Miracle-dz/UniFAR-FTUs huggingface dataset:
Killer immunoglobulin-like receptors (KIRs) and HLA-C allorecognition patterns implicative of dominant activation of natural killer cells contribute to recurrent miscarriages.

BACKGROUND Decidual natural killer (NK) cells play key developmental roles at the feto-maternal interface. Individual differences in NK-cell interactions are dependent on the combinations of variable killer immunoglobulin-like receptor (KIR) and HLA class-I gene products. As different receptor-ligand interactions may result in altered NK-cell-mediated immunity against pathogens, it is proposed that the relationship between these genes may be important in a state such as recurrent miscarriage (RM). We had earlier reported that the predisposition to RM is influenced by the maternal KIR gene content. In the present study, we have attempted to extend our findings in the light of contribution from the paternal antigens on the outcome of pregnancy, since maternal NK cells may potentially encounter non-self-paternal HLA-C alleles on trophoblasts. All HLA-C allotypes fall into two major KIR epitopes--C1 (HLA-C*01/*03/*07/*08/*12/*14/*16) and C2 (HLA-C*02/*04/*05/*06/*15/*17/*18)--on the basis of a dimorphism at position 80 of the α1 domain. METHODS PCR-sequence specific primer-based genotyping was used to determine the maternal KIR gene content and HLA-C genotypes down to allele level in couples experiencing RM and controls. RESULTS KIR2DL1 with both partners homozygous for HLA C2 was significantly higher in control couples when compared with the patients [P = 0.0004, odds ratio (OR) = 0.28, 95% confidence interval (CI) = 0.13-0.58]. The activating KIR2DS2 with both partners homozygous for HLA C1 was significantly higher in patients when compared with the controls (P = 0.002, OR = 2.83, 95% CI = 1.47-5.40). CONCLUSIONS Our results represented the 'top-end' of the activation spectrum of KIR-HLA-C compound genotype for NK cells and this may contribute to the immunological etiology of RM.
Beyond GWAS in COPD: Probing the Landscape between Gene-Set Associations, Genome-Wide Associations and Protein-Protein Interaction Networks

Objectives: To use a systems biology approach to integrate genotype and protein-protein interaction (PPI) data to identify disease network modules associated with chronic obstructive pulmonary disease (COPD) and to perform traditional pathway analysis. Methods: We utilized a standard gene-set association approach (FORGE) using gene-based association analysis and gene-set definitions from the molecular signatures database (MSigDB). As a discovery step, we analyzed GWAS results from 2 well-characterized COPD cohorts: COPDGene and GenKOLS. We used a third well-characterized COPD case-control cohort for replication: ECLIPSE. Next, we used dmGWAS, a method that integrates GWAS results with PPI, to identify COPD disease modules. Results: No gene-sets reached experiment-wide significance in either discovery population. We identified a consensus network of 10 genes identified in modules by integrating GWAS results with PPI that replicated in COPDGene, GenKOLS, and ECLIPSE. Members of 4 gene-sets were enriched among these 10 genes: (i) lung adenocarcinoma tumor-sequencing genes, (ii) IL-7 pathway genes, (iii) kidney cell response to arsenic, and (iv) CD4 T-cell responses. Further, several genes have also been associated with pathophysiology relevant to COPD including KCNK3, NEDD4L, and RIN3. In particular, KCNK3 has been associated with pulmonary arterial hypertension, a common complication in advanced COPD. Conclusion: We report a set of new genes that may influence the etiology of COPD that would not have been identified using traditional GWAS and pathway analyses alone.
Modeling and control of a colonoscopic tip under disturbance of the insertion of colonoscope

