Miracle-dz/UniFAR-FTUs huggingface dataset:
Accurate Prediction of the Functional Significance of Single Nucleotide Polymorphisms and Mutations in the ABCA1 Gene

The human genome contains an estimated 100,000 to 300,000 DNA variants that alter an amino acid in an encoded protein. However, our ability to predict which of these variants are functionally significant is limited. We used a bioinformatics approach to define the functional significance of genetic variation in the ABCA1 gene, a cholesterol transporter crucial for the metabolism of high density lipoprotein cholesterol. To predict the functional consequence of each coding single nucleotide polymorphism and mutation in this gene, we calculated a substitution position-specific evolutionary conservation score for each variant, which considers site-specific variation among evolutionarily related proteins. To test the bioinformatics predictions experimentally, we evaluated the biochemical consequence of these sequence variants by examining the ability of cell lines stably transfected with the ABCA1 alleles to elicit cholesterol efflux. Our bioinformatics approach correctly predicted the functional impact of greater than 94% of the naturally occurring variants we assessed. The bioinformatics predictions were significantly correlated with the degree of functional impairment of ABCA1 mutations (r 2 = 0.62, p = 0.0008). These results have allowed us to define the impact of genetic variation on ABCA1 function and to suggest that the in silico evolutionary approach we used may be a useful tool in general for predicting the effects of DNA variation on gene function. In addition, our data suggest that considering patterns of positive selection, along with patterns of negative selection such as evolutionary conservation, may improve our ability to predict the functional effects of amino acid variation.
Is Maternal Smoking During Pregnancy a Risk Factor for Cigarette Smoking in Offspring? A Longitudinal Controlled Study of ADHD Children Grown Up

Objective: This study examined whether exposure to maternal smoking during pregnancy in children with and without ADHD is associated with smoking in offspring and whether this association is selective to ADHD children. Method: Ninety-six exposed and 400 unexposed participants were derived from two longitudinal studies of boys and girls with and without ADHD. Maternal smoking during pregnancy was defined by interviews with participants’ mothers. Results: A significant association was observed between exposure to maternal smoking in pregnancy and cigarette smoking in offspring (p = .02). Exposed offspring were also more likely to have higher rates of major depression (p = .04), bipolar disorder (p = .04), and conduct disorder (p = .04), and lower IQ (p = .01), lower Global Assessment of Functioning (GAF) score (p = .02), and more impaired Social Adjustment Inventory for Children and Adolescents (SAICA) scores versus unexposed offspring, adjusting for social class. Conclusion: Maternal smoking during pregnancy was found to increase the risk for smoking and a wide range of adverse psychiatric, cognitive, and functional outcomes in youth.
Soft error rate estimation of digital circuits in the presence of Multiple Event Transients (METs)

In this paper, we present a very fast and accurate technique to estimate the soft error rate of digital circuits in the presence of Multiple Event Transients (METs). In the proposed technique, called Multiple Event Probability Propagation (MEPP), a four-value logic and probability set are used to accurately propagate the effects of multiple erroneous values (transients) due to METs to the outputs and obtain soft error rate. MEPP considers a unified treatment of all three masking mechanisms i.e., logical, electrical, and timing, while propagating the transient glitches. Experimental results through comparisons with statistical fault injection confirm accuracy (only 2.5% difference) and speed-up (10,000X faster) of MEPP.
Ischemia-Reperfusion Bilioduodenal anastomosis in rats with extra-hepatic biliary obstruction is followed by lesions ischemia and reperfusion-induced 1

