 percent. Findings – Structural equation modeling revealed that perceptions of psychological contract fulfillment were positively linked to organizational identification and job satisfaction, while psychological contract breach was negatively linked to these outcomes. NA was negatively linked to job satisfaction and positively linked to psychological distress. Psychological contract obligations were not associated with any of the employee outcomes. Research limitations/implications – Psychological cont.
GeneSigDB—a curated database of gene expression signatures

The primary objective of most gene expression studies is the identification of one or more gene signatures; lists of genes whose transcriptional levels are uniquely associated with a specific biological phenotype. Whilst thousands of experimentally derived gene signatures are published, their potential value to the community is limited by their computational inaccessibility. Gene signatures are embedded in published article figures, tables or in supplementary materials, and are frequently presented using non-standard gene or probeset nomenclature. We present GeneSigDB (http://compbio.dfci.harvard.edu/genesigdb) a manually curated database of gene expression signatures. GeneSigDB release 1.0 focuses on cancer and stem cells gene signatures and was constructed from more than 850 publications from which we manually transcribed 575 gene signatures. Most gene signatures (n = 560) were successfully mapped to the genome to extract standardized lists of EnsEMBL gene identifiers. GeneSigDB provides the original gene signature, the standardized gene list and a fully traceable gene mapping history for each gene from the original transcribed data table through to the standardized list of genes. The GeneSigDB web portal is easy to search, allows users to compare their own gene list to those in the database, and download gene signatures in most common gene identifier formats.
Visualization of Developmental Processes by Extrusion in Space-time

Developmental processes in nature may involve complex changes in the topology, shape, and patterns of growing structures. Processes taking place in one or two dimensions can be visualized as objects in three-dimensional space, obtained by extruding the growing structures along a line or curve representing the progress of time. In this paper, we extend the notion of L-systems with turtle interpretation to facilitate the construction of such objects. This extension is based on the interpretation of the entire derivation graph generated by an L-system, as opposed to the interpretation of individual words. We illustrate the proposed method by applying it to visualize the development of compound leaves, a sea shell with a pigmentation pattern, and a filamentous bacteria. In addition to serving as visualization examples, these models are of interest on their own. The sea shell model uses an L-system to express a reaction-diffusion process, thus relating these two models of morphogenesis. The model of bacteria, which is also of the reaction-diffusion type, sheds new light on one of the basic problems of morphogenesis, the formation of equally spaced organs in a developing medium.