Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteolysis by m-calpain enhances in vitro light scattering by crystallins from human and bovine lenses

Purpose. To determine if proteolysis by the calcium-activated protease m-calpain (EC 34.22.17) enhances in vitro light scattering in crystallins from human and bovine lenses. Methods. Total soluble proteins from bovine, human, and rodent lenses, ßH crystallin, or recombinant ßB1 polypeptide were pre-incubated in the presence or absence of activated m-calpain. Heat-induced light scattering was assayed by measuring changes in optical density at 405 nm. Pro-teolysis and cleavage sites were detected by SDS-PAGE, two dimensional electrophoresis, and N-terminal Edman sequencing. Results. The in vitro cleavage sites produced by m-calpain on the N-termini of human ßB1, ßA3, and ßB2-crystallins were similar to some of those on bovine and rat crystallins. Proteolysis of a- and ß-crystallins was associated with enhanced, heat-induced light scattering by human and bovine lens proteins. Conclusions. Proteolysis may be a contributing factor in the insolubilization of crystallins occurring during normal maturation of lens or during cataract formation in such species as man and cows.
Understanding urban development types and drivers in Wallonia: a multi-density approach

In this study, urban development process in the Walloon region (Belgium) has been analysed. Two main aspects of development are quantitatively measured: the development type and the definition of the main drivers of the urbanisation process. Unlike most existing studies that consider the urban development as a binary process, this research considers the urban development as a continuous process, characterised by different levels of urban density. Eight urban classes are defined based on the Belgian cadastral data for years 2000 and 2010. A multinomial logistic regression model is employed to examine the main driving forces of the different densities. Sixteen drivers were selected, including accessibility, geo-physical features, policies and socio-economic factors. Finally, the changes from the non-urban to one of the urban density classes are detected and classified into different development types. The results indicate that zoning status (political factor), slope, distance to roads, population densities and mean land price, respectively, have impact on the urbanisation process whatever maybe the density. The results also show that the impact of these factors highly varies from one density to another.
Late Gestational Exposure to the Fungicide Prochloraz Delays the Onset of Parturition and Causes Reproductive Malformations in Male but Not Female Rat Offspring1

Abstract Prochloraz (PZ) is an imidazole fungicide that displays multiple endocrine activities. It inhibits steroid synthesis via P450 modulation and acts as an androgen receptor (AR) antagonist, but its effects on male sexual differentiation have not been described. The purpose of the current study was to expand in vitro observations and to determine whether PZ affected sexual differentiation. PZ effects on AR-mediated gene expression were tested using a cell line (MDA-kb2) containing endogenous AR and stably transfected with an MMTV-luc reporter. PZ concentrations greater than 1 μM caused a dose-dependent inhibition of dihydrotestosterone-induced gene expression. PZ also inhibited R1881 binding to the rat AR (IC50 ∼60 μM). In vivo, pregnant rats received PZ by gavage from Gestational Day 14 to 18 at doses of 31.25, 62.5, 125, and 250 mg/kg of body weight per day. PZ delayed delivery in a dose-dependent manner and resulted in pup mortalities at the two highest doses. In male offspring, anogenital distance and body weight were slightly reduced at 3 days of age. Additionally, female-like areolas were observed at 13 days of age at frequencies of 31%, 43%, 41%, and 71% in the lowest-dose to highest-dose groups, respectively. Weights of androgen-dependent tissues showed dose-dependent reductions. Hypospadias and vaginal pouches were noted in all males treated with 250 mg/kg, whereas those defects were observed in 12.5% and 6.25%, respectively, of males treated with 125 mg/kg. Treatment did not affect age of preputial separation in animals without penile malformations. Despite severe malformations in males, no malformations were noted in females. Together, these results indicate that PZ alters sexual differentiation in an antiandrogenic manner.
All the right moves: How entrepreneurial firms compete effectively

