Miracle-dz/UniFAR-FTUs huggingface dataset:
Homozygous Type I Protein C Deficiency in Two Unrelated Families Exhibiting Thrombophilia Related to Ala136→Pro or Arg286→His Mutations

Summary Separate single nucleotide mutations have been identified in two unrelated homozygous type I protein C deficient individuals suffering from thrombophilia. Each mutation, initially established by direct DNA sequencing of polymerase chain reaction amplification products, results in an amino acid substitution. The first mutation (PCClamart) results in an Ala136 to Pro substitution in the protein’s second epidermal growth factor-like domain. The second mutation (PCMtinchen) results in an Arg286 to His substitution in the serine protease domain. Comparison of the location of these two mutations and the relative conservation of the two regions in homologous vitamin K-dependent plasma proteins is consistent with the difference in severity of protein C deficiency and disease in the two individuals. Both mutations result in the abolition of a naturally occurring restriction endonuclease site, thereby allowing independent confirmation of the mutations and rapid and unambiguous genetic analysis of protein C deficiency in family members. In both families, the genetic analysis has proven useful in cases where an assignment of the protein C status based upon clinical laboratory measurements was either ambiguous or incorrect.
Introduction to the Epidemiologic Considerations, Analytic Methods, and Foundational Results From the Pneumonia Etiology Research for Child Health Study

O’Brien, KL; Baggett, HC; Brooks, WA; Feikin, DR; Hammitt, LL; Howie, SRC; Deloria Knoll, M; Kotloff, KL; Levine, OS; Madhi, SA; +4 more. Murdoch, DR; Scott, JAG; Thea, DM; Zeger, SL; (2017) Introduction to the Epidemiologic Considerations, Analytic Methods, and Foundational Results From the Pneumonia Etiology Research for Child Health Study. Clinical infectious diseases, 64 (suppl). S179− S184.ISSN1058− 4838DOI : https : //doi.org/10.1093/cid/cix142 Downloaded from: http://researchonline.lshtm. ac.uk/3928367/ DOI: https://doi.org/10.1093/cid/cix142
Genetic disassembly and combinatorial reassembly identify a minimal functional repertoire of type III effectors in Pseudomonas syringae

The virulence of Pseudomonas syringae and many other proteobacterial pathogens is dependent on complex repertoires of effector proteins injected into host cells by type III secretion systems. The 28 well-expressed effector genes in the repertoire of the model pathogen P. syringae pv. tomato DC3000 were deleted to produce polymutant DC3000D28E. Growth of DC3000D28E in Nicotiana benthamiana was symptomless and 4 logs lower than that of DC3000ΔhopQ1-1, which causes disease in this model plant. DC3000D28E seemed functionally effectorless but otherwise WT in diagnostic phenotypes relevant to plant interactions (for example, ability to inject the AvrPto-Cya reporter into N. benthamiana). Various effector genes were integrated by homologous recombination into native loci or by a programmable or random in vivo assembly shuttle (PRIVAS) system into the exchangeable effector locus in the Hrp pathogenicity island of DC3000D28E. The latter method exploited dual adapters and recombination in yeast for efficient assembly of PCR products into programmed or random combinations of multiple effector genes. Native and PRIVAS-mediated integrations were combined to identify a minimal functional repertoire of eight effector genes that restored much of the virulence of DC3000ΔhopQ1-1 in N. benthamiana, revealing a hierarchy in effector function: AvrPtoB acts with priority in suppressing immunity, enabling other effectors to promote further growth (HopM1 and HopE1), chlorosis (HopG1), lesion formation (HopAM1-1), and near full growth and symptom production (AvrE, HopAA1-1, and/or HopN1 functioning synergistically with the previous effectors). DC3000D28E, the PRIVAS method, and minimal functional repertoires provide new resources for probing the plant immune system.
Simple algorithm for recurrent neural networks that can learn sequence completion

We can memorize long sequences like melodies or poems and it is intriguing to develop efficient connectionist representations for this problem. Recurrent neural networks have been proved to offer a reasonable approach here. We start from a few axiomatic assumptions and provide a simple mathematical framework that encapsulates the problem. A gradient-descent based algorithm is derived in this framework. Demonstrations on a benchmark problem show the applicability of our approach.
Comment: the global epidemic of childhood obesity: is there a role for the paediatrician?

