Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Resistance Studies of Hepatitis C Virus Serine Protease Inhibitors, VX-950 and BILN 2061

We have used a structure-based drug design approach to identify small molecule inhibitors of the hepatitis C virus (HCV) NS3·4A protease as potential candidates for new anti-HCV therapies. VX-950 is a potent NS3·4A protease inhibitor that was recently selected as a clinical development candidate for hepatitis C treatment. In this report, we describe in vitro resistance studies using a subgenomic replicon system to compare VX-950 with another HCV NS3·4A protease inhibitor, BILN 2061, for which the Phase I clinical trial results were reported recently. Distinct drug-resistant substitutions of a single amino acid were identified in the HCV NS3 serine protease domain for both inhibitors. The resistance conferred by these mutations was confirmed by characterization of the mutant enzymes and replicon cells that contain the single amino acid substitutions. The major BILN 2061-resistant mutations at Asp168 are fully susceptible to VX-950, and the dominant resistant mutation against VX-950 at Ala156 remains sensitive to BILN 2061. Modeling analysis suggests that there are different mechanisms of resistance to VX-950 and BILN 2061.
Early morphologic and spectroscopic magnetic resonance in severe traumatic brain injuries can detect "invisible brain stem damage" and predict "vegetative states".

A precise evaluation of the brain damage in the first days of severe traumatic brain injured (TBI) patients is still uncertain despite numerous available cerebral evaluation methods and imaging. In 5-10% of severe TBI patients, clinicians remain concerned with prolonged coma and long-term marked cognitive impairment unexplained by normal morphological T2 star, flair, and diffusion magnetic resonance imaging (MRI). For this reason, we prospectively assessed the potential value of magnetic resonance spectroscopy (MRS) of the brain stem to evaluate the functionality of the consciousness areas. Forty consecutive patients with severe TBI were included. Single voxel proton MRS of the brain stem and morphological MRI of the whole brain were performed at day 17.5 +/- 6.4. Disability Rating Scale and Glasgow Outcome Scale (GOS) were evaluated at 18 months posttrauma. MRS appeared to be a reliable tool in the exploration of brainstem metabolism in TBI. Three different spectra were observed (normal, cholinergic reaction, or neuronal damage) allowing an evaluation of functional damage. MRS disturbances were not correlated with anatomical MRI lesions suggesting that the two techniques are strongly complementarity. In two GOS 2 vegetative patients with normal morphological MRI, MRS detected severe functional damage of the brainstem (NAA/Cr < 1.50) that was described as "invisible brain stem damage. " MRI and MRS taken separately could not distinguish patients GOS 3 (n = 7) from GOS 1-2 (n = 11) and GOS 4-5 (n = 20). However, a principal component analysis of combined MRI and MRS data enabled a clear-cut separation between GOS 1-2, GOS 3, and GOS 4-5 patients with no overlap between groups. This study showed that combined MRI and MRS provide a reliable evaluation of patients presenting in deep coma, specially when there are insufficient MRI lesions of the consciousness pathways to explain their status. In the first few days post-trauma metabolic (brainstem spectroscopy) and morphological (T2 star and Flair) MRI studies can predict the long-term neurological outcome, especially the persistent vegetative states and minimally conscious state.
Financial and Social Performance of Socially Responsible Investments in the Netherlands

We analyse the performance of socially responsible investments in the Netherlands. It appears that the financial performance of the various types of socially responsible investments differs considerably. We construct a proxy for mutual funds' CSR policies and use information about the environmental and social impact of activities financed by "green" financial institutions. We find preliminary evidence that financial and CSR performance substantially differs per category of financial instrument analysed. In the Netherlands, tax policy significantly affects financial results and the government can affect the CSR impact of some financial instruments too. More coherent and consistent information about CSR is required to establish whether financial and social performance interact. Copyright (c) 2007 The Author; Journal compilation (c) 2007 Blackwell Publishing Ltd.
Risk Return Trade-offs from Hedging Oil Price Risk in Ecuador