Purpose: The aim of this study was to investigate alterations compatible with hepatic ischemia-reperfusion after bilioduodenal shunt (BD) in rats with obstructive jaundice (OB) . Methods:Thirty six animals were divided into 6 experimental groups: CO1 and CO2 – control groups, sham-operated (SO) and evaluated 6 and 24 hours after, respectively; OB1 and OB2, – obstructive jaundice groups, sham-operated 15 days after bile duct ligature and evaluated 6 and 24 hours after SO, respectively; DBD1and DBD2 – obstructive jaundice groups evaluated ,respectively, 6 and 24 hours after BD performed 15 days after bile duct ligature. The parameters evaluated were serum total bilirubin, aminotransferase activity (AST, ALT), TNFα, liver mitochondrial functions and parenchymatous injury. Results: Bilirubin decreased while aminotransferase activity increased 6 hours after BD (p<0.01); TNFα determination at the 6 hour after BD was higher than the one at the 24 hour (p<0.05); oxygen consumption in states 3 and 4 remained elevated in the BD initial phase , and liver cell damage worsened 24 hours after BD. Conclusion: The results demonstrated that surgical biliary decompression in obstructive jaundice is followed by alterations related to hepatic ischemiareperfusion.
Endothelial-related coagulation in cardiac surgery.

The endothelium appears to play an important role in the regulation of intravascular coagulation. Thrombomodulin is one of the anticoagulant substances that is expressed by endothelial cells. The influence of age and illness on the thrombomodulin-protein C system was studied prospectively in 80 cardiac surgery patients. Patients > 70 yr old (n = 20) were compared with patients < 50 yr (n = 20) (group I), and patients undergoing a simple cardiac procedure (n = 20) were compared with patients scheduled for complex surgery (n = 20) (group II). Thrombomodulin (normal < 40 ng ml-1), protein C and (free) protein S plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) after induction of anaesthesia (baseline values), during and after cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB and on the first day after operation. Blood loss and use of homologous blood and blood products were significantly greater in patients > 70 yr and in those undergoing complex surgery. At baseline, thrombomodulin concentration was increased in patients undergoing complex surgery (mean 52 (sd 9) ng ml-1). After bypass and after operation, thrombomodulin increased most in patients > 70 yr (from 40 (8) to 78 (10) ng ml-1) and in those patients who underwent complex cardiac operations (from 52 (8) to 79 (10 ng ml-1) (P < 0.05). Changes in protein C and protein S concentrations were similar in all groups. On the first day after operation only, protein C concentrations were reduced in patients > 70 yr and in patients who underwent complex cardiac surgery. (ABSTRACT TRUNCATED AT 250 WORDS)
Limitations on the Effectiveness of Forward Guidance at the Zero Lower Bound

The recent literature on monetary policy in the presence of a zero lower bound on interest rates has shown that forward guidance regarding the path of interest rates can be very effective in preserving macroeconomic stability in the face of a contractionary demand shock; moreover, that literature apparently leaves little scope for any further improvements in stabilization performance via nontraditional monetary policies. In this paper, we characterize optimal policy under commitment in a prototypical New Keynesian model and examine whether those conclusions are sensitive to the specification of the shock process and to the interest elasticity of aggregate demand. Although forward guidance is effective in offsetting natural rate shocks of moderate size and persistence, we find that the macroeconomic outcomes are much less appealing for larger and more persistent shocks, especially when the interest elasticity parameter is set to values widely used in the literature. Thus, while forward guidance could be sufficient for mitigating the effects of a 'Great Moderation'-style shock, a combination of forward guidance and other monetary policy measures - such as large-scale asset purchases - might well be called for in responding to a 'Great Recession'-style shock.
Evolved differences in larval social behavior mediated by novel pheromones

Pheromones, chemical signals that convey social information, mediate many insect social behaviors, including navigation and aggregation. Several studies have suggested that behavior during the immature larval stages of Drosophila development is influenced by pheromones, but none of these compounds or the pheromone-receptor neurons that sense them have been identified. Here we report a larval pheromone-signaling pathway. We found that larvae produce two novel long-chain fatty acids that are attractive to other larvae. We identified a single larval chemosensory neuron that detects these molecules. Two members of the pickpocket family of DEG/ENaC channel subunits (ppk23 and ppk29) are required to respond to these pheromones. This pheromone system is evolving quickly, since the larval exudates of D. simulans, the sister species of D. melanogaster, are not attractive to other larvae. Our results define a new pheromone signaling system in Drosophila that shares characteristics with pheromone systems in a wide diversity of insects. DOI: http://dx.doi. org/10.7554/eLife.04205. 001
Clinical Characteristics of Behavioral and Psychological Symptoms in Patients with Drug-naïve Alzheimer's Disease

