Miracle-dz/UniFAR-FTUs huggingface dataset:
Analytic non-supersymmetric background dual of a confining gauge theory and the corresponding plane wave theory of hadrons

We find a regular analytic 1st order deformation of the Klebanov-Strassler background. From the dual gauge theory point of view the deformation describes supersymmetry soft breaking gaugino mass terms. We calculate the difference in vacuum energies between the supersymmetric and the non-supersymmetric solutions and find that it matches the field theory prediction. We also discuss the breaking of the U(1)R symmetry and the space-time dependence of the gaugino bilinears two point function. Finally, we determine the Penrose limit of the non-supersymmetric background and write down the corresponding plane wave string theory. This string describes ``annulons''-heavy hadrons with mass proportional to large global charge. Surprisingly the string spectrum has two fermionic zero modes. This implies that the sector in the non-supersymmetric gauge theory which is the dual of the annulons is supersymmetric.
Elimination of Negative Feedback Control Mechanisms Along the Insulin Signaling Pathway Improves β-Cell Function Under Stress

OBJECTIVE Cellular stress and proinflammatory cytokines induce phosphorylation of insulin receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-1 signaling. Here, we examined the role of Ser phosphorylation of IRS-2 in mediating the inhibitory effects of proinflammatory cytokines and cellular stress on β-cell function. RESEARCH DESIGN AND METHODS Five potential inhibitory Ser sites located proximally to the P-Tyr binding domain of IRS-2 were mutated to Ala. These IRS-2 mutants, denoted IRS-25A, and their wild-type controls (IRS-2WT) were introduced into adenoviral constructs that were infected into Min6 cells or into cultured murine islets. RESULTS When expressed in cultured mouse islets, IRS-25A was better than IRS-2WT in protecting β-cells from apoptosis induced by a combination of IL-1β, IFN-γ, TNF-α, and Fas ligand. Cytokine-treated islets expressing IRS25A secreted significantly more insulin in response to glucose than did islets expressing IRS-2WT. This could be attributed to the higher transcription of Pdx1 in cytokine-treated islets that expressed IRS-25A. Accordingly, transplantation of 200 islets expressing IRS25A into STZ-induced diabetic mice restored their ability to respond to a glucose load similar to naïve mice. In contrast, mice transplanted with islets expressing IRS2WT maintained sustained hyperglycemia 3 days after transplantation. CONCLUSIONS Elimination of a physiological negative feedback control mechanism along the insulin-signaling pathway that involves Ser/Thr phosphorylation of IRS-2 affords protection against the adverse effects of proinflammatory cytokines and improves β-cell function under stress. Genetic approaches that promote IRS25A expression in pancreatic β-cells, therefore, could be considered a rational treatment against β-cell failure after islet transplantation.
A Critical Dose of Doxorubicin Is Required to Alter the Gene Expression Profiles in MCF-7 Cells Acquiring Multidrug Resistance

