Miracle-dz/UniFAR-FTUs huggingface dataset:
A systems-level integrative framework for genome-wide DNA methylation and gene expression data identifies differential gene expression modules under epigenetic control

MOTIVATION There is a growing number of studies generating matched Illumina Infinium HumanMethylation450 and gene expression data, yet there is a corresponding shortage of statistical tools aimed at their integrative analysis. Such integrative tools are important for the discovery of epigenetically regulated gene modules or molecular pathways, which play key roles in cellular differentiation and disease. RESULTS Here, we present a novel functional supervised algorithm, called Functional Epigenetic Modules (FEM), for the integrative analysis of Infinium 450k DNA methylation and matched or unmatched gene expression data. The algorithm identifies gene modules of coordinated differential methylation and differential expression in the context of a human interactome. We validate the FEM algorithm on simulated and real data, demonstrating how it successfully retrieves an epigenetically deregulated gene, previously known to drive endometrial cancer development. Importantly, in the same cancer, FEM identified a novel epigenetically deregulated hotspot, directly upstream of the well-known progesterone receptor tumour suppressor pathway. In the context of cellular differentiation, FEM successfully identifies known endothelial cell subtype-specific gene expression markers, as well as a novel gene module whose overexpression in blood endothelial cells is mediated by DNA hypomethylation. The systems-level integrative framework presented here could be used to identify novel key genes or signalling pathways, which drive cellular differentiation or disease through an underlying epigenetic mechanism. AVAILABILITY AND IMPLEMENTATION FEM is freely available as an R-package from http://sourceforge.net/projects/funepimod.
Detection and localization of appearance faults in reversible circuits

This work presents a testing scheme for detection of two new type of faults (gate appearance and control appearance fault) in reversible circuit. The testing scheme not only efficiently detects the specified faults with minimum number of test vectors but localizes it simultaneously. Our developed approach only requires a single test vector to detect gate appearance fault while to find control appearance fault it needs n test vectors, where n is the number of input lines present in the circuit. The proposed technique can also work for very large circuits as well. In way to verify logical correctness of our developed technique, we have successfully tested different types of benchmark circuits over our proposed algorithms and obtained results are given at the end of this work.
Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women.

BACKGROUND Results of experimental studies suggest that deviations in gut microbiota composition predispose to excessive energy storage and obesity. The mother influences the original inoculum and the development of infant microbiota, which in turn is associated with later weight gain. OBJECTIVE We characterized the gut microbiota in women according to their body mass index (BMI) and the effect of weight gain over pregnancy on the composition of microbiota before delivery. DESIGN Overweight women (n = 18) were selected according to their prepregnancy BMI from a prospective follow-up study. Normal-weight women (n = 36) were selected as controls in consecutive order of recruitment. Excessive weight gain during pregnancy was defined as >16.0 kg for normal-weight and >11.5 kg for overweight states according to Institute of Medicine recommendations. The composition of gut microbiota was analyzed by fluorescent in situ hybridization coupled with flow cytometry (FCM-FISH) and by quantitative real-time polymerase chain reaction (qPCR). RESULTS Bacteroides and Staphylococcus were significantly higher in the overweight state than in normal-weight women as assessed by FCM-FISH and qPCR. Mother's weight and BMI before pregnancy correlated with higher concentrations of Bacteroides, Clostridium, and Staphylococcus. Microbial counts increased from the first to third trimester of pregnancy. High Bacteroides concentrations were associated with excessive weight gain over pregnancy (P = 0.014). CONCLUSIONS Gut microbiota composition and weight are linked, and mother's weight gain is affected by microbiota. Microbiota modification before and during pregnancy may offer new directions for preventive and therapeutic applications in reducing the risk of overweight and obesity.
Code Suggestion of Method Call Statements Using a Source Code Corpus