During the conventional procedure of the colonoscopy, there are two important movements, the introduction of colonoscope in the colon and the maneuver of the distal end. In this paper, the authors focus on a new type of automatic bendable tip while keeping the advance of the colonoscope in the colon by endoscopist. The main purpose of this tip is to make the colonoscope overcome acute intestinal bends and make easier the progression of the colonoscope for the surgeon. Firstly, we model our current prototype tip, named EDORA (distal extremity with automatic orientation). Next, the parameters of the system are estimated by using the Levenberg-Margquardt's algorithm. Finally, by using the maximum of the sensitivity function a gain margin specification is made. A set point for a position controller is designed, thus the tip can stay in the middle of the colon with disturbance rejection due to the manipulation of the colonoscope. In the same time, this controller has been designed to make the tip have some degrees of compliance to reduce the contact force due to the undesirable contact with the colon. Simulation and experimental results for the controller would be presented by emulating the real environments.
Enhancement of  l‐phenylalanine production in Escherichia coli by heterologous expression of Vitreoscilla hemoglobin

l‐Phenylalanine is an important amino acid that is widely used in the production of food flavors and pharmaceuticals. Generally, l‐phenylalanine production by engineered Escherichia coli requires a high rate of oxygen supply. However, the coexpression of Vitreoscilla hemoglobin gene (vgb), driven bya tac promoter, with the genes encoding 3‐deoxy‐d‐arabinoheptulosonate‐7‐phosphate synthetase (aroF) and feedback‐resistant chorismate mutase/prephenate dehydratase (pheAfbr), led to increased productivity and decreased demand for aeration by E. coli CICC10245. Shake‐flask studies showed that vgb‐expressing strains displayed higher rates of oxygen uptake, and l‐phenylalanine production under standard aeration conditions was increased. In the aerobic fermentation process, cell growth, l‐phenylalanine production, and glucose consumption by the recombinant E. coli strain PAPV, which harbored aroF, pheAfbr, and tac‐vgb genes, were increased compared to that in the strain harboring only aroF and pheAfbr (E. coli strain PAP), especially under oxygen‐limited conditions. The vgb‐expressing strain PAPV produced 21.9% more biomass and 16.6% more l‐phenylalanine, while consuming only approximately 5% more glucose after 48 H of fermentation. This study demonstrates a method to enhance the l‐phenylalanine production by E. coli using less intensive and thus more economical aeration conditions.
Thermal stability of mullite RMn2O5 (R  =  Bi, Y, Pr, Sm or Gd): combined density functional theory and experimental study

Understanding and effectively predicting the thermal stability of ternary transition metal oxides with heavy elements using first principle simulations are vital for understanding performance of advanced materials. In this work, we have investigated the thermal stability of mullite RMn2O5 (R = Bi, Pr, Sm, or Gd) structures by constructing temperature phase diagrams using an efficient mixed generalized gradient approximation (GGA) and the GGA + U method. Simulation predicted stability regions without corrections on heavy elements show a 4–200 K underestimation compared to our experimental results. We have found the number of d/f electrons in the heavy elements shows a linear relationship with the prediction deviation. Further correction on the strongly correlated electrons in heavy elements could significantly reduce the prediction deviations. Our corrected simulation results demonstrate that further correction of R-site elements in RMn2O5 could effectively reduce the underestimation of the density functional theory-predicted decomposition temperature to within 30 K. Therefore, it could produce an accurate thermal stability prediction for complex ternary transition metal oxide compounds with heavy elements.
Thermal Shock and Thermal Fatigue Testing

A method is described for rapidly screening candidate materials used in severe thermal shock applications. The method involves electron beam heating the surface of specimens using a thermal flux equal to that experienced during actual service operation. Two methods of electron beam radiation are described. In one method, the electron beam is swept across a narrow path with the specimen translated across the beam. In the second method, the specimen remained stationary while the electron beam was repeatedly rastered over a square-shaped area. Similarity of thermal shock damage produced on rocket engine turbine blades during thermal shock tests and during engine firings indicates that computer-controlled electron beam radiation can be used for determining thermal shock resistance of turbine blade materials.
Hsp90 is required for c‐Mos activation and biphasic MAP kinase activation in Xenopus oocytes

