Miracle-dz/UniFAR-FTUs huggingface dataset:
Bid-induced Cytochrome c Release Is Mediated by a Pathway Independent of Mitochondrial Permeability Transition Pore and Bax*

Bid, a pro-apoptosis “BH3-only” member of the Bcl-2 family, can be cleaved by caspase-8 after Fas/TNF-R1 engagement. The p15 form of truncated Bid (tBid) translocates to mitochondria and induces cytochrome c release, leading to the activation of downstream caspases and apoptosis. In the current study, we investigated the mechanism by which tBid regulated cytochromec release in terms of its relationship to mitochondrial permeability transition and Bax, another Bcl-2 family protein. We employed an in vitro reconstitution system as well as cell cultures and an animal model to reflect the physiological environment where Bid could be functional. We found that induction of cytochromec release by tBid was not accompanied by a permeability transition even at high doses. Indeed, inhibition of permeability transition did not suppress the activity of tBid in vitronor could they block Fas activation-induced, Bid-dependent hepatocyte apoptosis in cultures. Furthermore, Mg2+, although inhibiting permeability transition, actually enhanced the ability of tBid to induce cytochrome c release. We also found that tBid did not require Bax to induce cytochrome crelease in vitro. In addition, mice deficient inbax were still highly susceptible to anti-Fas-induced hepatocyte apoptosis, in which cytochrome c release was unaffected. Moreover, although Bax-induced cytochrome crelease was not dependent on tBid, the two proteins could function synergistically. We conclude that Bid possesses the biochemical activity to induce cytochrome c release through a mechanism independent of mitochondrial permeability transition pore and Bax.
The relevance of health reform to community health and development

Over the past twelve months, Congress and the nation have been engaged in a discussion about how to make significant changes in the provision of health insurance and the financing of health care in the United States. The debate has seen its highs and lows: from the raucous August town hall meetings and charges that the reform would institute “death panels” for the elderly and lead to government-run health care to more candid conversations about the affordability of health insurance for typical Americans and the real impact of an inefficient and underperforming health-care system on the U.S. economy.
Adjusting Return Horizon According to Trade Activity with Application to Return Autocorrelation

We adopt a new approach to study individual stock returns' predictability from prior returns, and show that over short-horizons (daily to weekly), individual stock returns exhibit continuation for moderate prior returns, that is, those in the -1% to 1% interval, and reversal for extreme prior returns, that is, those outside the interval. Moreover, The region of continuation encompasses the central 40 percent of the distribution. We explain our findings with the interaction of the two effects, information asymmetry and inventory costs, influencing price formation process. We study the nonlinear pattern in the cross-section of stocks with different characteristics, such as idiosyncratic volatility, size, and liquidity, and find that only part of the pattern is due to the cross-sectional heterogeneity. More importantly, we show that the nonlinear pattern is invariant in the cross-section of stock returns with different trade activity. The critical requirement for this invariance is to compute returns over horizons that incorporate the variations in (and is inversely related to) stocks' trade activity.
Credit Spreads und ihre Determinanten in Deutschland

Fur Unternehmen kann die Analyse von Credit Spreads, d.h. der Differenz zwischen den Renditen von Unternehmensanleihen und laufzeitaquivalenten risikolosen Anlagen, nutzliche Informationen erbringen, da sich Veranderungen im Credit Spread auf ihre Finanzierungskonditionen auswirkt. Prof. Dr. Horst Rottmann, Fachhochschule Amberg-Weiden und Forschungsprofessor am ifo Institut, und Prof. Dr. Franz Seitz, Fachhochschule Amberg-Weiden, untersuchen hier die Bestimmungsfaktoren der Credit Spreads fur nicht-finanzielle DAX-Unternehmen. Sie zeigen, dass neben den traditionellen Determinanten Rating und Restlaufzeit auch die Volatilitat und der risikolose Zinssatz eine wichtige Rolle bei der Erklarung von Spreads spielen.
Fibrates and niacin: is there a place for them in clinical practice?

