Miracle-dz/UniFAR-FTUs huggingface dataset:
Sources of Escherichia coli in a Coastal Subtropical Environment

ABSTRACT Sources of Escherichia coli in a coastal waterway located in Ft. Lauderdale, Fla. , were evaluated. The study consisted of an extensive program of field measurements designed to capture spatial and temporal variations in E. coli concentrations as well as experiments conducted under laboratory-controlled conditions.E. coli from environmental samples was enumerated by using a defined substrate technology (Colilert-18). Field sampling tasks included sampling the length of the North Fork to identify the river reach contributing high E. coli levels, autosampler experiments at two locations, and spatially intense sampling efforts at hot spots. Laboratory experiments were designed to simulate tidal conditions within the riverbank soils. The results showed that E. coli entered the river in a large pulse during storm conditions. After the storm, E. coli levels returned to baseline levels and varied in a cyclical pattern which correlated with tidal cycles. The highest concentrations were observed during high tide, whereas the lowest were observed at low tide. This peculiar pattern of E. coli concentrations between storm events was caused by the growth of E. coli within riverbank soils which were subsequently washed in during high tide. Laboratory analysis of soil collected from the riverbanks showed increases of several orders of magnitude in soilE. coli concentrations. The ability of E. colito multiply in the soil was found to be a function of soil moisture content, presumably due to the ability of E. coli to outcompete predators in relatively dry soil. The importance of soil moisture in regulating the multiplication of E. coli was found to be critical in tidally influenced areas due to periodic wetting and drying of soils in contact with water bodies. Given the potential for growth in such systems, E. coliconcentrations can be artificially elevated above that expected from fecal impacts alone. Such results challenge the use of E. coli as a suitable indicator of water quality in tidally influenced areas located within tropical and subtropical environments.
Upper-extremity spinal reflex inhibition is reproducible and strongly related to grip force poststroke

Purpose: Impaired reflex regulation is assumed to contribute to upper-extremity motor impairment poststroke; however, the relationship between reflex inhibition and motor function remains unclear. To address this question, it is first necessary to determine the reproducibility of reflex responses. The objective of this study was to establish the test–retest reliability of flexor carpi radialis H-reflex inhibition in healthy control and stroke participants and investigate the correlation between H-reflex inhibition and grip strength. Materials and methods: Eighteen persons poststroke (mean ± SD: age 63 ± 13 years; 6 ± 5 years poststroke; 13 males) and 16 healthy controls (age: 62 ± 12 years) participated. Reflex inhibition was tested on 2 separate days by conditioning the H-reflex with radial nerve stimulation at two different interstimulus intervals: 13 ms (presynaptic Ia inhibition-PSI) and 0 ms (disynaptic inhibition). Pearson's and intraclass correlation coefficients [two-way mixed model-ICC (1, 2)], and standard error of measurement (SEM) were calculated. Results: Relative reliability (ICCs) ranged from good to excellent (0.61–0.78). SEM was low (range 10–19%, stroke; 15–20%, healthy controls). Paretic grip strength and paretic limb PSI revealed a positive correlation (r = 0.70; p < 0.0125). Disynaptic inhibition and paretic grip strength were not correlated. Conclusions: To our knowledge, this is the first study to demonstrate reproducibility of reflex inhibition in individuals poststroke. Furthermore, we quantify smallest real differences, which provide an estimate of the magnitude of effect required to determine a meaningful change, exceeding measurement error. The correlation between PSI and grip strength suggests the potential contribution of PSI to grip force production and upper-extremity motor function.
MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations

