Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenomics-guided discovery of a novel conserved cassette of short linear motifs in BubR1 essential for the spindle checkpoint

The spindle assembly checkpoint (SAC) maintains genomic integrity by preventing progression of mitotic cell division until all chromosomes are stably attached to spindle microtubules. The SAC critically relies on the paralogs Bub1 and BubR1/Mad3, which integrate kinetochore-spindle attachment status with generation of the anaphase inhibitory complex MCC. We previously reported on the widespread occurrences of independent gene duplications of an ancestral ‘MadBub’ gene in eukaryotic evolution and the striking parallel subfunctionalization that lead to loss of kinase function in BubR1/Mad3-like paralogs. We now present an elaborate subfunctionalization analysis that includes all known motifs in Bub1 and BubR1, and show that ancestral features are consistently retained in the same functional paralog: GLEBS/CDI/CDII/kinase in the Bub1-like and KEN1/KEN2/D-Box in the BubR1/Mad3-like. The recently described ABBA motif can be found in either or both paralogs. We however discovered two additional ABBA motifs that flank KEN2. This cassette of ABBA1-KEN2-ABBA2 forms a strictly conserved module in all ancestral and BubR1/Mad3-like proteins, suggestive of a specific and crucial SAC function. Indeed, deletion of the ABBA motifs in human BUBR1 abrogates the SAC and affects APC/C-Cdc20 interactions. Our detailed comparative genomics analyses thus enabled discovery of a conserved cassette of motifs essential for the SAC and shows how this approach can be used to uncover hitherto unrecognized functional protein features.
The Impact of Family and Parental Education on Adolescents' Substance Use: A Study of U.S. High School Seniors

This study explores the impact of family structure and parental education on adolescents' substance use using a racially diverse sample of 14,268, 12th-grade high school adolescents. Findings reveal that family structure affects adolescents' substance use. In addition, racial differences are noted. African American adolescents report a relatively lower rate of substance use compared to White and Hispanic adolescents, yet they are gravely affected by substance use outcomes. The study lends further support that family structure and parental education variables may buffer adolescents from substance abuse influences. Implications for practice and policy are discussed.
Variations in the relationships between total 59 Fe uptake and the uptakes into heme and nonheme fractions of spleen and bone marrow in irradiated mice and mouse radiation chimeras.

A chemical method for the separation of heme and nonheme iron-containing fractions in mouse tissues has been used to study the uptake of 59Fe into both the heme and nonheme iron fractions in spleen and femoral bone marrow, in order to investigate the possible relationships between the total uptake into spleen tissue and the rate of uptake into the heme fractions. In control mice, only about one third of the 59Fe is directly associated with heme during the first day after administration, and this fraction decreases as radioactive red cells are released from the spleen into blood. Ten days after X-irradiation of mice, the proportion of 59Fe in the spleen heme fraction 6 hr after intraperitoneal administration decreased from about 30 to 10% of the total splenic activity as the radiation dose was increased from 500 to 750 rads. A similar alteration in the proportion of 59 Fe in the spleen haem fraction occurred in mouse radiation chimeras as the dose of injected syngeneic bonemarrow cells was reduced from 5 x 105 to zero. Similar results were found in femoral bone marrow. These results indicate that in this system the rate of uptake into whole tissue is not a measure of the uptake into heme; it is necessary, therefore, to use the method involving the measurement of iron uptake into heme, rather than the total tissue uptake, when estimating hemoglobin synthesis or erythropoiesis.
Airway and Feeding Outcomes of Mandibular Distraction, Tongue-Lip Adhesion, and Conservative Management in Pierre Robin Sequence: A Prospective Study