Cellular mechanisms of multidrug resistance (MDR) are related to ABC transporters, apoptosis, antioxidation, drug metabolism, DNA repair and cell proliferation. It remains unclear whether the process of resistance development is programmable. We aimed to study gene expression profiling circumstances in MCF-7 during MDR development. Eleven MCF-7 sublines with incremental doxorubicin resistance were established as a valued tool to study resistance progression. MDR marker P-gp was overexpressed only in cells termed MCF-7/ADR-1024 under the selection dose approaching 1024 nM. MCF-7/ADR-1024 and authentic MCF-7/ADR shared common features in cell morphology and DNA ploidy status. MCF-7/ADR-1024 and authentic MCF-7/ADR down regulated repair genes BRCA1/2 and wild type p53, apoptosis-related gene Bcl-2 and epithelial-mesenchymal transition (EMT) epithelial marker gene E-cadherin. While detoxifying enzymes glutathione-S transferase-π and protein kinase C-α were up-regulated. The genes involving in EMT mesenchymal formation were also overexpressed, including N-cadherin, vimentin and the E-cadherin transcription reppressors Slug, Twist and ZEB1/2. PI3K/AKT inhibitor wortmannin suppressed expression of Slug, Twist and mdr1. Mutant p53 with a deletion at codons 127-133 markedly appeared in MCF-7/ADR-1024 and authentic MCF-7/ADR as well. In addition, MCF-7/ADR-1024 cells exerted CSC-like cell surface marker CD44 high/CD24 low and form mammospheres. Overall, results suggest that resistance marker P-gp arises owing to turn on/off or mutation of the genes involved in DNA repair, apoptosis, detoxifying enzymes, EMT and ABC transporters at a turning point (1.024 μM doxorubicin challenge). Behind this point, no obvious alterations were found in most tested genes. Selection for CSC-like cells under this dose may importantly attribute to propagation of the population presenting invasive properties and drug resistance. We thereby suggest two models in the induction of drug resistance. Model 1: Selection for CSC-like cells. Model 2: Mutations for gain-of resistance. Either model 1 or model 2 requires doxorubicin dose approaching 1 μM to alter gene regulation.
A quantitative link between globular clusters and the stellar haloes in elliptical galaxies

This paper explores the quantitative connection between globular clusters and the ‘diffuse’ stellar population of the galaxies they are associated with. Both NGC 1399 and NGC 4486 (M87) are well suited for this kind of analysis due to their large globular cluster populations. The main assumption of our Monte Carlo based models is that each globular cluster is formed along with a given diffuse stellar mass that shares the same spatial distribution, chemical composition and age. The main globular cluster subpopulations, that determine the observed bimodal colour distribution, are decomposed avoiding a priori parametric (e.g. Gaussian) fits and using a new colour (C−T1)–metallicity relation. The eventual detectability of a ‘blue’ tilt in the colour–magnitude diagrams of the blue globular cluster subpopulation is also addressed. A successful link between globular clusters and the stellar galaxy halo is established by assuming that the number of globular clusters per associated diffuse stellar mass t is a function of total abundance [Z/H] and behaves as t=γ exp(−δ[Z/H]) (i.e. increases when abundance decreases). The simulations allow the prediction of a surface brightness profile for each galaxy through these two free parameters' approximation. The γ, δ parameters that provide the best fit to the observed profiles in the B band, in turn, determine several features, namely, large-scale halo colour gradients, globular cluster–halo colour offset, clusters' cumulative specific frequencies, and stellar metallicity distributions, that compare well with observations. The results suggest the co-existence of two distinct stellar populations characterized by widely different metallicities and spatial distributions. One of these populations (connected with the blue globular clusters) is metal poor, highly homogeneous, exhibits an extended spatial distribution and becomes more evident at large galactocentric radius contributing with some 20 per cent of the total stellar mass. In turn, the stellar population associated with the red globular clusters is extremely heterogeneous and dominates the inner region of both galaxies. Remarkably, and although the cluster populations of these galaxies exhibit detectable differences in colour distribution, the δ parameter that determines the shape of the brightness profiles of both galaxies has the same value, δ≈ 1.1 to 1.2 ± 0.1.
Comparing probabilistic inference for mixed Bayesian networks

Bayesian Networks are graphical representation of dependence relationships between domain variables. They have been applied in many areas due to their powerful probabilistic inference such as data fusion, target recognition, and medical diagnosis, etc. There exists a number of inference algorithms that have different tradeoffs in computational efficiency, accuracy, and applicable network topologies. It is well known that, in general, the exact inference algorithms are either computationally infeasible for dense networks or impossible for mixed discrete-continuous networks. However, in practice, mixed Bayesian Networks are commonly used for various applications. In this paper, we compare and analyze the trade-offs for several inference approaches. They include the exact Junction Tree algorithm for linear Gaussian networks, the exact algorithm for discretized networks, and the stochastic simulation methods. We also propose an almost instant-time algorithm (AIA) by pre-compiling the approximate likelihood tables. Preliminary experimental results show promising performance.
A descriptor system approach to guaranteed cost control for nonlinear neutral systems