†, Background: Behavioral and psychological symptoms of dementia (BPSD) are less well-defined aspects of Alzheimer’s disease (AD). We designed this study to explore the followings: 1) the clinical profiles of BPSD 2) the clustered-groups domains of the Korean-Neuropsychiatric Inventory (K-NPI) assessment of BPSD 3) the clinical characteristics of the clustered-groups of BPSD in patients with drug-naive probable AD. Methods: Descriptive and cluster analyses of the 12 K-NPI domains were done in 220 patients with drug-naive probable AD. After clustering these domains, characteristics of these positive symptoms clustered-group of patients were compared with the negative symptoms groups of patients. Results: The mean Korean-Mini Mental Status Examination (K-MMSE), Clinical Dementia Rating (CDR) scale, and K-NPI scores were 15.0, 1.6, and 14.2, respectively. The CDR and K-MMSE scores correlated with total K- NPI scores, and depression was the most common symptom. According to cluster analysis, five major clus ters were identified. Using the associated neuropsychological dysfunctions, characteristics of each group were defined. Conclusions: This study identified the clustered-domains for K-NPI, and suggested the possible anatomical substrates for these groups in drug-naive AD patients. These attempts may clarify the complex and bizarre behavioral and psychological symptoms as more neurologically relevant symptoms.
Effects of pioglitazone and vildagliptin on coagulation cascade in diabetes mellitus – targeting thrombogenesis

Introduction: Type 2 diabetes mellitus (T2DM) is intricately allied with an increased risk of atherothrombotic disease. Thrombosis is the cause of mortality in 80% of patients with diabetes mellitus. Endothelial abnormalities lead to elevated inflammatory and coagulation biomarkers as seen in diabetes. Progression of atherothrombotic disease in diabetes has been linked with elevated levels of various coagulation factors including fibrinogen, plasminogen activator inhibitor-1, and von Willebrand factor. Areas covered: We review the existing evidence and most recent data elucidating the various inflammatory and coagulation biomarkers that are elevated in T2DM leading to thrombosis as well as the anti-inflammatory, anticoagulant and antithrombotic mechanisms of pioglitazone and vildagliptin in addition to their effect on glucose metabolism that may halt the progression of atherothrombotic disease. Expert opinion: The review highlights the pleiotropic effects of pioglitazone and vildagliptin on metabolic, inflammatory and coagulation processes that have the potential to influence cardiovascular disease progression at various points in the disease process, including hemostatic disturbances, inflammation, plaque rupture and atherogenesis in T2DM. Finally, the paper suggests a possible decline in T2DM-associated cardiovascular comorbidities once the antithrombotic potential of pioglitazone and vildagliptin is established through clinical investigation.
Transurethral resection of the prostate for chronic bacterial prostatitis

Forty‐nine patients with chronic bacterial prostatitis causing symptoms and receiving routine accepted treatment for many months or years, without permanent relief, were treated by transurethral prostatic resection (TURP). The purpose of the surgery was to remove the gland down to the true capsule (radical TURP). The patients' own appraisal of the results, the absence of symptoms and of infection, indicate 67% had a good result when assessed 1 year following surgery; 21% were improved and 12% received no benefit. Transurethral resection is recommended in selected cases and when the surgeon is able to remove all of the glandular tissue without causing large perforations through the true capsule. Acceptable results have been achieved in two‐thirds of cases. There was no mortality and insignificant morbidity. Patients experiencing no benefit and those who were only improved but not cured were either poorly selected or infected prostatic tissue was not removed.
Model-predicted distribution of wind-induced internal wave energy in the world's oceans

