Miracle-dz/UniFAR-FTUs huggingface dataset:
The Exclusive Society: Social Exclusion, Crime and Difference in Late Modernity

From Inclusive to Exclusive Society Crime and Discord in an Age of Late Modernity Cannibalism and Bulimia Essentialising the Other Demonisation and the Creation of Monstrosity The Criminology of Intolerance Zero Tolerance Policing and The American Prison Experiment A World Holding Together and Falling Apart Holding Chaos in Abeyance The Maintenance of Order amongst Lightly Engaged Strangers The Contradictory World of Late Modernity
The Antidiabetic Drug Ciglitazone Induces High Grade Bladder Cancer Cells Apoptosis through the Up-Regulation of TRAIL

Background Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines. Methodology/Principal Findings Using RT4 (derived from a well differentiated grade I papillary tumor) and T24 (derived from an undifferentiated grade III carcinoma) bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21waf1/CIP1 and p27Kip1 in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism. Conclusions/Significance Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers.
Molecular epidemiology of respiratory viruses in virus-induced asthma

Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma.
signal transduction proteins : nitrogen regulation and beyond

The PII proteins are one of the most widely distributed families of signal transduction proteins in nature. They are pivotal players in the control of nitrogen metabolism in bacteria and archaea, and are also found in the plastids of plants. Quite remarkably, PII proteins control the activities of a diverse range of enzymes, transcription factors and membrane transport proteins, and in recent years the extent of these interactions has been recognized to be much greater than heretofore described. Major advances have been made in structural studies of PII proteins, including the solution of the first structures of PII proteins complexed with their targets. We have also begun to gain insights into how the key effector molecules, 2-oxoglutarate and ATP/ADP, influence the activities of PII proteins. In this review, we have set out to summarize our current understanding of PII biology and to consider where future studies of these extraordinarily adaptable proteins might lead us.
On Interpolation and Automatization for Frege Systems

The interpolation method has been one of the main tools for proving lower bounds for propositional proof systems. Loosely speaking, if one can prove that a particular proof system has the feasible interpolation property, then a generic reduction can (usually) be applied to prove lower bounds for the proof system, sometimes assuming a (usually modest) complexity-theoretic assumption. In this paper, we show that this method cannot be used to obtain lower bounds for Frege systems, or even for TC0-Frege systems. More specifically, we show that unless factoring (of Blum integers) is feasible, neither Frege nor TC0-Frege has the feasible interpolation property. In order to carry out our argument, we show how to carry out proofs of many elementary axioms/theorems of arithmetic in polynomial-sized TC0-Frege. As a corollary, we obtain that TC0-Frege, as well as any proof system that polynomially simulates it, is not automatizable (under the assumption that factoring of Blum integers is hard). We also show under the same hardness assumption that the k-provability problem for Frege systems is hard.
Online Resource Allocation Using Decompositional Reinforcement Learning

This paper considers a novel application domain for reinforcement learning: that of "autonomic computing," i.e. selfmanaging computing systems. RL is applied to an online resource allocation task in a distributed multi-application computing environment with independent time-varying load in each application. The task is to allocate servers in real time so as to maximize the sum of performance-based expected utility in each application. This task may be treated as a composite MDP, and to exploit the problem structure, a simple localized RL approach is proposed, with better scalability than previous approaches. The RL approach is tested in a realistic prototype data center comprising real servers, real HTTP requests, and realistic time-varying demand. This domain poses a number of major challenges associated with live training in a real system, including: the need for rapid training, exploration that avoids excessive penalties, and handling complex, potentially non-Markovian system effects. The early results are encouraging: in overnight training, RL performs as well as or slightly better than heavily researched model-based approaches derived from queuing theory.
Maternal psychosocial well‐being in pregnancy and breastfeeding duration

Aim: An increased duration of breastfeeding has many advantages for the child and mother. However, little research to date has investigated the influence of maternal psychosocial well‐being during pregnancy on the duration of breastfeeding. This study aimed to examine whether experience of life stress events, social contact/support in pregnancy and postpartum emotional disturbance had an effect on breastfeeding duration.
SOCS2 mediates the cross talk between androgen and growth hormone signaling in prostate cancer.

