Miracle-dz/UniFAR-FTUs huggingface dataset:
Interferon‐β and interferon‐λ signaling is not affected by interferon‐induced refractoriness to interferon‐α in vivo

Therapy of chronic hepatitis C with pegylated interferon α (pegIFN‐α) and ribavirin achieves sustained virological responses in approximately half of the patients. Nonresponse to treatment is associated with constitutively increased expression of IFN‐stimulated genes in the liver already before therapy. This activation of the endogenous IFN system could prevent cells from responding to therapeutically injected (peg)IFN‐α, because prolonged stimulation of cells with IFN‐α induces desensitization of the IFN signal transduction pathway. Whether all types of IFNs induce refractoriness in the liver is presently unknown. We therefore treated mice with multiple injections and different combinations of IFN‐α, IFN‐β, IFN‐γ, and IFN‐λ. Pretreatment of mice with IFN‐α, IFN‐β, and IFN‐λ induced a strong expression of the negative regulator ubiquitin‐specific peptidase 18 in the liver and gut. As a result, IFN‐α signaling was significantly reduced when mice where reinjected 16 hours after the first injection. Surprisingly, both IFN‐β and IFN‐λ could activate the Janus kinase–signal transducer and activator of transcription (STAT) pathway and the expression of IFN‐stimulated genes despite high levels of ubiquitin‐specific peptidase 18. IFN‐λ treatment of human liver biopsies ex vivo resulted in strong and maintained phosphorylation of STAT1, whereas IFN‐α–induced STAT1 activation was transient. Conclusion: Contrary to the action of IFN‐α, IFN‐β, and IFN‐λ signaling in the liver does not become refractory during repeated stimulation of the IFN signal transduction pathway. The sustained efficacy of IFN‐β and IFN‐λ could be an important advantage for the treatment patients who are nonresponders to pegIFN‐α, through a preactivated endogenous IFN system. (HEPATOLOGY 2011;)
Modelling the price, performance and contract characteristics of IT outsourcing

The rapidly increasing use of outsourcing for IT services, both in the public and private sectors, has attracted much interest from researchers and practitioners alike. While early studies of IT outsourcing were largely qualitative in nature, more recent studies have attempted to analyse the outcomes achieved in quantitative terms. This paper is consistent with the latter, but goes further by modelling the price, performance and contract characteristics that are relevant to IT outsourcing. A two-equation recursive regression model was used to analyse 48 contracts for IT support and maintenance. The results did not reveal any quantitatively significant price–performance trade-off, but did suggest that first-term contracts (i.e. the first ever contract awarded by a client for the provision of a particular IT service) were more expensive than repeat contracts. Although competitive tendering did not result in lower prices than directly negotiated contracts, it was associated with comparatively better performance. Well-defined expectations of an organization's IT requirements were also likely to lead to improved performance when the service was outsourced.
Protein adsorption during LDL-apheresis: proteomic analysis.

BACKGROUND The aim of our study was to investigate the clearance of functional proteins by different low-density lipoprotein-apheresis (LDL-A) methods with the help of proteomic analyses. METHODS Proteins were eluated from the different LDL-A columns and investigated with 2D electrophoresis combined with mass spectrometry methods. In parallel, we quantified the plasma protein loss from patients treated with double-filtration plasmapheresis (DFPP; n = 9), direct adsorption of lipoproteins (DALI; n = 5) or heparin-induced extracorporeal LDL precipitation (HELP; n = 7) with routine laboratory methods and western blots. RESULTS Proteomic analyses of the column-bound proteins revealed a column-type-dependent loss with the highest number of protein spots in DALI-treated patients (1001 +/- 36), followed by HELP (881 +/- 25) and DFPP (535 +/- 20). More than 70 functional proteins were identified. These proteins are involved in the coagulation pathway (e.g. kininogen1) and have adhesive (e.g. fibronectin), rheological (e.g. fibrinogen) and immunological/inflammatory properties (e.g. complement components). Quantification with western blot analyses demonstrated a significant depletion (P < 0.01) of these proteins comparing serum samples before and after the column with a systemic lowering in patients' serum. CONCLUSIONS These data reveal strong interaction between column and serum proteins during LDL-A. The clearance of proteins with adhesive, rheological, and inflammatory characteristics may have beneficial effects on microcirculation and reduce chronic inflammation but may also concomitantly induce side effects such as an increased bleeding risk.
Outcomes and costs associated with initial maintenance therapy with fluticasone propionate-salmeterol xinafoate 250 microg/50 microg combination versus tiotropium in commercially insured patients with COPD.