[1] The distribution of wind-induced internal wave energy in the world's oceans is investigated using a full three-dimensional primitive equation model. Special attention is directed to the global energy input to the surface near-inertial motions and the subsequent downward energy propagation into the deep ocean. We find that the model results for near-inertial energy in the oceanic mixed layer, depth-integrated horizontal energy fluxes, and vertical structures of WKB-scaled kinetic energy are all consistent with the available observations in the regions of significant wind energy input and that the annual mean of the global wind energy input becomes ∼0.4 TW. It is also found that most of the wind-induced energy resides in high vertical modes, 75–85% of which is dissipated in the surface 150 m. The present study therefore predicts that the total wind-induced near-inertial energy available for deep-ocean mixing is limited to, at most, 0.1 TW, which is an order of magnitude smaller than previously estimated. Adding the energy flux from tide-topography interactions of ∼0.9 TW, we can conclude that the total energy available for deep-ocean mixing is ∼1.0 TW, obviously falling short of the required power to sustain the global overturning circulation. This might suggest the existence of other important energy sources, such as the one through geostrophic adjustment processes, and/or additional mechanisms sustaining the global overturning circulation, such as effects of Ekman upwelling in the Southern Ocean. Another possibility is that previous estimates of the volume transport of the global overturning circulation might be too large.
The clinical usefulness of D-dimer testing in cancer patients with suspected deep venous thrombosis.

BACKGROUND Little is known about the diagnostic value of a D-dimer test in cancer patients with clinically suspected deep venous thrombosis (DVT). OBJECTIVE To evaluate the clinical utility of a whole blood rapid D-dimer test (SimpliRED) in cancer patients compared with noncancer patients. METHODS In consecutive patients with suspected lower limb DVT, a D-dimer test and ultrasonogram were performed. Cancer status was recorded at presentation. If the D-dimer test and ultrasonogram results were normal, DVT was considered absent. If the D-dimer result was abnormal, ultrasonography was performed again 1 week later. Anticoagulant therapy was only instituted in those patients with an abnormal ultrasonography result. All patients were followed up for 3 months to record subsequent thromboembolic events. The accuracy of the D-dimer test was assessed, and the efficiency and safety of withholding additional ultrasonography in cancer patients with normal results on both D-dimer and ultrasonography was compared with noncancer patients. RESULTS A total of 1739 consecutive patients were studied, 217 (12%) of whom had cancer. The negative predictive value of the D-dimer test was 97% in both cancer and noncancer patients. In 63 (29%) of all 217 cancer patients, the D-dimer and ultrasonography results were normal at referral; therefore, the diagnosis of DVT was refuted and anticoagulant treatment was withheld. In these 63 patients, one thromboembolic event occurred during follow-up (1.6%; 95% confidence interval, 0.04%-8.53%). CONCLUSIONS The negative predictive value of a whole blood D-dimer test in cancer patients seems as high as in noncancer patients. In a substantial proportion of cancer patients, the diagnosis can likely be refuted at referral, based on normal D-dimer test and ultrasonogram results. Furthermore, it seems safe to withhold anticoagulant therapy in these patients.
The Neuroevolution of Motivation

Motivational concepts have been central to systematic psychological, behavioral, and social psychological theories over the past century (Berridge, 2004; Cofer & Appley, 1964; Higgins, 1997). Motivational theories have been highly diverse in their nature and focus, but for the most part they have been developed largely from psychological or behavioral data and concepts. This is true even for homeostatic motives, such as hunger and thirst, which have reasonably well-documented neural substrates. Although this single-level approach to theory building is perfectly appropriate, the question arises as to whether a multilevel, interdisciplinary approach to neurobehavioral organization may offer meaningful insights into, or constraints on, motivational concepts and theories (Berntson & Cacioppo, 2004; Cacioppo & Berntson, 1992). The present chapter considers some aspects of evolutionary neurodevelopment and neuraxial organization that offer a beginning framework for integrative neurobehavioral and neuropsychological models of motivation. We then consider the implications of this general approach for understanding social processes and behavior.
Temporal Variation of the Skin Bacterial Community and Batrachochytrium dendrobatidis Infection in the Terrestrial Cryptic Frog Philoria loveridgei