Is there a role for the paediatrician in the global epidemic of childhood obesity? The answer should be obvious. When parents and the society are concerned about child health, they still turn to health professionals caring for children and adolescents, such as paediatricians, family practitioners , general practitioners or nurses. The report of the International Obesity TaskForce to the World Health Organization in this issue of Obesity Reviews (1) estimates that about 10% of young people aged 5–17 years are overweight , among which 2–3% are obese, corresponding for the year 2000 to 155 million overweight children including 30–45 million obese children worldwide. This report also describes how the burden of paediatric obesity is unequally distributed between regions of the world, and even between populations within countries. While paediatric obesity is still a relatively marginal problem in Sub-Saharan Africa and in large parts of the Asia-Pacific region, it is rapidly becoming the most frequent chronic paediatric condition in many countries of the Americas, Europe and the Near/ Middle East. Therefore, at least in these regions, the primary health care providers for children can no longer ignore such a frequent problem. Most paediatricians actually are very concerned about obesity in their young patients, and feel that they have to do something about it, anything! But most also feel unprepared, ill-equipped, and frankly ineffective to address the problem (2). One of the reasons for the paediatrician's awkwardness with the obesity epidemic is that the approach of obese children and adolescents has almost only focused on weight loss. Pediatricians often do not have the training and the skills for weight management using behaviour modification (2), and such programmes are difficult to implement in the office setting under the classic acute paediatric care model. Most approaches involve a team, including a dietitian, a psychologist, or/and a physical activity specialist, resources that are usually not available in the paediatric office or even in referral centres. Therefore primary care providers are faced with pressing requests to which they are unable to respond alone. Even if they could, in many countries where medicine is not socialized, these efforts are not financially compensated (3), discouraging involvement outside the traditional boundaries of the paediatric practice. Clearly, considering the size of the obesity epidemic, not all obese children will be able to be treated by a specialized team, and creative solutions need to be generated for weight management in the …
Transparent Garbage Collection for C++

A number of possible approaches to automatic memory management in C++ have been considered over the years. Here we propose the reconsideration of an approach that relies on partially conservative garbage collection. Its principal advantage is that objects referenced by ordinary pointers may be garbage-collected. Unlike other approaches, this makes it possible to garbage-collect objects allocated and manipulated by most legacy libraries. This makes it much easier to convert existing code to a garbage-collected environment. It also means that it can be used, for example, to “repair” legacy code with deficient memory management. The approach taken here is similar to that taken by Bjarne Stroustrup’s much earlier proposal (N0932=96-0114). Based on prior discussion on the core reflector, this version does insist that implementations make an attempt at garbage collection if so requested by the application. However, since there is no real notion of space usage in the standard, there is no way to make this a substantive requirement. An implementation that “garbage collects” by deallocating all collectable memory at process exit will remain conforming, though it is likely to be unsatisfactory for some uses.
The vector-thread architecture

The vector-thread (VT) architectural paradigm unifies the vector and multithreaded compute models. The VT abstraction provides the programmer with a control processor and a vector of virtual processors (VPs). The control processor can use vector-fetch commands to broadcast instructions to all the VPs or each VP can use thread-fetches to direct its own control flow. A seamless intermixing of the vector and threaded control mechanisms allows a VT architecture to flexibly and compactly encode application parallelism and locality, and a VT machine exploits these to improve performance and efficiency. We present SCALE, an instantiation of the VT architecture designed for low-power and high-performance embedded systems. We evaluate the SCALE prototype design using detailed simulation of a broad range of embedded applications and show that its performance is competitive with larger and more complex processors.
Asian Foreign Exchange Risk Exposure

