Miracle-dz/UniFAR-FTUs huggingface dataset:
Rabies Virus Ocular Disease: T-Cell-Dependent Protection Is under the Control of Signaling by the p55 Tumor Necrosis Factor Alpha Receptor, p55TNFR

ABSTRACT Following brain infection, the Challenge Virus Standard strain of rabies virus infects the retina. Rabies virus ocular infection induces the infiltration of neutrophils and predominantly T cells into the eye. The role of tumor necrosis factor alpha (TNF-α)-lymphotoxin signaling in the control of rabies virus ocular infection and inflammatory cell infiltration was assessed using mice lacking the p55 TNF-α receptor (p55TNFR−/− mice). The incidence of ocular disease and the intensity of retinal infection were greater in p55TNFR−/− mice than in C57BL/6 mice: the aggravation correlated with less neutrophil and T-cell infiltration. This indicates that cellular infiltration is under the control of the p55 TNF-α receptor and suggests that inflammatory cells may protect the eye against rabies virus ocular infection. The role of T cells following rabies virus ocular disease was assessed by comparison of rabies virus infection in nude mice with their normal counterparts. Indeed, the incidence and severity of the rabies virus ocular disease were higher in athymic nude mice than in BALB/c mice, indicating that T lymphocytes are protective during rabies virus ocular infection. Moreover, few T cells and neutrophils underwent apoptosis in rabies virus-infected retina. Altogether, these data suggest that T lymphocytes and neutrophils are able to enter the eye, escape the immune privilege status, and limit rabies virus ocular disease. In conclusion, rabies virus-mediated eye disease provides a new model for studying mechanisms regulating immune privilege during viral infection.
Structural insights into binding of STAC proteins to voltage-gated calcium channels

Significance Skeletal muscle contraction is a tightly orchestrated event that starts with the depolarization of the T-tubular membrane. At the center is a functional and mechanical coupling between two membrane proteins: L-type voltage-gated calcium channels, located in the plasma membrane, and ryanodine receptors, located in the membrane of the sarcoplasmic reticulum. How exactly these proteins associate has remained a mystery, but recent reports have highlighted a key role for the STAC3 adaptor protein in this process. Here, we provide structural snapshots of the three STAC isoforms and identify a cytosolic loop of two CaV isoforms as a functional interaction site. A mutation linked to Native American myopathy is at the interface and abolishes the interaction. Excitation–contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (CaV1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface. We identify the linker connecting transmembrane repeats II and III in two different CaV isoforms as a binding site for the SH3 domains and report a crystal structure of the complex with the STAC2 isoform. The interaction site includes the location for a disease variant in STAC3 that has been linked to Native American myopathy (NAM). Introducing the mutation does not cause misfolding of the SH3 domains, but abolishes the interaction. Disruption of the interaction via mutations in the II–III loop perturbs skeletal muscle EC coupling, but preserves the ability of STAC3 to slow down inactivation of CaV1.2.
Provenance of the Pakawau Group and Farewell Formation (Late Cretaceous – Paleocene), Taranaki Basin, northwest Nelson, New Zealand

ABSTRACT Paleogeographic and tectonic models for the southern Taranaki Basin are refined with sandstone and conglomerate provenances determined from the Late Cretaceous fluvial Rakopi, marginal marine North Cape and Paleocene fluvial Farewell formations. These syn-rift deposits were controlled by the Wakamarama Fault, which bounds the eastern side of the Pakawau Sub-basin graben. The conglomerates of the North Cape and Farewell formations are dominated by metasedimentary clasts with petrography and geochemistry consistent with the Takaka Terrane; minor Takaka Terrane volcanics; and minor Separation Point Suite granitoids and an unknown A-type granite. The sandstones have Takaka Terrane/Separation Point Suite provenance. This indicates that the deposits were sourced from the east with sediments fed into the basin from the Wakamarama Fault, in contrast to previous works indicating axial drainage and southern Buller Terrane provenance. The Farewell Formation has decreasing labile components up-section, indicating increased chemical weathering with the cessation of rifting.
Local delivery of zoledronate from a poly (D,L‐lactide)—Coating increases fixation of press‐fit implants