When writing source code, developers often reuse existing source code or use libraries in order to effectively develop new software. We propose an approach to suggest method call statements to source code developers. In our study, we focus on method call statements in existing source code. A source code corpus is automatically constructed in advance from existing source code. The corpus stores method call statements before/after a method call statement. Appropriate method call statements are recommended to the developer from the corpus. We implement the proposed approach as an Eclipse plugin and clarify the effectiveness of the approach through evaluations. The evaluation results show that appropriate method call statements are ranked highly in the candidate list.
Security assessment of synthesized actuation sequences for digital microfluidic biochips

In this paper, we address the problem of security in the context of Digital Microfluidic Biochips (DMFB) realizations, more specifically, we take up the concern of security threats on a given actuation sequence. Given a bio-chemical reaction synthesized for actuation on a given DMF architecture, we propose an automated method for verifying whether the synthesized actuation sequence is secure against malicious dispense attacks, using droplets dispensed by an attacker when the desired reaction is in execution. The foundation of our method lies in symbolic encoding. We highlight the benefits of the proposed approach through simulations on some well-known assay benchmarks.
Filtering Random Graph Processes Over Random Time-Varying Graphs

Graph filters play a key role in processing the graph spectra of signals supported on the vertices of a graph. However, despite their widespread use, graph filters have been analyzed only in the deterministic setting, ignoring the impact of stochasticity in both the graph topology and the signal itself. To bridge this gap, we examine the statistical behavior of the two key filter types, finite impulse response and autoregressive moving average graph filters, when operating on random time-varying graph signals (or random graph processes) over random time-varying graphs. Our analysis shows that 1) in expectation, the filters behave as the same deterministic filters operating on a deterministic graph, being the expected graph, having as input signal a deterministic signal, being the expected signal, and 2) there are meaningful upper bounds for the variance of the filter output. We conclude this paper by proposing two novel ways of exploiting randomness to improve (joint graph-time) noise cancellation, as well as to reduce the computational complexity of graph filtering. As demonstrated by numerical results, these methods outperform the disjoint average and denoise algorithm and yield a (up to) four times complexity reduction, with a very little difference from the optimal solution.
Effects of historically familiar and novel predator odors on the physiology of an introduced prey

Abstract Predator odors can elicit fear responses in prey and predator odor recognition is generally associated with physiological responses. Prey species are often more likely to respond to the odor of familiar rather than alien predators. However, predator naïvety in an introduced prey species has rarely been investigated. We examined the physiological response, as shown by changes in ventilatory variables, of an introduced terrestrial herbivore, the European rabbit Oryctolagus cuniculus, in Australia, to the odor of potential predators and to control odors (distilled water and horse), to explore if responses were limited to historical (cat and fox) predators, or extended to historically novel predators (snake and quoll). All odors except distilled water elicited a response, with rabbits showing long-term higher respiratory frequencies and lower tidal volumes after introduction of the odors, indicating an increase in alertness. However, the intensity of the rabbits’ reaction could not be directly linked to any pattern of response with respect to the history of predator–prey relationships. Rabbits exhibited significantly stronger reactions in response to both cat and quoll odors than they did to distilled water, but responses to horse, fox, and snake odor were similar to that of water. Our results show that the introduced rabbit can respond to both historical and novel predators in Australia, and suggest that shared evolutionary history is not necessarily a prerequisite to predator odor recognition.
The Phenomenon of “Fluid Creep” in Acute Burn Resuscitation