This paper examines whether there exists any relationship between individual Asian firms' stock returns and fluctuations in foreign exchange rates. We find that about 25 percent of these firms experienced economically significant exposure effects to the U.S. dollar and 22.5 percent to the Japanese yen for the period January 1993 to January 2003. While there is time-variation in contemporaneous exposure effects at the individual firm level, the overall extent of exposure is not sample dependent; a depreciating (appreciating) Asian currency against foreign currencies has a net negative (positive) impact on Asian stock returns. The extent to which firms are exposed to exchange rate fluctuations varies with return horizons; short-term exposure seems to be relatively well hedged, where considerable evidence of long-term exposure is found. Firms with weak liquidity positions, in terms of high dividend payout ratios, or less profitable firms, tend to have smaller exposures. We also find that highly leveraged firms or firms with a lower quick ratio are more exposed to exchange rate risk.
Stack distance based worst-case instruction cache performance analysis

The worst-case execution time (WCET) analysis is critical to ensure the schedulability and correctness of hard real-time systems. Modern microprocessors, however, make the WCET analysis complicated, mainly because of their performance acceleration features like caches, pipelines, out-of-order execution, etc. This paper focuses on studying an accurate static timing analysis approach for instruction caches with the LRU-based strategy by computing the worst-case stack distance. The experimental results indicate that our approach can accurately predict worst-case instruction cache performance. Also, the stack distance based timing analysis approach can efficiently categorize worst-case instruction cache misses into cold, conflict and capacity misses, which can provide useful insights to improve the worst-case instruction cache performance.
A Probabilistic Approach for Robust Leakage-Based MU-MIMO Downlink Beamforming with Imperfect Channel State Information

Multi-user multiple-input and multiple-output (MU-MIMO) wireless systems have the potential to increase system capacity significantly by separating multiple users in the space domain through appropriate signal processing. These techniques require accurate channel state information at transmitter (CSIT) for their proper operations. With inevitable channel imperfections in practice, robustness has become an important issue in the development of beamforming techniques. In this work, we propose a robust leakage-based transmit beamforming design for multi-user MIMO systems by introducing a probabilistic constraint. In a multi-user system, the main challenge for transmit beamforming is to suppress the co-channel interference (CCI) from other users. Our approach optimizes the average signal-to-interference-plus-noise ratio (SINR) performance implicitly by maximizing the average signal power subject to probabilistic leakage and noise power constraint. Moreover, both the single-stream-per-user and multiple-stream-per-user cases are considered.In the latter case, a hybrid scheme is suggested by incorporating Alamouti code into the proposed design. Simulation results show that under proper control of the probabilistic constraint, both beamformers achieve good bit-error-rate (BER) performances, reliability of SINR levels as well as robustness against channel uncertainties.
Relationship between Stroop performance and resting state functional connectivity in cognitively normal older adults.

OBJECTIVE Early biomarkers of Alzheimer's disease (AD) are needed for developing therapeutic interventions. Measures of attentional control in Stroop-type tasks discriminate healthy aging from early stage AD and predict future development of AD in cognitively normal individuals. Disruption in resting state functional connectivity MRI (rs-fcMRI) has been reported in AD and in healthy controls at risk for AD. We explored the relationship among Stroop performance, rs-fcMRI, and CSF Aβ₄₂ levels in cognitively normal older adults. METHOD A computerized Stroop task (along with standard neuropsychological measures), rs-fcMRI, and CSF were obtained in 237 cognitively normal older adults. We compared the relationship between Stroop performance, including measures from reaction distributional analyses, and composite scores from four resting state networks (RSNs; default mode [DMN], salience [SAL], dorsal attention [DAN], and sensory-motor [SMN]), and the modulatory influence of CSF Aβ₄₂ levels. RESULTS A larger Stroop effect in errors was associated with reduced rs-fcMRI within the DMN and SAL. Reaction time (RT) distributional analyses indicated the slow tail of the RT distribution was related to reduced rs-fcMRI functional connectivity within the SAL. Standard psychometric measures were not related to RSN composite scores. A relationship between Stroop performance and DMN (but not SAL) functional connectivity was stronger in CSF Aβ₄₂-positive individuals. CONCLUSIONS A link exists between RSN composite scores and specific attentional performance measures. Both measures may be sensitive biomarkers for AD.
The Level of Protein in Milk Formula Modifies Ileal Sensitivity to LPS Later in Life in a Piglet Model