Background: Pierre Robin sequence is characterized by mandibular retrognathia and glossoptosis resulting in airway obstruction and feeding difficulties. When conservative management fails, mandibular distraction osteogenesis or tongue-lip adhesion may be required to avoid tracheostomy. The authors’ goal was to prospectively evaluate the airway and feeding outcomes of their comprehensive approach to Pierre Robin sequence, which includes conservative management, mandibular distraction osteogenesis, and tongue-lip adhesion. Methods: A longitudinal study of newborns with Pierre Robin sequence treated at a pediatric academic medical center between 2010 and 2015 was performed. Baseline feeding and respiratory data were collected. Patients underwent conservative management if they demonstrated sustainable weight gain without tube feeds, and if their airway was stable with positioning alone. Patients who required surgery underwent tongue-lip adhesion or mandibular distraction osteogenesis based on family and surgeon preference. Postoperative airway and feeding data were collected. Results: Twenty-eight patients with Pierre Robin sequence were followed prospectively. Thirty-two percent had a syndrome. Ten underwent mandibular distraction osteogenesis, eight underwent tongue-lip adhesion, and 10 were treated conservatively. There were no differences in days to extubation or discharge, change in weight percentile, requirement for gastrostomy tube, or residual obstructive sleep apnea between the three groups. No patients required tracheostomy. The greatest reduction in apnea-hypopnea index occurred with mandibular distraction osteogenesis, followed by tongue-lip adhesion and conservative management. Conclusions: Careful selection of which patients with Pierre Robin sequence need surgery, and of the most appropriate surgical procedure for each patient, can minimize the need for postprocedure tracheostomy. A comprehensive approach to Pierre Robin sequence that includes conservative management, mandibular distraction osteogenesis, and tongue-lip adhesion can result in excellent airway and feeding outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.
VHDL-AMS modelling of current convoyer cell for integration in RF-application

In this paper we present a library which contains different second generation current conveyor CCII models described with the material description language VHDL-AMS and classified with an increase range of complexity in order to be used in high level design concerning current controlled oscillator and multi-function programmable filters. The proposed CCII models and the presented applications are tested with VHDL- AMS simulations using CMOS 0.35u technology to verify the theoretical results.
Controllability of a multibody mobile robot

Presents a proof of controllability for multibody mobile robots. An instance of such systems correspond to a car pulling and pushing trailers, like a luggage carrier in an airport. Three modeling levels are built: geometrical, differential and control models respectively. The authors shows that four different control systems correspond to a same differential model. The differential model is then used to give a same proof of controllability for four distinct multibody mobile robot systems. <<ETX>>
TLR2 Deficiency Aggravates Lung Injury Caused by Mechanical Ventilation

ABSTRACT Innate immunity pathways are found to play an important role in ventilator-induced lung injury. We analyzed pulmonary expression of Toll-like receptor 2 (TLR2) in humans and mice and determined the role of TLR2 in the pathogenesis of ventilator-induced lung injury in mice. Toll-like receptor 2 gene expression was analyzed in human bronchoalveolar lavage fluid (BALF) cells and murine lung tissue after 5 h of ventilation. In addition, wild-type (WT) and TLR2 knockout (KO) mice were ventilated with either lower tidal volumes (VT) of 7 mL/kg with positive end-expiratory pressure (PEEP) or higher VT of 15 mL/kg without PEEP for 5 h. Spontaneously breathing mice served as controls. Total protein and immunoglobulin M levels in BALF, neutrophil influx into the alveolar compartment, and interleukin 6 (IL-6), IL-1&bgr;, and keratinocyte-derived chemokine concentrations in lung tissue homogenates were measured. We observed enhanced TLR2 gene expression in BALF cells of ventilated patients and in lung tissue of ventilated mice. In WT mice, ventilation with higher VT without PEEP resulted in lung injury and inflammation with higher immunoglobulin M levels, neutrophil influx, and levels of inflammatory mediators compared with controls. In TLR2 KO mice, neutrophil influx and IL-6, IL-1&bgr;, and keratinocyte-derived chemokine were enhanced by this ventilation strategy. Ventilation with lower VT with PEEP only increased neutrophil influx and was similar in WT and TLR2 KO mice. In summary, injurious ventilation enhances TLR2 expression in lungs. Toll-like receptor 2 deficiency does not protect lungs from ventilator-induced lung injury. In contrast, ventilation with higher VT without PEEP aggravates inflammation in TLR2 KO mice.
Gene Therapy Targeting Nuclear Factor-κB: Towards Clinical Application in Inflammatory Diseases and Cancer