In this article, we examine competitive moves by which firms achieve superior performance. In contrast to prior work that has focused on moves and the related competitive advantages of large firms, we draw attention to entrepreneurial firms. Based on 32 runs of a multi-round experiential simulation and in-depth participant interviews, we find that entrepreneurial firms require competitive strategies that are different from those of a control group of comparable large firms. Entrepreneurial firms that stay below the radar in established markets and are quick to explore in new markets perform better. They succeed in established markets with a strategy that works around large firm competition but ultimately surprises them, and in new markets with a strategy that sets the standards of competition swiftly by continuously creating and destroying new strongholds ahead of large firms. Overall, successful entrepreneurs use a combination of selective, invisible, and asynchronous strategies that vary depending on whether the market is established or new. Our findings contribute to literatures on evolutionary learning, exploration and exploitation, and competitive dynamics.
A reexamination of the association between CEO compensation and the components of accounting earnings

In this paper we reexamine the association between CEO compensation and the cash and accrual components of reported earnings and investigate whether the association has changed over time. we find that whether we look at bonuses, total cash or total direct compensation, the association between compensation and cash flows from operations increases over the period under examination, while that between compensation and the accrual components of earnings decreases. Analyzing the reasons for this change, we find the decreasing emphasis on the use of accruals in the setting of compensation is inversely related to the increase in magnitude of accruals.
Assessment of Long‐Term Outcomes of Community‐Acquired Hepatitis C Infection in a Cohort With Sera Stored From 1971 to 1975

The aim of this study was to examine the long‐term effects of hepatitis C virus (HCV) infection on a cohort of patients admitted with acute viral hepatitis from 1971 through 1975. The availability of stored sera from this time enabled testing to identify those who were anti‐HCV–positive on admission. Sixteen percent (n = 238) of the cohort tested anti‐HCV–positive. The unexposed group was selected from those who were anti‐HCV–negative. Systematic approaches were used to locate the cohort and health outcomes assessed by a study‐specific questionnaire and clinical, serological, virological, and biochemical assessment. Complete follow‐up was achieved on 98 anti‐HCV–positive individuals and 201 negatives. Injecting drug use (IDU) was the presumed route of infection. At a mean of 25 years' follow‐up, 54% of the anti‐HCV–positive group had evidence of chronic HCV infection (both anti‐HCV– and HCV‐RNA–positive); the remainder were HCV‐RNA–negative. Sixty‐nine percent of those chronically infected had elevated serum alanine transaminase (ALT) levels, but only 8% had progressed to overt cirrhosis, and no cases of hepatocellular carcinoma (HCC) were identified. In summary, anti‐HCV–positive subjects were 8 times more likely to have died from suicide or drug overdose than from HCV‐related disease. Anti‐HCV–positive study subjects were at increased risk of liver‐related pathology after 25 years' follow‐up, but few had progressed to overt cirrhotic liver disease. Excess mortality in this group was not the result of liver disease. This suggests that the natural history of community‐acquired HCV may be more benign than previously thought.
The Unusual Nature of Recent Snowpack Declines in the North American Cordillera

The snowpack covering the mountains of western North America has decreased dramatically during the past 50 years. In western North America, snowpack has declined in recent decades, and further losses are projected through the 21st century. Here, we evaluate the uniqueness of recent declines using snowpack reconstructions from 66 tree-ring chronologies in key runoff-generating areas of the Colorado, Columbia, and Missouri River drainages. Over the past millennium, late 20th century snowpack reductions are almost unprecedented in magnitude across the northern Rocky Mountains and in their north-south synchrony across the cordillera. Both the snowpack declines and their synchrony result from unparalleled springtime warming that is due to positive reinforcement of the anthropogenic warming by decadal variability. The increasing role of warming on large-scale snowpack variability and trends foreshadows fundamental impacts on streamflow and water supplies across the western United States.
Out of hours service in Denmark: evaluation five years after reform