BACKGROUND Milk formulas have higher protein contents than human milk. This high protein level could modify the development of intestinal microbiota, epithelial barrier and immune functions and have long-term consequences. METHODOLOGY/PRINCIPAL FINDINGS We investigated the effect of a high protein formula on ileal microbiota and physiology during the neonatal period and later in life. Piglets were fed from 2 to 28 days of age either a normoprotein (NP, equivalent to sow milk) or a high protein formula (HP, +40% protein). Then, they received the same solid diet until 160 days. During the formula feeding period ileal microbiota implantation was accelerated in HP piglets with greater concentrations of ileal bacteria at d7 in HP than NP piglets. Epithelial barrier function was altered with a higher permeability to small and large probes in Ussing chambers in HP compared to NP piglets without difference in bacterial translocation. Infiltration of T cells was increased in HP piglets at d28. IL-1β and NF-κB sub-units mRNA levels were reduced in HP piglets at d7 and d28 respectively; plasma haptoglobin also tended to be reduced at d7. Later in life, pro-inflammatory cytokines secretion in response to high doses of LPS in explants culture was reduced in HP compared to NP piglets. Levels of mRNA coding the NF-κB pathway sub-units were increased by the challenge with LPS in NP piglets, but not HP ones. CONCLUSIONS/SIGNIFICANCE A high protein level in formula affects the postnatal development of ileal microbiota, epithelial barrier and immune function in piglets and alters ileal response to inflammatory mediators later in life.
Update on atrial remodelling owing to rate; does atrial fibrillation always 'beget' atrial fibrillation?

Atrial fibrillation is the most common arrhythmia in humans. The mechanisms underlying its induction and maintenance are not fully understood. However, it seems likely that, similar to sustained ventricular tachyarrhythmias, atrial fibrillation induction and maintenance are related to the presence of an anatomical and/or electrophysiological substrate, activated by specific triggers (ectopic beats), in the presence of a modulating factor (autonomic system status). It has been suggested, by Moe in the 1960s and subsequently confirmed by atrial mapping in animals and humans, that the substrate comprises multiple wavelets. This hypothesis states that the induction of sustained atrial fibrillation depends on the average number of reentrant circuits present in the atria. If the number of the wavelets is high, the statistical probability that they will die at the same time will be small and atrial fibrillation will persist; on the other hand, when the number of reentrant wavelets is small, the chance that they will die out simultaneously is higher, and the termination of the arrhythmia more likely. The number of wavelets that can coexist is determined both by the atrial tissue mass and the wavelength (wavelength= conduction velocity refractory period) of the atrial impulse. The smaller the wavelength of circulating wavelets the more easily atrial fibrillation is induced and maintained. Consequently, a slower conduction velocity, a shorter refractory period or both reduce the wavelength, thus increasing the number of possible circuits in the atria and leading to a more stable atrial fibrillation.
New Generation of Linux Meta-installers

One of the points that differentiates most Linux distributions nowadays is the meta-installer. Meta-installers are software programs that run over RPM / DEB / TGZ installation systems, providing for automatic resolution of dependencies. Meta-installers like Apt-get, Smart or Yum are used widely and are starting to have more features. A framework for the new generation of meta-installers are being devised by a joint group of research and commercial partners of EDOS project (Environment for the development and Distribution of Open Source software)[1]. This article presents the new meta-installer features that are being developed and the ones that are still under research such as: rollback, new dependency solving and hardware support by RPM / DEB packages. These features have as common point the fact they extend the packaging system.
Semi-join algorithms for multiprocessor systems