Introduction: Niacin and fibrates are lipid-lowering drugs with actions to raise high density lipoprotein cholesterol (HDL-C), reduce triglycerides and non-HDL-C but with modest (if any) effect in reducing low density lipoprotein cholesterol (LDL-C). Niacin and fibrates have an evidence base from monotherapy trials starting from the Coronary Drug Project and more recently in combination therapy with statins. Areas covered: This article reviews their place as lipid-lowering drugs in the light of recent trials adding them to baseline statin therapy. Literature searches were conducted using the terms ‘cardiovascular disease (CVD)’ and either ‘niacin’ or ‘fibrate’ (including individual compounds), concentrating on evidence from randomised controlled trials, meta-analyses and recent guideline statements. Expert opinion: Statins are the first choice for treating increased CVD risk due to raised non-HDL-C. Though raised triglycerides and reduced HDL-C, contribute to risk statins, are effective in reducing CVD events in all patients. Extra therapies add little in current trials. Niacin will have little role in the treatment of hyperlipidaemia. Other options in development to lower LDL-C further, raise HDL-C or reduce lipoprotein(a), may have the potential to replace niacin in particular. In contrast, fibrates may continue to have a role in the treatment of extreme hypertriglyceridaemia and in mixed hyperlipidaemia as they reduce CVD events and have additional benefits in improving diabetes and microvascular outcomes.
Tests of exogeneity for long-run PPP and uncovered interest parity in an identified model of the United Kingdom effective exchange rate

Abstract: This article presents results for a model of the UK effective exchange rate over the period 1973q3 to 1991q4. A key featur e is the identification of l ong-run behaviour and the role of tests of exogeneity in this context. As a consequence of the identification process, the article tests for Purchasing Power Parity (PPP) and Interest Rate Parity (IRP) in the long-run, and defines a procedure for identifying long-run behaviour using an ordering based on the exogeneity status of variables. The order condition necessary for identification is augmented by conditions sufficient for global identification. The paper tests the over-identifying restrictions and for identifiability. The minimal set of cointegrating vectors includes a Fisher effect. Keywords: Cointegration, Exogeneity, Fisher Effect, Identification, Identifiability, Interest Rate Parity, Purchasing Power Parity. JEL : C32. * An earlier version of this paper was presented at ESEM96, we would like to thank David Barr, Lucio Sarno, Ariane Szafarz, Renato Flores and Bent Neilson for their discussion of some of the ideas presented in this paper. Addr ess correspondence to Dr J Hunte r, Department of Economics, Brunel University, Uxbridge, Middlesex, UB8 3PH, UK.
Writer Identification Using a Statistical and Model Based Approach

The state-of-the-art writer identification systems use a variety of different features and techniques in order to identify the writer of the handwritten text. In this paper several statistical and model based features are presented. Specifically, an improvement of a statistical feature, the edge hinge distribution, is attempted. Furthermore, the combination of this feature with a model-based feature is explored, that is based on a codebook of graphemes. For the evaluation, the Fire maker DB was used, which consists of 250 writers, including 4 pages per writer. The best result for the statistical suggested approach, the skeleton hinge distribution, achieved accuracy of 90.8%, while the combination of this method with the codebook of graphemes reached 96%.
Screening and Rational Design of Hepatitis C Virus Entry Inhibitory Peptides Derived from GB Virus A NS5A

ABSTRACT Chronic infection by hepatitis C virus (HCV) is a cause of the global burden of liver diseases. HCV entry into hepatocytes is a complicated and multistep process that represents a promising target for antiviral intervention. The recently reported amphipathic α-helical virucidal peptide (C5A) from the HCV NS5A protein suggests a new category of antiviral drug candidates. In this study, to identify C5A-like HCV inhibitors, synthetic peptides derived from the C5A-corresponding NS5 protein region of selected Flaviviridae viruses were evaluated for their anti-HCV activities. A peptide from GB virus A (GBV-A), but not other flaviviruses, demonstrated an inhibitory effect on HCV infection. Through a series of sequence optimizations and modifications of the peptide helicity and hydrophobicity, we obtained a peptide designated GBVA10-9 with highly potent anti-HCV activity. GBVA10-9 suppressed infection with both cell culture-derived and pseudotyped HCV in vitro, and the 50% cell culture inhibitory concentration ranged from 20 nM to 160 nM, depending on the genotypic origin of the envelope proteins. GBVA10-9 had no detectable effects on either HCV attachment to Huh7.5. 1 cells or viral RNA replication. No virucidal activity was found with GBVA10-9, suggesting an action mechanism distinct from that of C5A. The inhibitory effect of GBVA10-9 appeared to occur at the postbinding step during viral entry. Taken together, the results with GBVA10-9 demonstrated a potent activity for blocking HCV entry that might be used in combination with other antivirals directly targeting virus-encoded enzymes. Furthermore, GBVA10-9 also provides a novel tool to dissect the detailed mechanisms of HCV entry.
Allografting ovarian cortex between genetically non-identical sisters: authors' correction (Donnez et al.).

