Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutralization of antifactor VIII inhibitors by recombinant porcine factor VIII

Summary. Background: Inhibitory antibodies to factor (F) VIII (FVIII inhibitors) present a major clinical challenge as a complication of hemophilia A and as acquired autoantibodies in non‐hemophiliacs. Porcine FVIII is a potentially useful therapeutic agent because of its low crossreactivity with many inhibitors. Recombinant porcine FVIII (rpFVIII) is undergoing clinical trials in inhibitor patients. Objectives: The goals of this study were to neutralize human FVIII inhibitors in vitro with rpFVIII and to characterize the relationship between recovery of FVIII activity and the antiporcine FVIII inhibitor titer. Methods: rpFVIII was added to 28 antihuman FVIII inhibitor plasmas and assayed either immediately or after a 2 h preincubation at 37 °C. The concentration of rpFVIII required for recovery of FVIII activity to 50% of normal (EC50) was determined by polynomial regression analysis and compared with the antiporcine FVIII inhibitor titer measured by Bethesda assay. Results: Six of nine plasmas classified as non‐crossreactive by Bethesda assay had detectable inhibitory activity in the FVIII recovery assay. Recovery was decreased following a 2 h preincubation compared with immediate assay for the 19 plasmas with detectable antiporcine FVIII inhibitors. There was a linear relationship between EC50 and inhibitor titer for plasmas with antiporcine FVIII titers ranging from 0.6 to 10 BU per milliliter in both the immediate and the 2 h preincubation assays. Conclusion: A quantitative method for analysis of inhibitor neutralization in vitro has been developed, which may be useful for comparison with pharmacodynamic studies of rpFVIII in FVIII inhibitor patients and subsequent rational dosing in this patient population.
From a Scholarly Big Dataset to a Test Collection for Bibliographic Citation Recommendation

The problem of designing recommender systems for scholarly article citations has been actively researched with more than 200 publications appearing in the last two decades. In spite of this, no definitive results are available about what approaches work best. Arguably the most important reason for this lack of consensus is the dearth of standardised test collections and evaluation protocols, such as those provided by TREC-like forums. CiteSeerX, a "scholarly big dataset" has recently become available. However, this collection provides only the raw material that is yet to be moulded into Cranfield style test collections. In this paper, we discuss the limitations of test collections used in earlier work, and describe how we used CiteSeerX to design a test collection with a well-defined evaluation protocol. The collection consists of over 600,000 research papers and over 2,500 queries. We report some preliminary experimental results using this collection, which are indicative of the performance of elementary content-based techniques. These experiments also made us aware of some shortcomings of CiteSeerX itself.
An Irradiation-Free Nonmyeloablative Bone Marrow Transplantation Model: Importance of the Balance between Donor T-cell Number and the Intensity of Conditioning

Background. Animal allogeneic bone marrow transplantation (BMT) models with nonmyeloablative conditioning regimens have so far required irradiation or antibodies in addition to immunosuppressive drugs for engraftment. Moreover, although it is known that the balance between donor T-cell number and the dose of immunosuppressive drugs would be critical for engraftment, it has not been experimentally clarified in a nonmyeloablative regimen. Methods. We used C57BL/6 mice as donors and DBA/2 mice as recipients with a nonmyeloablative regimen including fludarabine (Flu) and cyclophosphamide (CPA) without irradiation or antibodies. To determine the adequate doses, we injected recipients with various doses of Flu and CPA, and 2×107 bone marrow cells (BMC) and 5×107 splenocytes (SC). Furthermore, using T-cell-depleted BMC and enriched T cells, we investigated the balance between donor T-cell number and the dose of Flu. Results. Doses of Flu at 150 mg/kg/day×6 and CPA at 150 mg/kg/day×2 were most appropriate for engraftment with low mortality. All mice appropriately pretreated and transplanted with both BMC and SC exhibited complete donor chimeras. Donor cell engraftment was not enhanced by any increase of BMC transplanted, and dose escalation of donor T cells but not BMC led to the reduction of Flu dose required for engraftment of donor cells. Conclusions. We have established a murine nonmyeloablative BMT model in a fully MHC-mismatched combination for donor cell engraftment with complete donor chimerism. Simultaneously, we have quantitatively demonstrated that the balance between donor T-cell number and the dose of immunosuppressive drugs is critical for stable engraftment.
Influence of Pregnancy on the 75-g OGTT: A Prospective Multicenter Study