Semi-join is a relational operator that decreases the cost of processing queries involving binary operations. This is accomplished by initially selecting the data relevant to answer the queries and thereby reducing the size of the operand relations. This paper presents and analyzes algorithms for computing semi-joins in a multiprocessor database machine. First, an architecture model of a multiprocessor system is described. The model incorporates 1-0, CPU and messages transmission cost parameters to enable the evaluation of these algorithms in terms of their execution costs. Then two equi-semi-join algorithms are presented and compared and one inequi-semi-join algorithm is proposed. The execution cost of these algorithms are generally lineary proportional to the size of the operand and result relations and inversely proportional to the number of processors. Then, the method by joining two relations and the method by joining their semi-joins are compared. Finally it is shown that the method using semi-joins is generally better.
Hierarchical Density-Based Clustering of White Matter Tracts in the Human Brain

Diffusion tensor magnetic resonance imaging (DTI) provides a promising way of estimating the neural fiber pathways in the human brain non-invasively via white matter tractography. However, it is difficult to analyze the vast number of resulting tracts quantitatively. Automatic tract clustering would be useful for the neuroscience community, as it can contribute to accurate neurosurgical planning, tract-based analysis, or white matter atlas creation. In this paper, the authors propose a new framework for automatic white matter tract clustering using a hierarchical density-based approach. A novel fiber similarity measure based on dynamic time warping allows for an effective and efficient evaluation of fiber similarity. A lower bounding technique is used to further speed up the computation. Then the algorithm OPTICS is applied, to sort the data into a reachability plot, visualizing the clustering structure of the data. Interactive and automatic clustering algorithms are finally introduced to obtain the clusters. Extensive experiments on synthetic data and real data demonstrate the effectiveness and efficiency of our fiber similarity measure and show that the hierarchical density-based clustering method can group these tracts into meaningful bundles on multiple scales as well as eliminating noisy fibers.
Tropical Sprue

One of the more mysterious and still rather poorly understood diseases seen in the tropical regions of the world is Tropical Sprue (TS). TS is a clinical syndrome with an unknown etiology typically characterized by an acquired chronic diarrheal illness, small bowel mucosal abnormalities and malabsorption resulting in nutritional deficiencies and weight loss [1]. These are vague symptoms which can be produced by a large spectrum of diseases. Findings on endoscopy and histology can be nonspecific which can make the diagnosis of TS challenging [2].
Fragmented QRS as a Marker of Conduction Abnormality and a Predictor of Prognosis of Brugada Syndrome

Background— Conduction abnormalities serve as a substrate for ventricular fibrillation (VF) in patients with Brugada syndrome (BS). Signal-averaged electrograms can detect late potentials, but the significance of conduction abnormalities within the QRS complex is still unknown. The latter can present as multiple spikes within the QRS complex (fragmented QRS [f-QRS]). We hypothesized that f-QRS could indicate a substrate for VF and might predict a high risk of VF for patients with BS. Methods and Results— In study 1, we analyzed the incidence of f-QRS in 115 patients with BS (13 resuscitated from VF, 28 with syncope, and 74 asymptomatic). f-QRS was observed in 43% of patients, more often in the VF group (incidence of f-QRS: VF 85%, syncope 50%, and asymptomatic 34%, P<0.01). SCN5A mutations occurred more often in patients with f-QRS (33%) than in patients without f-QRS (5%). In patients with syncope or VF, only 6% without f-QRS experienced VF during follow-up (43±25 months), but 58% of patients with f-QRS had recurrent syncope due to VF (P<0.01). In study 2, to investigate the mechanism of f-QRS, we studied in vitro models of BS in canine right ventricular tissues (n=4) and optically mapped multisite action potentials. In the experimental model of BS, ST elevation resulted from a large phase 1 notch of the action potential in the epicardium, and local epicardial activation delay reproduced f-QRS in the transmural ECG. Conclusions— f-QRS appears to be a marker for the substrate for spontaneous VF in BS and predicts patients at high risk of syncope.