During Xenopus oocyte maturation, the Mos protein kinase is synthesized and activates the MAP kinase cascade. In this report, we demonstrate that the synthesis and activation of Mos are two separable processes. We find that Hsp90 function is required for activation and phosphorylation of Mos and full activation of the MAP kinase cascade. Once Mos is activated, Hsp90 function is no longer required. We show that Mos interacts with both Hsp90 and Hsp70, and that there is an inverse relationship between association of Mos with these two chaperones. We propose that Mos protein kinase is activated by a novel mechanism involving sequential association with Hsp70 and Hsp90 as well as phosphorylation. We also present evidence for a two‐phase activation of MAP kinase in Xenopus oocytes.
Modeling Adaptive Educational Methods with IMS Learning Design

The paper describes a classification system for adaptive methods developed in the area of adaptive educational hypermedia based on four dimensions: What components of the educational system are adapted? To what features of the user and the current context does the system adapt? Why does the system adapt? How does the system get the necessary information? Based on this taxonomy several classical methods of adaptive educational hypermedia are classified. In a second step the paper gives an overview of key features in IMS-LD for implementing adaptive educational methods and gives some examples. In the last section the work is integrated and IMS-LD features are identified which can be used for the four dimensions of the classification system. Editors: Daniel Burgos.
Design, development and experimental assessment of a robotic end-effector for non-standard concrete applications

Despite the recent advances in, and the adoption of robotic technologies in the construction industry, the architectural processes which demand a high degree of geometric freedom still remain largely labour intensive and manual. This is due to the inherent difficulties in robotizing the current implementation of such processes coupled with the lack of alternate robotic technologies. A specific example, which is also the focus of this paper, is that of building a steel reinforced concrete structure, with varying curvature or cross-section. This process still remains rather manual and requires extensive support of customized form-work. In this paper, first we describe an alternate novel robotic fabrication process for building steel wire meshes which act as both reinforcement and formwork. The robotization of such a process is discussed with the use of a previously developed mobile robotic system. Based on the specifications derived from the process, design of a novel custom designed robotic end-effector, enabling this process, is detailed. Automation of the full robotic system comprising the mobile robotic system and the robotic end-effector is discussed from simulation to control. Through experimental evaluation of the robotic system, we demonstrate the ability to fully automate the construction of non-standard steel reinforced steel meshes of varying curvature and cell sizes.
Tendon Contraction After Cyclic Elongation Is an Age-Dependent Phenomenon

Background: Tendons are viscoelastic tissues that deform (elongate) in response to cyclic loading. However, the ability of a tendon to recover this elongation is unknown. Hypothesis: Tendon length significantly increases after in vivo or in vitro cyclic loading, and the ability to return to its original length through a cell-mediated contraction mechanism is an age-dependent phenomenon. Study Design: Controlled laboratory study. Methods: In vitro, rat tail tendon fascicles (RTTfs) from Sprague-Dawley rats of 3 age groups (1, 3, and 12 months) underwent 2% cyclic strain at 0.17 Hz for 2 hours, and the percentages of elongation were determined. After loading, the RTTfs were suspended for 3 days under tissue culture conditions and photographed daily to determine the amount of length contraction. In vivo, healthy male participants (n = 29; age, 19-49 years) had lateral, single-legged weightbearing radiographs taken of the knee at 60° of flexion immediately before, immediately after, and 24 hours after completing eccentric quadriceps loading exercises on the dominant leg to fatigue. Measurements of patellar tendon length were taken from the radiographs, and the percentages of tendon elongation and subsequent contraction were calculated. Results: In vitro, cyclic loading increased the length of all RTTfs, with specimens from younger (1 and 3 months) rats demonstrating significantly greater elongation than those from older (12 months) rats (P = .009). The RTTfs contracted to their original length significantly faster (P < .001) and in an age-dependent fashion, with younger animals contracting faster. In vivo, repetitive eccentric loading exercises significantly increased patellar tendon length (P < .001). Patellar tendon length decreased 24 hours after exercises (P < .001) but did not recover completely (P < .001). There was a weak but significant (R 2 = 0.203, P = .014) linear correlation between the amount of tendon contraction and age, with younger participants (<30 years) demonstrating significantly more contraction (P = .014) at 24 hours than older participants (>30 years). Conclusion: Cyclic tendon loading results in a significant increase in tendon elongation under both in vitro and in vivo conditions. Tendons in both conditions demonstrated an incomplete return to their original length after 24 hours, and the extent of this return was age dependent. Clinical Relevance: The age- and time-dependent contraction of tendons, elongated after repetitive loading, could result in transient alterations in the mechanobiological environment of tendon cells. This, in turn, could induce the onset of catabolic changes associated with the pathogenesis of tendinopathy. These results suggest the importance of allowing time for contraction between bouts of repetitive exercise and may explain why age is a predisposing factor in tendinopathy.
In vitro interactions of LytA, the major pneumococcal autolysin, with two bacteriophage lytic enzymes (Cpl-1 and Pal), cefotaxime and moxifloxacin against antibiotic-susceptible and -resistant Streptococcus pneumoniae strains.

