Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination Treatment with PPARγ Ligand and Its Specific Inhibitor GW9662 Downregulates BIS and 14-3-3 Gamma, Inhibiting Stem-Like Properties in Glioblastoma Cells

PPARγ is a nuclear receptor that regulates differentiation and proliferation and is highly expressed in many cancer cells. Its synthetic ligands, such as rosiglitazone and ciglitazone, and its inhibitor GW9662, were shown to induce cellular differentiation, inhibit proliferation, and lead to apoptosis. Glioblastoma is a common brain tumor with poor survival prospects. Recently, glioblastoma stem cells (GSCs) have been examined as a potential target for anticancer therapy; however, little is known about the combined effect of various agents on GSCs. In this study, we found that cotreatment with PPARγ ligands and GW9662 inhibited stem-like properties in GSC-like spheres, which significantly express SOX2. In addition, this treatment decreased the activation of STAT3 and AKT and decreased the amounts of 14-3-3 gamma and BIS proteins. Moreover, combined administration of small-interfering RNA (siRNA) transfection with PPARγ ligands induced downregulation of SOX2 and MMP2 activity together with inhibition of sphere-forming activity regardless of poly(ADP-ribose) polymerase (PARP) cleavage. Taken together, our findings suggest that a combination therapy using PPARγ ligands and its inhibitor could be a potential therapeutic strategy targeting GSCs.
Institutional Emergence in an Era of Globalization: The Rise of Transnational Private Regulation of Labor and Environmental Conditions1

Why have systems of “transnational private regulation” recently emerged to certify corporate social and environmental performance? Different conceptions of institutional emergence underlie different answers to this question. Many scholars argue that firms create certification systems to solve problems in the market—a view rooted in a conception of institutions as solutions to collective action problems. The author develops a different account by viewing institutions as the outcome of political contestation and by analyzing conflict and institutional entrepreneurship among a wide array of actors. Using a comparative case study design, the analysis shows how these arguments explain the formation of social and environmental certification associations. Both theoretical approaches are needed, but strong versions of the market‐based approach overlook an important set of dynamics that the author calls the “political construction of market institutions. ” The analysis shows how both problem solving in markets and political contention generate new institutional forms.
Rapid Identification of Candida Species by Confocal Raman Microspectroscopy

ABSTRACT Candida species are important nosocomial pathogens associated with high mortality rates. Rapid detection and identification of Candida species can guide a clinician at an early stage to prescribe antifungal drugs or to adjust empirical therapy when resistant species are isolated. Confocal Raman microspectroscopy is highly suitable for the rapid identification of Candida species, since Raman spectra can be directly obtained from microcolonies on a solid culture medium after only 6 h of culturing. In this study, we have used a set of 42 Candida strains comprising five species that are frequently encountered in clinical microbiology to test the feasibility of the technique for the rapid identification of Candida species. The procedure was started either from a culture on Sabouraud medium or from a positive vial of an automated blood culture system. Prior to Raman measurements, strains were subcultured on Sabouraud medium for 6 h to form microcolonies. Using multivariate statistical analyses, a high prediction accuracy (97 to 100%) was obtained with the Raman method. Identification with Raman microspectroscopy may therefore be significantly faster than identification with commercial identification systems that allow various species to be identified and that often require 24 to 48 h before a reliable identification is obtained. We conclude that confocal Raman microspectroscopy offers a rapid, accurate, and easy-to-use alternative for the identification of clinically relevant Candida species.
Identification of a polar targeting determinant for Bacillus subtilis DivIVA

