Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation and modeling of the impact of coexposures to VOC mixtures on urinary biomarkers

Abstract Context: Urinary biomarkers are widely used among biomonitoring studies because of their ease of collection and nonintrusiveness. Chloroform and TEX (i.e., toluene, ethylbenzene, and m-xylene) are chemicals that are often found together because of common use. Although interactions occurring among TEX are well-known, no information exists on possible kinetic interactions between these chemicals and chloroform at the level of parent compound or urinary biomarkers. Objective: The objective of this study was therefore to study the possible interactions between these compounds in human volunteers with special emphasis on the potential impact on urinary biomarkers. Materials and methods: Five male volunteers were exposed by inhalation for 6 h to single, binary, and quaternary mixtures that included chloroform. Exhaled air and blood samples were collected and analyzed for parent compound concentrations. Urinary biomarkers (o-cresol, mandelic, and m-methylhippuric acids) were quantified in urine samples. Published PBPK model for chloroform was used, and a Vmax of 3.4 mg/h/kg was optimized to provide a better fit with blood data. Adapted PBPK models from our previous study were used for parent compounds and urinary biomarkers for TEX. Results: Binary exposures with chloroform resulted in no significant interactions. Experimental data for quaternary mixture exposures were well predicted by PBPK models using published description of competitive inhibition among TEX components. However, no significant interactions were observed at levels used in this study. Conclusion: PBPK models for urinary biomarkers proved to be a good tool in quantifying exposure to VOC.
Phenotypic, Histopathologic and Genomic Diagnosis of A Novel Fish Pathogen Vagococcus salmoninarum in Turkey

In the present study, the aim was to diagnose Vagococcus salmoninarum by using phenotypic, histopathologic and genomic methods together. Vagococcosis is a novel and emerging disease in rainbow trout ( Oncorhynchus mykiss ) farms and outbreak of the disease results in considerable economic losses to the aquaculture industry worldwide. The sixty bacterial isolates from fish tissues which had widespread infection were identified and characterized as V. salmoninarum by studying the cultural pattern and biochemical-enzymatic traits with BBL Crystal TM identification system. Among sixty phenotypical positive isolates, only 30% percent were verified as V. salmoninarum by PCR amplification of bacterial 16S rDNA gene. Further, observed spots of bacterial accumulation in histological sections of heart and kidney were subsequently diagnosed as V. salmoninarum with 16S rDNA gene amplification.
Self-Enforcing Cooperation with Graduated Punishments ∗

Case studies of self-enforcing cooperation in repeated interactions usually find that the punishments inflicted on deviators are mild to start with, and increase only if there is evidence of persistent deviation. We model this using a combination of imperfect monitoring and asymmetric information in a one-sided prisoner’s dilemma. Call the player with the temptation to cheat player B, and the other player A. Player B can be one of several types, distinguished by the size of this temptation; B’s type is his private information. A’s payoff may be high or low, and the probability of a low payoff is higher if B has cheated. If player A receives the low payoff, he can inflict an immediate punishment on B, at a cost to himself. We find that A’s optimal choice of punishment is generally a non-concave problem, and the comparative statics can be discontinuous and asymmetric. If the temptation of each type of B is non-stochastic, A’s optimal choice of punishment is not lowered after a high payoff, and may be raised or lowered after a bad payoff depending on the prior distribution of B’s types. With stochastic temptations, as the prior probability of B being a bad type increases, the optimal level of punishment chosen by A is initially low and decreasing, but then jumps to a higher level and increases further thereafter, and for very high levels of this probability the relationship may be terminated. Non-extreme levels of punishment are most informative about B’s type, and the value of this information to A is highest when the prior probabilities are also non-extreme. ∗This is an extremely preliminary statement of work still in progress. It was prepared by Dixit for an informal seminar presentation to elicit feedback, and has not yet been read or approved by the coauthors. Comments very welcome, addressed to dixitak@princeton.edu .
BCL2 accelerates inflammation-induced BALB/c plasmacytomas and promotes novel tumors with coexisting T(12;15) and T(6;15) translocations.