We have previously identified a region containing 16 CpGs within the MGMT CpG islands which is critical for the transcriptional control of MGMT (Malley, Acta Neuropathol 2011). To investigate the patterns and incidence of MGMT methylation in astrocytic and oligodendroglial tumors, we quantitatively assessed methylation at these 16 CpGs using bisulfite modification followed by pyrosequencing of 362 gliomas not treated with temozolomide, and correlated the findings with previously identified patterns of genetic abnormalities, patients' age and survival. The MGMT gene was considered to be methylated when the mean methylation of the 16 CpGs was 10% or higher. This cut‐off value distinguished diffuse astrocytomas with high and low MGMT expression. Within each tumor type, the patterns of methylation were highly variable and also highly heterogeneous across the 16 CpGs. A high incidence of MGMT methylation was observed in all subtypes of gliomas included in this study. Among a subset of 97 tumors where conventional methylation‐specific PCR (MSP) was also applied, methylation was detected by both methods in 54 tumors, while the pyrosequencing results identified a further 17 tumors. No additional cases were found using MSP alone, indicating that pyrosequencing is a robust method for methylation analysis. All tumors with IDH1/IDH2 mutations except two had MGMT methylation, while there were many tumors with MGMT methylation, particularly primary glioblastomas, which had no mutations of IDH1/2. We suggest that MGMT methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors.
Impaired Ventilatory Responses to Hypoxia in Mice Deficient in Endothelin-Converting-Enzyme-1

Endothelin-converting-enzyme (ECE-1) catalyzes the proteolytic activation of big endothelin-1 to mature endothelin-1. Most homozygous ECE-1−/− embryos die in utero and show severe craniofacial, enteric, and cardiac malformations precluding ventilatory function assessment. In contrast, heterozygous ECE-1+/− embryos develop normally. Their respiratory function at birth has not been studied. Taking into account previous respiratory investigations in mice with endothelin-1 gene disruption, we hypothesized that ECE-1-deficient mice may have impaired ventilatory control. We analyzed ventilatory responses to hypercapnia (8% CO2) and hypoxia (10% O2) in newborn and adult mice heterozygous for ECE-1 deficiency (ECE-1+/−) and in their wild-type littermates (ECE-1+/+). Ventilation, breath duration, and tidal volume were measured using whole-body plethysmography. Ventilatory responses to hypoxia were significantly weaker in ECE-1+/− than in ECE-1+/+ newborn mice (percentage ventilation increase: 1 ± 25%versus 33 ± 29%, p = 0.010). Baseline breathing variables and ventilatory responses to hypercapnia were normal in the ECE-1+/− newborn mice. No differences were observed between adult ECE-1+/− and ECE-1+/+ mice. We conclude that ECE-1 is required for normal ventilatory response to hypoxia at birth.
Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on rats with persistent inflammation.

OBJECTIVE Ruxiang, or Gummi olibanum, an herbal medicine derived from the gum resin of Boswellia carterii Birdw. (BC) of the family Burseraceae, has been used traditionally in China to alleviate pain and reduce inflammation. The present study is an investigation of the effects of a BC extract on persistent hyperalgesia and edema in rats with peripheral inflammation. DESIGN In this randomized, blinded study, the antihyperalgesic and antiedema effects of 3 dosages of BC were compared to a vehicle control. Inflammation was induced in rats by injecting complete Freund's adjuvant (CFA) into one hind paw. A single oral dose of the BC extract was administered daily for 7 days, beginning one day before CFA. Hyperalgesia was assessed using a paw withdrawal latency (PWL) test pre-CFA and 2 hours, 5 hours, 1 day, and 5 days post-CFA. Edema was determined by measuring paw thickness at the same time points. Spinal Fos protein expression was analyzed 2 hours post-CFA. Adverse effects of the extract were monitored by observing the animals closely for unusual behavioral changes. RESULTS Compared to control, a dosage of 0.45 g/kg BC significantly lengthened PWL and reduced paw edema on day 5 post-CFA. At 0.90 g/kg, BC significantly lengthened PWL at 5 hours, 1 day, and 5 days, and reduced paw edema at 2 hours, 5 hours, 1 day, and 5 days. This dosage also significantly suppressed spinal Fos expression in the medial half of laminae I-II. At 1.80 g/kg, BC significantly lengthened PWL and reduced paw edema at all time points. No noticeable adverse effects were observed in animals given the lower dosages of BC, but adverse effects in some animals were observed at 1.80 g/kg per day. In the acute toxicity study, the maximal single dose of 2.50 g/kg produced no adverse effects in the treated rats during the 14 days of observation. CONCLUSIONS The data suggest that BC produces significant antihyperalgesia and anti-inflammation effects and that the antihyperalgesia may be mediated by suppressed inflammation-induced Fos expression in the spinal dorsal horn neurons.
Susceptibility to Peer Pressure, Self-Esteem, and Health Locus of Control as Correlates of Adolescent Substance Abuse