This paper analyses methods to reduce the price risk of Ecuadorian oil exports through hedging in the oil futures market. I simulate ex ante cross hedges over the 1991–96 period and find that in every case, ex ante hedging would have been effective in reducing risk. I provide quantitative estimates of the return/risk trade-offs from hedging Ecuadorian oil and find that for risk minimising short hedges, a 1 per cent reduction in risk would have cost a reduction in return of 0.65 per cent. In sum, I find that oil futures hedging offers Ecuador significant risk-reduction potential.
The Natural History of Depression up to 15 Years After Stroke: The South London Stroke Register

Background and Purpose— Evidence on the natural history of depression after stroke is still insufficient to inform prognosis and treatment strategies. This study estimates the incidence, cumulative incidence, prevalence, time of onset, duration, and recurrence rate of depression up to 15 years after stroke. Methods— Data from patients registered in the South London Stroke Register between 1995 and 2009 were used (N=4022 at registration. Maximum number of participants for these analyses n=1233). Depression was assessed in all patients with the Hospital Anxiety and Depression Scale (scores >7=depression) 3 months after stroke, 1 year after stroke, and annually thereafter up to 15 years after stroke. Inverse probability weighting was used to calculate the estimates accounting for missing data. Results— The poststroke incidence of depression ranged from 7% to 21% in the 15 years after a stroke, with cumulative incidence of 55% and prevalence ranging from 29% to 39%. Most episodes of depression started within a year of stroke, with 33% of the cases starting in the 3 months after a stroke, and none from year 10 onward. Fifty percent of the patients with depression at 3 months had recovered 1 year after stroke. The proportion of recurrent episodes of depression after stroke increased gradually from 38% in year 2 to 100% in years 14 and 15. Conclusions— The natural history of depression after stroke is dynamic. Depression affects most of the stroke patients with episodes that have a short duration but a high risk of recurrence in the long term.
SAMs, THE SNA AND NATIONAL ACCOUNTING CAPABILITIES

In this paper, the author argues for radical revision of the 1968 SNA in the direction of simplification, in order to give greater emphasis to essential concepts, and for flexibility, so that each country can develop its own SAMs within a general conceptual framework as a response to domestic priorities and issues. It is suggested that general equilibrium models should replace input-output as the central conceptualisation of the system, leading to an equal emphasis on prices and quantities, and an equal concern within the SNA for income distribution, factor markets and production structure, set in the context of external flows and balances. Copyright 1991 by The International Association for Research in Income and Wealth.
Population Ageing and Productivity: Implications and Policy Options for New Zealand

This paper critically evaluates the effects of population ageing on labour productivity with particular reference to New Zealand. A number of potential long run mechanisms are considered: complementarity of workers by age, age-specific productivity of individuals, new technology discoveries and adoptions, fertility and human capital investments. Potential short run channels include: the ‘second demographic dividend’, changes in industry composition, incentives to seek labour saving technologies. Simulations tentatively suggest that workers could become more complimentary by age which would boost labour productivity. The magnitude of this effect on living standards could entirely offset the projected 12 per cent fall in the support ratio over the next 40 years. The most effective policies for mitigating the national economic burden of ageing are policies to boost labour participation of older workers and to boost immigration.
Ethanol production from Jerusalem artichoke tubers (Helianthus tuberosus) using Kluyveromyces marxianus and Saccharomyces rosei