The Bacillus subtilis protein DivIVA controls both the positioning of the vegetative cell division site and the polar attachment of the chromosome during sporulation. In vegetative growth DivIVA attracts the bipartite cell division inhibitor MinCD away from the cell centre and towards the cell pole. This process ensures the inactivation of old polar division sites and leaves the cell centre free for the assembly of a new cell division complex. During sporulation MinCD and DivIVA levels fall, but DivIVA remains at the cell poles and becomes involved in the migration of the chromosomes to the pole. In order to investigate polar targeting of DivIVA, we undertook a mutational analysis of the 164‐amino‐acid protein. These studies identified one mutant (divIVAR18C) that could not localize to the cell pole but which retained the ability to support both vegetative growth and 50% sporulation efficiency. Further analysis revealed that, in the absence of polar targeting, DivIVAR18C localized to the nucleoid during vegetative growth in a Spo0J/Soj‐dependent manner and required Spo0J/Soj and MinD to orientate the chromosomes correctly during sporulation. We demonstrate that polar targeting of DivIVAR18C is not essential during vegetative growth because the mutant can recognize the cell division site and influences the localization of MinD. Similarly we show that DivIVAR18C can function during sporulation because it can support the Spo0J/Soj orientation of the chromosome. In addition, we establish that both residues 18 and 19 constitute a DivIVA polar targeting determinant.
STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor

Significance An important part of the response to invading pathogens is activation of the transcription factor STAT3 in response to IL-6. This normal response is terminated rapidly by the major negative regulator suppressor of cytokine signaling 3 (SOCS3). Abnormal prolonged activation of STAT3 contributes to the pathology of cancer and to chronic inflammatory diseases. We show that prolonged activation of STAT3 results from association of the IL-6 receptor with the epidermal growth factor receptor, which in turn activates STAT3 in a way that is not inhibited by SOCS3. Prolonged STAT3 activation supports sustained expression of a subset of proteins that play important roles in inflammation and in cancer, where both IL-6 secretion and epidermal growth factor receptor levels are often elevated. The activation of STAT3 by tyrosine phosphorylation, essential for normal development and for a normal inflammatory response to invading pathogens, is kept in check by negative regulators. Abnormal constitutive activation of STAT3, which contributes to the pathology of cancer and to chronic inflammatory diseases such as rheumatoid arthritis, occurs when negative regulation is not fully effective. SOCS3, the major negative regulator of STAT3, is induced by tyrosine-phosphorylated STAT3 and terminates STAT3 phosphorylation about 2 h after initial exposure of cells to members of the IL-6 family of cytokines by binding cooperatively to the common receptor subunit gp130 and JAKs 1 and 2. We show here that when the epidermal growth factor receptor (EGFR) is present and active, STAT3 is rephosphorylated about 4 h after exposure of cells to IL-6 or oncostatin M and remains active for many hours. Newly synthesized IL-6 drives association of the IL-6 receptor and gp130 with EGFR, leading to EGFR-dependent rephosphorylation of STAT3, which is not inhibited by the continued presence of SOCS3. This second wave of STAT3 activation supports sustained expression of a subset of IL-6-induced proteins, several of which play important roles in inflammation and cancer, in which both IL-6 secretion and EGFR levels are often elevated.
Trabecular Bone Structure Correlates with Hand Posture and Use in Hominoids

Bone is capable of adapting during life in response to stress. Therefore, variation in locomotor and manipulative behaviours across extant hominoids may be reflected in differences in trabecular bone structure. The hand is a promising region for trabecular analysis, as it is the direct contact between the individual and the environment and joint positions at peak loading vary amongst extant hominoids. Building upon traditional volume of interest-based analyses, we apply a whole-epiphysis analytical approach using high-resolution microtomographic scans of the hominoid third metacarpal to investigate whether trabecular structure reflects differences in hand posture and loading in knuckle-walking (Gorilla, Pan), suspensory (Pongo, Hylobates and Symphalangus) and manipulative (Homo) taxa. Additionally, a comparative phylogenetic method was used to analyse rates of evolutionary changes in trabecular parameters. Results demonstrate that trabecular bone volume distribution and regions of greatest stiffness (i.e., Young's modulus) correspond with predicted loading of the hand in each behavioural category. In suspensory and manipulative taxa, regions of high bone volume and greatest stiffness are concentrated on the palmar or distopalmar regions of the metacarpal head, whereas knuckle-walking taxa show greater bone volume and stiffness throughout the head, and particularly in the dorsal region; patterns that correspond with the highest predicted joint reaction forces. Trabecular structure in knuckle-walking taxa is characterised by high bone volume fraction and a high degree of anisotropy in contrast to the suspensory brachiators. Humans, in which the hand is used primarily for manipulation, have a low bone volume fraction and a variable degree of anisotropy. Finally, when trabecular parameters are mapped onto a molecular-based phylogeny, we show that the rates of change in trabecular structure vary across the hominoid clade. Our results support a link between inferred behaviour and trabecular structure in extant hominoids that can be informative for reconstructing behaviour in fossil primates.
Age-specific determinants of post-partum fatigue in primiparous women.

