Miracle-dz/UniFAR-FTUs huggingface dataset:
Ebola virus: new insights into disease aetiopathology and possible therapeutic interventions

Ebola virus (EBOV) gained public notoriety in the last decade largely as a consequence of the highly publicised isolation of a new EBOV species in a suburb of Washington, DC, in 1989, together with the dramatic clinical presentation of EBOV infection and high case-fatality rate in Africa (near 90% in some outbreaks), and the unusual and striking morphology of the virus. Furthermore, there are no vaccines or effective therapies currently available. Progress in understanding the origins of the pathophysiological changes that make EBOV infections of humans so devastating has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the mechanisms of EBOV pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. Notably, identifying factors triggering the haemorrhagic complications that characterise EBOV infections led to the development of a strategy to modulate coagulopathy; this therapeutic modality successfully mitigated the effects of EBOV haemorrhagic fever in nonhuman primates. This review summarises our current understanding of EBOV pathogenesis and discusses various approaches to therapeutic intervention based on our current understanding of how EBOV produces a lethal infection.
y-Randomization and Its Variants in QSPR/QSAR

y-Randomization is a tool used in validation of QSPR/QSAR models, whereby the performance of the original model in data description (r2) is compared to that of models built for permuted (randomly shuffled) response, based on the original descriptor pool and the original model building procedure. We compared y-randomization and several variants thereof, using original response, permuted response, or random number pseudoresponse and original descriptors or random number pseudodescriptors, in the typical setting of multilinear regression (MLR) with descriptor selection. For each combination of number of observations (compounds), number of descriptors in the final model, and number of descriptors in the pool to select from, computer experiments using the same descriptor selection method result in two different mean highest random r2 values. A lower one is produced by y-randomization or a variant likewise based on the original descriptors, while a higher one is obtained from variants that use random number pseudodescriptors. The difference is due to the intercorrelation of real descriptors in the pool. We propose to compare an original model's r2 to both of these whenever possible. The meaning of the three possible outcomes of such a double test is discussed. Often y-randomization is not available to a potential user of a model, due to the values of all descriptors in the pool for all compounds not being published. In such cases random number experiments as proposed here are still possible. The test was applied to several recently published MLR QSAR equations, and cases of failure were identified. Some progress also is reported toward the aim of obtaining the mean highest r2 of random pseudomodels by calculation rather than by tedious multiple simulations on random number variables.
Impact of the serogroup A meningococcal conjugate vaccine, MenAfriVac, on carriage and herd immunity.

BACKGROUND The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of 1-29-year-olds in Burkina Faso in 2010. It is not known whether MenAfriVac has an impact on NmA carriage. METHODS We conducted a repeated cross-sectional meningococcal carriage study in a representative portion of the 1-29-year-old population in 3 districts in Burkina Faso before and up to 13 months after vaccination. One district was vaccinated in September 2010, and the other 2 were vaccinated in December 2010. We analyzed 25 521 oropharyngeal samples, of which 22 093 were obtained after vaccination. RESULTS In October-November 2010, NmA carriage prevalence in the unvaccinated districts was comparable to the baseline established in 2009, but absent in the vaccinated district. Serogroup X N. meningitidis (NmX) dominated in both vaccinated and unvaccinated districts. With 4 additional sampling campaigns performed throughout 2011 in the 3 districts, overall postvaccination meningococcal carriage prevalence was 6.95%, with NmX dominating but declining for each campaign (from 8.66% to 1.97%). Compared with a baseline NmA carriage prevalence of 0.39%, no NmA was identified after vaccination. Overall vaccination coverage in the population sampled was 89.7%, declining over time in 1-year-olds (from 87.1% to 26.5%), as unvaccinated infants reached 1 year of age. NmA carriage was eliminated in both the vaccinated and unvaccinated population from 3 weeks up to 13 months after mass vaccination (P = .003). CONCLUSIONS The disappearance of NmA carriage among both vaccinated and unvaccinated populations is consistent with a vaccine-induced herd immunity effect.
EHF for Satellite Communications: The New Broadband Frontier