OBJECTIVES In an innovative therapeutic exploitation against antibiotic-resistant Streptococcus pneumoniae, here we have evaluated the in vitro activity of a purified bacterially-encoded cell wall lytic enzyme, LytA (the major pneumococcal autolysin), and compared it with those of Cpl-1 and Pal (pneumococcal phage lytic enzymes) and two antibiotics versus four pneumococcal strains. METHODS Two serotype 3, penicillin-susceptible strains and two penicillin-resistant (serotypes 19F and 19A, respectively) S. pneumoniae clinical isolates were used. The effect of several combinations of lytic enzymes and antibiotics (cefotaxime and moxifloxacin) was studied by chequerboard and time-kill assays, the latter at concentrations of 0.25 x MIC. RESULTS LytA was more active than Cpl-1 and Pal. By the chequerboard technique, the combination of LytA and cefotaxime was synergistic for one of the two cefotaxime-resistant strains studied. The combined use of Cpl-1 and Pal was synergistic for three of the four strains, as was Cpl-1 with antibiotics for two of the three strains studied. In the time-kill assays, after 5 h of exposure to LytA, Cpl-1 or Pal, the mean differences in colony counts versus controls were -3.55, -2.66 and -2.71 log(10) cfu/mL, respectively. The combination of LytA/Pal reduced the bacterial inoculum >2 log units for three of the four strains. LytA combined with cefotaxime or moxifloxacin achieved >3 log units decrease for the strains tested. Particularly, a strong synergism was observed with LytA/cefotaxime for one cefotaxime-resistant meningeal strain. LytA/moxifloxacin was synergistic for the quinolone-resistant strain when tested by time-kill methodology, and just close to synergistic (fractional inhibitory concentration index of 0.58) by the chequerboard technique. Antagonism was not observed for any combination when assayed by either method. CONCLUSIONS LytA, Cpl-1 or Pal, alone or in combination, might prove to be effective in combination therapy, as well as in monotherapy against S. pneumoniae. These results suggest avenues of research to study the cell wall lytic enzymes as anti-pneumococcal therapeutic agents.
Adjuncts to physical training of patients with severe COPD: oxygen or noninvasive ventilation?

BACKGROUND Previous studies have shown positive effects from noninvasive ventilation (NIV) or supplemental oxygen on exercise capacity in patients with COPD. However, the best adjunct for promoting physiologic adaptations to physical training in patients with severe COPD remains to be investigated. METHODS Twenty-eight patients (mean +/- SD age 68 +/- 7 y) with stable COPD (FEV(1) 34 +/- 9% of predicted) undergoing an exercise training program were randomized to either NIV (n = 14) or supplemental oxygen (n = 14) during group training to maintain peripheral oxygen saturation (S(pO2)) >/= 90%. Physical training consisted of treadmill walking (at 70% of maximal speed) 3 times a week, for 6 weeks. Patients were assessed at baseline and after 6 weeks. Assessments included physiological adaptations during incremental exercise testing (ratio of lactate concentration to walk speed, oxygen uptake [V (O2)], and dyspnea), exercise tolerance during 6-min walk test, leg fatigue, maximum inspiratory pressure, and health-related quality of life. RESULTS Two patients in each group dropped out due to COPD exacerbations and lack of exercise program adherence, and 24 completed the training program. Both groups improved 6-min walk distance, symptoms, and health-related quality of life. However, there were significant differences between the NIV and supplemental-oxygen groups in lactate/speed ratio (33% vs -4%), maximum inspiratory pressure (80% vs 23%), 6-min walk distance (122 m vs 47 m), and leg fatigue (25% vs 11%). In addition, changes in S(pO2)/speed, V (O2), and dyspnea were greater with NIV than with supplemental-oxygen. CONCLUSIONS NIV alone is better than supplemental oxygen alone in promoting beneficial physiologic adaptations to physical exercise in patients with severe COPD.
Tsallis Regularized Optimal Transport and Ecological Inference