Abstract Objective: Five years after its introduction, to evaluate the 1992 reform in the out of hours service in Denmark. Design: Comparison of data before and after reform. Data were collected from published reports, Danish national health statistics, and the Danish trade union for general practitioners. Setting: Denmark. Main outcome measures: Number of out of hours services; workload of general practitioners; cost of the service; patient satisfaction. Results: Five years after the reform, the percentage of telephone consultations had almost doubled, to 48%. Consultations in doctors' surgeries were relatively unchanged, but home visits were much reduced, to 18%. The percentage of doctors who worked 5 hours or more out of hours per week dropped from about 70% to about 50%. Overall patient satisfaction in 1995 was high (72%). Conclusion: The organisation of the out of hours service, with a fully trained general practitioner in a telephone triage function, is working satisfactorily. Many calls that previously would have required home visits are now dealt with by telephone or through consultations. The out of hours workload for general practitioners has decreased considerably. Key messages The out of hours reform in Denmark has resulted in an organisation with a fully trained general practitioner performing the telephone triage function Hours on call for general practitioners have decreased consideraby Home visits have largely been replaced by telephone consultations Patient satisfaction has declined slightly
Outcomes of a Peer HIV Prevention Program with Injection Drug and Crack Users: The Risk Avoidance Partnership

The Risk Avoidance Partnership (RAP) Project conducted in Hartford, Connecticut, tested a program to train active drug injectors and crack cocaine users as “Peer Health Advocates” (PHAs) to deliver a modular HIV, hepatitis, and STI prevention intervention to hard-to-reach drug users in their networks and others in the city. The intervention was designed to diffuse health promotion and risk-reduction interventions by supporting PHAs to model prevention practices and deliver risk- and harm-reduction materials and information. We compared change in behaviors and attitudes between baseline and 6-month follow-up of 112 primarily African-American and Latino PHAs, 223 of their drug-user network contact referrals, and 118 other study recruits (total n = 523). Results indicated significant HIV risk reduction among all study participants, associated with significant health advocacy action conducted by PHAs, and a relationship between exposure to the RAP peer-delivered intervention and risk reduction among all study groups. Findings suggest that active drug users' engagement in peer health advocacy can set in motion a feedback and diffusion process that supports both the continued work of the PHAs and the adoption of harm reduction and mimicking of health advocacy by their peers.
Effects of Thyroid Hormone Withdrawal and Recombinant Human Thyrotropin on Glomerular Filtration Rate During Radioiodine Therapy for Well-Differentiated Thyroid Cancer.

BACKGROUND Renal function is related to thyroid hormonal status, and glomerular filtration rate (GFR) seems to be impaired in patients with hypothyroidism. The aim of this work was to evaluate quantitatively the effect of hypothyroidism on GFR using a (51)Cr-EDTA radioisotope assay. METHODS Twenty-eight patients without known renal disease or dysfunction who had been referred for radioiodine therapy (RIT) after total thyroidectomy were enrolled in this study and divided into two groups. Group A underwent thyroid hormone withdrawal (THW) resulting in hypothyroidism, while group B underwent recombinant human thyrotropin (rhTSH) stimulation and hence remained euthyroid. GFR was assessed by (51)Cr-EDTA before and after THW or rhTSH. RESULTS No clinical differences were observed between the two groups. The mean ± SD GFRs were 94 ± 19 mL/min/1.73 m(2) before THW and 76 ± 16 mL/min/1.73 m(2) after THW for group A (p = 0.009), and 91 ± 18 mL/min/1.73 m(2) before rhTSH and 93 ± 15 mL/min/1.73 m(2) after rhTSH for group B (p = 0.613). The percent decrease in GFR during hypothyroidism is approximately 18-22%. CONCLUSION GFR decreases in patients with normal kidney function during THW for RIT, and rhTSH preserves GFR in these patients. This GFR impairment following thyroidectomy is related to hypothyroidism due to a significant reduction in thyroid hormone levels and is not due to a rise in the TSH level.
A Two-Stage Multi-objective Optimization of Erasure Coding in Overlay Networks