In animals and plants, symbiotic bacteria can play an important role in disease resistance of host and are the focus of much current research. Globally, amphibian population declines and extinctions have occurred due to chytridiomycosis, a skin disease caused by the pathogen Batrachochytrium dendrobatidis (Bd). Currently amphibian skin bacteria are increasingly recognized as important symbiont communities with a relevant role in the defense against pathogens, as some bacteria can inhibit the growth of B. dendrobatidis. This study aims to document the B. dendrobatidis infection status of wild populations of a terrestrial cryptic frog (Philoria loveridgei), and to determine whether infection status is correlated with changes in the skin microbial communities. Skin samples of P. loveridgei were collected along an altitudinal range within the species distribution in subtropical rainforests in southeast Australia. Sampling was conducted in two years during two breeding seasons with the first classified as a “La Niña” year. We used Taqman real-time PCR to determine B. dendrobatidis infection status and 16S amplicon sequencing techniques to describe the skin community structure. We found B. dendrobatidis-positive frogs only in the second sampling year with low infection intensities, and no correlation between B. dendrobatidis infection status and altitude, frog sex or size. Skin bacterial diversity was significantly higher in P. loveridgei frogs sampled in the 1st year than in the 2nd year. In addition, 7.4% of the total OTUs were significantly more abundant in the 1st year compared to the 2nd year. We identified 67 bacterial OTUs with a significant positive correlation between infection intensity and an OTU’s relative abundance. Forty-five percent of these OTUs belonged to the family Enterobacteriaceae. Overall, temporal variation was strongly associated with changes in B. dendrobatidis infection status and bacterial community structure of wild populations of P. loveridgei.
Cat-a-Cone: an interactive interface for specifying searches and viewing retrieval results using a large category hierarchy

This paper introduces a novel user interface that integrates search and browsing of very large category hierarchies with their associated text collections. A key component is the separate but simultaneous display of the representations of the categories and the retrieved documents. Another key component is the display of multiple selected categories simultaneously, complete with their hierarchical context. The prototype implementation uses animation and a three-dimensional graphical workspace to accommodate the category hierarchy and to store intermediate search results. Query speci cation in this 3D environment is accomplished via a novel method for painting Boolean queries over a combination of category labels and free text. Examples are shown on a collection of medical text.
Participation vs. Effectiveness of Paid Endorsers in Social Advertising Campaigns: A Field Experiment

We investigate the participation and effectiveness of paid endorsers in viral-for-hire social advertising. Specifically, we investigate (i) how the financial incentive affects endorsers’ participation and effectiveness in paid endorsement campaigns, (ii) what types of endorsers are most effective in generating online engagements (likes, comments, and retweets), and (iii) whether that varies across types of engagements that require different levels of efforts from followers. We conduct a field experiment with an invitation design in which we manipulate both incentives and a soft eligibility requirement to participate in the campaign. The latter provides a strong and valid instrument to separate participation from outcomes effects. Since likes, comments, and retweets are count variables, and since potential endorsers can self-select to participate in multiple campaigns, we use a Poisson lognormal model with sample selection and correlated random effects to analyze variations in participation and effectiveness. There are three main findings. (1) Payments higher than the average reward a potential endorser received in the past do not increase participation, whereas lower payments decrease participation. Neither gains nor losses affect performance. (2) Potential endorsers who are more likely to participate tend to be less effective. (3) Which characteristics are associated with effectiveness depends on whether success is measured in likes, comments, or retweets. These findings provide new insights on how marketers can improve social advertising campaigns by better targeting and incenting potential endorsers. ​
Propagation of Singularities for Schrödinger Equations on the Euclidean Space with a Scattering Metric

Given a scattering metric on the Euclidean space. We consider the Schrödinger equation corresponding to the metric, and study the propagation of singularities for the solution in terms of the “homogeneous wavefront set”. We also prove that the notion of the homogeneous wavefront set is essentially equivalent to that of the quadratic scattering wavefront set introduced by Wunsch (1999). One of the main results in Wunsch (1999) follows on the Euclidean space with a weaker, almost optimal condition on the potential.