Sir, This letter concerns two manuscripts published in Human Reproduction: ‘Restoration of ovarian function after allografting of ovarian cortex between genetically non-identical sisters’ and ‘Livebirth after allografting of ovarian cortex between genetically non-identical sisters’. We wish to draw to the attention of the journal’s readership, two points that have recently come to light. Firstly, in the latter paper, one of the three cases (Patient II) had ovarian failure with elevated FSH levels after chemotherapy at 15 years of age. In this paper, we reported when she received an ovarian transplant at age 32, the ovarian biopsy did not reveal the presence of any follicles in five serial sections of a fragment measuring 1 mm × 1.5 mm. It has now been shown that another fragment of the same ovary sent to a different lab did contain some primordial follicles (PFs). Recent immunohistochemical studies revealed that these PFs were non-functional (the oocyte being +++ positive for Caspase 3 and the granulosa cells being negative for Ki67). This presence of ovarian follicles does not change the clinical diagnosis, the indications for surgery or the cause of the restoration of ovarian activity. Since the birth, the sister donor has been identified as one genetic parent of the child. The following points support these conclusions.
In vitro thermal therapy of AT-1 Dunning prostate tumours

To advance the utility of prostate thermal therapy, this study investigated the thermal thresholds (temperature-time) for prostate tissue destructionin vitro. The AT-1 Dunning prostate tumour model was chosen for the study. Three hundred micron thick sections were subjected to controlled temperature-time heating, which ranged from low (40°C, 15 min) to high thermal exposures (70°C, 2 min) (n = 6). After subsequent tissue culture at 37°C, the sections were evaluated for tissue injury at 3, 24 and 72 h by two independent methods: histology and dye uptake. A graded increase in injury was identified between the low and high thermal exposures. Maximum histologic injury occurred above 70°C, 1 min with >95% of the tissue area undergoing significant cell injury and coagulative necrosis. The control and 40°C, 15 min sections showed histologic evidence of apoptosis following 24 and 72 h in culture. Similar signs of apoptosis were minimal or absent at higher thermal histories. Vital-dye uptake quantitatively confirmed complete cell death after 70°C, 2 min. Using the dye data, Arrhenius analysis showed an apparent breakpoint at 50°C, with activation energies of 135.8 kcal/mole below and 4.7 kcal/mole above the threshold after 3 h in culture. These results can be used as a conservative benchmark for thermal injury in the cancerous prostate. Further characterization of the response to thermal therapy in an animal model and in human tissues will be important in establishing the efficacy of the procedure
Communal nesting under climate change: fitness consequences of higher incubation temperatures for a nocturnal lizard

Communal nesting lizards may be vulnerable to climate warming, particularly if air temperatures regulate nest temperatures. In southeastern Australia, velvet geckos Oedura lesueurii lay eggs communally inside rock crevices. We investigated whether increases in air temperatures could elevate nest temperatures, and if so, how this could influence hatching phenotypes, survival, and population dynamics. In natural nests, maximum daily air temperature influenced mean and maximum daily nest temperatures, implying that nest temperatures will increase under climate warming. To determine whether hotter nests influence hatchling phenotypes, we incubated eggs under two fluctuating temperature regimes to mimic current ‘cold’ nests (mean = 23.2 °C, range 10–33 °C) and future ‘hot’ nests (27.0 °C, 14–37 °C). ‘Hot’ incubation temperatures produced smaller hatchlings than did cold temperature incubation. We released individually marked hatchlings into the wild in 2014 and 2015, and monitored their survival over 10 months. In 2014 and 2015, hot‐incubated hatchlings had higher annual mortality (99%, 97%) than cold‐incubated (11%, 58%) or wild‐born hatchlings (78%, 22%). To determine future trajectories of velvet gecko populations under climate warming, we ran population viability analyses in Vortex and varied annual rates of hatchling mortality within the range 78– 96%. Hatchling mortality strongly influenced the probability of extinction and the mean time to extinction. When hatchling mortality was >86%, populations had a higher probability of extinction (PE: range 0.52– 1.0) with mean times to extinction of 18–44 years. Whether future changes in hatchling survival translate into reduced population viability will depend on the ability of females to modify their nest‐site choices. Over the period 1992–2015, females used the same communal nests annually, suggesting that there may be little plasticity in maternal nest‐site selection. The impacts of climate change may therefore be especially severe on communal nesting species, particularly if such species occupy thermally challenging environments.
Purification and characterization of benzoate-coenzyme A ligase and 2-aminobenzoate-coenzyme A ligases from a denitrifying Pseudomonas sp