This study reports the responses to a 75-g oral glucose tolerance test (OGTT) in 1009 pregnant women from throughout Europe. We reached the following conclusions. 1) A pregnant woman tends to have blood glucose concentrations that are elevated for a longer period of time after an oral glucose load. Therefore, ∼ 10% of women will reach or exceed 8 mM glucose at 2 h, but it is unlikely that 10% of European women have disordered carbohydrate metabolism. 2) The fasting and 1-h values should be included in any analysis of the response of the patient. By doing this, many fewer women will have responses regarded as abnormal; in this series, it reduced the 79 women with a 2-h value >8 mM to 15 who were considered to have carbohydrate intolerance (2 with diabetes, 13 with impaired glucose tolerance [IGT]). 3) By increasing the 2-h cutoff value to >9 mM, the number of women regarded as at risk would be reduced by >50% (from 79 to 32 in this series), but 10 of the 13 women with two abnormal values would still have been detected, as would the 2 diabetic women. 4) From the obstetric viewpoint, mothers who screen positive do not have bigger babies, they deliver close to term, and they do not have particular stigmas such as a family history of diabetes or an increased tendency to smoke or to have an adverse obstetric outcome. However, they do tend to be older and heavier. This raises the question of whether the apparent longer-term consequences such as coronary artery disease and hypertension are not in some measure due to these factors rather than carbohydrate intolerance alone. 5) We recommend that the screening test for disordered carbohydrate tolerance should be based on a 75-g OGTT with at least three blood samples: fasting, 60 min, and 120 min. The fasting value should not exceed 7 mM, the 1-h level should be <11 mM, and the 2-h value should be <9 mM. To diagnose IGT, either the fasting or 1-h concentration should be above the stated values in addition to a 2-h value >9 mM. Diabetes should be diagnosed with the existing World Health Organization criteria. 6) The term gestational diabetes should be reserved for those in whom blood glucose levels are diagnostic of diabetes and not IGT. If the term IGT during pregnancy is too long, the abbreviation gestational IGT is a reasonable alternative.
India–ASEAN Relations

The terminology of the Indo-Pacific is beginning to gain more relevance in recent times with several countries referring to this term in their official pronouncements. Widely understood to be the region that stretches from the western Indian Ocean to the western Pacific Ocean, this term has come to mean different things to the states that constitute this strategic and geopolitical concept. For India, its foreign policy initiative called the Look East and Act East policy is centred around the Association of Southeast Asian Nations (ASEAN) and extends to the countries beyond the ASEAN region to East Asia and the Pacific. This article attempts to understand the Act East policy as the core of India’s engagement eastwards, focusing on four broad themes: first, how do regional states look at the terminology of the Indo-Pacific? Second, what constitutes India’s core understanding of this term, and what are India’s overarching priorities in the region? Third, how does the Act East policy towards the ASEAN form the core of India’s Indo-Pacific strategy, and in the fourth concluding theme, how does the return of the Quadrilateral Dialogue (Quad) implicate the future of India–ASEAN relations?
The Early Effects of Dietary Restriction on the Pathogenesis of Chronic Renal Disease in Sprague-Dawley Rats at 12 Months

This study evaluated the effects of different diets and dietary regimens on the pathogenesis of chronic renal disease (CRD) in Sprague-Dawley rats at 52 wk and correlated these data with survival at 106 wk. A commercial diet (5002) was compared to a modified diet (5002-9) with less protein, fat, and energy and more fiber. Both diets were fed by ad libitum (AL) or dietary restriction (DR) regimens. The glomerular area (GA), glomerular sclerotic index (GSI), tubulo-interstitial index (TII), and tubular labeling index (tubular LI) were measured. The 5002-9 diet fed AL did not decrease the severity of CRD or increase survival, nor did the 5002 diet fed 6.5 hr/day. Both diets fed by DR did improve CRD and survival. Both AL groups had higher indices, and the 5002 AL males had the highest GA and GSI. These data indicate that the initial events in CRD occur as glomerular hypertrophy. Because the TII and tubular LI were only increased with advanced CRD, tubulo-interstitial damage did not occur until the glomerular changes were established. The 52-wk glomerular indices correlated with survival at 106 wk. Increased GA at 52 wk predicted low survival rates at 106 wk. These findings support a hypothesis that glomerular sclerosis and tubulo-interstitial damage occur secondary to early initial glomerular hypertrophy that is mitigated by caloric restriction.
Modelling of brain sources using the modified saint Venant's method in FEM resolution of EEG forward problem