The exploitation of extremely high-frequency (EHF) bands (30-300 GHz) for broadband transmission over satellite links is currently a hot research topic. In particular, the Q-V band (30-50 GHz) and W-band (75-110 GHz) seem to offer very promising perspectives. This paper aims at presenting an overview of the current status of research and technology in EHF satellite communications and taking a look at future perspectives in terms of applications and services. Challenges and open issues are adequately considered together with some viable solutions and future developments. The proposed analysis highlighted the need for a reliable propagation model based on experimental data acquired in orbit. Other critical aspects should be faced at the PHY-layer level in order to manage the tradeoff between power efficiency, spectral efficiency, and robustness against link distortions. As far as networking aspects are concerned, the large bandwidth availability should be converted into increased throughput by means of suitable radio resource management and transport protocols, able to support very high data rates in long-range aerospace scenarios.
Different effects of recJ and recN mutations on the postreplication repair of UV-damaged DNA in Escherichia coli K-12

Two mutations known to affect recombination in a recB recC sbsBC strain, recJ284::Tn10 and recN262, were examined for their effects on the postreplication repair of UV-damaged DNA. The recJ mutation did not affect the UV radiation sensitivity of uvrB and uvrB recF cells, but it increased the sensitivity of uvrB recN (approximately 3-fold) and uvrB recB (approximately 8-fold) cells. On the other hand, the recN mutation did not affect the UV sensitivity of uvrB recB cells, but it increased the sensitivity of uvrB (approximately 1.5-fold) and uvrB recF (approximately 4-fold) cells. DNA repair studies indicated that the recN mutation produced a partial deficiency in the postreplication repair of DNA double-strand breaks that arise from unrepaired daughter strand gaps, while the recJ mutation produced a deficiency in the repair of daughter strand gaps in uvrB recB cells (but not in uvrB cells) and a deficiency in the repair of both daughter strand gaps and double-strand breaks in uvrA recB recC shcBC cells. Together, these results indicate that the recJ and recN genes are involved in different aspects of postreplication repair.
Daily Intake of Probiotic as well as Conventional Yogurt Has a Stimulating Effect on Cellular Immunity in Young Healthy Women

Background/Aims: The aim of this work was to study the effects of daily yogurt consumption on the cellular immunity of young healthy women and to compare a conventional with a probiotic product. Methods: 33 young healthy women (22–29 years) consumed 100 g/day of either probiotic or conventional commercially available yogurt for 2 weeks and 200 g/day for another 2 weeks followed by a 2-week washout period with no fermented food at all. Before the intervention and after each phase, a complete white blood count was done, the percentage of activated CD69+ T lymphocytes after stimulation of whole blood with pokeweed mitogen was determined as well as the natural cytotoxicity of peripheral blood mononuclear cells against a human erythroleukemic target cell line (K562). All analyses were done by flow cytometry. Results: In the probiotic group only, the numbers of cytotoxic T lymphocytes (CD3+CD16+CD56+) increased significantly (+30.8% with p = 0.001, +22.1 and +32.7% with p = 0.002, for T2, T3 and T4 compared to T1). There were no major changes for other cell populations, and all remained within the physiological range. In both groups, the expression of CD69 on T lymphocytes increased after yogurt consumption, especially on CD8+ (conventional: T2 +23%, T3 +27.2%, probiotic: T2 +15.7%; T3 +10.8% compared to T1) and to a lesser extent on CD4+ (conventional: T2 +7.7%, T3 +14.9%, probiotic: T2 +4% compared to T1. The cytotoxic activity also augmented following the intake, this effect persisting after cessation of consumption. However, there were no significant differences between the probiotic and the conventional yogurt group. Conclusion: Daily yogurt intake has a stimulating effect on cellular immune functions, but in this study the probiotic product did not perform better than the traditional one.
A Hierarchical Semantics-Aware Distributional Similarity Scheme