PURPOSE To compare, in commercially-insured individuals 240 years old, the risk of chronic obstructive pulmonary disease (COPD) exacerbations and COPD-related health care utilization and costs in patients initiating maintenance treatment with fluticasone propionate/salmeterol xinafoate 250 microg/50 microg (FSC) with those in patients initiating treatment with tiotropium bromide (TIO). DESIGN Retrospective observational cohort study. METHODOLOGY The risk of COPD exacerbation (moderate, severe, and any), COPD-related health care utilization, and COPD-related costs (overall and by service setting) were assessed over 12 months after the initiation of treatment with FSC or TIO in commercially-insured patients > or =40 years old diagnosed with COPD. PRINCIPAL FINDINGS After adjusting for covariates, treatment with FSC compared with treatment with TIO was associated with a 14% reduction in risk of severe exacerbation (p = 0.0406), defined as the occurrence of a COPD-related hospitalization; with less health care utilization across several categories of care; with 25% lower COPD-related medical costs ($1814 versus $2258 per patient, p < 0.0001); and with 10% lower COPD-related total costs ($2991 versus $3304 per patient, p < 0.0001) over a 12-month follow-up period. Pharmacy costs were equivalent between FSC and TIO. CONCLUSION Initiation of maintenance therapy with FSC compared with TIO was associated with significant reductions in the risk of severe exacerbations, health care utilization, and COPD-related medical and total costs. Considered in the context of other findings, these data suggest that earlier maintenance treatment with FSC offers clinical and economic benefits over maintenance treatment with TIO.
Restless legs syndrome is frequently overlooked in patients being evaluated for polyneuropathies

Restless legs syndrome (RLS) often presents with paresthesias and dysesthesisas. We have investigated the prevalence and clinical features of RLS in a cohort of patients referred for clinical suspicion of peripheral neuropathy (PN). Sixty‐four patients with sensory symptoms, and 101 age‐matched controls were prospectively evaluated for RLS, PN and causes of both conditions. In the 64 patients (60 ± 14 years), none were referred with a suspicion of RLS. Forty‐one had a sensori‐motor PN of which 22 had a definite RLS (54%). When excluding other causes of RLS, 8 of 41 patients had a RLS associated with a neuropathy (20%). The proportion of RLS in the healthy controls was 10%, lower than in the cohort of patients. In patients without PN, 57% had a RLS, and 55% in the whole cohort, a higher proportion than in the healthy controls (P < 0.0001). Patients with PN and RLS had more sleep disorders (P < 0.04), and legs and calves symptoms (P = 0.09) than patients with PN without RLS. Toes symptoms were more frequently observed in patients with PN but without RLS (P < 0.02). We conclude that RLS frequently presents with symptoms suggestive of peripheral neuropathy, and therefore, is often overlooked.
The Role of Metaphors in Strategic Information Systems Planning

This paper posits that (1) metaphors perform a crucial role in enacting strategy and linking strategic thinking with IT planning; (2) the war metaphor, which underlies many previous discussions of strategic information systems (SIS) is inadequate, possibly obsolete, in today's environment, and the shift away from this metaphor in the past few years is evidence of this; (3) other metaphors offer potentially more useful foundations for strategic thinking and SIS planning in today's world than the war metaphor; and (4) explicit articulation and exploration of alternative metaphors help identify strategic opportunities for information technology (IT) applications, designing SIS for global enterprises, and formulating research on SIS issues. This paper outlines these arguments and identifies desirable characteristics of metaphors, and discusses alternative metaphors of the organization as: an adapting organism, city-state, participant in organized team sports, an expression of philosophy, and expression of economic forces. The paper concludes with suggestions for research on the use of metaphor in strategy formulation and IT planning.
Performance Thresholds in Managerial Incentive Contracts

Performance thresholds are commonly used in executive compensation contracts. We examine the contractual nonlinearity associated with performance thresholds and its incentive implications. Incorporating a performance threshold into a standard principal-agent model of a linear contract, we show that pay schemes using a performance threshold are optimal. By truncating a linear scheme at poor performance, the threshold mitigates agency costs associated with the downside risk of production. Examining CEO compensation data, we find evidence of the role of performance thresholds. As a consequence of under-threshold performance, the tobit estimator is shown to increase pay-performance sensitivity, notably improving upon the standard OLS estimator.
Mammary tumors of the rat: a review.

