Miracle-dz/UniFAR-FTUs huggingface dataset:
Hotspots of Large Rare Deletions in the Human Genome

Background We have examined the genomic distribution of large rare autosomal deletions in a sample of 440 parent-parent-child trios from the Quebec founder population (QFP) which was recruited for a study of Attention Deficit Hyperactivity Disorder. Methodology/Principal Findings DNA isolated from blood was genotyped on Illumina Hap300 arrays. PennCNV combined with visual evaluation of images generated by the Beadstudio program was used to determine deletion boundary definition of sufficient precision to discern independent events, with near-perfect concordance between parent and child in about 98% of the 399 events detected in the offspring; the remaining 7 deletions were considered de novo. We defined several genomic regions of very high deletion frequency (‘hotspots’), usually of 0.4–0.6 Mb in length where independent rare deletions were found at frequencies of up to 100 fold higher than the average for the genome as a whole. Five of the 7 de novo deletions were in these hotspots. The same hotspots were also observed in three other studies on members of the QFP, those with schizophrenia, with endometriosis and those from a longevity cohort. Conclusions/Significance Nine of the 13 hotspots carry one gene (7 of which are very long), while the rest contain no known genes. All nine genes have been implicated in disease. The patterns of exon deletions support the proposed roles for some of these genes in human disease, such as NRXN1 and PARKIN, and suggest limited roles or no role at all, for others, including MACROD2 and CTNNA3. Our results also offer an alternative interpretation for the observations of deletions in tumors which have been proposed as reflecting tumor-suppressive activity of genes in these hotspots.
Quantitative microstructural characterisation of concrete cured under realistic temperature conditions

The curing temperature is known to influence the strength and durability of concrete. In general, curing at elevated temperature results in high early strength gain, but impairs the long-term strength and transport properties. Previous investigations have not provided a complete understanding of these effects; in particular, no quantitative relation between microstructural and macroscopic changes has been developed. This work has adopted a combination of macro and micro characterisation to further a comprehensive and quantitative understanding of the property development under different curing conditions, through approaches which include both qualitative and quantitative microstructural analysis with SEM, EDS, XRD, NMR and TG. A systematic study on several mix designs and curing regimes has been carried out, to relate microstructural properties such as degree of hydration, C-S-H composition, C-S-H relative density and capillary porosity to compressive strength and water sorptivity. The results show that the Ca/(Si+Al) ratio of C-S-H is constant with temperature, and the increase in relative C-S-H brightness is thus attributed to the higher C-S-H density and lower chemically bound water at higher temperatures. The early hydration of concretes is accelerated by high temperatures, but the ultimate value is not limited, as opposed to widely reported lower values in the literature. This discrepancy is explained by the fact that previous workers have assumed that the bound water is constant for different curing temperatures whereas this is not the case. Linear relationships were established between the degree of hydration and the compressive strength of concretes, which depend on curing temperatures and mix design. Through their influence on the density and distribution of hydration products, elevated temperatures increase the ultimate capillary porosity of concretes. The relationship between capillary porosity and compressive strength seems independent of temperature to a first approximation, but no unique relationship is shown between sorptivity and compressive strength. Materials which were exposed to higher temperatures for only short periods of time, such as might be experienced in prefabrication or in the curing of large masses, showed some recovery in both microstructure and mechanical properties from the detrimental effects of high temperature.
An Experimental Study of Compressibility Effects on the Film Cooling Effectiveness Using PSP and PIV Techniques

() An experimental study was performed to examine effects of compressibility on film cooling effectiveness for coolant flowing from cylindrical holes in a flat plate. The incoming flow Mach number was set at 0.07, 0.30, 0.50 and 0.70. The Pressure Sensitive Paint (PSP) technique, which is based on a mass transfer analogy, was used to map the adiabatic film cooling effectiveness distribution on the surface of interest. The highresolution PSP measurement result showed that there was marginal enhancement of film cooling performance for higher Mach number flow comparing to the Ma=0.07 case. A high-resolution Particle Image Velocimetry (PIV) system was also used to conduct detailed flow field measurements to uncover the underlying physics of film cooling in the high speed flow, which showed similar flow field measurement results at M=0.4 for both Ma=0.07 and 0.30 cases, but slightly different ensemble-averaged velocity distribution was found for M=1.25 case.
Channel and constructional meaning: A collostructional case study

