Miracle-dz/UniFAR-FTUs huggingface dataset:
Transient Inhibition of CD28 and CD40 Ligand Interactions Prolongs Adenovirus-Mediated Transgene Expression in the Lung and Facilitates Expression after Secondary Vector Administration

ABSTRACT Recombinant adenovirus vectors have been used to transfer genes to the lungs in animal models, but the extent and duration of primary transgene expression and the ability to achieve expression after repeated vector administration have been limited by the development of antigen-specific immunity to the vector and, in some cases, to vector-transduced foreign proteins. To determine if focused modulation of the immune response could overcome some of these limitations, costimulatory interactions between T cells and B cells/antigen-presenting cells were transiently blocked around the time of vector administration. Systemic treatment at the time of primary-vector administration with a monoclonal antibody (MR1) against murine CD40 ligand, combined with recombinant murine CTLA4Ig and intratracheal coadministration of an adenovirus vector transducing the expression of murine CTLA4Ig, prolonged adenovirus-transduced β-galactosidase expression in the airways for up to 28 days and resulted in persistent alveolar expression for >90 days (the duration of the experiment). Consistent with these results, this treatment regimen reduced local inflammation and markedly reduced the T-cell and T-cell-dependent antibody response to the vector. A secondary adenovirus vector, administered >90 days after the last systemic dose of MR1 and muCTLA4Ig, resulted in alkaline phosphatase expression at levels comparable to those seen with primary-vector administration. Expression of the secondary transgene persisted in the alveoli (but not in the airways) for up to 24 days (the longest period of observation) at levels similar to those observed on days 3 to 4. These results indicate that transient inhibition of costimulatory molecule interactions substantially enhanced gene transfer to the alveoli but was much less effective in the airways. This suggests that there are differences in the efficiency or nature of mechanisms limiting transgene expression in the airways and in the alveoli.
Impact of preoperative anemia on cardiac surgery in octogenarians.

OBJECTIVES Preoperative anemia has been related with adverse outcomes in elective valve replacement and CABG surgery. Impact of preoperative anemia on outcome in octogenarians submitted to cardiopulmonary bypass (CPB) has not yet been precisely described. METHODS We analyzed association between preoperative hemoglobin level, minimum intraoperative and immediate postoperative hematocrit (HCT), and other co-morbidities and occurrence of adverse outcomes in 227 octogenarians who underwent cardiac surgery. RESULTS Frequency of preoperative anemia was 41.9% (40.4% in male and 43.5% in female patients). Postoperative mortality was 13.2% (9% in non-anemic patients vs. 18.9% in anemic). 44.5% of patients suffered at least one postoperative adverse outcome (43.1% non-anemic vs. 46.3% anemic). In multivariate analysis (after adjusting independent preoperative risk factors for operative mortality and EuroSCORE) preoperative creatinine level [odds ratio (OR), 2.29; 95% confidence interval (CI), 1.06-4.98; P=0.035], immediate postoperative HCT <24% (OR, 2.78; 95% CI, 1.04-7.38; P=0.039), perioperative red blood cell (RBC) transfusion (OR, 1.58; 95% CI, 1.24-2.00; P=0.0001), peripheral vascular disease (OR, 4.92; 95% CI, 1.45-16.69; P=0.012) and urgent surgery (OR, 10.57; 95% CI, 2.54-43.91; P=0.0001) were identified as independent predictors for in-hospital mortality. CONCLUSIONS Mortality and adverse postoperative outcome increase in anemic octogenarians undergoing cardiac surgery. Although mortality is directly related to immediate postoperative anemia, adverse outcomes mainly depend on associated co-morbidities.
Approaches to pornography : a consideration of harm beyond the moralist/civil libertarian dichotomy