Previous studies on peritoneal plasmacytomas (PCTs) in BALB/c (C) mice suggested that the enforced expression of the death repressor BCL2 in B cells might facilitate the malignant transformation of aberrant B cells containing Myc-activating T(12;15) translocations, generating an improved model of plasmacytomagenesis. To investigate this hypothesis, we backcrossed a human BCL2 transgene onto strain C and performed a PCT induction study with pristane in the newly generated C.BCL2 congenics. In specific pathogen-free-maintained C.BCL2 mice, PCT incidence (19 of 34, 56%) was 24 times higher than in specific pathogen-free-maintained C mice (1 of 44, 2.3%), and tumor onset (113 days) was half that of conventionally maintained C mice (220 days). BCL2 transgenic PCT harbored T(12;15) translocations (12 of 12 tumors) with an unusual clustering of translocation breakpoints in the near 5' flank of Myc (4 of 5 tumors, 80%). Five tumors contained coexisting T(12;15) and T(6;15) translocations (not observed in >300 karyotyped PCTs from conventionally maintained C mice). BCL2 transgenic C57BL/6 mice exclusively developed B lymphomas (11 of 20, 55%) that also contained T(12;15) translocations (11 of 11 cases) with breakpoints in the near 5' flank of Myc (five of five tumors). We conclude that BCL2 accelerates PCT with novel Myc-activating translocations independently of environmental antigen stimulation. Accelerated plasmacytomagenesis in strain C.BCL2 may be useful for designing and testing BCL2 inhibition strategies in human plasma cell tumors overexpressing BCL2, such as Waldenström's macroglobulinemia and multiple myeloma.
Inflammatory mediators act at renal pericytes to elicit contraction of vasa recta and reduce pericyte density along this medullary vascular network

Regardless of initiating cause, renal injury promotes a potent pro-inflammatory environment in the outer medulla and a concomitant sustained decrease in medullary blood flow (MBF). This decline in MBF is believed to one of the critical events in the pathogenesis of acute kidney injury (AKI), yet the precise cellular mechanism underlying this are still to be fully elucidated. MBF is regulated by contractile pericyte cells that reside on the descending vasa recta (DVR) capillaries, which are the primary source of blood flow to the medulla. Using the rodent and murine live kidney slice models, we sought to investigate the acute effects of key medullary inflammatory mediators TNF-α, IL-1β, IL-33, IL-18, C3a and C5a on vasa recta pericytes. Live kidney slices taken from both mice and rats and exposed to TNF-α, IL-18, IL-33, and C5a demonstrated a real-time pericyte-mediated constriction of DVR. When pro-inflammatory mediators were applied in the presence of the AT1-R blocker Losartan the inflammatory-mediated constriction that had previously been observed was significantly attenuated. When live kidney slices were exposed to inflammatory mediators for 4-hours, we noted a significantly reduction in the number of NG2+ positive pericytes along vasa recta capillaries in both rodent and murine kidney slices. Data collected in this study, demonstrate that inflammatory mediators can dysregulate pericytes to constrict DVR diameter and reduce the density of pericytes along vasa recta vessels, further diminishing the regulatory capacity of the capillary network. We postulate that preliminary findings here suggest pericytes play a role in AKI. New & Noteworthy How medullary blood flow (MBF) becomes disproportionately dysregulated following renal injury is poorly understood yet is associated with worse prognostic outcomes following AKI. This study shows in both rats and mice that inflammatory mediators associated with AKI have acute and sustained microvascular actions at pericytes eliciting dysregulation of descending vasa recta (DVR) diameter and their loss from the DVR. This work highlights a possible pathology behind the dysregulation and reduction of MBF observed following AKI.
Urban particle-induced apoptosis and phenotype shifts in human alveolar macrophages.