Early secure fixation of total joint replacements is crucial for long‐term survival. Antiresorptive agents such as bisphosphonates have been shown to increase implant fixation. We investigated whether local delivery of zoledronate from poly‐D, L‐lactide (PDLLA)‐coated implants could improve implant fixation and osseointegration. Experimental titanium implants were bilaterally inserted press‐fit into the proximal tibiae of 10 dogs. On one side the implant was coated with PDLLA containing zoledronate. The contralateral implant was uncoated and used as control. Observation period was 12 weeks. Implant fixation was evaluated with histomorphometry and biomechanical push‐out test. We found an approximately twofold increase in all biomechanical parameters when comparing data from the zoledronate group with their respective controls. Histomorphometry showed increased amount of preserved bone and increased bone formation around the zoledronate implants. This study indicates that local delivery of zoledronate from a PDDLA coating has the potential to increase implant fixation. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:65–71, 2016.
Determinants of Substrate Recognition by the Escherichia coli Multidrug Transporter MdfA Identified on Both Sides of the Membrane*

The Escherichia coli multidrug transporter MdfA contains a membrane-embedded charged residue (Glu-26) that was shown to play an important role in substrate recognition. To identify additional determinants of multidrug recognition we isolated 58 intragenic second-site mutations that restored the function of inactive MdfA E26X mutants. In addition, two single-site mutations that enhanced the activity of wild-type MdfA were identified. Most of the mutations were found in two regions, the cytoplasmic half of transmembrane segments (TMs) 4, 5, and 6 (cluster 1) and the periplasmic half of TM 1 and 2 (cluster 2). The identified residues were mutated to cysteines in the background of a functional cysteine-less MdfA, and substrate protection against alkylation was analyzed. The results support the suggestion that the two clusters are involved in substrate recognition. Using inverted membrane vesicles we observed that a proton electrochemical gradient (Δ&̃mu;H+, inside positive and acidic) enhanced the substrate-protective effect in the cytoplasmic region, whereas it largely reduced this effect in the periplasmic side of MdfA. Therefore, we propose that substrates interact with two sites in MdfA, one in the cytoplasmic leaflet of the membrane and the other in the periplasmic leaflet. Theoretically, these domains could constitute a large part of the multidrug pathway through MdfA.
Are the factors affecting the quality of IS projects identical in large corporations and manufacturing SMEs?

The purpose of this research is to investigate the differences of factors influencing IS project quality between large corporations and small and medium manufacturing enterprises (SMMEs), and to examine whether the moderating effect on the system type including enterprise systems and unit systems exist or not. To this end, a questionnaire survey was carried out. 100 responses were analyzed. The results showed that the factors influencing IS project quality in large corporations and to SMMEs were different. In addition, moderating effects on the system type existed. This is the first empirical study to discover that the factors are not the same between the large companies and SMMEs. The implications and conclusions are also explained.
Information-Content Of Annual Earnings Announcements Revisited

Studies which use residual variance information measures to investigate the information content of earnings reports (e.g., Beaver [1968] and May [1971]) exclude firms with fiscal years ending on December 31 for two reasons. First, since December 31 fiscal year-end firms' annual earnings announcements are clustered together in the months of January, February, and March, some of the "information effects" of firms' earnings may be eliminated when the market return is removed (via a market model) from an individual firm's security returns. Moreover, the residuals of such firms may be correlated due to extramarket factors such as industry factors. Second, the inclusion of December 31 fiscal year-end firms in the sample may induce a bias, since they are, on average, relatively large and as such are generally associated with greater flows of additional information from sources other than earnings reports. Patell [1976], as a reference point in his study of earnings forecasts, employed the residual variance information measures to examine the information content of 273 annual earnings announcements of a subsample of firms with December 31 fiscal year-end. His results were less dramatic (about 10 percent above-normal price reactions) and were based on firms which also voluntarily disclosed their earnings forecasts along with annual earnings. However, Patell did not examine the validity of the methodological concerns alluded to by Beaver and May regarding December 31 fiscal year-end firms. In the next two sections of this paper, I discuss the methodological
The Use of the ISIS Optical Scanner in the Management of the Braced Adolescent Idiopathic Scoliosis Patient