The "problem" of pornograph1 is analyzed here through an examination of published literature and Canadian case law and legislation. Feminist analyses of the harms associated with pornography and corresponding feminist remedies are presented as attractive alternatives to traditional moralist and civil libertarian approaches. The history of obscenity legislation is traced from its earliest focus on heresy and sedition to the law's contemporary consideration of sexual materials. The relationships between federal obscenity restrictions and provincial and municipal Pornography controls are outlined. The "community standards" concept is discussed in terms of its central role in the circumscription of pornography in Canada. The controversy Surrounding its ambiguous nature and arbitrary application is profiled. The validity of the standard of intolerance as a basis for criminal law is questioned. Feminist analyses of the existence and function of Pornography address the unequal power relationships within a patriarchal society. Anti-pornography and anti-censorship views "re contrasted to illustrate the diversity of approaches which coexist within the feminist camp. The incoherent state of the "pornography effects" literature militates against the possibility of an empirical answer to the harm question.
Role of von Willebrand factor in vascular disease

Summary Plasma levels of von Willebrand factor (VWF) are increased in patients with cardiovascular risk factors. Various studies aimed to elucidate the relation of VWF with thrombo - embolic cardiovascular events, ischaemic stroke as well as with peripheral arterial occlusive disease. In the general population, there is only a weak association between VWF levels and future cardiovascular events or stroke. In contrast, VWF levels are predictive in patients with documented vascular disease. Those patients with increased VWF suffer a higher incidence of major adverse cardiac events including death. The extent of the VWF release and its levels independently predict clinical outcome in patients with acute coronary syndromes. Elevated VWF levels have also been observed in patients with atrial fibrillation compared to controls and predict outcome. This may at least in part be attributable to the association of VWF with underlying cardiovascular risk factors. Hence, VWF correlates with Framingham and CHADS stroke risk stratification score and can be used as a marker in patients with AF. However, VWF is not only a predictor; it also plays a crucial role in thrombogenesis. This fact has made VWF a promising target for research into new antiplatelet therapies that specifically inhibit VWF. This review focuses on the role of VWF in ACS, ischaemic stroke and peripheral arterial disease and the relevance of therapeutic interventions targeting VWF for ACS patients.
Crystal Structure of the Dimeric C-terminal Domain of TonB Reveals a Novel Fold*

The TonB-dependent complex of Gram-negative bacteria couples the inner membrane proton motive force to the active transport of iron·siderophore and vitamin B12 across the outer membrane. The structural basis of that process has not been described so far in full detail. The crystal structure of the C-terminal domain of TonB fromEscherichia coli has now been solved by multiwavelength anomalous diffraction and refined at 1.55-Å resolution, providing the first evidence that this region of TonB (residues 164–239) dimerizes. Moreover, the structure shows a novel architecture that has no structural homologs among any known proteins. The dimer of the C-terminal domain of TonB is cylinder-shaped with a length of 65 Å and a diameter of 25 Å. Each monomer contains three β strands and a single α helix. The two monomers are intertwined with each other, and all six β-strands of the dimer make a large antiparallel β-sheet. We propose a plausible model of binding of TonB to FhuA and FepA, two TonB-dependent outer-membrane receptors.
The Effect of AlloDerm Envelopes on Periprosthetic Capsule Formation with and without Radiation

Background: The pathobiology of radiation-induced periprosthetic capsular formation and factors that may ameliorate its development have not been fully elucidated. The authors hypothesized that AlloDerm would diminish radiation-induced capsular formation. Methods: Two 5-ml implants were placed submuscularly in the backs of 41 rats. The right implant was wrapped with AlloDerm and the left remained bare. After 48 hours, 20 animals underwent irradiation to each implant, and 21 animals underwent no further treatment and served as controls. After 3 and 12 weeks, the capsules were harvested and submitted for tensile strength and histologic examination. Intraprosthetic pressures were measured in each implant at the time of surgery and when the animals were killed. Results: The intraprosthetic pressure decrease was uniform among all groups at 3 and 12 weeks. Between 3 and 12 weeks, capsular tensile strength increased in nonirradiated bare implants. There was considerable invasion of nonirradiated AlloDerm by inflammatory infiltrates at 3 weeks, and AlloDerm thickness decreased over time. Cellular invasion of AlloDerm was decreased with irradiation at both time points. Capsular tensile strength and thickness of the irradiated bare and AlloDerm capsules did not change between 3 and 12 weeks. Radiation increased inflammation of bare capsules at 12 weeks, but it was significantly reduced in irradiated AlloDerm capsules. The majority of irradiated bare capsules developed pseudoepithelium, whereas AlloDerm protected capsules from this transformation. Conclusion: AlloDerm decreases radiation-related inflammation and delays or diminishes pseudoepithelium formation and thus may slow progression of capsular formation, fibrosis, and contraction.
Role of podocyte slit diaphragm as a filtration barrier (Review Article)