Optimal transport is a powerful framework for computing distances between probability distributions. We unify the two main approaches to optimal transport, namely Monge-Kantorovitch and Sinkhorn-Cuturi, into what we define as Tsallis regularized optimal transport (TROT). TROT interpolates a rich family of distortions from Wasserstein to Kullback-Leibler, encompassing as well Pearson, Neyman and Hellinger divergences, to name a few. We show that metric properties known for Sinkhorn-Cuturi generalize to TROT, and provide efficient algorithms for finding the optimal transportation plan with formal convergence proofs. We also present the first application of optimal transport to the problem of ecological inference, that is, the reconstruction of joint distributions from their marginals, a problem of large interest in the social sciences. TROT provides a convenient framework for ecological inference by allowing to compute the joint distribution -— that is, the optimal transportation plan itself — when side information is available, which is e.g. typically what census represents in political science. Experiments on data from the 2012 US presidential elections display the potential of TROT in delivering a faithful reconstruction of the joint distribution of ethnic groups and voter preferences.
Pedestrian Detection by Boosting Soft-Margin SVM with Local Feature Selection

We present an example-based algorithm for detecting objects in images by integrating component-based clas-siﬂers, which automaticaly select the best local-feature for each classiﬂer and are combined according to Ad-aBoost algorithm. The system employs soft-margin SVM for base learner, which is trained for all local-features and the optimal feature is selected at each stage of boosting. The proposed method is applied to the MIT CBCL pedestrian image database, and shows fairly good result with 10 local-features such as full image, upper half, lower half, right half, left half, head, right arm, left arm, legs, and body center.
Puzzling Findings in Studying the Outcome of “Real World” Adolescent Mental Health Services: The TRAILS Study

Background The increased use and costs of specialist child and adolescent mental health services (MHS) urge us to assess the effectiveness of these services. The aim of this paper is to compare the course of emotional and behavioural problems in adolescents with and without MHS use in a naturalistic setting. Method and Findings Participants are 2230 (pre)adolescents that enrolled in a prospective cohort study, the TRacking Adolescents' Individual Lives Survey (TRAILS). Response rate was 76%, mean age at baseline 11.09 (SD 0.56), 50.8% girls. We used data from the first three assessment waves, covering a six year period. Multiple linear regression analysis, propensity score matching, and data validation were used to compare the course of emotional and behavioural problems of adolescents with and without MHS use. The association between MHS and follow-up problem score (β 0.20, SE 0.03, p-value<0.001) was not confounded by baseline severity, markers of adolescent vulnerability or resilience nor stressful life events. The propensity score matching strategy revealed that follow-up problem scores of non-MHS-users decreased while the problem scores of MHS users remained high. When taking into account future MHS (non)use, it appeared that problem scores decreased with limited MHS use, albeit not as much as without any MHS use, and that problem scores with continuous MHS use remained high. Data validation showed that using a different outcome measure, multiple assessment waves and multiple imputation of missing values did not alter the results. A limitation of the study is that, although we know what type of MHS participants used, and during which period, we lack information on the duration of the treatment. Conclusions The benefits of MHS are questionable. Replication studies should reveal whether a critical examination of everyday care is necessary or an artefact is responsible for these results.