Epidemiological studies report a small but positive association between short-term increases in airborne particulate matter and small increases in morbidity and mortality from respiratory and cardiovascular disease in urban areas. However, the lack of a mechanistic explanation to link particle exposure and human health effects makes it difficult to validate the human health effects. The present study tested the hypothesis that urban particles could cause apoptosis of human alveolar macrophages(AM) and a shift of their phenotypes to a higher immune active state, which would provide a mechanism to explain an inflammatory response. Freshly isolated human AM were incubated for 24 hr with urban particles (#1648 and #1649), Mount Saint Helen's ash (MSH), and residual oil fly ash (ROFA). Cell viability was assessed by trypan blue exclusion and apoptosis was demonstrated by morphology, cell death ELISA, and DNA ladder formation. Additionally, AM were characterized according to RFD1(+) (immune stimulatory macrophages) and RFD1(+)7(+) (suppressor macrophages) phenotypes by flow cytometry. ROFA particles caused AM necrosis at concentrations as low as 10 microg/ml, urban particles had no effect except at 200 microg/ml, and MSH had no effect at 200 microg/ml. ROFA (25 microg/ml) and particles #1648 or #1649 (100 microg/ml) caused apoptosis of AM by all three criteria, but 200 microg/ml MSH had no effect. Finally, 25 microg/ml ROFA and 100 microg/ml particles #1648 or #1649 up regulated the expression of the RFD1(+) AM phenotype, while only ROFA decreased the RFD1(+)7(+) phenotype. Consequently, ROFA and urban particles can induce apoptosis of human AM and increase the ratio of AM phenotypes toward a higher immune active state (i.e., increased RFD1(+):RFD1(+)7(+) ratio). Ifurban particles cause similar changes in vivo, this could result in lung inflammation and possible increased pulmonary and cardiovascular disease. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5
Rehydroxylation Dating: An Assessment of Archaeological Application

xxxv Chapter 1: Introduction 1 1.1 Fired Clay Ceramics in Archaeology 1 1.2 Dating of Ceramics 3 1.3 Rehydroxylation Dating 5 1.4 Thesis Motivation, Aim and Objectives 7 1.5 Thesis Outline 13 Chapter 2: Background 15 2.
Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia

When migrating away from a primary tumour, cancer cells interact with and remodel the extracellular matrix (ECM). Matrix metalloproteinases (MMPs), and in particular the transmembrane MT1-MMP (also known as MMP-14), are key enzymes in tumour-cell invasion. Results from recent in vitro studies highlight that MT1-MMP is implicated both in the breaching of basement membranes by tumour cells and in cell invasion through interstitial type-I collagen tissues. Remarkably, MT1-MMP accumulates at invadopodia, which are specialized ECM-degrading membrane protrusions of invasive cells. Here we review current knowledge about MT1-MMP trafficking and its importance for the regulation of protease activity at invadopodia. In invasive cells, endocytosis of MT1-MMP by clathrin- and caveolae-dependent pathways can be counteracted by several mechanisms, which leads to protease stabilization at the cell surface and increased pericellular degradation of the matrix. Furthermore, the recent identification of cellular components that control delivery of MT1-MMP to invadopodia brings new insight into mechanisms of cancer-cell invasion and reveals potential pharmacological targets.
Denture acceptance among newly rehabilitated elderly population in old age homes in South India

Introduction: Elders in old age homes are mainly those who have been abandoned by their family and have one or more physical or mental disabilities. It is a major challenge for the dental professional to plan oral health strategy for this group of patients. Aim of the Study: Aim of the present study is to observe and determine the acceptance of new dental prosthesis among the elderly residing as inmates of 3 old age homes in Mangalore City. Materials and Methods: This cross-sectional study was conducted using a survey proforma. Information regarding their experience with the new denture, 1-month, 3 months and 6 months after denture insertion was gathered. Statistical analysis of the data was done using the Chi-square test with the P < 0.05 considered significant. Results: One hundred and eighty-three residents out of a total of 400 residents in 3 old age homes were denture wearers. Among them, 101 (55.2%) were females, and 82 (44.8%) were males. Dental prosthesis whether worn regularly, discomfort, retention, cleansing of denture during a period of 1-month, 3 months and 6 months was found to be significant satisfaction with the prosthesis, denture adhesives used, food accumulation during a period of 1-month, 3 months and 6 months was found to be nonsignificant. Conclusion: The emotional makeup of the patient must be taken into consideration during the entire procedure. We must understand that the success of the prosthesis depends mainly on the patient's confidence in the dentist rather than the quality of the prosthesis.
The Binding Specificity and Selective Antagonism of Vedolizumab, an Anti-α4β7 Integrin Therapeutic Antibody in Development for Inflammatory Bowel Diseases