Several reports have documented that modern burn patients receive far more resuscitation fluid than predicted by the Parkland formula—a phenomenon termed “fluid creep. ” This article reviews the incidence, consequences, and possible etiologies of fluid creep in modern practice and uses this information to propose some therapeutic strategies to reduce or eliminate excessive fluid resuscitation in burn care. A literature review was performed of historical references that form the foundation of modern fluid resuscitation, as well as reports of fluid creep and its consequences. The original Parkland formula required a 24-hour volume of 4 ml/kg/%TBSA lactated Ringer's solution followed by an infusion of 0.3–0.5 ml/kg/%TBSA plasma. Modern iterations of this formula have omitted the colloid bolus. Numerous exceptions to the formula have been noted, most consistently patients with inhalation injuries. In contrast, recent reports document greatly increased fluid requirements in unselected patients, which seems to consist largely of progressive edema formation in unburned areas, increasing after the first 8 hours post-burn. This has been linked to occurrence of the abdominal compartment syndrome and other serious complications. Strategies to reduce fluid creep include the avoidance of early overresuscitation, use of colloid as a routine component of resuscitation or for “rescue,” and adherence to protocols for fluid resuscitation. Fluid creep is a significant problem in modern burn care. Review of original investigations of burn shock, coupled with modern reports of fluid creep, suggests several mechanisms by which this problem can be controlled. Prospective trials of these therapies are needed to confirm their effectiveness.
Spontaneous Rupture of a Hepatic Adenoma: Diagnostic Nuances and the Necessity of Followup

We present the case of a young female on oral contraceptives (OCs) who was diagnosed with focal nodular hyperplasia (FNH) and remained on oral contraceptives. Months later, the patient presented with acute abdominal pain and intratumoral hemorrhage in the liver. The patient was taken to the operating room (OR) and was diagnosed with a ruptured hepatic adenoma (HA). We review the key diagnostic features of FNH and HA, the different management guidelines including use of OCs, and potential surgical indications. HA compared to FNH has a significantly higher rate of sequelae despite being a benign lesion, thus providers must accurately distinguish between the two diagnoses to prevent potential morbidity and mortality.
25 Oxytocin and Vasopressin: Genetics and Behavioral Implications

Oxytocin (OT) and vasopressin (VP) can profoundly affect animal physiology and behavior. Over the past 20 years, the genes that encode OT and VP, as well as their respective receptors, have been identified and intensively studied leading to a greater understanding of the hormones’ functions. The use of transgenic animals, including knockout mice, and viral vectors have opened new vistas of research on the behavioral roles of OTand VP. In this chapter, we briefly review the history and the evolutionary origins of OTand VP, as well as their structures, regulation, and neuroanatomy. Finally, we highlight recently explored roles for OT and VP in physiology and behavior. List of Abbreviations: ACTH, adrenocorticotropic hormone; AH, anterior hypothalamus; AP‐2, activator protein‐2; ATF‐2, activating transcription factor‐2; AVT, arginine vasotocin; BNST, bed nucleus of the stria terminalis; CeM, central amygdala; CNS, central nervous system; CRF, corticotropin releasing factor; DAG, diacylglycerol; ERE, estrogen response element; GRE, glucocorticoid response element; ICV, intracerebroventricularly; IGR, intergenic region; IP3, 1,4,5 inositol triphosphate; LS, lateral septum; MeA, medial amygdala; MPOA, medial preoptic area; MPOA‐AH, medial preoptic area‐anterior hypothalamus; OT, oxytocin; OTKO, oxytocin knockout; OTR, oxytocin receptor; PIP2, phosphatidylinositol 4,5‐bisphosphate; PLC, phospholipase C; PVN, paraventricular nucleus; SCN, suprachiasmatic nucleus; SON, supraoptic nucleus; V1aR, vasopressin 1a receptor; V1aRKO, vasopressin 1a receptor knockout; V1bR, vasopressin 1b receptor; V1bRKO, vasopressin 1b receptor knockout; VACM‐1, vasopressin‐activated calcium‐mobilizing receptor; VLH, ventrolateral hypothalamus; VMH, ventromedial hypothalamus; VP, vasopressin; VP‐ir, vasopressin immunoreactivity
What-If Model Construction and Validation of Web Systems Based on Log Mining

To maintain a complex modern web-based system, the what-if analysis is quite useful for predicting the impact of any workload growth or planned change on the performance of individual components, even the entire system. In this paper we propose an approach based on log mining to build what-if models of web-based systems and validate them by using OPNET simulation tool. Three contributions of this paper are: (1) the construction of what-if models based on log mining to automate the task of modeling and validation, (2) the technique to address complexity of user behaviors including users' browser caching, clustering of requests and users, etc., (3) and two real-life cases to evaluate the effectiveness and accuracy of this approach. The preliminary results show that the relative errors between logged data and simulation results are less than 18% in most cases including number of requests and network throughput.
MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis.