SUMMARY: Although the role of glomerular basement membrane has been emphasised as the barrier for retaining plasma proteins in the past three decades, some recent studies have demonstrated that the slit diaphragm of the glomerular epithelial cell (podocyte) is the structure likely to be the barrier in the glomerular capillary wall. Nephrin and podocin were identified as gene products mutated in Finnish‐type congenital nephrotic syndrome and autosomal recessive steroid‐resistant nephrotic syndrome, respectively. Nephrin s located at the outer leaflet of plasma membranes of the slit diaphragm. Podocin is reported to have an interaction with nephrin. The anti‐nephrin antibody is capable of inducing massive proteinuria, which indicates that nephrin is a key functional molecule in the slit diaphragm. The expression of nephrin and podocin was reduced in glomeruli of minimal change nephrotic syndrome, which suggested that the altered expression of these molecules contributes to the development of proteinuria also in acquired diseases. Some recent studies demonstrated that CD2‐associated protein (CD2AP) is also a functional molecule in the slit diaphragm, and its expression is altered in membranous nephropathy. These observations suggested that alteration of the molecular arrangement in the slit diaphragm is involved in the development of proteinuria in several kinds of glomerular diseases.
Finite element simulations of dynamic shear rupture experiments and dynamic path selection along kinked and branched faults

We analyze the nucleation and propagation of shear cracks along nonplanar, kinked, and branched fault paths corresponding to the configurations used in recent laboratory fracture studies by Rousseau and Rosakis (2003, 2009). The aim is to reproduce numerically those shear rupture experiments and from that provide an insight into processes which are active when a crack, initially propagating in mode II along a straight path, interacts with a bend in the fault or a branching junction. The experiments involved impact loading of thin Homalite-100 (a photoelastic polymer) plates, which had been cut along bent or branched paths and weakly glued back together everywhere except along a starter notch near the impact site. Strain gage recordings and high-speed photography of isochromatic lines provided characterization of the transient deformation fields associated with the impact and fracture propagation. We found that dynamic explicit 2-D plane-stress finite element analyses with a simple linear slip-weakening description of cohesive and frictional strength of the bonded interfaces can reproduce the qualitative rupture behavior past the bend and branch junctions in most cases and reproduce the principal features revealed by the photographs of dynamic isochromatic line patterns. The presence of a kink or branch can cause an abrupt change in rupture propagation velocity. Additionally, the finite element results allow comparison between total slip accumulated along the main and inclined fault segments. We found that slip along inclined faults can be substantially less than slip along the main fault, and the amount depends on the branch angle and kink or branch configuration.
An Empirical Study of the Scalability of Performance Analysis Tools in the Cloud

Calculation of performance metrics such as steadystate probabilities and response time distributions in large Markov and semi-Markov models can be accomplished using parallel implementations of well-known numerical techniques. In the past these implementations have usually been run on dedicated computational clusters and networks of workstations, but the recent rise of cloud computing offers an alternative environment for executing such applications. It is important, however, to understand what effect moving to a cloud-based infrastructure will have on the performance of the analysis tools themselves. In this paper we investigate he scalability of two existing parallel performance analysistools (one based on Laplace transform inversion and the other on uniformisation) on Amazon’s Elastic Compute Cloud, and compare this with their performance on traditional dedicated hardware. This provides insight into whether such tools can be used effectively in a cloud environment, and suggests factors which must be borne in mind when designing nextgeneration performance tools specifically for the cloud. Keywords-Cloud computing; Performance analysis; Parallel computing; Empirical study;
QCD Sum Rules for Exclusive Decays of Heavy Mesons