Vedolizumab is a humanized monoclonal antibody that targets the α4β7 integrin exclusively, and modulates inflammation in the gastrointestinal tract without inducing the systemic immunosuppression that characterizes anti-α4 chain monoclonal antibodies, such as natalizumab. This unique pharmacologic profile is largely attributable to four determinants. The first determinant is the restriction of the expression of the α4β7 integrin to subsets of leukocytes. Vedolizumab does not bind to the majority of memory CD4+ T lymphocytes (60%), neutrophils, and most monocytes. The highest level of vedolizumab binding is to a subset (∼25%) of human peripheral blood memory CD4+ T lymphocytes that include gut-homing interleukin 17 T-helper lymphocytes. Vedolizumab also binds to eosinophils at high levels, and to naive T-helper lymphocytes, naive and memory cytotoxic T lymphocytes, B lymphocytes, natural killer cells, and basophils at lower levels; vedolizumab binds to memory CD4+ T and B lymphocytes with subnanomolar potency (EC50 = 0.3–0.4 nM). The second determinant is binding specificity; vedolizumab binds exclusively to the α4β7 integrin, and not to the α4β1 and αEβ7 integrins. The third determinant is selective antagonism; vedolizumab selectively inhibits adhesion of α4β7-expressing cells to mucosal addressin cell adhesion molecule 1 (median inhibition concentration [IC50] = 0.02–0.06 μg/ml) and fibronectin (IC50 = 0.02 μg/ml), but not vascular cell adhesion molecule 1. The fourth determinant is the gastrointestinal-specific tropism of the α4β7 integrin function. These pharmacologic properties of vedolizumab, in conjunction with the gastrointestinal tropism of α4β7 integrin function, may ultimately confer an improved risk-to-benefit profile for patients with inflammatory bowel diseases.
Addictive Internet Use among Korean Adolescents: A National Survey

Background A psychological disorder called ‘Internet addiction’ has newly emerged along with a dramatic increase of worldwide Internet use. However, few studies have used population-level samples nor taken into account contextual factors on Internet addiction. Methods and Findings We identified 57,857 middle and high school students (13–18 year olds) from a Korean nationally representative survey, which was surveyed in 2009. To identify associated factors with addictive Internet use, two-level multilevel regression models were fitted with individual-level responses (1st level) nested within schools (2nd level) to estimate associations of individual and school characteristics simultaneously. Gender differences of addictive Internet use were estimated with the regression model stratified by gender. Significant associations were found between addictive Internet use and school grade, parental education, alcohol use, tobacco use, and substance use. Female students in girls' schools were more likely to use Internet addictively than those in coeducational schools. Our results also revealed significant gender differences of addictive Internet use in its associated individual- and school-level factors. Conclusions Our results suggest that multilevel risk factors along with gender differences should be considered to protect adolescents from addictive Internet use.
Environmental Influences on Vibrio Populations in Northern Temperate and Boreal Coastal Waters (Baltic and Skagerrak Seas)

ABSTRACT Even if many Vibrio spp. are endemic to coastal waters, their distribution in northern temperate and boreal waters is poorly studied. To identify environmental factors regulating Vibrio populations in a salinity gradient along the Swedish coastline, we combined Vibrio-specific quantitative competitive PCR with denaturant gradient gel electrophoresis-based genotyping. The total Vibrio abundance ranged from 4 × 103 to 9.6 × 104 cells liter−1, with the highest abundances in the more saline waters of the Skagerrak Sea. Several Vibrio populations were present throughout the salinity gradient, with abundances of single populations ranging from 5 × 102 to 7 × 104 cells liter−1. Clear differences were observed along the salinity gradient, where three populations dominated the more saline waters of the Skagerrak Sea and two populations containing mainly representatives of V. anguillarum and V. aestuarianus genotypes were abundant in the brackish waters of the Baltic Sea. Our results suggest that this apparent niche separation within the genus Vibrio may also be influenced by alternate factors such as nutrient levels and high abundances of dinoflagellates. A V. cholerae/V. mimicus population was detected in more than 50% of the samples, with abundances exceeding 103 cells liter−1, even in the cold (annual average water temperature of around 5°C) and low-salinity (2 to 4‰) samples from the Bothnian Bay (latitude, 65°N). The unsuspected and widespread occurrence of this population in temperate and boreal coastal waters suggests that potential Vibrio pathogens may also be endemic to cold and brackish waters and hence may represent a previously overlooked health hazard.
Evidence of minimal carbon sequestration in the productive Amundsen Sea polynya