The context type and similarity calculation are two essential features of a distributional similarity scheme (DSS). In this paper, we propose a hierarchical semanticaware DSS that exploits semantic relation words as extra context information to guide the similarity calculation. First, we define and extract five types of semantic relations, and then develop relation-based similarities from the distributional similarities among the top-ranked relation words. Finally, we integrate various similarities using learning-to-rank technique. Experiments show that semantic relations are beneficial to predicting accurate similarity. On 6904 pairwise similarity comparisons, the predictive accuracy of our approach reaches 83.9%, which significantly outperforms the baseline approaches. We also conduct intrinsic analysis by varying the quality of semantic relations and the usage of individual similarities.
Reduction in blood glutathione levels occurs similarly in patients with primary-open angle or normal tension glaucoma.

PURPOSE To investigate in parallel the systemic glutathione levels of patients suffering from primary open angle glaucoma (POAG) or normal tension glaucoma (NTG) with comparable functional loss. METHODS Thirty-four POAG patients, 30 NTG patients, and 53 controls were subjected to blood analysis to detect the level of circulating glutathione in its reduced (GSH) and oxidized (GSSG) forms. Systemic blood pressure (BP) and ocular perfusion pressure (OPP) parameters were also determined. RESULTS Independent of age, POAG and NTG patients demonstrated significantly lower GSH and t-GSH levels than age-matched controls (P < 0.001). Additionally, a lower redox index was found, but in POAG patients only, in comparison to both NTG and control groups (P = 0.020). GSSG levels were, however, similar between all study groups (P > 0.05). CONCLUSIONS This study demonstrates, for the first time, that both POAG and NTG patients exhibit lower GSH and t-GSH levels than age-matched controls, indicating a similar general compromise of the antioxidant defense systems may exist in both conditions.
Multivariate models for operational risk

Böcker and Klüppelberg [Risk Mag. , 2005, December, 90–93] presented a simple approximation of OpVaR of a single operational risk cell. The present paper derives approximations of similar quality and simplicity for the multivariate problem. Our approach is based on the modelling of the dependence structure of different cells via the new concept of a Lévy copula.
Immature oxidative stress management as a unifying principle in the pathogenesis of necrotizing enterocolitis: insights from an agent-based model.

BACKGROUND Necrotizing enterocolitis (NEC) is a complex disease involving prematurity, enteral feeding, and bacterial effects. We propose that the underlying initial condition in its pathogenesis is reduced ability of the neonatal gut epithelial cells (NGECs) to clear oxidative stress (OS), and that when such a NGEC population is exposed to enteral feeding, the increased metabolic OS tips the population toward apoptosis, inflammation, bacterial activation, and eventual necrosis. The multi-factorial complexity of NEC requires characterization with computational modeling, and herein, we used an agent-based model (ABM) to instantiate and examine our unifying hypothesis of the pathogenesis of NEC. METHODS An ABM of the neonatal gut was created with NGEC computational agents incorporating rules for pathways for OS, p53, tight junctions, Toll-like receptor (TLR)-4, nitric oxide, and nuclear factor-kappa beta (NF-κB). The modeled bacteria activated TLR-4 on contact with NGECs. Simulations included parameter sweeps of OS response, response to feeding, addition of bacteria, and alterations in gut mucus production. RESULTS The ABM reproduced baseline cellular respiration and clearance of OS. Reduction in OS clearance consistent with clinical NEC led to senescence, apoptosis, or inflammation, with disruption of tight junctions, but rarely to NGEC necrosis. An additional "hit" of bacteria activating TLR-4 potentiated a shift to NGEC necrosis across the entire population. The mucus layer was modeled to limit bacterial-NGEC interactions and reduce this effect, but concomitant apoptosis in the goblet cell population reduced the efficacy of the mucus layer and limited its protective effect in simulated experiments. This finding suggests a means by which increased apoptosis at the cellular population level can lead to a transition to the necrosis outcome. CONCLUSIONS Our ABM incorporates known components of NEC and demonstrates that impaired OS management can lead to apoptosis and inflammation of NGECs, rendering the system susceptible to an additional insult involving regionalized mucus barrier failure and TLR-4 activation, which potentiates the necrosis outcome. This type of integrative dynamic knowledge representation can be a useful adjunct to help guide and contextualize research.
Amino Acid Sequence of a-Subunit in Hen Egg White Ovomucin Deduced from Cloned cDNA