As part of a school-based alcohol misuse prevention study, questionnaires were ad ministered to 2,589 fifth and sixth grade students to determine levels of use of alcohol, marijuana, and cigarettes, intentions to use these substances, and problems resulting from alcohol misuse. The questionnaire also included 45 items concerning susceptibil ity to peer pressure, self-esteem, and health locus of control. These 45 items were factor analyzed separately for two groups formed by random assignment. Six factors were identified which were both internally consistent and replicable, and indices were constructed. The indices measuring susceptibility to peer pressure, self-esteem, and internal health locus of control were significantly and negatively correlated with most of the substance use, misuse, and intention items, and an external health locus of con trol index was not significantly related to most of the substance use, misuse, and inten tion items. The "Susceptibility to Peer Pressure" index correlated more highly with the adolescent substance use, misuse, and intention items than the self-esteem or the health locus of control indices, and it had the highest alpha coefficient. Implications for the design of school-based substance abuse prevention programs are discussed.
The bovine arterially-perfused eye: an in vitro method for the study of drug mechanisms on IOP, aqueous humour formation and uveal vasculature.

A method is reported in which the isolated bovine eye is perfused through a long posterior ciliary artery with buffered physiological saline, to provide simultaneous monitoring of drug effects on intraocular pressure (IOP), vascular resistance and the condition of the blood-aqueous barrier. With perfusion under constant pressure of 45 mm Hg, perfusate flows at 1.64 +/- 0.12 ml.min-1 (mean +/- SEM) and IOP is 7.26 +/- 0.16 mm Hg. Applying a constant flow rate of 2.25 ml.min-1, IOP averages 10.19 +/- 0.32 mm Hg and in both cases this can be maintained for around 2h. Increasing the perfusion flow rate from 1.5 to 3.5 ml.min-1 produces a 76% rise in perfusion pressure but IOP increases only insignificantly (< 10%). The inclusion in the perfusion fluid of dextran and albumin to maintain oncotic pressure similar to that of plasma makes no difference to the IOP achieved and does not affect the leakiness of the barrier. The preparation shows a net consumption of oxygen, supporting the hypothesis that the aqueous humour formed is secreted by active transport processes. Timolol (in bolus doses of 1-300 nmol) injected into the perfusing fluid is shown to induce a dose-dependent fall in IOP within 5 min, reaching a steady state within 40 min. Timolol, however, causes no significant change in vascular resistance, whether this is measured as perfusion flow rate under constant pressure or as perfusion pressure at constant flow rate, nor does it alter the permeability of the barrier. Other beta-blockers such as oxprenolol and betaxolol also induce dose-dependent decreases in IOP. By applying a fluorescein dilution technique, it is found that the aqueous formation rate (K(out) = 0.0046 min-1, or 12.9 microliters.min-1) is also reduced by timolol and, in a dose-dependent manner, by the new carbonic anhydrase inhibitor, MK-927. The bovine perfused eye offers a useful method for studying the mechanisms of action of drugs on IOP and aqueous humour formation, in isolation from the complicating influences of the CNS and the cardiovascular system and without the necessity to kill animals for experimental purposes.
Ewing Marion Kauffman School Evaluation Impact Report: Year 3

The Kauffman School is a charter school in Kansas City, Missouri that opened in 2011 to serve middle and high school students from the cityâ€™s most economically disadvantaged neighborhoods. This report evaluates the effectiveness of the school at improving student achievement, attendance, and suspension outcomes during its first three years of operation.
Mitochondrial disulfide relay mediates translocation of p53 and partitions its subcellular activity