Nuclear factor (NF)-κB is regarded as one of the most important transcription factors and plays an essential role in the transcriptional activation of pro-inflammatory cytokines, cell proliferation and survival. NF-κB can be activated via two distinct NF-κB signal transduction pathways, the so-called canonical and non-canonical pathways, and has been demonstrated to play a key role in a wide range of inflammatory diseases and various types of cancer. Much effort has been put in strategies to inhibit NF-κB activation, for example by the development of pharmacological compounds that selectively inhibit NF-κB activity and therefore would be beneficial for immunotherapy of transplantation, autoimmune and allergic diseases, as well as an adjuvant approach in patients treated with chemotherapy for cancer. Gene therapy targeting NF-κB is a promising new strategy with the potential of long-term effects and has been explored in a wide variety of diseases, ranging from cancer to transplantation medicine and autoimmune diseases. In this review we discuss recent progress made in the development of NF-κB targeted gene therapy and the evolution towards clinical application.
New Knowledge for and About Primary Care: A View Through the Looking Glass of the Annals of Family Medicine

PURPOSE At this second anniversary of the Annals of Family Medicine, we sought to characterize primary care research and to identify opportunities for new directions by analyzing the content of the first and second volumes of the Annals. METHODS Using an a priori classification scheme, 2 editors independently categorized each research article and essay published in 2003 and 2004, excluding supplements. We categorized the domain of knowledge, methods, topical content, whether articles represented core values of primary care, and looked for articles that studied health/illness/symptoms from a uniquely primary care experience. We reconciled differences by discussion. RESULTS Among 110 articles, knowledge domains reflected the 4 quadrants of the clinician (n = 6), patient, family, or community (10), health care system (32), disease (22), or the interface (39) between these quadrants. The most frequent methods were cross-sectional studies (23), cohorts (15), randomized clinical trials (13), qualitative interviews (11), analyses of secondary data (11), systematic reviews (11), methods/theory development (10), self-reflections (8), and mixed methods (5). The most common topical areas were chronic disease and prevention. Core primary care values were represented in 75% of articles. Only 2 articles represented an integrative illness/healing perspective. CONCLUSIONS Despite contemporary forces driving a reductionistic approach, primary care research, as reflected by articles published in the Annals of Family Medicine, addresses the domains of knowledge that contribute to comprehensive, relationship-centered health care. More work is needed to understand the nature of health and illness in whole people and ways to integrate diverse knowledge, methods and fragmented health care.
Diet-Induced Metabolic Improvements in a Hamster Model of Hypercholesterolemia Are Strongly Linked to Alterations of the Gut Microbiota

ABSTRACT The mammalian gastrointestinal microbiota exerts a strong influence on host lipid and cholesterol metabolism. In this study, we have characterized the interplay among diet, gut microbial ecology, and cholesterol metabolism in a hamster model of hypercholesterolemia. Previous work in this model had shown that grain sorghum lipid extract (GSL) included in the diet significantly improved the high-density lipoprotein (HDL)/non-HDL cholesterol equilibrium (T. P. Carr, C. L. Weller, V. L. Schlegel, S. L. Cuppett, D. M. Guderian, Jr., and K. R. Johnson, J. Nutr. 135:2236-2240, 2005). Molecular analysis of the hamsters' fecal bacterial populations by pyrosequencing of 16S rRNA tags, PCR-denaturing gradient gel electrophoresis, and Bifidobacterium-specific quantitative real-time PCR revealed that the improvements in cholesterol homeostasis induced through feeding the hamsters GSL were strongly associated with alterations of the gut microbiota. Bifidobacteria, which significantly increased in abundance in hamsters fed GSL, showed a strong positive association with HDL plasma cholesterol levels (r = 0.75; P = 0.001). The proportion of members of the family Coriobacteriaceae decreased when the hamsters were fed GSL and showed a high positive association with non-HDL plasma cholesterol levels (r = 0.84; P = 0.0002). These correlations were more significant than those between daily GSL intake and animal metabolic markers, implying that the dietary effects on host cholesterol metabolism are conferred, at least in part, through an effect on the gut microbiota. This study provides evidence that modulation of the gut microbiota-host metabolic interrelationship by dietary intervention has the potential to improve mammalian cholesterol homeostasis, which has relevance for cardiovascular health.
A phase II study of DAS181, a novel host directed antiviral for the treatment of influenza infection.