In the recent years, overlay networks have emergedas a crucial platform for deployment of various distributed applications. Many of these applications rely on data redundancy techniques, such as erasure coding, to achieve higher fault tolerance. However, erasure coding applied in large scale overlay networksentails various overheads in terms of storage, latency and datarebuilding costs. These overheads are largely attributed to theselected erasure coding scheme and the encoded chunk placementin the overlay network. This paper explores a multi-objective optimization approach for identifying appropriate erasure codingschemes and encoded chunk placement in overlay networks. Theuniqueness of our approach lies in the consideration of multipleerasure coding objectives such as encoding rate and redundancyfactor, with overlay network performance characteristics likestorage consumption, latency and system reliability. Our approach enables a variety of tradeoff solutions with respect tothese objectives to be identified in the form of a Pareto front. To solve this problem, we propose a novel two stage multi-objective evolutionary algorithm, where the first stage determinesthe optimal set of encoding schemes, while the second stageoptimizes placement of the corresponding encoded data chunksin overlay networks of varying sizes. We study the performanceof our method by generating and analyzing the Pareto optimalsets of tradeoff solutions. Experimental results demonstrate thatthe Pareto optimal set produced by our multi-objective approachincludes and even dominates the chunk placements delivered bya related state-of-the-art weighted sum method.
Allelopathic effect of aqueous extract from root systems of Johnson grass on seed germination and initial development of soybean, pea and vetch

This paper presents the results of the research on allelopathic effect of cold aqueous extracts from root systems of Johnson grass (Sorghum halepense (L.) Pers. ) on the seed germination and the initial development of soybean (Glycine max (L.)), pea (Pisum sativum (L.)) and vetch (Vicia sativa (L.)) under laboratory conditions. It was established that the inhibitory effect of aqueous root extracts on the seed germination of soybean, peas and vetch varied between 28.8 and 86.3%. Furthermore, the inhibitory effect of aqueous root extracts of Johnson grass varied between 17.1 and 86.1% on the development of the initial germ and between 8.3% and 97.9% on the accumulation of fresh biomass in the initial germ of soybean, peas and vetch. The values of LC50(P=0.05) were established to vary between 46.40 and 98.28 g l-1 dry biomass from root systems of Johnson grass and can be arranged in the following order: soybean → peas → vetch.
Human Gene Mutation Database: towards a comprehensive central mutation database

We write in response to a number of very specific criticisms of the Human Gene Mutation Database (HGMD; www.hgmd.org) made in the recently published article by George et al ( see review on p 65 ). 1 All seven claims made were amenable to empirical testing. Having tested these claims, we find all of them to be either false or highly misleading. In the text that follows, we refute or rebut each claim in turn. HGMD represents an attempt to collate known (published) gene lesions responsible for human inherited disease. HGMD comprises various types of germ-line mutation within the coding, splicing and regulatory regions of human nuclear genes. HGMD currently (1 December 2007) contains 76 011 different mutations in 2876 human genes. Claim 1: 143 genes are present in OMIM but have no corresponding HGMD entry Response —This claim is wholly misleading. OMIM (Online Mendelian Inheritance in Man) records many types of gene mutation which HGMD does not, such as somatic lesions, neutral polymorphisms and mitochondrial mutations. It is therefore to be expected that there will be some entries in OMIM that do not have a corresponding HGMD entry. We received the list of 143 genes from George et al and performed our own analysis. After careful comparison with OMIM, we found the following:
Comparison of peripapillary choroidal thickness measurements via spectral domain optical coherence tomography with and without enhanced depth imaging