Applications of QCD sum rules to exclusive decays of heavy mesons are reviewed. In detail, we discuss the calculations of the B and $D$ decay constants, the heavy-to-light form factors $f^+(p^2)$ and $f^0(p^2)$, and the strong couplings $g_{B^*B\pi}$ and $g_{D^*D\pi}$. Predictions are presented for the semileptonic weak decays $B \to \pi \bar{l} \nu_l$ and $B \to \rho \bar{l} \nu_l$, and used to extract $V_{ub}$ from the measured decay widths. Results are also shown on $D \to \pi \bar{l} \nu_l$ and $D^* \to D \pi$. Furthermore, we reconsider the factorization hypothesis in nonleptonic two-body decays, and describe a sum rule estimate of the nonfactorizable contribution to the amplitude of $B \to J/\psi K$.
The self-adaptive Pareto differential evolution algorithm

The Pareto differential evolution (PDE) algorithm was introduced and showed competitive results. The behavior of PDE, as in many other evolutionary multiobjective optimization (EMO) methods, varies according to the crossover and mutation rates. In this paper, we present a new version of PDE with self-adaptive crossover and mutation. We call the new version self-adaptive Pareto differential evolution (SPDE). The emphasis of this paper is to analyze the dynamics and behavior of SPDE. The experiments also show that the algorithm is very competitive with other EMO algorithms.
Leadership, Decision Making and Performance of Sales Managers: A Multi-Level Approach

What distinguishes high performing sales managers from those whose performance is lower? Based on data collected from first-level sales managers, their superiors, and over 400 sales reps reporting to them, high performing managers exhibit more transactional and transformational leadership. Low performing managers are more avoidant and less rational in their decision making styles. Reps supervised by high performing managers exhibit less role stress, more satisfaction, and greater loyalty.
The Economic Value of Mangroves: A Meta-Analysis

This paper presents a synthesis of the mangrove ecosystem valuation literature through a meta-regression analysis. The main contribution of this study is that it is the first meta-analysis focusing solely on mangrove forests, whereas previous studies have included different types of wetlands. The number of studies included in the regression analysis is 44 for a total of 145 observations. We include several regressions with the objective of addressing outliers in the data as well as the possible correlations between observations of the same study. We also investigate possible interaction effects between type of service and GDP per capita. Our findings indicate that mangroves exhibit decreasing returns to scale, that GDP per capita has a positive effect on mangrove values and that using the replacement cost and contingent valuation methods produce higher estimates than do other methods. We also find that there are statistically significant interaction effects that influence the data. Finally, the results indicate that employing weighted regressions provide a better fit than others. However, in terms of forecast performance we find that all the estimated models performed similarly and were not able to conclude decisively that one outperforms the other.
High-intensity intermittent running and field hockey skill performance in the heat

Nine well-trained, unacclimatized female hockey players performed the Loughborough Intermittent Shuttle Test (LIST) interspersed with three field hockey skill tests in hot (30°C, 38% relative humidity) and moderate (19°C, 51% relative humidity) environmental conditions. Field hockey skill performance declined in both the hot and moderate conditions following 30 and 60 min of the LIST compared with pre-LIST values (P < 0.01). This decrement in performance was compounded in the hot environment with a 6% poorer performance in the heat recorded for the second skill test at 30 min (P < 0.05, hot 101.7 ± 3.6 vs moderate 95.7 ± 2.9 s; mean ± s x). However, no difference was found in the decision-making element of the skill test. Fifteen-metre sprint times were slower in the hot condition (P < 0.01). In the hot environment, rectal temperature (P < 0.01), perceived exertion (P < 0.05), perceived thirst (P < 0.01), blood glucose concentration (P < 0.05) and serum aldosterone concentration (P < 0.01) were higher. Estimated mean ( ± s x) sweat rate was higher in the hot trial (1.27 ± 0.10 l · h−1) than in the moderate trial (1.05 ± 0.12 l · h−1) (P < 0.05). Body mass was well maintained in both trials. No differences in serum cortisol, blood lactate, plasma volume or plasma ammonia concentrations were found. These results demonstrate that field hockey skill performance is decreased following intermittent high-intensity shuttle running and that this decrease is greater in hot environmental conditions. The exact mechanism for this decrement in performance remains to be elucidated, but is unlikely to be due to low glycogen concentration or dehydration.
Factored MLLR Adaptation Algorithm for HMM-based Expressive TTS