This paper investigates the guaranteed cost control and optimization design for a class of nonlinear neutral systems. Using a descriptor system model transformation approach, a sufficient condition for the existence of guaranteed cost controller is given in terms of linear matrix inequalities(LMIs). In this method, the nonlinear parameter perturbation is viewed as effective information. Further, the design of an optimal guaranteed cost controller is reduced to a convex optimization problem. Finally, two examples are given to illustrate the controller design method and show the advantages of the obtained results over the existing results in the literatures.
Hypoxia induces macrophage polarization and re-education toward an M2 phenotype in U87 and U251 glioblastoma models

Hypoxia is a common feature of solid tumors, particularly in glioblastoma (GBM), and known to be a poor prognosis factor in GBM patients. The growth of GBM is also associated with a marked inflammation partially characterized by an accumulation of macrophage (MΦ) of the M2 phenotype. However, the transition between M1 MΦ (antitumoral) and M2 MΦ (protumoral) phenotypes is a dynamic process. We made the assumption that oxygen (O2) availability could be a major regulator of this transition and that the intratumoral O2 gradient is of importance. We evaluated, in vivo, the impact of hypoxia on MΦ tropism and polarization in two models of human GBM, well differentiated by their degree of hypoxia. MΦ migration in the tumor was more pronounced in the more hypoxic tumor of the two GBM models. In the more hypoxic of the models, we have shown that MΦ migrated at the tumor site only when hypoxia takes place. We also demonstrated that the acquisition of the M2 phenotype was clearly an evolving phenomenon with hypoxia as the major trigger for this transition. In support of these in vivo finding, M0 but also M1 MΦ cultured in moderate or severe hypoxia displayed a phenotype close to that of M2 MΦ whose phenotype was further reinforced by severe hypoxia. These results highlight the role of hypoxia in the aggressiveness of GBM, in part, by transforming MΦ such that a protumoral activity is expressed.
An Examination of Late-Registering Students’ Success in Online and On-Campus Classes

ABSTRACT Late registration is a common practice in community colleges, but the evidence-based argument for the presumed deleterious effects of late registration on student success is weaker than is commonly believed, and there has been no published research on how success rates may differ for late registrants in online and on-campus classes, and for students who complete a college success skills course. Using nearly 100,000 matched enrollment cases from Virginia’s Community Colleges, we predict the effect of late registration on student success for first-time-in-college students. The statistically significant results indicate late registration is negatively related to student success, especially for students with other success risk factors. Attending face-to-face classes as well as completing a college skills course were independently and positively related to course success. Interestingly, late registration interacted with both course delivery mode and college skills course completion indicating that late registration does not impact students equally.
Recent findings in bipolar affective disorder *