The Amundsen Sea polynya (ASP) is reportedly the most productive among the coastal polynyas around Antarctica. However, observational constraints limit our understanding of the biological pump and carbon cycle in the ASP. We measured various carbon‐related parameters such as primary production, bacterial production, sinking flux of particulate organic carbon (POC), and accumulation of organic carbon in the sediment as well as hydrographic parameters during field observations and by instrument moorings. Over 95% of the photosynthetically produced POC was converted to suspended POC and/or dissolved carbon forms in the upper ~400 m layer. We postulate that most of the carbon transported to the water column by the biological pump in the ASP was flushed out of the shelf without being sequestered for long‐term storage in sediments. Lack of bottom water formation due to intrusion of Circumpolar Deep Water in the lower layer reduces carbon sequestration efficiency.
Capital Structure and Asset Prices: Some Effects of Bankruptcy Procedures

We examine the impact of the U.S. bankruptcy procedure on the valuation of corporate securities and capital structure decisions. We provide closed-form solutions for corporate debt and equity values when defaulting firms can either liquidate their assets or renegotiate outstanding debt under court protection. We show that the possibility to renegotiate the debt contract (i) has an ambiguous impact on leverage choices and (ii) increases credit spreads on corporate debt. The sharing rule of cash flows during bankruptcy has a large impact on optimal leverage. By contrast, credit spreads on corporate debt show little sensitivity to this very parameter.
Comparison of the [13C]glucose breath test to the hyperinsulinemic-euglycemic clamp when determining insulin resistance.

OBJECTIVE With increasing emphasis on the recognition of the metabolic syndrome and early type 2 diabetes, a clinically useful measure of insulin resistance is desirable. The purpose of this study was to evaluate whether an index of glucose metabolism, as measured by (13)CO(2) generation from ingested [(13)C]glucose, would correlate with indexes from the hyperinsulinemic-euglycemic clamp. RESEARCH DESIGN AND METHODS A total of 26 subjects with varying degrees of insulin sensitivity underwent both the [(13)C]glucose breath test and the hyperinsulinemic-euglycemic clamp. Results from the [(13)C]glucose breath test were compared with measures of insulin sensitivity from the glucose clamp as well as with other commonly used indexes of insulin sensitivity. RESULTS There was a strong correlation between the [(13)C]glucose breath test result and the glucose disposal rate (r = 0.69, P < 0.0001) and insulin sensitivity index (r = 0.69, P < 0.0001) from the insulin clamp. The magnitude of these correlations compared favorably with QUICKI and were superior to the homeostasis model assessment. CONCLUSIONS The [(13)C]glucose breath test may provide a useful noninvasive assessment of insulin sensitivity.
Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases

Aim: To identify predisposing factors and to define clinical and microbiological characteristics of bacterial keratitis in current practice. Methods: A retrospective analysis of the hospital records of patients presenting with bacterial keratitis and treated at the Quinze-Vingts National Center of Ophthalmology, Paris, France, was performed during a 20 month period. A bacterial keratitis was defined as a suppurative corneal infiltrate and overlying epithelial defect associated with presence of bacteria on corneal scraping and/or that was cured with antibiotic therapy. Risk factors, clinical and microbiological data were collected. Results: 300 cases (291 patients) of presumed bacterial keratitis were included. Potential predisposing factors, usually multiple, were identified in 90.6% of cases. Contact lens wear was the main risk factor (50.3%). Trauma or a history of keratopathy was found in 15% and 21% of cases, respectively. An organism was identified in 201 eyes (68%). 83% of the infections involved Gram positive bacteria, 17% involved Gram negative bacteria, and 2% were polymicrobial. Gram negative bacteria were associated with severe anterior chamber inflammation (p=0.004), as well as greater surface of infiltrates (p=0.01). 99% of ulcers resolved with treatment, but only 60% of patients had visual acuity better than the level at admission, and 5% had very poor visual outcome. Conclusions: Contact lens wear is the most important risk factor. Most community acquired bacterial ulcers resolve with appropriate treatment.