In order to reconstruct the electrical brain activities, both the inverse and the forward problems have to be solved. The inverse problem consists of finding brain activities (sources) which are responsible for the measured signals. The forward problem is calculating the potentials at the sensor electrodes placed on the scalp from a given source inside the brain. Its resolution involves models of head and models of sources. The finite-element method (FEM) is investigated in this paper for its ability to model realistic geometry and physical proprieties. However, using this method, the point source introduces singularity in the calculation and impacts the accuracy. Different techniques have been developed to avoid this singularity but the accuracy of the most techniques decrease as the current dipole approaches the interface of different tissues with different conductivities. In this paper, the forward problem is solved by the FEM using a spherical head model and the saint Venant's principle is used to avoid the source's singularity. Near the interface of different brain tissues, a modification on the saint Venant's method is introduced. Simulation results show that this new modification gives good accuracy as compared with the traditional approaches.
Protective effect of ginkgo proanthocyanidins against cerebral ischemia/reperfusion injury associated with its antioxidant effects

Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proanthocyanidins (20, 40, 80 mg/kg) were intraperitoneally administered 1, 24, 48 and 72 hours before reperfusion. Results showed that ginkgo proanthocyanidins could effectively mitigate neurological disorders, shorten infarct volume, increase superoxide dismutase activity, and decrease malondialdehyde and nitric oxide contents. Simultaneously, the study on grape seed proanthocyanidins (40 mg/kg) confirmed that different sources of proanthocyanidins have a similar effect. The neurological outcomes of ginkgo proanthocyanidins were similar to that of nimodipine in the treatment of cerebral ischemia/reperfusion injury. Our results suggest that ginkgo proanthocyanidins can effectively lessen cerebral ischemia/reperfusion injury and protect ischemic brain tissue and these effects are associated with antioxidant properties.
Pancreaticoduodenectomy – the transition from a low- to a high-volume center

Abstract Objective. Previous studies have identified a significant volume–outcome relationship for hospitals performing pancreaticoduodenectomy (PD). However, scant information exists concerning the effects of increased caseload of PD within the same hospital. Here, we describe the effects of becoming a high-volume provider of PD. Material and methods. The study group comprised 221 patients who underwent PD between 2000 and 2012. Hospital volume was allocated into three groups: low-volume (<10 PDs/year), years 2000–2004, n = 25; medium-volume (10–24 PDs/year), years 2005–2009, n = 86; and high-volume (≥25 PDs/year), years 2010–2012, n = 110. Results. The annual number of PDs increased from 5 in 2000 to 39 in 2012. The median operative duration decreased over the volume categories (p < 0.001). Intraoperative blood loss dropped (p < 0.001). The need for intraoperative blood transfusion was reduced (p < 0.001). Increasing hospital volume was associated with fewer reoperations (p = 0.041) and shorter postoperative length of stay (p = 0.010). There was a tendency toward reduced mortality: 4.0% for the low-volume period, 2.3% for the medium-volume period, and 0% for the high-volume period (p = 0.066). Conclusions. The transition from a low- to a high-volume center resulted in optimized outcomes for PD and 0% operative mortality, favoring the continued centralization of this high-risk operation.
Some Meaning Procedures of Ontological Semantics

This paper presents implemented algorithms for interpreting the meaning of certain context-dependent lexical items within the Ontological Semantic text processing environment. We discuss the form, function and rationale behind three meaning procedures, all of which are, in a certain sense, numerically oriented. We show that only a knowledge-rich processing system can fully interpret such entities, and that an integrated combination of static resources and processors provides sufficient foundation for high-quality text interpretation.
Further Biochemical and Kinetic Characterization of Human Eukaryotic Initiation Factor 4H*