BACKGROUND DAS181, a novel host-directed antiviral in development for influenza treatment, was assessed in this phase II clinical trial. METHODS This study was a double-blind, placebo-controlled phase II clinical trial assessing influenza viral load and patient safety in otherwise healthy influenza-infected participants. Participants were randomized to a single-dose, multiple-dose, or placebo group and were followed for safety and virologic outcomes. RESULTS A total of 177 laboratory-confirmed influenza-infected participants were enrolled in the trial, which encompassed 3 influenza seasons from 2009-2011 in both the Northern and Southern Hemispheres. Thirty-seven percent of participants had confirmed infection with influenza B, 33% with seasonal H3N2, 29% with pandemic 2009 H1N1, and 1 participant was positive for both influenza B and pandemic 2009 H1N1. Significant effects were observed in regard to decreased change from baseline viral load and viral shedding in the multiple-dose group compared with placebo as measured by quantitative polymerase chain reaction (P < .05). No instances of H274Y were observed among viral isolates from this trial. Overall, the drug was generally well tolerated. CONCLUSIONS DAS181 significantly reduced viral load in participants infected with influenza, thus warranting future clinical development of this novel host-directed therapy. CLINICAL TRIALS.GOV IDENTIFIER: NCT01037205.
Friendship Prediction in Composite Social Networks

Friendship prediction is an important task in social network analysis (SNA). It can help users identify friends and improve their level of activity. Most previous approaches predict users' friendship based on their historical records, such as their existing friendship, social interactions, etc. However, in reality, most users have limited friends in a single network, and the data can be very sparse. The sparsity problem causes existing methods to overfit the rare observations and suffer from serious performance degradation. This is particularly true when a new social network just starts to form. We observe that many of today's social networks are composite in nature, where people are often engaged in multiple networks. In addition, users' friendships are always correlated, for example, they are both friends on Facebook and Google+. Thus, by considering those overlapping users as the bridge, the friendship knowledge in other networks can help predict their friendships in the current network. This can be achieved by exploiting the knowledge in different networks in a collective manner. However, as each individual network has its own properties that can be incompatible and inconsistent with other networks, the naive merging of all networks into a single one may not work well. The proposed solution is to extract the common behaviors between different networks via a hierarchical Bayesian model. It captures the common knowledge across networks, while avoiding negative impacts due to network differences. Empirical studies demonstrate that the proposed approach improves the mean average precision of friendship prediction over state-of-the-art baselines on nine real-world social networking datasets significantly.
The Tumor Suppressor Cylindromatosis (CYLD) Acts as a Negative Regulator for Toll-like Receptor 2 Signaling via Negative Cross-talk with TRAF6 and TRAF7*

Toll-like receptor 2 (TLR2) plays an important role in host defense against bacterial pathogens. Activation of TLR2 signaling not only induces the activation of innate immunity and instructs the development of the acquired immunity but also leads to the detrimental inflammatory responses in inflammatory and infectious diseases. To avoid detrimental inflammatory responses, TLR2 signaling must be tightly regulated. In contrast to the relative known positive regulation of TLR2 signaling, its negative regulation, however, is largely unknown. In addition the distal signaling components that link TLR2 to its downstream signaling pathways have yet to be further defined. In the present study we have provided direct evidence for the negative regulation of TLR2 signaling by the tumor suppressor cylindromatosis (CYLD). We showed that activation of TLR2 signaling by TLR2 ligands including peptidoglycan (PGN), MALP-2, and Pam3CSK4 induces activation of IKKs-IκBα and MKK3/6-p38 pathways not only by TRAF6 but also by TRAF7, a recently identified TRAF family member. The activation of both pathways leads to the transcription of TNF-α, IL-1β, and IL-8 as well as CYLD. CYLD in turn leads to the inhibition of TRAF6 and TRAF7 likely via a deubiquitination-dependent mechanism. The present studies thus unveil a novel autoregulatory feedback mechanism that negatively controls TLR2-IKKs-IκBα/MKK3/6-p38-NF-κB-dependent induction of immune and inflammatory responses via negatively cross-talking with both TRAF6 and TRAF7. These findings provide novel insights into autoregulation and negative regulation of TLR signaling.
Characterizing the software process: a maturity framework