The primary amino acid sequence of α-subunit in ovomucin (OVM) from hen thick egg white was determined. The 2087 amino acid residues with a relative molecular mass of 230.9 kDa along the full length of the α-subunit were represented. The α-subunit contains domains, arranged from the N- to C-terminals in the following order: D1-D2-D′-D3-R (central region)-D4-C1-CK (Cystine-knot), in a manner similar to the arrangement of D, C and CK domains in human pre-pro-von Willebrand factor (hpp-vWF) and hMUC2. The α-subunit showed identities on amino acid sequences with hpp-vWF and hMUC2 at 33 and 41% in the N-terminal region and 30 and 38% in the C-terminal region, respectively. The numbers and positions of cysteine residues were highly conserved among α-subunit, hpp-vWF and hMUC2. However, R showed no virtual sequence homology with the corresponding regions in two proteins. It was estimated that α-subunit was not part of a large peptide of OVM, but was independently synthesized from β-subunit.
Establishing an Integrative Medicine Program Within an Academic Health Center: Essential Considerations

Integrative medicine (IM) refers to the combination of conventional and “complementary” medical services (e.g., chiropractic, acupuncture, massage, mindfulness training). More than half of all medical schools in the United States and Canada have programs in IM, and more than 30 academic health centers currently deliver multidisciplinary IM care. What remains unclear, however, is the ideal delivery model (or models) whereby individuals can responsibly access IM care safely, effectively, and reproducibly in a coordinated and cost-effective way. Current models of IM across existing clinical centers vary tremendously in their organizational settings, principal clinical focus, and services provided; practitioner team composition and training; incorporation of research activities and educational programs; and administrative organization (e.g., reporting structure, use of medical records, scope of clinical practice) and financial strategies (i.e., specific business plans and models for sustainability). In this article, the authors address these important strategic issues by sharing lessons learned from the design and implementation of an IM facility within an academic teaching hospital, the Brigham and Women’s Hospital at Harvard Medical School; and review alternative options based on information about IM centers across the United States. The authors conclude that there is currently no consensus as to how integrative care models should be optimally organized, implemented, replicated, assessed, and funded. The time may be right for prospective research in “best practices” across emerging models of IM care nationally in an effort to standardize, refine, and replicate them in preparation for rigorous cost-effectiveness evaluations.
The Polarity Protein Scrib Is Essential for Directed Endothelial Cell Migration

Rationale: Polarity proteins are involved in the apico-basal orientation of epithelial cells, but relatively little is known regarding their function in mesenchymal cells. Objective: We hypothesized that polarity proteins also contribute to endothelial processes like angiogenesis. Methods and Results: Screening of endothelial cells revealed high expression of the polarity protein Scribble (Scrib). On fibronectin-coated carriers Scrib siRNA (siScrib) blocked directed but not random migration of human umbilical vein endothelial cells and led to an increased number and disturbed orientation of cellular lamellipodia. Coimmunoprecipitation/mass spectrometry and glutathione S-transferase (GST) pulldown assays identified integrin &agr;5 as a novel Scrib interacting protein. By total internal reflection fluorescence (TIRF) microscopy, Scrib and integrin &agr;5 colocalize at the basal plasma membrane of endothelial cells. Western blot and fluorescence activated cell sorting (FACS) analysis revealed that silencing of Scrib reduced the protein amount and surface expression of integrin &agr;5 whereas surface expression of integrin &agr;V was unaffected. Moreover, in contrast to fibronectin, the ligand of integrin &agr;5, directional migration on collagen mediated by collagen-binding integrins was unaffected by siScrib. Mechanistically, Scrib supported integrin &agr;5 recycling and protein stability by blocking its interaction with Rab7a, its translocation into lysosomes, and its subsequent degradation by pepstatin-sensitive proteases. In siScrib-treated cells, reinduction of the wild-type protein but not of PSD95, Dlg, ZO-1 (PDZ), or leucine rich repeat domain mutants restored integrin &agr;5 abundance and directional cell migration. The downregulation of Scrib function in Tg(kdrl:EGFP)s843 transgenic zebrafish embryos delayed the angiogenesis of intersegmental vessels. Conclusions: Scrib is a novel regulator of integrin &agr;5 turnover and sorting, which is required for oriented cell migration and sprouting angiogenesis.
Propionate-Degrading Bacterium, Syntrophobacter wolinii sp. nov. gen. nov., from Methanogenic Ecosystems