Goodwin (2000) famously argued that bipolar disorder was the Cinderella of psychiatry. It certainly should not be: there is no doubt of the anguish caused by the condition, in particular the excess of natural mortality and the great excess of death by suicide (Ösby et al. 2001). In this issue, Mitchell et al. (2004) report that 26% of their cases of bipolar disorder had attempted suicide at some point. This reflects the sheer persistence of personal suffering: Judd and colleagues (2002, 2003) demonstrated in a long and detailed follow-up that patients with bipolar disorder were symptomatic at least half the time. The Australian National Survey of Psychotic Disorders found levels of disability in affective psychosis equal to those of schizophrenia (Jablensky et al. 2000), and bipolar cases are more likely to score highly on measures of disability than unipolar cases (Mitchell et al. 2004). People with bipolar disorder are more likely to be single, widowed or divorced than both the general populace and those with unipolar depression (Mitchell et al. 2004). Das Gupta & Guest (2002) recently estimated the annual direct and indirect costs of bipolar disorder to the UK economy at £2 billion, of which only 10% were direct treatment costs. And yet, despite this burden, to sufferers, carers and the community alike, there is a real dearth of research activity in bipolar disorder in comparison to schizophrenia. This has been confirmed in the bibliographical study by Clement and colleagues (2003). However, the good news is that the imbalance may be diminishing (Watson & Young, 2003). Recent initiatives have included the setting up of the Stanley Foundation Bipolar Network (Post et al. 2001). There has been a burgeoning of research studies and a growing interest in underlying processes, particularly in the new millennium, which is reflected in the contents of this issue of Psychological Medicine. So what are the key explicanda in bipolar disorder? In schizophrenia research, after a period of dejection, genetic studies have now implicated several chromosomal regions and candidate genes. It is being acknowledged that genes do not themselves encode for mental disorders, and that explanation is required linking individual genes with neuroanatomical findings, with neurocognitive deficits, and with deficiencies in social cognition (Weinberger, 2002) in a cascade of processes including crucial gene-environment interactions that must precede symptoms (Garety et al. 2001). Symptoms have now become the target of explanatory research in their own right. The research agenda may appear Himalayan, but at least we can discern its outlines. It also feeds into the design of treatments. Could it be that we are approaching a similar situation in bipolar disorder? I think we are. Although bipolar research may be 10 years behind that in schizophrenia, it is already following similar paths. Consequently, there are huge opportunities for collaborative and multidisciplinary investigation.
The effects of cancer research participation on patient experience: a mixed‐methods analysis

Patient‐reported benefits of research participation have been described by study participants; however, many studies have small sample sizes or are limited to patient groups with poor prognoses. The purpose of this study was to explore the effects of research participation on patient experience using survey responses from a large, national sample of cancer patients (N = 66 462) and interviews with breast cancer patients attending a London trust. Multivariate logistic regression was used to investigate associations between taking part in research and positive patient experience. Based on our analysis, patients who participated in research were more likely to rate their overall care and treatment as ‘very good/excellent’ (OR adj:1.64, 95%CI: 1.53–1.76, P < 0.001) and to describe positive patient experiences, such as better access to non‐standard care, better interactions with staff and being treated as an individual. However, findings from our interviews indicated that there was no common understanding of what constitutes cancer research and no clear delineation between research participation and standard care, from the patient perspective. Further work to explore how participation positively influences patient experience would be useful to develop strategies to improve care and treatment for all patients regardless of whether or not they choose, or have the opportunity, to take part in research.
Previous Stress Facilitates Fear Memory, Attenuates GABAergic Inhibition, and Increases Synaptic Plasticity in the Rat Basolateral Amygdala

In experiments designed to investigate the relationship between stress and the acquisition of new fear memories, it was found that previous exposure to a restraint session increased fear conditioning in a contextual fear paradigm. Moreover, the infusion of bicuculline, a competitive antagonist of GABAA receptors, into the basolateral amygdala complex (BLA), but not into the central amygdaloid nucleus, induced the same behavioral effect. Pretreatment with midazolam (MDZ), a positive modulator of GABAA sites, prevented the facilitating influence on fear memory of both stress and GABAA receptor blockade in the BLA. These data suggest that facilitation of fear conditioning could be causally related to increased neuronal excitability attributable to depressed GABAergic inhibition in the BLA. To test this hypothesis, evoked potentials were studied in brain slices from stressed animals. Potentials evoked in the BLA by single stimuli applied to the external capsule showed multispike responses, suggestive of GABAergic disinhibition. These multiple responses were no longer evident after the slices were perfused with diazepam or if the stressed animals were pretreated with MDZ. In slices from stressed rats, paired-pulse inhibition (GABA dependent) was suppressed. Also, in stressed animals, long-term potentiation (LTP) was induced with a single train of high-frequency stimulation, which did not induce LTP in control rats. Moreover, MDZ pretreatment prevented the facilitating influence of stress on LTP induction. All of these findings support the hypothesis that previous stress attenuates inhibitory GABAergic control in the BLA, leading to neuronal hyperexcitability and increased plasticity that facilitates fear learning.
Estimating errors in concept selection