Thirty-four adolescent female patients with right thoracic idiopathic scoliosis were followed for a mean of 8.6 months to document progression of scoliosis curvature during bracewear. Prediction of change by deviation of the lateral asymmetry index on ISIS examination were compared with measured change on standard upright roentgenograms. A one-to-one correlation was found in 50% of the patients; five patients were predicted to have stayed the same or decreased by ISIS and showed increase on x-ray measurement. Eight patients were predicted to have stayed the same or decreased by x-ray measurement and showed increase by ISIS. Although a weak positive correlation exists between change by x-ray examination and change by ISIS examination in a braced population, the clinical usefulness of the ISIS method in following a braced population has not been proven.
Narrowness of habitat selection in woodland and grassland birds

Conservationists have long been concerned about population declines among both woodland and grassland birds, especially those that require extensive areas of a preferred habitat type and avoid mixed habitats. Of the two groups, grassland species have declined even more rapidly than woodland species. We examined whether requirements for uninterrupted habitat could contribute to the greater population declines among grassland birds. To do this, we plotted frequency of occurrence in relation to tree cover in the landscape to evaluate narrowness of range in habitat selection, or stenotopicity, for woodland and grassland species. We created plots at three scales of 200 m, 400 m, and 1200 m around bird observations. At all scales, the most stenotopic woodland species had thresholds of occurrence of 10–30% tree cover. In contrast, most grassland species had thresholds of 80–90% grassland. Favored ranges of grassland species were also narrower than those of woodland species. Grassland species thus are dramatically more stenotopic than woodland species. Although habitat loss is a serious consideration for both groups, grassland birds face a double vulnerability, with high sensitivity to habitat extent as well as extreme habitat loss. This study highlights the importance of increasing systematic strategies to conserve grassland habitat at the regional scale. Spécificité de la sélection d'habitat par les oiseaux forestiers et de prairies RÉSUMÉ. Depuis longtemps, les conservationnistes sont préoccupés par les diminutions de populations d'oiseaux forestiers et de prairies, particulièrement ceux qui recherchent de vastes étendues de leur type d'habitat préféré et évitent les milieux mixtes. Parmi ces deux groupes, les espèces de prairies ont diminué encore plus rapidement que les espèces forestières. Nous avons examiné si le besoin d'un habitat homogène pouvait contribuer aux baisses plus prononcées des oiseaux de prairies. À cette fin, nous avons mis en relation la fréquence d'observation et le couvert forestier dans le paysage pour évaluer la spécificité de la sélection d'habitat, soit la sténotopicité, des espèces forestières et de prairies. Nous avons défini des zones de 200 m, 400 m et 1200 m autour des observations d'oiseaux. À chaque échelle, les espèces forestières les plus sténotopiques avaient des seuils de présence à 10-30 % de couvert forestier, alors que la plupart des espèces de prairies avaient des seuils à 80-90 % de prairies. Les fourchettes favorites des espèces de prairies étaient aussi plus étroites que celles des espèces forestières. Les espèces de prairies sont donc carrément plus sténotopiques que les espèces forestières. Bien que la perte d'habitat soit une préoccupation importante pour les deux groupes d'espèces, les oiseaux de prairies sont doublement vulnérables, car ils sont sensibles à l'étendue d'habitat et font face à une perte considérable d'habitat. Notre étude souligne l'importance de favoriser les stratégies ciblant la conservation systématique de prairies à l'échelle régionale.
Cardiovascular secondary prevention: patients' knowledge of cardiovascular risk factors and their attitude to reduce the risk burden, and the practice of family doctors. The "Help Your Heart Stay Young" study.