A review of the pertinent studies on mammary tumors of the rat is presented. The major topics discussed are: 1) origin and characteristics 2) induced mammary tumors 3) whether virus is implicated in rat mammary tumors 4) mammary tumor-host relationship and 5) chemotherapeutic studies. Millar and Noble demonstrated that although small doses of estrogen increased the tumor growth rate larger doses caused a marked depression of growth. Progesterone has been reported to have no effect on tumor growth or to stimulate growth. If . 6 mg of alpha-estradiol were added to an iv injection of carcinogenic hydrocarbons there was a higher incidence and earlier appearance of tumors. Diethylstilbestrol caused an increase in the total number of tumors. Treatment with . 1 mcg daily of estradiol-17beta produced a normal incidence of tumors in ovariectomized females. A dose of 1 mcg delayed the appearance of tumors. Progesterone at a dose of 4 mg daily accelerated the time of appearance. Continuous administration of estrogen to rats has been followed by a high incidence of mammary tumors. The injection of estrogens or implantation sc as pellets also induces a high incidence of tumors.
National survey of venereal disease treated by physicians in 1968.

Private physicians in the United States were questioned regarding treatment of venereal disease in a three-month period of 1968. Of those queried, 134,633 physicians (65.3%) responded—43,720 (32.5% of responding physicians) indicated treatment of syphilis or gonorrhea in the period; 4,370 (3.2% of responding physicians) indicated treatment of 8,849 cases of infectious syphilis; 10,934 physicians had treated 22,022 cases of "other syphilis"; and 39,392 had treated 185,548 cases of gonorrhea. Comparison of survey indications of cases treated with cases reported in the period showed only 12% (18.7%) of infectious syphilis cases and 10.9% (16.9%) of gonorrhea cases had been reported if estimates for nonresponding physicians are included (or excluded). Syphilis and gonorrhea remain vastly underreported although the reporting of syphilis and gonorrhea has slightly improved since 1962.
Chemical changes and influences of rapeseed antinutritional factors on lamb physiology and performance 2 . Plasma substances and activity of the thyroid

In order to study the effects of a high level of rapeseed meal in the diet on endocrine function and thyroid activity, sixty six Texel, Suffolk or crossbred lambs allocated to three groups were fed ad libitum with concentrates containing 0% (Control) or 25% of rapeseed meal obtained with either Samourai (Samourai) or Honk (Honk) rapeseed varieties. Lambs were weaned at 88 8 days of age and 24 5 kg of live weight and were slaughtered when their fattening state was estimated to be satisfactory. Blood samples were taken fortnightly for the determinations of hormones, glucose and transaminases (GOT and GPT). To evaluate the capacity of hormone production, the thyroid glands were collected at slaughter and the in-vitro release of thyroid hormones was recorded. The plasma concentrations in triiodothyronine (T3) and thyroxine (T4) decreased (P <0.05) with the age of lambs and were lower (P <0.05) in the Samourai and Honk groups than in the Control. Moreover, the capacity of T3 and T4 production by the thyroid gland shown by the in-vitro T3 and T4 accumulation in the thyroid tissues was higher (P <0.05) in the Control than in the two rapeseed groups. In contrast, the concentrate with rapeseed meal had no effect on the plasma concentrations in GH, cortisol and insulin nor on other substances (glucose, GOT and GPT). These results indicate that the ingestion of rapeseed meal induces a low functional disorder of the thyroid without affecting the animal performance of lambs, as we reported previously. This is because the thyroid hormones do not appear to play a major role in the processes of growth and Animal Feed Science and Technology
The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.