BACKGROUND & AIMS Myofibroblast transdifferentiation generates hepatic myofibroblasts, which promote liver fibrogenesis. The peroxisome proliferator-activated receptor gamma (PPARgamma) is a negative regulator of this process. We investigated epigenetic regulation of PPARgamma and myofibroblast transdifferentiation. METHODS Chromatin immunoprecipitation (ChIP) assays assessed the binding of methyl-CpG binding protein 2 (MeCP2) to PPARgamma and chromatin modifications that silence this gene. MeCP2(-/y) mice and an inhibitor (DZNep) of the epigenetic regulatory protein EZH2 were used in the carbon tetrachloride model of liver fibrosis. Liver tissues from mice were assessed by histologic analysis; markers of fibrosis were measured by quantitative polymerase chain reaction (qPCR). Reverse transcription PCR detected changes in expression of the microRNA miR132 and its target, elongated transcripts of MeCP2. Myofibroblasts were transfected with miR132; PPARgamma and MeCP2 expressions were analyzed by qPCR or immunoblotting. RESULTS Myofibroblast transdifferentiation of hepatic stellate cells is controlled by a combination of MeCP2, EZH2, and miR132 in a relay pathway. The pathway is activated by down-regulation of miR132, releasing the translational block on MeCP2. MeCP2 is recruited to the 5' end of PPARgamma, where it promotes methylation by H3K9 and recruits the transcription repressor HP1alpha. MeCP2 also stimulates expression of EZH2 and methylation of H3K27 to form a repressive chromatin structure in the 3' exons of PPARgamma. Genetic and pharmacologic disruptions of MeCP2 or EZH2 reduced the fibrogenic characteristics of myofibroblasts and attenuated fibrogenesis. CONCLUSIONS Liver fibrosis is regulated by an epigenetic relay pathway that includes MeCP2, EZH2, and miR132. Reagents that interfere with this pathway might be developed to reduce fibrogenesis in chronic liver disease.
Searching for the Bacterial Effector: The Example of the Multi-Skilled Commensal Bacterium Faecalibacterium prausnitzii

Faecalibacterium prausnitzii represents approximately 5% of the total fecal microbiota in healthy adults being one of the most abundant bacterium in the human intestinal microbiota of healthy adults. Furthermore, this bacterium has been proposed to be a sensor and a major actor of the human intestinal health because of its importance in the gut ecosystem. In this context, F. prausnitzii population levels have been found to be reduced in patients suffering from several syndromes and diseases such as inflammatory bowel diseases. These diseases are characterized by a breakage of the intestinal homeostasis called dysbiosis and the use of F. prausnitzii as a next generation probiotic (also called live biotherapeutics) has been proposed as a natural tool to restore such dysbiosis within the gut. Nevertheless, despite the potential importance of this bacterium in human health, little is known about its main effectors underlying its beneficial effects. In this perspective note, we aim to present the actual state in the research about F. prausnitzii effectors and the future milestones in this field.
Stroke: Highlights of Selected Articles.