AIM Post-partum fatigue is a serious concern for mothers worldwide. The aim of this study was to identify age-specific determinants of self-perceived fatigue after childbirth among Japanese primiparous women. METHODS A multicenter prospective cohort study was conducted in Japan. The degree of fatigue was assessed using the Postnatal Accumulated Fatigue Scale during the hospital stay after childbirth. Associated factors were stratified into two age groups (<35 or ≥35 years old); data were analyzed using stepwise multiple regression. RESULTS In the younger group, significant determinants of post-partum fatigue included: anticipated difficulties in child-rearing after discharge; perception of inadequate sleep conditions; dissatisfaction with childbirth; shorter sleep and meal times; longer duration between feeding and infant bedtime; unemployment; and having hyperemesis gravidarum. In the older group, significant determinants of post-partum fatigue included: anticipated difficulties in child-rearing after discharge; perception of inadequate sleep conditions; shorter meal times; formula feeding; and dissatisfaction with childbirth. CONCLUSION Primiparous mothers who anticipated new life with their infants to be difficult and who had an irregular lifestyle tended to report higher levels of fatigue during the post-partum hospital stay. Nurses and midwives should assess maternal sleep and eating conditions, providing support to ensure adequate maternal rest. Special efforts should be made to reduce anxiety about new life with infants among younger primiparous women who had experienced hyperemesis gravidarum.
VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation.

The Arabidopsis thaliana NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), acts as a key regulator of xylem vessel differentiation. In order to identify direct target genes of VND7, we performed global transcriptome analysis using Arabidopsis transgenic lines in which VND7 activity could be induced post-translationally. This analysis identified 63 putative direct target genes of VND7, which encode a broad range of proteins, such as transcription factors, IRREGULAR XYLEM proteins and proteolytic enzymes, known to be closely associated with xylem vessel formation. Recombinant VND7 protein binds to several promoter sequences present in candidate direct target genes: specifically, in the promoter of XYLEM CYSTEINE PEPTIDASE1, two distinct regions were demonstrated to be responsible for VND7 binding. We also found that expression of VND7 restores secondary cell wall formation in the fiber cells of inflorescence stems of nst1 nst3 double mutants, as well as expression of NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3, however, the vessel-type secondary wall deposition was observed only as a result of VND7 expression. These findings indicated that VND7 upregulates, directly and/or indirectly, many genes involved in a wide range of processes in xylem vessel differentiation, and that its target genes are partially different from those of NSTs.
Working Paper / Document de travail 2012-18 Consumer Bankruptcy and Information