The enzymes catalyzing the formation of coenzyme A (CoA) thioesters of benzoate and 2-aminobenzoate were studied in a denitrifying Pseudomonas sp. anaerobically grown with these aromatic acids and nitrate as sole carbon and energy sources. Three different rather specific aromatic acyl-CoA ligases, E1, E2, and E3, were found which catalyze the formation of CoA thioesters of benzoate, fluorobenzoates, and 2-aminobenzoate. ATP is cleaved into AMP and pyrophosphate. The enzymes were purified, their N-terminal amino acid sequences were determined, and their catalytic and molecular properties were studied. Cells anaerobically grown on benzoate and nitrate contain one CoA ligase (AMP forming) for benzoic acid (E1). It is a homodimer of Mr 120,000 which prefers benzoate as a substrate but shows some activity also with 2-aminobenzoate and fluorobenzoates, although with lower Km. Cells anaerobically grown on 2-aminobenzoate and nitrate contain three different CoA ligases for aromatic acids. The first one is identical with benzoate-CoA ligase (E1). The second enzyme is a 2-aminobenzoate-CoA ligase (E2). It is a monomer of Mr 60,000 which prefers 2-aminobenzoate but also activates benzoate, fluorobenzoates and, less effectively, 2-methylbenzoate, with lower affinities to the latter substrates. The enzymes E1 and E2 have similar activity levels; a third minor CoA ligase activity is due to a different 2-aminobenzoate-CoA ligase. The enzyme (E3) is a monomer of Mr, 65,000 which 2-aminobenzoate pathway (U. Altenschmidt, C. Eckerskorn, and G. Fuchs, Eur. J. Biochem. 194:647-653, 1990); apparently, it is not completely repressed under anaerobic conditions and therefore also is induced to a small extent by 2-aminobenzoate under anaerobic growth conditions.
Intradiscal electrothermal therapy (IDET) for treatment of chronic lumbar discogenic pain: a minimum 2-year clinical outcome study.

OBJECTIVE To determine the long-term efficacy of IDET in the treatment of chronic lumbar discogenic pain. DESIGN Prospective case series clinical outcome study. METHODS IDET was performed on 62 consecutive patients with chronic discogenic pain of greater than 6 months duration and consecutively enrolled in a non-randomized prospective case series outcome study. Outcome measures included visual numeric pain scale (VNS) for low back (LB) and lower extremity (LE) pain, Roland-Morris disability scale (RM), and North American Spine Society (NASS) patient satisfaction index. Outcome success was defined as a change of more than 2 points on VNS and RM as well as a positive NASS satisfaction response. Data were collected at baseline and post-procedure at 1, 3, and 6 months and then annually for up to 4 years. RESULTS Fifty-one out of 62 patients (82%) were available for a minimum of 2-year follow-up. Average age was 41.4 years; average symptom duration was 46 months; and average follow-up was 34 months. Overall, there was statistically significant improvement in LB-VNS, RM, and LE pain scores of 3.2, 6.6, and 2.3 (p<0.001), respectively. Twenty-seven of 51 (53%) patients demonstrated clinically significant VNS and RM improvements of greater than 2. On NASS index, 63% (32/51) responded positively. Neither the number of disc levels treated nor the insurance status of patients made any difference in outcome. CONCLUSION IDET appears to be an effective treatment for chronic lumbar discogenic pain in a well-selected group of patients with favorable long-term outcome.
Effects of moderate static magnetic fields on the voltage-gated sodium and calcium channel currents in trigeminal ganglion neurons