UNLABELLED Anabolic signals such as androgens and the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis play an essential role in the normal development of the prostate but also in its malignant transformation. In this study, we investigated the role of suppressor of cytokine signaling 2 (SOCS2) as mediator of the cross talk between androgens and GH signals in the prostate and its potential role as tumor suppressor in prostate cancer (PCa). We observed that SOCS2 protein levels assayed by immunohistochemistry are elevated in hormone therapy-naive localized prostatic adenocarcinoma in comparison with benign tissue. In contrast, however, castration-resistant bone metastases exhibit reduced levels of SOCS2 in comparison with localized or hormone naive, untreated metastatic tumors. In PCa cells, SOCS2 expression is induced by androgens through a mechanism that requires signal transducer and activator of transcription 5 protein (STAT5) and androgen receptor-dependent transcription. Consequentially, SOCS2 inhibits GH activation of Janus kinase 2, Src and STAT5 as well as both cell invasion and cell proliferation in vitro. In vivo, SOCS2 limits proliferation and production of IGF-1 in the prostate in response to GH. Our results suggest that the use of GH-signaling inhibitors could be of value as a complementary treatment for castration-resistant PCa. SUMMARY Androgen induced SOCS2 ubiquitin ligase expression and inhibited GH signaling as well as cell proliferation and invasion in PCa, whereas reduced SOCS2 was present in castration-resistant cases. GH-signaling inhibitors might be a complementary therapeutic option for advanced PCa.
Evolving biochemical systems

The interaction of biological compounds in cells has been enforced to a proper understanding by the numerous bioinformatics projects which contributed with a vast amount of biological information. The construction of biochemical systems (systems of chemical reactions) which include both topology and kinetic rates of the chemical reactions is an NP-hard problem. In this paper we propose a hybrid architecture which combines genetic programming and simulated annealing in order to generate and optimize both the topology (the network) and the reaction rates of a biochemical systems. Simulations and analysis of two real models show promising results for the proposed method.
Rational Design of a Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated and Immunogenic in Mice and Macaques

Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2′-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2′-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2′-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.
The effects of growth hormone treatment on bone mineral density and body composition in girls with turner syndrome.

BACKGROUND Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition. OBJECTIVE The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS. METHOD In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006. RESULTS The two groups were similar in age (12.3 yr, sd 2.9), bone age (11.5 yr, sd 2.6), and weight (42.8 kg, sd 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (sd 3.2) yr (range 1-14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1-L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P < 0.001), whereas body fat percent was lower (P < 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously. CONCLUSIONS Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity.
Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats

BACKGROUND Dietary fibres have been proposed as protective agents against colon cancer but results of both epidemiological and experimental studies are inconclusive. AIMS Hypothesising that protection against colon cancer may be restricted to butyrate producing fibres, we investigated the factors needed for long term stable butyrate production and its relation to susceptibility to colon cancer. METHODS A two part randomised blinded study in rats, mimicking a prospective study in humans, was performed using a low fibre control diet (CD) and three high fibre diets: starch free wheat bran (WB), type III resistant starch (RS), and short chain fructo-oligosaccharides (FOS). Using a randomised block design, 96 inbred rats were fed for two, 16, 30, or 44 days to determine the period of adaptation to the diets, fermentation profiles, and effects on the colon, including mucosal proliferation on day 44. Subsequently, 36 rats fed the same diets for 44 days were injected with azoxymethane and checked for aberrant crypt foci 30 days later. RESULTS After fermentation had stabilised (44 days), only RS and FOS produced large amounts of butyrate, with a trophic effect in the large intestine. No difference in mucosal proliferation between the diets was noted at this time. In the subsequent experiment one month later, fewer aberrant crypt foci were present in rats fed high butyrate producing diets (RS, p=0.022; FOS, p=0.043). CONCLUSION A stable butyrate producing colonic ecosystem related to selected fibres appears to be less conducive to colon carcinogenesis.
Shaping the learning curve: epigenetic dynamics in neural plasticity

A key characteristic of learning and neural plasticity is state-dependent acquisition dynamics reflected by the non-linear learning curve that links increase in learning with practice. Here we propose that the manner by which epigenetic states of individual cells change during learning contributes to the shape of the neural and behavioral learning curve. We base our suggestion on recent studies showing that epigenetic mechanisms such as DNA methylation, histone acetylation, and RNA-mediated gene regulation are intimately involved in the establishment and maintenance of long-term neural plasticity, reflecting specific learning-histories and influencing future learning. Our model, which is the first to suggest a dynamic molecular account of the shape of the learning curve, leads to several testable predictions regarding the link between epigenetic dynamics at the promoter, gene-network, and neural-network levels. This perspective opens up new avenues for therapeutic interventions in neurological pathologies.
Genotyping-by-Sequencing (GBS) Revealed Molecular Genetic Diversity of Iranian Wheat Landraces and Cultivars