Bank of Canada working papers are theoretical or empirical works-in-progress on subjects in economics and finance. The views expressed in this paper are those of the authors. No responsibility for them should be attributed to the Bank of Canada. ii Acknowledgements We thank the Office of the Superintendent of Bankruptcy for their support. We thank Abstract We analyze the relationship between the intensity of banks' use of soft-information and household bankruptcy patterns. Using a unique data set on the universe of Canadian household bankruptcies, we document that bankruptcy rates are higher in markets where the collection of soft, or qualitative locally gathered information, is the weakest. Using two Canadian bank mergers as exogenous variation in local market structure, we show that the differences in bankruptcy rates are not due to changes in the supply of credit. Our findings indicate that screening via hard-information is not a perfect substitute for soft-information. Instead, the two appear to be complements. Résumé Les auteurs analysent la relation qu'il y a entre l'intensité avec laquelle les banques exploitent des données subjectives ou « informelles » et les tendances entourant les faillites de ménages. À partir d'un ensemble unique de données sur les faillites de ménages canadiens, ils confirment que les taux de faillite sont plus élevés dans les marchés où il se recueille le moins d'informations subjectives, c. -à-d. de renseignements qualitatifs obtenus par les succursales. En traitant deux fusions de banques canadiennes comme des facteurs de variation exogènes de la structure d'un marché local, les auteurs montrent que les différences entre les taux de faillite ne sont pas causées par des modifications de l'offre de crédit. Leurs résultats indiquent que les données objectives utilisées pour la sélection des emprunteurs ne constituent pas de substituts parfaits des données subjectives : en réalité, les deux types d'informations s'avèrent complémentaires.
Can severe plastic deformation alone generate a nanocrystalline structure?

Many studies suggest that severe plastic deformation (SPD) can produce nanocrystalline metallic structures. Based on structural characterization using transmission electron microscopy, dislocation cellular structures are indeed produced by SPD. However, should we regard such nanocellular structures as nanocrystalline? In other words, can SPD alone produce a well-defined nanocrystalline structure? In this study, we applied SPD to surfaces of Cu–30Ni alloy specimens by repeated punching and divided them into two groups; one of which was subjected to subsequent annealing (recovery treatment) and the other was not. Both groups showed similar nanocrystalline morphologies under an atomic force microscope. However, their surface and electrochemical properties are quite different, evidenced by differences in the electron work function, electrochemical polarization behavior, and other properties. This indicates that simply categorizing the SPD-produced structures with cellular domains as nanocrystalline structures is questionable.
Correlation of clinical, magnetic resonance imaging, and cerebrospinal fluid findings in optic neuritis

We found 42 of 74 patients (57%) with isolated monosymptomatic optic neuritis to have 1 to 20 brain lesions, by magnetic resonance imaging (MRI). All of the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). None of the patients had ever experienced neurologic symptoms prior to the episode of optic neuritis. During 5.6 years of follow‐up, 21 patients (28%) developed definite MS on clinical grounds. Sixteen of the 21 converting patients (76%) had abnormal MRIs; the other 5 (24%) had MRIs that were normal initially (when they had optic neuritis only) and when repeated after they had developed clinical MS in 4 of the 5. Of the 53 patients who have not developed clinically definite MS, 26 (49%) have abnormal MRIs and 27 (51%) have normal MRIs. The finding of an abnormal MRI at the time of optic neuritis was significantly related to the subsequent development of MS on clinical grounds, but interpretation of the strength of that relationship must be tempered by the fact that some of the converting patients had normal MRIs and approximately half of the patients who did not develop clinical MS had abnormal MRIs. We found that abnormal IgG levels in the cerebrospinal fluid correlated more strongly than abnormal MRIs with the subsequent development of clinically definite MS.
Notch1 control of oligodendrocyte differentiation in the spinal cord

We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo.
Estimating the Effective Number of Breeders of Brook Trout, Salvelinus fontinalis, Over Multiple Generations in Two Stream Systems