A cDNA encoding human eukaryotic initiation factor (eIF) 4H was subcloned into a bacterial expression plasmid for purification of recombinant protein. Recombinant human eIF4H (heIF4H) was purified to greater than 95% homogeneity and shown to have similar physical characteristics to eIF4H purified from rabbit reticulocyte lysate as described previously. Functional studies have revealed that recombinant heIF4H functions identically to rabbit eIF4H in stimulating protein synthesis, and the ATP hydrolysis and helicase activities of eIF4A. More detailed enzymatic studies revealed that eIF4H increases the affinity of eIF4A for RNA by 2-fold, but has no effect on the binding of ATP by eIF4A. eIF4H stimulates the helicase activity of eIF4A at least 4-fold, and it is postulated that this stimulation occurs through increasing the processivity of eIF4A. Northern blot analysis shows that eIF4H is expressed ubiquitously in human tissues, and displays different levels of expression in given tissues relative to eIF4B. Secondary structure analysis of heIF4H by circular dichroism suggest that eIF4H has a mostly β-sheet structure, which appears similar to other RNA recognition motif-containing proteins. Finally, it is suggested that eIF4H functions in translation initiation through protein-protein interactions that possibly stabilize conformational changes that occur in eIF4A during RNA binding, ATP hydrolysis, and RNA duplex unwinding.
Cloud Optical Depth Retrievals From Solar Background “Signals” of Micropulse Lidars

Pulsed lidars are commonly used to retrieve vertical distributions of cloud and aerosol layers. It is widely believed that lidar cloud retrievals (other than cloud base altitude) are limited to optically thin clouds. Here, we demonstrate that lidars can retrieve optical depths of thick clouds using solar background light as a signal, rather than (as now) merely a noise to be subtracted. Validations against other instruments show that retrieved cloud optical depths agree within 10%-15% for overcast stratus and broken clouds. In fact, for broken cloud situations, one can retrieve not only the aerosol properties in clear-sky periods using lidar signals, but also the optical depth of thick clouds in cloudy periods using solar background signals. This indicates that, in general, it may be possible to retrieve both aerosol and cloud properties using a single lidar. Thus, lidar observations have great untapped potential to study interactions between clouds and aerosols.
Seasonal Migrant Labor in the Forest Industry of the Southeastern United States: The Impact of H-2B Employment on Guatemalan Livelihoods

Abstract Migrant labor is a global phenomenon and remittances of migrant workers from non-industrial nations can play an important role in improving quality of life at family, community, and national levels. We focus on workers from Guatemala who obtain visas from the United States (US) Department of Immigration’s H-2B program that allow them to spend six or seven months a year planting and maintaining pine plantations in the southeastern US. Forestry is economically important in this region and the industry has come to depend on migrant labor. Our specific interest is how the H-2B program affects livelihood strategies of these workers, their families, and their communities. Based on primary data from 49 interviews conducted in eight Guatemalan communities, we explain motivations to engage in seasonal migration and positive changes brought about by the H-2B program in nutrition, housing, healthcare and long-term investments in agricultural lands, microenterprise development, education, and family stability.
Experimental Regulation of STAT Gene Expression Reveals an Involvement of STAT5 in Interleukin-4-Driven Cell Proliferation

Abstract The precise roles of signal transducers and activators of transcription (STATs) in cytokinetriggered control of cell physiology are not sufficiently well understood. We have established cell lines in which the individual functional contributions of STAT6 and STAT5a/b to interleukin(IL) 3 and -4-dependent processes can be readily studied. Mutants of STAT6, STAT5a and 5b lacking the transcriptional transactivation domain were fused to the green fluorescent protein (GFP) and expressed in the murine proB cell line Ba/F3 in a regulatable fashion. The expression of these truncated STAT variants could be tightly controlled over a wide range by doxycycline in the medium. They specifically bound to cognate DNA elements upon cytokine stimulation and acted dominantnegatively on the transcription of respective reporter genes in response to IL-3 and -4. The system was applied to the question of STAT contributions to cytokinedependent cell proliferation. Expression of dominantnegative STAT6 had no significant effect on cell growth in response to both IL-3 and IL-4. In contrast, truncated STAT5 interfered with cell proliferation in response to IL-3, and, interestingly, also to IL-4. The results support our earlier findings on a role of STAT5 in IL-4-induced intracellular signaling and indicate that STAT5b in particular is involved in IL-4 receptortriggered control of cell proliferation.
Calu-3: a human airway epithelial cell line that shows cAMP-dependent Cl- secretion.