Background: Genetic diversity is an essential resource for breeders to improve new cultivars with desirable characteristics. Recently, genotyping-by-sequencing (GBS), a next-generation sequencing (NGS) technology that can simplify complex genomes, has now be used as a high-throughput and cost-effective molecular tool for routine breeding and screening in many crop species, including the species with a large genome. Results: We genotyped a diversity panel of 369 Iranian hexaploid wheat accessions including 270 landraces collected between 1931 and 1968 in different climate zones and 99 cultivars released between 1942 to 2014 using 16,506 GBS-based single nucleotide polymorphism (GBS-SNP) markers. The B genome had the highest number of mapped SNPs while the D genome had the lowest on both the Chinese Spring and W7984 references. Structure and cluster analyses divided the panel into three groups with two landrace groups and one cultivar group, suggesting a high differentiation between landraces and cultivars and between landraces. The cultivar group can be further divided into four subgroups with one subgroup was mostly derived from Iranian ancestor(s). Similarly, landrace groups can be further divided based on years of collection and climate zones where the accessions were collected. Molecular analysis of variance indicated that the genetic variation was larger between groups than within group. Conclusion: Obvious genetic diversity in Iranian wheat was revealed by analysis of GBS-SNPs and thus breeders can select genetically distant parents for crossing in breeding. The diverse Iranian landraces provide rich genetic sources of tolerance to biotic and abiotic stresses, and they can be useful resources for the improvement of wheat production in Iran and other countries.
Transforming the Morbidity and Mortality Conference into an Instrument for Systemwide Improvement

Objective: The morbidity and mortality conference (M&MC) is a traditional forum that provides clinicians with an opportunity to discuss medical error and adverse events. In an effort to promote patient safety at our institution, we implemented a monthly interdisciplinary morbidity, mortality, and improvement (MM&I) conference, which focused on systemwide problems. The participants included physicians, nursing staff, pharmacy, and other clinical departments, as well as senior hospital administrators. Methods: A Mortality Review Task Force selects cases for presentation at the monthly MM&I. A resident representative presents the case, and a designated senior faculty member facilitates a discussion of the case with audience participation. Key issues that contributed to the undesired outcome of the case are identified and outlined on a cause-andeffect diagram (Ichikawa diagram). Workgroups are created to target systems-based problems. At the end of the conference, attendees are asked to complete an evaluation and provide feedback for subsequent consideration by the task force. Results: Twenty-one cases (12 medical, 9 surgical) representing adverse events were presented at the MM&I conference from January 2005 to February 2007. The mean number of participants per session was 88 (range, 62-115). Adverse events triggering case selection included unexpected deaths (six), unplanned intubations (two), prolonged medical care in the setting of poor prognosis (one), delay in care (nine), and procedural complications (three). The most common factors contributing to adverse or “nearmiss” outcomes in these cases were communication failures and inadequate coordination of care. In all, 33 action items were created, and 23 (70 percent) have been completed to date. Conclusion: A structured hospital-wide MM&I conference is an effective means of engaging physicians, nurses, and key administrative leaders in the discussion of adverse events. The identification of potential system failures and the creation of workgroups to address specific systems-based problems can promote initiatives to improve patient care and safety. Background In order to provide high quality patient care, members of a multidisciplinary health care team must engage in objective, nonjudgmental review of adverse outcomes and commit to systematic process change. The morbidity and mortality conference (M&MC) is one forum that provides clinicians with an opportunity to discuss medical error and adverse events. The M&MC became a major part of physician education in the early 20 century, following the publication of the Flexner report on medical education in 1910 and the creation of the American College of
The relationship between burnout and job satisfaction amongst fire fighters in a local authority

Fire fighters are involved in critical decision making situations, and under-performance and lack of job satisfaction due to burnout could adversely affect the welfare of the people that are being provided with the service. This study thus investigated the relationship between burnout and job satisfaction amongst operational fire fighters. Two measuring instruments were used: the Pines, Aronson & Kafry (1981) Burnout Index, and the Smith, Hulin and Kendall (1969) Job Descriptive Index. This study was conducted amongst 102 fire fighters working for a local authority. Through a literature review, burnout and job satisfaction were defined, and a link between the two constructs outlined. Through an empirical study, the relationship between burnout and job satisfaction was determined. Supporting evidence indicates a negative correlation between burnout and job satisfaction, as well as revealing social support amongst co-workers as being an important buffer against the effects of burnout.
Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue

Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7−CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates. Furthermore, there were differences between the prostate conditions regarding the percentage of T-cells expressing several activation markers and co-inhibitory receptors. In conclusion, many prostate-infiltrating T-cells express co-inhibitory receptors PD-1 and LAG-3, regardless of prostate condition. Despite the observed increase in counts and percentages of PD-1+ T-cells in PC, the concomitant demonstration of high percentage of PD-1+ T-cells in control prostates suggests that PD-1 may play a role in controlling the homeostasis of the prostate rather than in contributing to PC-associated immune-suppression. Thus, PD-1 may not be a good candidate for checkpoint blockade in PC and these data are relevant for evaluation of clinical trials and in designing future immunotherapeutic approaches of PC.