This article examines the potential of Jerusalem artichoke as a source for ethanol and single‐cell protein SCP. In addition, experimental results are presented on batch fermentation kinetics employing two strains of Kluyveromyces marxianus and one strain of Saccharomyces rosei grown on the extract derived from the tubers of Jerusalem artichoke. Of the three cultures examined, Kluyveromyces marxianus UCD (FST) 55–82 was found to be the best producer of ethanol grown in a simple medium at 35°C. The ethanol production was found to be growth‐associated having a μmax = 0.41. h−1 and the ethanol and biomass yields were determined to be Yp/s = 0.45 (88% of the theoretical) and Yx/s = 0.04 with 92% of the original sugars utilized. On the basis of carbohydrate yields of Jerusalem artichoke reported in the literature and these batch kinetic studies with K. maxxianus, the calculated ethanol yields were found to range from 1400 kg ethanol acre −1 yr−1to a maximum of 2700 kg ethanol acre −1 yr−1. The SCP yields for K. marxianus were calculated to range between 130 to 250 kg dry wt cell acre −1 yr−1. The potential for developing an integrated process to produce ethanol and SCP is also discussed.
Humps and Bumps in Lifetime Consumption

In this paper we argue that once one departs from the simple classroom example, or `stripped down life-cycle model,' the empirical model for consumption growth can be made flexible enough to fit the main features of the data. More specifically, we show that allowing demographics to affect household preferences and relaxing the assumption of certainty equivalence can generate hump-shaped consumption profiles over age that are very similar to those observed in household-level data sources, without appealing to alternative explanations (such as liquidity constraints, myopia or mental accounting). The hump-shape is partly attributable to precautionary savings, and partly due to demographics; the tracking (whereby consumption jumps with income) is instead due to the permanent nature of the income shocks. We use US household-level data to estimate preference parameters and income profiles, and then simulate consumption profiles for different education groups. Our simulated profiles show that the key features observed in the data can be closely matched in simulation. We also show that neglecting uncertainty produces consumption profiles that are `too flat,' whereas neglecting demographics generates consumption profiles that peak `too late. '
(How) Do Stock Market Returns React to Monetary Policy? An ARDL Cointegration Analysis for Germany*

Is a central bank able to influence stock market returns? In order to answer this question, we test for cointegration between stock market returns and central bank interest rates in Germany for the period 1974 – 2003. Problems related to spurious regression could arise from the mixed order of integration of the series used, from reverse causation between the variables and from the lack of a long run relationship among the variables of the model. We address these problems by applying the bounds testing approach and autoregressive distributed lag models developed by Pesaran and others. The empirical results are also compared with those obtained from a more standard econometric approach, the Johansen procedure. Seen on the whole, we cannot empirically reject the view that the Bundesbank – and then the ECB – have had a significant short- and long-run impact on stock market returns. We conclude that short-term rates drive stock market returns but not vice versa. But the results are confined to a single stock market return measure, namely dividend growth.
Paracervical Block Efficacy in Office Hysteroscopic Sterilization: A Randomized Controlled Trial

OBJECTIVE: To estimate the efficacy of paracervical block compared with saline for pain relief during office hysteroscopic sterilization. METHODS: This study was a randomized, placebo-controlled study of women desiring hysteroscopic sterilization. A paracervical block of 1% lidocaine or normal saline was administered before office hysteroscopic sterilization. Patients and investigators were blinded to assignments. A pre hoc power analysis determined that 40 women would be required per arm to detect a difference of 0.9 cm on a visual analog scale. Pain was recorded on a visual analog scale at multiple procedure time points. Individualized standardized pain scores were constructed by weighted reporting of objective and subjective sensation. RESULTS: A total of 103 consecutive women were eligible, and 80 women were randomized, with 40 per group. Thirty-seven (93%) in each group had successful placement. The lidocaine group showed significantly lower pain scores for tenaculum placement (mean±standard deviation: 0.97±1.28 compared with 3.00±2.41, P<.001) traversing the external cervical os (1.46±1.71 compared with 3.77±2.68, P<.001) and internal os (1.79±2.11 compared with 4.10±2.77, P<.001). There was no significant observed difference with device placement in tubal ostium (3.15±2.69 compared with 3.74±2.73, P=.33). Multivariable linear regression analysis demonstrated a relationship of pain to procedural time (P=.047) and to group assignment (P<.01). CONCLUSION: Paracervical block with 1% lidocaine provides effective pain relief for cervical manipulations during office hysteroscopic sterilization, but does not reduce the pain associated with upper uterine/tubal manipulation when placing the devices. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials. gov, NCT00811187. LEVEL OF EVIDENCE: I
The nature of market orientation and the ambidexterity of innovations