CONTEXT The World Health Organization defines preterm birth as birth at less than 37 completed gestational weeks, but most studies have focused on very preterm infants (birth at <32 weeks) because of their high risk of mortality and serious morbidity. However, infants born at 32 through 36 weeks are more common and their public health impact has not been well studied. OBJECTIVE To assess the quantitative contribution of mild (birth at 34-36 gestational weeks) and moderate (birth at 32-33 gestational weeks) preterm birth to infant mortality. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study using linked singleton live birth-infant death cohort files for US birth cohorts for 1985 and 1995 and Canadian birth cohorts (excluding Ontario) for 1985-1987 and 1992-1994. MAIN OUTCOME MEASURES Relative risks (RRs) and etiologic fractions (EFs) for overall and cause-specific early neonatal (age 0-6 days), late neonatal (age 7-27 days), postneonatal (age 28-364 days), and total infant death among mild and moderate preterm births vs term births (at >/=37 gestational weeks). RESULTS Relative risks for infant death from all causes among singletons born at 32 through 33 gestational weeks were 6.6 (95% confidence interval [CI], 6.1-7.0) in the United States in 1995 and 15.2 (95% CI, 13.2-17.5) in Canada in 1992-1994; among singletons born at 34 through 36 gestational weeks, the RRs were 2.9 (95% CI, 2.8-3.0) and 4.5 (95% CI, 4.0-5.0), respectively. Corresponding EFs were 3.2% and 4.8%, respectively, at 32 through 33 gestational weeks and 6.3% and 8.0%, respectively, at 34 through 36 gestational weeks; the sum of the EFs for births at 32 through 33 and 34 through 36 gestational weeks exceeded those for births at 28 through 31 gestational weeks. Substantial RRs were observed overall for the neonatal (eg, for early neonatal deaths, 14.6 and 33.0 for US and Canadian infants, respectively, born at 32-33 gestational weeks; EFs, 3.6% and and 6. 2% for US and Canadian infants, respectively) and postneonatal (RRs, 2.1-3.8 and 3.0-7.0 for US and Canadian infants, respectively, born at 32-36 gestational weeks; EFs, 2.7%-5.8% and 3.0%-7.0% for the same groups, respectively) periods and for death due to asphyxia, infection, sudden infant death syndrome, and external causes. Except for a reduction in the RR and EF for neonatal mortality due to infection, the patterns have changed little since 1985 in either country. CONCLUSIONS Mild- and moderate-preterm birth infants are at high RR for death during infancy and are responsible for an important fraction of infant deaths. JAMA. 2000;284:843-849
Joint system for speech separation from speaking and non-speaking background, and de-reverberation: Application on real-world recordings

In real-life environment, the speech of interest is often correlated with different kinds of perturbation. Perturbation can be caused by speaking or non-speaking noise, or even by reverberation. This could make the speech signal auditable but not intelligible. In this case, speech cannot be exploited by other automated applications such as voice-command or speech/speaker identification and identification. Extracting a meaningful signal of good quality is a bigger challenge in monaural case. In this paper, we propose an extensible full joint system that deals with real-environment perturbations that include speaking and non-speaking background as well as reverberation. After introducing the input signal, a decision is taken on the process to opt for. The main chain blocks of the proposed system are speech denoising, speech separation and speech de-reverberation. The system operates in single channel case in a fully unsupervised manner. Furthermore, it requires minimal information about the reference signal. As the system is targeting real-time enhancement, results evaluation is conduct in terms of non-intrusive metrics in addition to intrusive metrics. The evaluation results prove the effectiveness of the proposed system in cancelling difficult noise types, in extracting desired speaker from speaking background, and in enhancing reverberated speech.
Efficacy and Stability of Quantal GABA Release at a Hippocampal Interneuron–Principal Neuron Synapse