iii ACKNOWLEDGEMENTS I want to thank my advisor, Andrew Whiteley, for all of his encouragement and support throughout my graduate studies: for taking me on as a student, supporting me as a research assistant, helping me understand the concepts described in this thesis and patiently guiding me through this research. I also want to express my sincere thanks to my committee members Ben Letcher and Dave Kittredge for their feedback and encouragement. Special thanks to Matt O'Donnell for all of his help with the Stanley Brook data and field work. and many others were of great help to me and the larger studies. Jason Coombs was extremely helpful with genotyping questions and providing insight into brook trout biology. I thank Maili Page, and everyone in the conservation genetics lab at UMass. I deeply appreciate the friendly environment provided by the ECo department and my fellow grad students throughout my graduate studies. Tim Lens, whose undergraduate honors thesis helped get my own research going, was a great help, as were Elizabeth Crowley and Meaghan Horak. Lastly I want to thank my family for their love and support, and I am especially grateful towards my parents for their encouragement and understanding. The use of genetic markers in monitoring populations has become increasingly important for conservation purposes, and can take many forms. While effective population size (N e) is of great interest to conservation genetics, it may be much easier and more practical to estimate the effective number of breeders (N b) per cohort as a tool for genetic monitoring of populations. Few studies have estimated N b for the same species over long periods of time in comparison with demographic or environmental variables. I estimated N b of the eastern brook trout, Salvelinus fontinalis, as part of long-term studies of two stream systems: West Brook (WB) in Massachusetts and Stanley Brook (SB) in Maine. I used eight microsatellite loci for all available young of the year (YOY) from each cohort in WB and a random subset of YOY distributed evenly throughout SB to obtain genetic-based estimates. I estimated adult abundance (N C) from mark-recapture data, and used seasonal stream flow as an environmental variable. I performed linear models with N b as the response variable and family structure (number of families and variance in family size), N C , and seasonal stream flow as predictor variables. I found that both the number …
Use of maximal sterile barriers during central venous catheter insertion: clinical and economic outcomes.

BACKGROUND We performed a cost-effectiveness analysis to determine the effect of maximal sterile barriers (MSBs) on reducing central venous catheter (CVC)--related infections. Use of MSBs when placing CVCs may reduce the risk of infections but is more cumbersome, time-consuming, and expensive than other techniques. METHODS We developed a decision analytic model in which a patient could have a CVC placed with either an MSB or a less stringent technique. We calculated total direct medical costs and the incidences of catheter-related bloodstream infections, catheter colonization, and death. RESULTS Use of MSBs lowered costs (from 621 dollars to 369 dollars per catheter insertion) and decreased the incidences of catheter-related bloodstream infections (from 5.3% to 2.8%), catheter colonization with local infection (from 5.5% to 2.9%) and death (from 0.8% to 0.4%). MSBs improved patient safety throughout all sensitivity analyses. CONCLUSIONS Use of MSBs during CVC insertion likely lowers medical costs and decreases the incidences of catheter colonization, catheter-related bloodstream infections, and death. Cost savings were found over a wide range of clinical and economic assumptions, suggesting that MSBs should be routinely used when CVCs are inserted.
Diagnosis of Male Chlamydia trachomatis Urethritis by Polymerase Chain Reaction

Background and Objectives A quick and highly sensitive diagnostic test would be valuable in the diagnosis of Chlamydia trachomatis. Goal of this Study We compared a new polymerase chain reaction (PCR) technique to Chlamydiazyme (Abbott, North Chicago, IL) in the detection of male chlamydial urethritis, and evaluated the performance of PCR on urine samples. Study Design Urethral samples for analysis by PCR and Chlamydiazyme were obtained from 474 unselected patients attending a sexually transmitted diseases (STD) clinic. Urine samples were analyzed by PCR from 362 of these patients. Results Twenty seven (5.7%) urethral samples were positive by Chlamydiazyme, while 64 (13.5%) were positive by PCR. After resolution of discrepant results, the sensitivity of PCR on urethral swabs was 98.4% and the specificity was 99.0%, with positive and negative predictive values of 93.8% and 99.8%, respectively. These same measures for Chlamydiazyme were 43.5%, 100%, 100%, and 92.2%, respectively. The sensitivity of PCR on urine samples was 87.1%, the specificity was 98.0%, and the positive and negative predictive values were 90.0% and 97.4%, respectively. Conclusions This PCR test is more sensitive than Chlamydiazyme in detecting male urethral chlamydial infections in an STD clinic population, and appears to be equally efficacious on urethral swabs and urine samples.