In this longitudinal study, Falkstedt et al explored the association between early exposure to tobacco, cannabis and alcohol, and risk of stroke till the age of 59 years. The study sample was constructed from males aged 18 to 20 years enlisted for compulsory military service in 1969/1970 in Sweden. Toxic exposures were quantified based on selfreporting in structured questionnaires, and follow-up data were captured using a nationwide registry. The authors found no association between early life cannabis exposure and overall stroke incidence. A positive association between heavy cannabis consumption and ischemic stroke was significantly attenuated when adjusting for tobacco and alcohol use. Of the 3 substance exposures, only tobacco smoking retained an independent positive association with risk of overall and ischemic stroke before the age of 60 years; a dose–response relationship was also apparent: smoking >20 cigarettes/d carried a ≈2-fold risk when compared with smoking 1 to 10 cigarettes. Despite its sample size, length of follow-up and completeness of data capture the study has limitations that need to be taken into account: it concerns a male only, racially very homogeneous sample that limits its generalizability. There are no data on continued use of cannabis later in life, and the practices of substance use reflect social habits and norms of an era that might be different when compared with our age. Notwithstanding these limitations, the study offers useful insight on the role of early exposure to cannabis in cerebrovascular disease, amid a time of dramatic changes in the landscape of medical and recreational cannabis use in the United States. See p 265.
pepKalc: scalable and comprehensive calculation of electrostatic interactions in random coil polypeptides

Motivation: Polypeptide sequence length is the single dominant factor hampering the effectiveness of currently available software tools for de novo calculation of amino acid‐specific protonation constants in disordered polypeptides. Results: We have developed pepKalc, a robust simulation software for the comprehensive evaluation of protein electrostatics in unfolded states. Our software completely removes the limitations of the previously reported Monte‐Carlo approaches in the computation of protein electrostatics by using a hybrid approach that effectively combines exact and mean‐field calculations to rapidly obtain accurate results. Paired with a modern architecture GPU, pepKalc is capable of evaluating protonation behavior for an arbitrary‐size polypeptide in a sub‐second time regime. Availability and implementation: http://protein‐nmr.org and https://github.com/PeptoneInc/pepkalc
D'Artagnan: An Embedded DSL Framework for Distributed Embedded Systems

Programming distributed embedded systems gives rise to a number of challenges. The distributed nodes are typically resource constrained, requiring expert systems programming skills to manage the limited power, communication bandwidth, and memory and computation constraints. The challenge of raising the level of abstraction of programming such systems without incurring too high of an execution performance penalty is thus an important one. In this paper we present a framework and domain specific language, to enable programming of such systems at a global network level --- macroprogramming. Our framework, D'Artagnan, enables the compilation, analysis, transformation and interpretation of high-level descriptions of stream processing applications in which information is received and processed in real-time. D'Artagnan, is a functional macroprogramming language embedded in Haskell, hiding where possible low-level detail, but allowing the developer to add hints and information to enable more efficient compilation to different target architectures.
VERSE‐guided parallel RF excitations using dynamic field correction

In parallel RF pulse design, peak RF magnitudes and specific absorption rate levels are critical concerns in the hardware and safety limits. The variable rate selective excitation (VERSE) method is an efficient technique to limit the peak RF power by applying a local‐only RF and gradient waveform reshaping while retaining the on‐resonance profile. The accuracy of the excitation performed by the VERSEd RF and gradient waveforms strictly depends on the performance of the employed hardware. Any deviation from the nominal gradient fields as a result of frequency dependent system imperfections violates the VERSE condition similarly to off‐resonance effects, leading to significant excitation errors and the RF pulse not converging to the targeted peak RF power. Moreover, for iterative VERSE‐guided RF pulse design (i.e. reVERSE), the k‐space trajectory actually changes at every iteration, which is assumed to be constant. In this work, we show both theoretically and experimentally the effect of gradient system imperfections on iteratively VERSEd parallel RF excitations. In order to improve the excitation accuracy besides limiting the RF power below certain thresholds, we propose to integrate gradient field monitoring or gradient impulse response function (GIRF) estimations of the actual gradient fields into the RF pulse design problem. A third‐order dynamic field camera comprising a set of NMR field sensors and GIRFs was used to measure or estimate the actual gradient waveforms that are involved in the VERSE algorithm respectively. The deviating and variable k‐space is counteracted at each iteration of the VERSE‐guided iterative RF pulse design. The proposed approaches are demonstrated for accelerated multiple‐channel spatially selective RF pulses, and highly improved experimental performance was achieved at both 3 T and 7 T.