Significance p53 is one of the most highly studied proteins in biomedical research because of its importance in preventing cancer and its direct or indirect role in many biological processes. It is best known as a nuclear protein that is critical for maintaining genomic integrity and regulating gene expression. We have uncovered a molecular mechanism by which p53 translocates into the mitochondria, depending on respiration, and facilitates the repair of oxidative damage to mitochondrial DNA. The dynamic partitioning of p53 between the nuclear and mitochondrial compartments has important implications for cancer and the many other essential functions of p53 in normal physiology. p53, a critical tumor suppressor, regulates mitochondrial respiration, but how a nuclear protein can orchestrate the function of an organelle encoded by two separate genomes, both of which require p53 for their integrity, remains unclear. Here we report that the mammalian homolog of the yeast mitochondrial disulfide relay protein Mia40 (CHCHD4) is necessary for the respiratory-dependent translocation of p53 into the mitochondria. In the setting of oxidative stress, increased CHCHD4 expression partitions p53 into the mitochondria and protects its genomic integrity while decreasing p53 nuclear localization and transcriptional activity. Conversely, decreased CHCHD4 expression prevents the mitochondrial translocation of p53 while augmenting its nuclear localization and activity. Thus, the mitochondrial disulfide relay system allows p53 to regulate two spatially segregated genomes depending on oxidative metabolic activity.
MicroRNA expression profiling in human Barrett's carcinogenesis

Barrett's esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barrett's mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barrett's adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barrett's carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low‐grade intraepithelial neoplasia, 5 with high‐grade intra‐epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real‐time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long‐segment BE. We identified a miRNA signature of Barrett's carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barrett's carcinogenesis, also identifying molecular markers of cancer progression.
LMO2 is a novel predictive marker for a better prognosis in pancreatic cancer.

PURPOSE LIM domain only 2 (LMO2) has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors. We investigate the involvement of LMO2 in pancreatic cancer. EXPERIMENTAL DESIGN We evaluated LMO2 expression in cultured cells, bulk tissues, and microdissected cells from pancreatic cancers by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS Of 164 pancreatic cancers, 98 (60%) were positive for LMO2 expression. LMO2 was more frequently detected in high-grade pancreatic intraepithelial neoplasia (PanIN) lesions (PanIN-2 and -3) than in low-grade PanIN lesions (PanIN-1A and -1B; P < .001) and was not detected in normal pancreatic ductal epithelium. The LMO2 messenger RNA levels were significantly higher in invasive ductal carcinoma cells than in normal pancreatic cells as evaluated by quantitative reverse transcription-polymerase chain reaction analyses of microdissected cells (P = .036). We also found higher incidence of LMO2 expression in histologic grade G1/G2 cancers than in grade G3 cancers (P < .001). The median survival time of LMO2-positive patients was significantly longer than that of LMO2-negative patients (P < .001), and multivariate analyses revealed that high LMO2 expression was an independent predictor of longer survival (risk ratio, 0.432, P < .001). Even among patients with a positive operative margin, LMO2-positive patients had a significant survival benefit compared with LMO2-negative patients. We further performed a large cohort study (n = 113) to examine the LMO2 messenger RNA levels in formalin-fixed paraffin-embedded samples and found similar results. CONCLUSIONS LMO2 is a promising marker for predicting a better prognosis in pancreatic cancer.
In vitro mechanical integrity of hydroxyapatite coated magnesium alloy