A description is given of a software-process maturity framework that has been developed to provide the US Department of Defense with a means to characterize the capabilities of software-development organizations. This software-development process-maturity model reasonably represents the actual ways in which software-development organizations improve. It provides a framework for assessing these organizations and identifying the priority areas for immediate improvement. It also helps identify those places where advanced technology can be most valuable in improving the software-development process. The framework can be used by any software organization to assess its own capabilities and identify the most important areas for improvement. <<ETX>>
Yield Improvement, Fault-Tolerance to the Rescue?

With the technology entering the nano dimension, manufacturing processes are less and less reliable, thus drastically impacting the yield. A possible solution to alleviate this problem in the future could consist in using fault tolerant architectures to tolerate manufacturing defects. In this paper, we analyze the conditions that make the use of a classical triple modular redundancy (TMR) architecture interesting for a yield improvement purpose.
A Pilot Experiment to Quantify the Effect of Documentation Accuracy on Maintenance Tasks

This paper reports the results and some challenges we discovered during the design and execution of a pilot experiment with 21 bachelor students aimed at investigating the effect of documentation accuracy during software maintenance and evolution activities. As documentation we considered: a high level system functionality description and UML documents. Preliminary results indicate a benefit of +15% in terms of efficiency (computed as number of correct tasks per minute) when a more accurate documentation is used. The discovered challenging aspects to carefully consider in future executions of the experiment are as follows: selecting "the right" documentation artefacts, maintenance tasks and documentation versions, verifying that the subjects really used the documentation during the experiment and measuring documentation-code alignment.
Failure Mechanism for Fine Pitch Microbump in Cu/Sn/Cu System During Current Stressing

Current-induced failures in fine pitch Sn microbump with Cu pillar have been investigated under a current density of 3.2 × 104 A/cm2 and temperature of 150 °C. This process takes place in 2000 h of electromigration test. From the focused ion beam image and energy dispersive X-ray analysis, we observed the intermetallic compound formation, Kirkendall effect, and crack contributed to this failure. There are two stages of failure process for Cu pillar with microbump during current stressing. In the first stage, the whole Sn solder was transformed into intermetallic compound and Kirkendall voids were formed at the interface between the Cu pillar and Cu3Sn intermetallic compound. In the second stage, the Kirkendall voids coalesced into larger porosities then formed continual crack by current stressing, leading more bump resistance increase.
Water fluoridation, osteoporosis, fractures--recent developments.

BACKGROUND Optimal (1ppm) water fluoridation is seen as the most socially equitable way to prevent dental caries, however concerns about the safety of fluoridation are periodically raised. METHODS Research on effects on bone published since the 1991 National Health and Medical Research Council report on water fluoridation was reviewed. RESULTS Thirty-three studies were identified. Adverse effects in animal feeding studies were only seen at doses much greater than those currently used in artificial water fluoridation. The majority of animal studies showed no effect or a beneficial effect of low fluoride doses. The results of ecological studies were conflicting. One of the two cohort studies showed an increase in fracture incidence at fluoride levels four times greater than optimal water fluoridation and the other showed no effect after 20 years' optimal fluoridation. The cross-sectional studies showed a favourable effect on bone mineral density. The clinical trials predominantly showed increased bone density in several sites associated with fluoride treatment of 9-22.6mg fluoride per day for one-four years. CONCLUSION These studies provide a substantial body of evidence that fluoride at up to 1ppm does not have an adverse effect on bone strength, bone mineral density or fracture incidence.