BACKGROUND Whether the practice of family doctors of assessing the global cardiovascular risk profile improves the knowledge of cardiovascular risk factors and the attitude to lifestyle change in patients' secondary cardiovascular prevention is unknown. METHODS We evaluated subjects who visited their family doctors and those with self-reported cardiovascular disease in the urban area of Naples, Italy. Patients self-administered a simple standard questionnaire to evaluate their knowledge of cardiovascular risk factors and of simple lifestyle modifications to reduce the cardiovascular risk burden. For each participant, family doctors, blinded to the information provided by patients, had to provide a global coronary risk based on the risk factors recorded in their electronic database, or report the missing information. RESULTS The study sample comprised 560 subjects, 61% male, with mean age 60 +/- 9 years. Angina pectoris (49%) and myocardial infarction (40.9%) were the most frequently self-reported cardiovascular diseases in the study sample. The self-reported data revealed that 46% of the sample was overweight and an additional 20% overtly obese. Among those who self-reported arterial hypertension, approximately 11% admitted that they were unaware of their blood pressure, and 26% believed that they were normotensive but reported a recently detected blood pressure > 140/90 mmHg. Approximately 8% were not aware of whether they had high cholesterol levels, and among those who declared having normal cholesterol levels, 9% referred levels > 200 mg/dl. Of the sample, 22% self-reported diabetes, but 7% did not know whether they were diabetic or not. Thirty percent of the sample were smokers and among these, 40% smoked > 20 cigarettes/day. A low level of education was reported in 66% of the study sample. Women were more frequently obese, more often reported high cholesterol levels, had a low level of education and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than men. Patients > 55 years more often reported an elevated blood pressure among those who defined themselves as normotensive, and achieved a lower score from the questionnaire on knowledge of cardiovascular risk factors than younger patients. CONCLUSIONS With regard to secondary cardiovascular prevention, the study population was found to have insufficient knowledge of cardiovascular risk factors and of the correct approach to reduce their global risk despite the fact that the attitude of their family doctors in detecting and recording risk factors was above average.
Visual Factors Affecting the Rod-And-Frame Illusion: Role of Gap Size and Frame Components

In two studies the effect of the distance between the tip of the rod and the frame sides (gap) in the rod-and-frame (RF) illusion was examined and the effect of a full-square condition was compared with that of two different frame amputations. In both studies, there were more rod-setting errors in the direction of the tilt of the inducing figure with a small gap than with a large one. These findings are consistent with the idea that in the case of small gap size local interactions contribute to determining the RF illusion. The actual length of the rod was varied in order to keep the gap constant across different frame tilts; therefore these findings cannot be due to the co-variation between gap size and frame tilt which is typical of standard apparatuses. The effect of frame amputations was compared to the full-square condition. According to Wenderoth and Beh, amputations that maintain the two orthogonal contours of the square produce the typical angular function of the RF illusion. This prediction was confirmed in both studies. However, results indicate that the full square has a stronger illusory effect in the case of a small degree of tilt of the inducing stimulus, irrespective of gap size. It is suggested that this ‘square superiority’ effect is related to global, not local, mechanisms. To pursue Wenderoth and Beh's observations, amputations close to the vertical meridian were used in one experiment and those close to the horizontal meridian in the second experiment. Contrary to predictions, these conditions produced overlapping results.
Trade agreements and labour standards clauses: Explaining labour standards developments through a qualitative comparative analysis of US free trade agreements

Whereas a number of studies have been conducted to investigate causal relations between individual conditions (e.g. trade relations and labour standards), there is a lack of consensus among practitioners and scholars about the conditions that favour or cause labour standards improvements and, specifically, it is still unclear whether the increasing pervasiveness of Free Trade Agreements (FTAs) is conducive to enhancing labour conditions. The aim of this study is to shed light on whether labour clauses in FTAs are conducive to better labour standard practices, whether the content of a clause makes a difference, and whether changes have anything to do with other (external) pressures that play a role in changing labour standards. The main argument of the article is that FTAs do not play a determinant role in improving labour standards in signatory states. The analysis is done by looking at 13 FTAs signed by the United States with 19 countries. The United States is chosen because of its relatively extensive collection of FTAs including different conditions on labour standards. The empirical dataset is analysed with Qualitative Comparative Analysis (QCA) method, which permits to trace the combined effect of independent variables rather than to focus on the direct and individual causality with each of them.
Marital disruption in Spain: class selectivity and deterioration of economic conditions