Purpose – This study aims to consider that a proactive‐ and responsive‐market orientated firm is able to align with the development of radical (exploratory) innovations as well as incremental (exploitative) innovations to realize its organizational ambidexterity.Design/methodology/approach – The paper is based on a questionnaire survey/analysis of a sample of 227 high‐technology firms in Taiwan.Findings – The research findings reveal that both types of market orientation provide different managerial efforts to develop and foster different types of innovation competencies; and then, those effects would be moderated through external and organizational factors.Practical implications – Through the deployment of ambidextrous structures, managers could effectively arrange the portfolio of product‐markets with an array of proactive‐ and responsive‐ market orientation to align the potential conflicts concerning the exploration and the exploitation.Originality/value – This study is a pioneer in the field that reve.
Money, Inflation, and Growth in Pakistan

This paper attempts to investigate the linkage between the excess money supply growth and inflation in Pakistan and to test the validity of the monetarist stance that inflation is a monetary phenomenon. The results from the correlation analysis indicate that there is a positive association between money growth and inflation. The money supply growth at first-round affects real GDP growth and at the second round it affects inflation in Pakistan. The important finding from the analysis is that the excess money supply growth has been an important contributor to the rise in inflation in Pakistan during the study period, thus supporting the monetarist proposition that inflation in Pakistan is a monetary phenomenon. This may be due to the loose monetary policy adopted by the State Bank of Pakistan to show the high priority of the growth objective. The important policy implication is that inflation in Pakistan can be cured by a sufficiently tight monetary policy. The formulation of monetary policy must consider development in the real and financial sector and treat these sectors as constraints on the policy.
One hundred pregnancies after treatment with pulsatile luteinising hormone releasing hormone to induce ovulation.

OBJECTIVE--To review treatment with pulsatile luteinising hormone releasing hormone in infertile women who do not ovulate and are resistant to clomiphene after 100 pregnancies achieved with this treatment. DESIGN--Retrospective analysis of 146 courses of treatment over 434 cycles. SETTING--Infertility clinic. PATIENTS--118 Women whose failure to ovulate was due to idiopathic hypogonadotrophic hypogonadism (n = 39), amenorrhoea related to low weight (n = 17), organic pituitary disease (n = 15), or polycystic ovaries (n = 47). INTERVENTIONS--Dose of 15 micrograms luteinising hormone releasing hormone/pulse subcutaneously every 90 minutes given with a miniaturised pump throughout cycle monitored by ultrasound. Women with hypogonadotrophic hypogonadism had 48 courses, women with amenorrhoea related to low weight 23, women with organic pituitary disease 18, and women with polycystic ovaries 57. END POINT--Follow up of 100 pregnancies achieved in 77 women during six years after introducing treatment. MEASUREMENTS and main results--One hundred pregnancies (seven multiple, 28 miscarriages). Cumulative rates of pregnancy were 93-100% at six months in women with idiopathic hypogonadotrophic hypogonadism, amenorrhoea related to low weight, and organic pituitary disease. In women with polycystic ovaries (cumulative rate of pregnancy 74%) adverse prognostic factors were obesity, hyperandrogenism, and high luteinising hormone concentrations, which were also associated with a high rate of early pregnancy loss. CONCLUSIONS--Treatment with pulsatile luteinising hormone releasing hormone is safe, simple, and effective, and the preferred method of inducing ovulation in appropriately selected patients. Compared with exogenous gonadotrophin treatment there is little need for monitoring, no danger of hyperstimulation, and a low rate of multiple pregnancies.
Structural investigation of the C-terminal catalytic fragment of presenilin 1