One of the most popular approaches to parameter adaptation in hidden Markov model (HMM) based systems is the maximum likelihood linear regression (MLLR) technique. In our previous work, we proposed factored MLLR (FMLLR) where an MLLR parameter is defined as a function of a control parameter vector. We presented a method to train the FMLLR parameters based on a general framework of the expectation-maximization (EM) algorithm. To show the effectiveness, we applied the FMLLR to adapt the spectral envelope feature of the reading-style speech to those of the singing voice. In this paper, we apply the FMLLR to the HMM-based expressive speech synthesis task and compare its performance with conventional approaches. In a series of experimental results, the FMLLR shows better performance than conventional methods.
Mutagen sensitivity as a susceptibility marker for human hepatocellular carcinoma.

Although the pathogenesis of hepatocellular carcinoma (HCC) remains poorly understood, hepatitis B virus and dietary aflatoxin exposures are established etiological factors for this disease. We conducted a pilot study of 28 patients with HCC and 110 healthy controls matched for age, sex, and ethnicity to determine whether constitutional genetic instability, based on the quantification of mutagen-induced chromatid breaks in cultured lymphocytes, modifies an individual's risk of HCC development. The mean numbers of bleomycin-induced breaks per cell for cases and controls were 0.92 and 0.55, respectively (P < 0.0001). For benzo(a)pyrene diol epoxide (BPDE) sensitivity, the values were 0.90 for cases and 0.46 for controls (P < 0.0001). Nearly 68% of the cases but only 27% of the controls exhibited bleomycin sensitivity (i.e., had > or = 0.68 breaks per cell). Eighty % of the case group but only 22% of the control group exhibited BPDE sensitivity (i.e., had > or = 0.58 breaks per cell). On multivariate analyses, both bleomycin sensitivity and BPDE sensitivity were associated with significantly elevated risks for HCC, with odds ratios (95% confidence intervals) of 5.63 (2.30, 13.81) and 14.13 (3.52, 56.68), respectively. For individuals who were sensitive to both assays, the risk was 35.88. A synergistic interaction between the bleomycin sensitivity and BPDE sensitivity in HCC risk was suggested. These preliminary findings suggest that differences in host factors related to the predisposition to chromosome breakage, the capacity for DNA repair, or both may be involved in HCC development by influencing the predisposition of hepatitis B virus integration into human DNA or that the carcinogens induced DNA damage susceptibility. A larger study is needed to confirm these intriguing results.
Elemental Profiles of Whisk(e)y Allow Differentiation by Type and Region

Elemental fingerprints could provide an analytical approach to product differentiation and authentication, and have been used in the past for various distilled spirits, including brandy, gin, bourbon and tequila. However, a comparison of elemental differences between different whisk(e)y types, such as Bourbon and Scotch, is still missing. In this study we compare the elemental fingerprints of 68 commercial whiskies for differentiation by type (Bourbon, Tennessee, Scotch, Irish, Japanese) and region. Concentrations from sub-μg/L to mid-mg/L of 53 different elements were determined with inductively-coupled plasma—mass spectrometry (ICP-MS) and microwave plasma—atomic emission spectroscopy (MP-AES), and used in subsequent statistical analyses. Significant differences in several elements were found for type, and allowed a classification according to whisk(e)y type. Elemental differences were also found for different production areas within Scotland, thus, providing further evidence that Scotch whiskies could be differentiated by elemental analysis. Major sources of elemental differences seem to be processing equipment (Cu, Fe, Ni, Cd, Sn, Mo, V) and raw materials, such as water (Ca, Mg, Fe, Mn, Sr).
Asymptotic and Bayesian Confidence Intervals for Sharpe Style Weights

Sharpe style regression has become a widespread analytic tool in the financial community. The style regression allows one to investigate such interesting issues as style composition, style sensitivity, and style change over time. All previous methods to obtain the distribution and confidence intervals of the style coefficients are statistically valid only in the special case in which none of the true style weights are zero or one. In practice it is quite plausible to have zero or one for the values of some style weights. In this paper we apply new results of Andrews (1997a, 1999) and develop a comparable Bayesian method to obtain statistically valid distributions and confidence intervals regardless of the true values of style weights.