A new genus and species of a nonmotile gram-negative rod, Syntrophobacter wolinii, is the first bacterium described which degrades propionate only in coculture with an H2-using organism and in the absence of light or exogenous electron acceptors such as O2, sulfate, or nitrate. It was isolated from methanogenic enrichments from an anaerobic municipal sewage digestor, using anaerobic roll tubes containing a medium with propionate as the energy source in association with an H2-using, sulfate-reducing Desulfovibrio sp. which cannot utilize fatty acids other than formate. S. wolinii produced acetate and, presumably, CO2 and H2 (or formate) from propionate. In media without sulfate and with Methanospirillum hungatei, a methanogen that uses only H2-CO2 or formate as an energy source, acetate, methane, and, presumably, CO2 were produced from propionate and only small amounts of Desulfovibrio sp. were present. Isolation in coculture with the methanogen was not successful. S. wolinii does not use other saturated fatty acids as energy sources.
Diaphragmatic Shape Change After Lung Volume Reduction Surgery

Diaphragmatic shape in normal patients was significantly different from shape in emphysema patients. Postoperative diaphragmatic shape in patients with good clinical outcome differed from preoperative shape and was similar to shape in normal patients. In patients with poor clinical outcome, surgery appeared to have little effect on diaphragm shape.
Death Following Creatine Kinase-MB Elevation After Coronary Intervention: Identification of an Early Risk Period: Importance of Creatine Kinase-MB Level, Completeness of Revascularization, Ventricular Function, and Probable Benefit of Statin Therapy

Background—Creatine kinase (CK)-MB elevation after percutaneous coronary intervention (PCI) has been associated with subsequent cardiac death. The patients at risk, the timing of risk, and potential treatment implications are uncertain. Methods and Results—Eight thousand, four hundred nine consecutive non– acute myocardial infarction patients with successful PCI and no emergency surgery or Q-wave myocardial infarction were followed for 38±25 months; 1446 (17.2%) had post-PCI CK-MB above normal on routine ascertainment. Patients were prospectively stratified into those with CK-MB 1 to 5× or CK-MB >5× normal. No patient with CK-MB 1 to 5× normal died during the first week after PCI, and excess risk of early death for patients with CK-MB elevation occurred primarily in the first 3 to 4 months. The actuarial 4-month risk of death was 8.9%, 1.9%, and 1.2% for patients with CK-MB >5×, CK-MB 1 to 5×, and CK-MB ≤1× normal (P <0.001). Death within 4 months was independently correlated with the degree of CK-MB elevation, creatinine ≥2 mg%, post-PCI C-reactive protein, low ejection fraction, age, and congestive heart failure class (P <0.01 for all). In a matched subset analysis, incomplete revascularization (P <0.001), congestive heart failure class (P =0.005), and no statin treatment at hospital discharge (P =0.009) were associated with death. Conclusions—Patients with CK-MB elevation after PCI are at excess risk of death for 3 to 4 months, although prolonging hospitalization for CK-MB 1 to 5× is unlikely to modify risk. CK-MB >5× normal, incomplete revascularization, elevated C-reactive protein, heart failure, the elderly, and hospital discharge without on statin therapy increases risk. Several of these factors suggest that inflammation may play a part in the excess risk of death.