The γ-secretase complex has a decisive role in the development of Alzheimer’s disease, in that it cleaves a precursor to create the amyloid β peptide whose aggregates form the senile plaques encountered in the brains of patients. Γ-secretase is a member of the intramembrane-cleaving proteases which process their transmembrane substrates within the bilayer. Many of the mutations encountered in early onset familial Alzheimer’s disease are linked to presenilin 1, the catalytic component of γ-secretase, whose active form requires its endoproteolytic cleavage into N-terminal and C-terminal fragments. Although there is general agreement regarding the topology of the N-terminal fragment, studies of the C-terminal fragment have yielded ambiguous and contradictory results that may be difficult to reconcile in the absence of structural information. Here we present the first structure of the C-terminal fragment of human presenilin 1, as obtained from NMR studies in SDS micelles. The structure reveals a topology where the membrane is likely traversed three times in accordance with the more generally accepted nine transmembrane domain model of presenilin 1, but contains unique structural features adapted to accommodate the unusual intramembrane catalysis. These include a putative half-membrane-spanning helix N-terminally harboring the catalytic aspartate, a severely kinked helical structure toward the C terminus as well as a soluble helix in the assumed-to-be unstructured N-terminal loop.
The Impact of Product Market Competition on Earnings Quality

The objective of this paper is to examine the impact of product market competition on earnings quality. Based on a sample from the US manufacturing sector for the period 1996–2005, we find consistent evidence showing a positive relation between product market competition and earnings quality. Additional tests also confirm a positive relation between product market competition and the precision of public and private information held by investors and analysts. We also provide evidence that firms competing in concentrated and heterogeneous industries are associated with a number of earnings attributes and information quality not shared by those competing in concentrated but homogeneous industries. These findings are consistent with the intuition that firms enjoying a monopolistic advantage tend to avoid the attention of their competitors and politicians by creating a more opaque information environment.
Intracellular transport of soluble and membrane‐bound glycoproteins: folding, assembly and secretion of anchor‐free influenza hemagglutinin.

The influenza hemagglutinin precursor (HA0) and many other glycoproteins fold and oligomerize in the endoplasmic reticulum (ER). Only correctly folded oligomers are transported to the cell surface. To analyse the rules which determine this type of ER sorting, we have extended our analysis of hemagglutinin transport to two soluble, anchor‐free recombinant HA0s derived from X31/A/Aichi/68 and A/Japan/305/57 influenza A. The results showed that individual monomers rapidly acquired a folded structure similar to that of monomeric membrane‐anchored HA0. They were efficiently transported and secreted, but oligomerization was not required for secretion. Trimers or higher order complexes were either not formed (X31 HA0), or appeared during passage through the late compartments of the secretory pathway, with no effect on the rate of transport (Japan HA0). However, when initial folding was disturbed by inhibition of N‐linked glycosylation, anchor‐free X31 HA0 was misfolded and retained in the ER as disulfide‐linked complexes associated with binding protein, BiP (GRP78). The complexes were similar to those seen for the nonglycosylated membrane‐bound HA0, but instead of forming immediately after synthesis they appeared with a half‐time of 6 min. Taken together, the data demonstrate that the structural criteria that makes the anchor‐free HA0 transport competent are less stringent than those for the membrane form; they must fold correctly but do not need to oligomerize.
Residents' Attitudes Toward Tourism and Perceived Personal Benefits in a Rural Community

This research focuses on residents' perceptions of personal benefits from tourism, identifying not only the relationships between personal benefits from tourism and residents' attitudes toward tourism but also the nature of benefits associated with tourism. The study was conducted in a small rural community where tourism is still at its emerging stage. It was found that residents' perceptions of personal benefits from tourism were closely associated with their attitudes toward tourism in a positive direction. The significant contribution of this study falls on the recognition of noneconomic perspective of tourism benefits for residents in a community where tourism has not yet explicitly emerged. In particular, the data lend support for social exchange theory and improve its understanding in tourism investigations.