Of 12 cell lines derived from human lung cancers, only Calu-3 cells showed high transepithelial resistance (Rte) and increases in short-circuit current (Isc) in response to mediators. Calu-3 cells formed polarized monolayers with tight junctions and Rte of approximately 100 omega.cm2. Baseline Isc was approximately 35 microA/cm2 and was increased by approximately 75 microA/cm2 on elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) by isoproterenol. Flux studies showed that the increase in Isc was due to Cl- secretion. Forskolin and permeant analogues of cAMP also increased Isc. Consistent with the presence of cAMP-dependent Cl- secretion, immunoprecipitation demonstrated the presence of the cystic fibrosis transmembrane conductance regulator (CFTR). Bradykinin, methacholine, trypsin, and histamine all transiently (15-30 s) elevated Isc, probably by increasing intracellular Ca concentration. Experiments in which the basolateral membrane was permeabilized with nystatin indicated that CFTR was substantially activated under baseline conditions and that Ca-activated Cl- channels were absent from the apical membrane. We anticipate that Calu-3 cells will prove useful in the study of Cl- secretion and other functions of human airway epithelial cells.
Viral protein synthesis is required for Enterovirus 71 to induce apoptosis in human glioblastoma cells

Human glioblastoma cells (SF268) develop apoptosis, as characterized by DNA fragmentation and caspase activation, upon infection with Enterovirus 71 (EV71). To determine the step in virus replication that triggers apoptosis, the authors used ultraviolet (UV)-inactivated virus, inhibitors of protein and viral RNA synthesis, and chloroquine to block virus uncoating. Activation of caspase-3 was detected 24 h after infection with EV71 but not with UV-inactivated EV71. Apoptosis was inhibited when EV71-infected cells were treated with chloroquine, guanidine HCl, or cycloheximide. In summary, the authors studied the event(s) required to induce apoptosis in EV71-infected human glioblastoma cells, a subject much less studied than the possible role of viral proapoptotic genes, concluding that EV71 induces apoptosis in the infected SF268 cell in the presence of viral protein synthesis and virus replication, whereas virus adsorption, internalization, entry, uncoating, and viral RNA replication are all not required to trigger the apoptosis.
Transmission of Whole-Body Vibration and Its Effect on Muscle Activation

Abstract Tankisheva E, Jonkers I, Boonen S, Delecluse C, van Lenthe GH, Druyts HLJ, Spaepen P, and Verschueren SMP. Transmission of whole-body vibration and its effect on muscle activation. J Strength Cond Res 27(9): 2533–2541, 2013—The aim of current study was to measure the transmission of whole-body vibration through the entire body and to relate this to body posture and induced muscular activation. Eight clinically healthy subjects performed 3 static body postures—high squat (135°), deep squat (110°), and erect stance, whereas vibration transmission was assessed over a wide range of accelerations (from 0.33 to 7.98 g) and frequencies (from 30 to 50 Hz). To assess the vibration transmission, 9 triaxial accelerometers were attached from the ankle up to the head and the root mean square of acceleration signal of each site-specific body point was calculated. Additionally, muscle activity from 7 lower limb muscles was recorded. The results showed a significant attenuation of the platform accelerations transmitted from the feet to the head. Compared with erect stance, knee bent posture significantly diminished vibration transmission at the hip, spine, and the head (p < 0.05). Vibration transmission to the spine was significantly lower in deep vs. high squat (p < 0.05), suggesting that further knee bending may reduce the risk of overloading the spine. Vibration increased the muscle activity in most leg and hip muscles during both squat postures, although, on average, no clear dose–response relationship between the acceleration and/or frequency and muscle response was found. The muscular activation of vastus medialis and rectus femoris showed clear negative correlation to the vibration transmission at the sternum. The specific vibration parameters used in the present study can be considered as safe and suitable for a training program. Moreover, the present results contribute to optimize the most advantageous whole-body vibration protocol and to determine the beneficial effects on muscle and bone.