In recent decades the probability of divorce and separation among married and cohabiting couples has increased significantly in most European countries. Focusing on both economic and social aspects, this comprehensive volume explores the consequences of partnership dissolution at the individual level. The contributors use personal characteristics, properties of the partnerships and the institutional context to explain coping behaviours.
Selenoprotein Expression in Macrophages Is Critical for Optimal Clearance of Parasitic Helminth Nippostrongylus brasiliensis*

The plasticity of macrophages is evident in helminthic parasite infections, providing protection from inflammation. Previously we demonstrated that the micronutrient selenium induces a phenotypic switch in macrophage activation from a classically activated (pro-inflammatory; M1/CAM) toward an alternatively activated (anti-inflammatory; M2/AAM) phenotype, where cyclooxygenase (COX)-dependent cyclopentenone prostaglandin J2 (15d-PGJ2) plays a key role. Here, we hypothesize that dietary selenium modulates macrophage polarization toward an AAM phenotype to assist in the increasing clearance of adult Nippostrongylus brasiliensis, a gastrointestinal nematode parasite. Mice on a selenium-adequate (0.08 ppm) diet significantly augmented intestinal AAM presence while decreasing adult worms and fecal egg production when compared with infection of mice on selenium-deficient (<0.01 ppm) diet. Further increase in dietary selenium to supraphysiological levels (0.4 ppm) had very little or no impact on worm expulsion. Normal adult worm clearance and enhanced AAM marker expression were observed in the selenium-supplemented Trspfl/flCreWT mice that express selenoproteins driven by tRNASec (Trsp), whereas N. brasiliensis-infected Trspfl/flCreLysM selenium-supplemented mice showed a decreased clearance, with lowered intestinal expression of several AAM markers. Inhibition of the COX pathway with indomethacin resulted in delayed worm expulsion in selenium-adequate mice. This was rescued with 15d-PGJ2, which partially recapitulated the effect of selenium supplementation on fecal egg output in addition to increasing markers of AAMs in the small intestine. Antagonism of PPARγ blocked the effect of selenium. These results suggest that optimal expression of selenoproteins and selenium-dependent production of COX-derived endogenous prostanoids, such as Δ12-PGJ2 and 15d-PGJ2, may regulate AAM activation to enhance anti-helminthic parasite responses.
A 4.6GHz resonant global clock distribution network

A resonant global clock-distribution network operating at 4.6GHz is designed in a 90nm 1.0V CMOS technology. Unique to this approach is the set of on-chip spiral inductors that resonate with the clock capacitance, resulting in 20% recycling of global clock power.
The ab initio simulation of the Earth's core

The Earth has a liquid outer and solid inner core. It is predominantly composed of Fe, alloyed with small amounts of light elements, such as S, O and Si. The detailed chemical and thermal structure of the core is poorly constrained, and it is difficult to perform experiments to establish the properties of core–forming phases at the pressures (ca. 300 GPa) and temperatures (ca. 5000–6000 K) to be found in the core. Here we present some major advances that have been made in using quantum mechanical methods to simulate the high–P/T properties of Fe alloys, which have been made possible by recent developments in high–performance computing. Specifically, we outline how we have calculated the Gibbs free energies of the crystalline and liquid forms of Fe alloys, and so conclude that the inner core of the Earth is composed of hexagonal close packed Fe containing ca. 8.5% S (or Si) and 0.2% O in equilibrium at 5600 K at the boundary between the inner and outer cores with a liquid Fe containing ca. 10% S (or Si) and 8% O.