Numerical concept selection methods are used throughout industry to determine which among several design alternatives should be further developed. The results, however, are rarely believed at face value. Uncertainties (or errors) in subjective choices, modeling assumptions, and measurement errors are fundamental causes of this disbelief. This paper describes a methodology developed to predict overall final error ranges and to estimate a confidence measure in the numerical evaluation results, based upon assigning error ranges to the individual ratings and weightings. Each numerical assignment is given an associated error range, and then treated as a probability error to create a simple means to propagate the errors into an overall error range on the final rating value. Further, a degree of confidence is derived, similar to a statistical t-test, to indicate an induced confidence level in the final decision. Two preliminary concept selections are shown, to illustrate the methodology. Results from these concept selections indicate that (1) uncertainties can be suitably captured and quantified; (2) critical design questions are addressed during the process of numerical concept selection with error propagation; and (3) designers can make more informed and confident decisions through error estimation.
In Silico Prediction of Pregnane X Receptor Activators by Machine Learning Approache

Pregnane X receptor (PXR) regulates drug metabolism and is involved in drug-drug interactions. Prediction of PXR activators is important for evaluating drug metabolism and toxicity. Computational pharmacophore and quantitative structure-activity relationship models have been developed for predicting PXR activators. Because of the structural diversity of PXR activators, more efforts are needed for exploring methods applicable to a broader spectrum of compounds. We explored three machine learning methods (MLMs) for predicting PXR activators, which were trained and tested by using significantly higher number of compounds, 128 PXR activators (98 human) and 77 PXR non-activators, than those of previous studies. The recursive feature-selection method was used to select molecular descriptors relevant to PXR activator prediction, which are consistent with conclusions from other computational and structural studies. In a 10-fold cross-validation test, our MLM systems correctly predicted 81.2 to 84.0% of PXR activators, 80.8 to 85.0% of hPXR activators, 61.2 to 70.3% of PXR nonactivators, and 67.7 to 73.6% of hPXR nonactivators. Our systems also correctly predicted 73.3 to 86.7% of 15 newly published hPXR activators. MLMs seem to be useful for predicting PXR activators and for providing clues to physicochemical features of PXR activation.
Application of Molecular Modeling for Prediction of Substrate Specificity in Cytochrome P450 1A2 Mutants

Molecular dynamics (MD) simulations of 7-ethoxy- and 7-methoxyresorufin bound in the active site of cytochrome P450 (P450) 1A2 wild-type and various mutants were used to predict changes in substrate specificity of the mutants. A total of 26 multiple mutants representing all possible combinations of five key amino acid residues, which are different between P450 1A1 and 1A2, were examined. The resorufin substrates were docked in the active site of each enzyme in the productive binding orientation, and MD simulations were performed on the enzyme-substrate complex. Ensembles collected from MD trajectories were then scored on the basis of geometric parameters relating substrate position with respect to the activated oxoheme cofactor. The results showed a high correlation between the previous experimental data on P450 1A2 wild-type and single mutants with respect to the ratio between 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-demethylase (MROD) activities and the equivalent in silico “E/M scores” (the ratio of hits obtained with 7-ethoxyresorufin to those obtained with 7-methoxyresorufin). Moreover, this correlation served to establish linear regression models used to evaluate E/M scores of multiple P450 1A2 mutants. Seven mutants, all of them incorporating the L382V substitution, were predicted to shift specificity to that of P450 1A1. The predictions were then verified experimentally. The appropriate P450 1A2 multiple mutants were constructed by site-directed mutagenesis, expressed in Escherichia coli, and assayed for EROD and MROD activities. Of six mutants, five demonstrated an increased EROD/MROD ratio, confirming modeling predictions.