Abstract Aim: To study the effects of static magnetic fields (SMF) on the electrophysiological properties of voltage-gated sodium and calcium channels on trigeminal ganglion (TRG) neurons. Methods: Acutely dissociated TRG neurons of neonatal SD rats were exposed to 125-mT and 12.5-mT SMF in exposure devices and whole-cell patch-clamp recordings were carried out to observe the changes of voltage-gated sodium channels (VGSC) and calcium channels (VGCC) currents, while laser scanning confocal microscopy was used to detect intracellular free Ca2+ concentration in TRG neurons, respectively. Results: (1) No obvious change of current–voltage (I–V) relationship and the peak current densities of VGSC and VGCC currents were found when TRG neurons were exposed to 125-mT and 12.5-mT SMF. However, the activation threshold, inactivation threshold and velocity of the channel currents above were significantly altered by 125-mT and 12.5-mT SMF. (2) The fluctuation of intracellular free Ca2+ concentration within TRG neurons were slowed by 125-mT and 12.5-mT SMF. When SMF was removed, the Ca2+ concentration level showed partial recovery in the TRG neurons previously exposed by 125-mT SMF, while there was a full recovery found in 12.5-mT-SMF-exposed neurons. Conclusions: Moderate-intensity SMF could affect the electrophysiological characteristics of VGCS and VGCC by altering their activation and inactivation threshold and velocity. The fluctuations of intracellular free Ca2+ caused by SMF exposure were not permanent in TRG neurons.
Unions, Safety Committees and Workplace Injuries

This paper exploits the Workplace Industrial Relations Survey from 1990 (WIRS3) to examine the determinants of workplace injuries for a sample of manufacturing establishments in the UK. A key focus of this paper is an assessment of the role played by union-appointed safety representatives and joint health and safety consultative committees in reducing the frequency of workplace accidents. We find that joint consultative committees, with all employee representatives appointed by unions, significantly reduce workplace injuries relative to those establishments where the management alone determine health and safety arrangements. However, an important role is also found for those joint consultative commitees where no employee representatives are appointed by unions.
Combining multiple similarity metrics for corner matching

Corner matching is an important operation in digital image processing and computer vision where it is used for a range of applications including stereo vision and image registration. A number of corner similarity metrics have been developed to facilitate matching, however, any individual metric has a limited effectiveness depending on the content of images to be registered and the different types of distortions that may be present. This paper explores combining corner similarity metrics to produce more effective measures for corner matching. In particular the combination of two similarity metrics is investigated using experiments on a number of images exhibiting different types of transformations and distortions. The results suggest that a linear combination of different similarity metrics may produce more accurate and robust assessments of corner similarity.
Design of low distortion high voltage coaxial-type transmission line for quasi-square wave nano-pulse with several hundred kilovolts in vacuum

A high voltage quasi-square wave pulse with an amplitude of above 500 kV is successfully transmitted using a coaxial-type matched transmission line in vacuum. To enhance the surface flashover voltage and reduce the distortion of pulse shape, the matched symmetric coaxial solid dielectric configuration with the positive angle of 45° and the socket-type field shaper are proposed and applied to the coaxial transmission line. This type of transmission line provides not only the high capability of hold off voltage but also good pulse shape corresponding to the input pulse. The transmission of quasi-square wave short pulse with an amplitude of above 500 kV, a pulse duration of above 20 ns, and a rise time of 20-30 ns without the surface flashover and the pulse distortion phenomena is experimentally and numerically presented.
Are consultants blowing smoke? An empirical test of the impact of menu layout on item sales

For years, menu design consultants have asserted that the layout of the items on menus is asociated with item sales. To date, no scientific studies exist either supporting or refuting this assertion. In order to test this relationship we conducted a field experiment in which we tracked the pre‐ and post‐treatment sales of items on a three‐page menu over a period of four months. The treatment consisted of switching the contents of pages 2 and 3 of the menu. The data revealed no significant differences in item sales from time 1 to time 2. Implications for restaurant managers are discussed.