The mechanical integrity of resorbable implants during service, especially in load bearing orthopaedic applications, is critical. The high degradation rate of resorbable magnesium and magnesium-based implants in body fluid may potentially cause premature in-service failure. In this study, a magnesium alloy (AZ91) was potentiostatically coated with hydroxyapatite at different cathodic voltages in an attempt to enhance the mechanical integrity. The mechanical integrity of the uncoated and hydroxyapatite coated alloys was evaluated after in vitro testing of the coated samples in simulated body fluid (SBF). The uncoated alloy showed 40% loss in the mechanical strength after five days exposure to SBF. However, the hydroxyapatite coated alloy exposed to SBF showed 20% improvement in the mechanical strength as compared to that of the uncoated alloy. The alloy coated potentiostatically at −2 V performed better than the −3 V coated alloy. The cross-sectional analysis of the coatings revealed relatively uniform coating thickness for the −2 V coated alloy, whereas the −3 V coated alloy exhibited areas of uneven coating. This can be attributed to the increase in hydrogen evolution on the alloy during −3 V coating as compared to −2 V coating. The scanning electron micrographs of the in vitro tested alloy revealed that hydroxyapatite coating significantly reduced the localized corrosion of the alloy, which is critical for better in-service mechanical integrity. Thus, the study suggests that the in vitro mechanical integrity of resorbable magnesium-based alloy can be improved by potentiostatic hydroxyapatite coating.
Abnormalities in the thyroid function tests as surrogate marker of advancing HIV infection in infected adults.

OBJECTIVE To study thyroid function tests in patients infected with human immunodeficiency virus (HIV) infection at various stages of the illness and to correlate the results with the disease progression. METHODS In a prevalence study of 50 HIV infected patients at various stages of illness thyroid function tests consisting of free-thyroxin (FT-4), free tri-iodothyronine (FT-3), and serum thyroid stimulating hormone (s. TSH) were done. Subjects belonged to both sexes and all subjects were newly diagnosed HIV+ patients and were not receiving antiretroviral therapy (ART) when enrolled in the study. Patients were studied in two groups: Group-1 had 25 patients having AIDS and Group-2 had 25 patients who were HIV+ but were not having AIDS as per 1993 revised CDC classification for HIV infection in adolescents and adults. The results were statistically analyzed and correlation of abnormalities in thyroid function tests with the disease progression was studied. RESULTS Out of 50 cases, thyroid function abnormalities were observed in substantial number of patients. Nine (18%) patients had FT-3 levels below the normal range, ten (20%) patients had decreased FT-4 levels and twelve (24%) patients had s. TSH levels above the normal range. When the results were statistically analyzed for the 50 patients enrolled in our study using Pearson's correlation coefficient, there was a direct correlation between CD4 count and FT3 and FT4 values (r = 0.357 with p < 0.05; r = 0.650 with p < 0.05 respectively). There was an inverse correlation of CD4 counts with serum TSH levels (r = -0.470 with p < 0.050). CONCLUSION Thyroid dysfunction is frequent in HIV infection and with progression of disease there is a primary hypothyroid like stage that occurs in patients with HIV infection. FT3 /FT4/serum TSH can be used as a surrogate marker of the progression of the disease.
Urokinase-type Plasminogen Activator Receptor (CD87) Is a Ligand for Integrins and Mediates Cell-Cell Interaction*

Binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR/CD87) regulates cellular adhesion, migration, and tumor cell invasion. However, it is unclear how glycosyl phosphatidylinositol-anchored uPAR, which lacks a transmembrane structure, mediates signal transduction. It has been proposed that uPAR forms cis-interactions with integrins as an associated protein and thereby transduces proliferative or migratory signals to cells upon binding of uPA. We provide evidence that soluble uPAR (suPAR) specifically binds to integrins α4β1, α6β1, α9β1, and αvβ3 on Chinese hamster ovary cells in a cation-dependent manner. Anti-integrin and anti-uPAR antibodies effectively block binding of suPAR to these integrins. Binding of suPAR to α4β1 and αvβ3 is blocked by known soluble ligands and by the integrin mutations that inhibit ligand binding. These results suggest that uPAR is an integrin ligand rather than, or in addition to, an integrin-associated protein. In addition, we demonstrate that glycosyl phosphatidylinositol-anchored uPAR on the cell surface specifically binds to integrins on the apposing cells, suggesting that uPAR-integrin interaction may mediate cell-cell interaction (trans-interaction). These previously unrecognized uPAR-integrin interactions may allow uPAR to transduce signals through the engaged integrin without a hypothetical transmembrane adapter and may provide a potential therapeutic target for control of inflammation and cancer.