ABSTRACT Objectives: To compare peripapillary choroidal thickness (PP-CT) measurements using a spectral domain optical coherence tomography (SD-OCT) device with and without enhanced depth imaging (EDI). Methods: Sixty healthy subjects aged from 18 to 40 years were included in this study. PP-CTs were measured in the right eyes by manual segmentation via SD-OCT both with and without EDI. The intraclass correlation coefficient (ICC) for each technique and comparison of PP-CT measurements between two techniques were evaluated. The correlation between retinal nerve fiber layer (RNFL) thickness and PP-CT was also explored on images of SD-OCT without EDI. Results: The PP-CT measurements of 55 subjects were evaluated. The ICC was 0.999 (95% CI: 0.998–1.0, p < 0.001) for SD-OCT with EDI and 0.996 (95% CI: 0.995–0.997, p < 0.001) for SD-OCT without EDI. The mean PP-CT measurements in all regions and the overall mean PP-CT measurements between the two techniques were not different (p > 0.05). Additionally, there was no correlation between RNFL thickness and PP-CT (r = −0.109; p = 0.335). Conclusions: The PP-CT measurements via SD-OCT without EDI were consistent with the measurements via SD-OCT with EDI. Ophthalmologists who do not have access to EDI technology can use images of SD-OCT without EDI to measure the peripapillary choroid for research purposes. However, thicker peripapillary choroids cannot be measured using this technique and require further modifications or newer technologies, such as SD-OCT with EDI
Dynamic aspects of intermediate filament networks in BHK-21 cells.

A procedure was developed for the conjugation of vimentin with biotin. Biotinylated vimentin was then microinjected into BHK-21 cells and the fate of the labeled protein was determined at various times postinjection by indirect immunofluorescence. Microinjected vimentin could be traced through a specific sequence of morphological changes ultimately resulting in the formation of a filamentous network. The injected protein was first detected in spots dispersed throughout the cytoplasm. Subsequently, these spots appeared to cluster near the nucleus where they merged into a diffuse "cap. " This cap coincided with a concentration of endogenous intermediate filaments and eventually gave rise to a filamentous network that was coincident with the endogenous intermediate filament network as determined by double-label immunofluorescence. The results indicate that the incorporation of exogenous vimentin into a filamentous network is initiated in a perinuclear region and progresses in a polarized fashion toward the cell surface.
Curcumin, a medicinal herbal compound capable of inducing the heat shock response

Objective There is interest in developing pharmacologic inducers of the heat shock response as a means to confer cytoprotection in the clinical setting. We propose that a potential strategy for screening novel pharmacologic inducers of the heat shock response is to examine known inhibitors of the transcription factor nuclear factor-&kgr;B. Curcumin, derived from the tropical herb Curcuma longa, is a recently described inhibitor of nuclear factor-&kgr;B and is widely used in Eastern medicinal practices. We tested the hypothesis that curcumin can induce expression of heat shock protein 70. Design Experimental. Setting University laboratory. Subjects HeLa cells. Interventions HeLa cells were exposed to varying concentrations of curcumin and analyzed for expression of heat shock protein 70 by Western blot. Measurements and Main Results Activation of the transcription factor, heat shock factor-1, was analyzed by electromobility shift assays. Curcumin-mediated inhibition of nuclear factor-&kgr;B activation was measured by transiently transfecting cells with a nuclear factor-&kgr;B luciferase reporter plasmid. The role of heat shock factor-1 in curcumin-mediated expression of heat shock protein 70 was tested in embryonic fibroblasts derived from heat shock factor-1 knockout mice. Induction of the heat shock response was quantified by transiently transfecting cells with a heat shock protein 70 promoter-luciferase reporter plasmid. Cell viability was measured by using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Curcumin induced expression of heat shock protein 70, the major inducible heat shock protein in cells undergoing the heat shock response, in a dose-dependent and time-dependent manner. Curcumin induced specific nuclear translocation and activation of heat shock factor-1. Curcumin-mediated expression of heat shock protein 70 was reduced substantially in fibroblasts having genetic ablation of heat shock factor-1. The extent of induction of the heat shock response correlated, in part, with cellular toxicity. Conclusions Curcumin, a widely used medicinal compound, induces the heat shock response in vitro as measured by expression of heat shock protein 70. The mechanism of heat shock protein 70 induction depends on activation of heat shock factor-1. Examining known inhibitors of nuclear factor-&kgr;B for their ability to induce heat shock protein 70 may be a valid screening method to discover novel pharmacologic inducers of the heat shock response.