We have examined factors that determine the strength and dynamics of GABAergic synapses between interneurons [dentate gyrus basket cells (BCs)] and principal neurons [dentate gyrus granule cells (GCs)] using paired recordings in rat hippocampal slices at 34°C. Unitary IPSCs recorded from BC–GC pairs in high intracellular Cl− concentration showed a fast rise and a biexponential decay, with mean time constants of 2 and 9 msec. The mean quantal conductance change, determined directly at reduced extracellular Ca2+/Mg2+concentration ratios, was 1.7 nS. Quantal release at the BC–GC synapse occurred with short delay and was highly synchronized. Analysis of IPSC peak amplitudes and numbers of failures by multiple probability compound binomial analysis indicated that synaptic transmission at the BC–GC synapse involves three to seven release sites, each of which releases transmitter with high probability (∼0.5 in 2 mmCa2+/1 mm Mg2+). Unitary BC–GC IPSCs showed paired-pulse depression (PPD); maximal depression, measured for 10 msec intervals, was 37%, and recovery from depression occurred with a time constant of 2 sec. Paired-pulse depression was mainly presynaptic in origin but appeared to be independent of previous release. Synaptic transmission at the BC–GC synapse showed frequency-dependent depression, with half-maximal decrease at 5 Hz after a series of 1000 presynaptic action potentials. The relative stability of transmission at the BC–GC synapse is consistent with a model in which an activity-dependent gating mechanism reduces release probability and thereby prevents depletion of the releasable pool of synaptic vesicles. Thus several mechanisms converge on the generation of powerful and sustained transmission at interneuron–principal neuron synapses in hippocampal circuits.
Haematological and hepatotoxic effects of isoprocarb in chicken

The haematological and hepatotoxic effects were studied after oral administration of Isoprocarb at 75, 112.5 and 150 mg kg−1 daily for 21 days in male and female chicken Gallus gallus domesticus (White Leghorns). The toxic effects as observed 10 or 21 days after medication include a statistically significant reduction in haemoglobin (Hb) content, haematocrit (Ht), protein and serum glutamate pyruvate transaminase (SGPT), and an increase in glucose, serum glutamate oxaloacetate transaminase (SOOT) and serum acid phosphatase (SAP) activities of male and female chicken. The changes in other haematological parameters were generally insignificant, except for one or two doses in RBC, WBC, mean corpuscular haemoglobin concentration (MCHC) and chloride. A significant inhibition of RBC acetylcholinesterase was noticed after 21 days of dosing only at the high dose (150 mg kg−1) in hens. The decrease in food intake and body weights of males and females indicated the overt signs of toxicity. In addition to haematological alterations, the results suggest both hepatotoxic and stress effects and pinpoint that these early biochemical changes induced by Isoprocarb may be predictive of pesticide toxicity.
Impact of Fast Interface States on Effective Mobility of Heavily-Doped MOSFET's

We show that for MOSFET's with a heavily doped channel, the well-established experimental procedure for measurement of electron mobility is affected by a systematic error. Due to quantization of electron states in the channel, interface traps close to the conduction-band edge contribute significantly to the gate-channel capacitance, leading to underestimate the mobility in the near-threshold region.
Economic Evaluation of HIV Risk Reduction Intervention in African‐American Male Adolescents

Purpose: To evaluate the cost‐effectiveness of a cognitive‐behavioral HIV risk reduction intervention for African‐American male adolescents that has previously been shown to be effective at reducing sexual risk taking. Methods: Standard techniques of cost‐utility analysis were employed. A societal perspective and a 3% discount rate were used in the main analysis. Program costs were ascertained retrospectively. A mathematical model of HIV transmission was used to translate observed changes in sexual behavior into an estimate of the number of HIV infections the intervention averted. Intervention effects were assumed to last for 1 year. For each infection averted, the corresponding savings in future HIV‐related medical care costs and quality‐adjusted life years (QALYs) were estimated. The overall net cost per QALY saved (cost‐utility ratio) was then calculated. Sensitivity analyses were performed to assess the robustness of the main results. Results: The cost‐utility ratio was approximately $57,000 U.S. per QALY saved when training costs were included, and $41,000 U.S. per QALY saved when they were excluded. The intervention appeared substantially more cost‐effective when the analysis was restricted to the subgroup of participants who reported being sexually active at baseline. Assumptions about the prevalence of HIV infection and the duration of intervention effectiveness also greatly affected the cost‐utility ratio. Conclusions: The HIV prevention intervention was moderately cost‐effective in comparison with other health care programs. Selectively implementing the intervention in high‐HIV prevalence communities and with sexually active youth can enhance cost‐effectiveness.