Research on grammatical structure, including construction-based research, is sometimes criticized for not paying sufficient attention to variational dimensions such as register, channel, etc. Our recent research on constructions, which is based on a set of quantitative corpus methods that we refer to as collostructional analysis, is theoretically subject to such criticism, as we have investigated the meaning of a range of constructions without paying attention to these variables at all. In this paper, we address this potential criticism. Using recent methodological extensions of our method, we show how variables like channel can be included in collostructional analysis. On the basis of three case studies, we show that (i) constructions may display channel-specific associations to individual lexical items, (ii) constructions differ with respect to their channel sensitivity, and (iii) the meaning of a given construction does not vary across channels. We argue that the inclusion of channel-specific information is a necessary addition to the specification of a construction’s properties even though it does not interact substantially with constructional semantics.
Viscoplastic Collapse of Thin-Walled Tubes Under Cyclic Bending

This paper presents the experimental result on the response and stability of thin walled tubes subjected to cyclic bending with different curvature-rates. The curvature ovalization measurement apparatus, designed by Pan et al. (1998), was used fo conducting the present curvature-controlled experiments on thin-walled tubular specimens of 304 stainless steel. It is observed that the higher the applied curvature-rate the greater is the degree of hardening of metal tube. However, the ovalization of tube cross-section increases when the applied curvature-rate increases. Furthermore due to the higher degree of the ovalization of tube cross-section for higher curvature rates under cyclic bending, the number of cycles to produce buckling is correspondingly reduced.
Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation: The Role of Hydrogen Peroxide

Obstructive sleep apnea (OSA) is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH). Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy) to decompensating changes (such as failure). CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.
Dimension reduction for anisotropic Bose–Einstein condensates in the strong interaction regime

We study the problem of dimension reduction for the three dimensional Gross–Pitaevskii equation (GPE) describing a Bose–Einstein condensate confined in a strongly anisotropic harmonic trap. Since the gas is assumed to be in a strong interaction regime, we have to analyse two combined singular limits: a semi-classical limit in the transport direction and the strong partial confinement limit in the transversal direction. We prove that both limits commute together and we provide convergence rates. The by-products of this work are approximated models in reduced dimension for the GPE, with a priori estimates of the approximation errors.
IT Investments, Alignment and Firm Performance: Evidence from an Emerging Economy

This study presents and tests a model in which the effect of IT investments on firm revenues is associated with the dimensions of IT-business alignment in an emerging market context. We disaggregate firms’ IT business alignment into three dimensions: (1) IT investment-business strategy alignment, (2) IT delivery-business priority alignment, and (3) IT change-business change alignment. Using a secondary data set comprising more than two hundred Indian companies, we find that IT delivery-business priority alignment and IT change-business change alignment more strongly moderate the relationship between IT investments and firm revenues. Specifically, firms with IT change-business change alignment and IT delivery-business priority alignment have higher revenue at higher levels of IT investment than firms that display IT investmentbusiness strategy alignment. Our additional exploratory analyses demonstrate firms with IT change-business change alignment outperform firms that show alignment at other dimensions of IT-business alignment at the high levels of software and service investments.
Dynamic recruitment of phospholipase Cγ at transiently immobilized GPI-anchored receptor clusters induces IP3–Ca2+ signaling: single-molecule tracking study 2

Clusters of CD59, a glycosylphosphatidylinositol-anchored receptor (GPI-AR), with physiological sizes of approximately six CD59 molecules, recruit Gαi2 and Lyn via protein–protein and raft interactions. Lyn is activated probably by the Gαi2 binding in the same CD59 cluster, inducing the CD59 cluster's binding to F-actin, resulting in its immobilization, termed stimulation-induced temporary arrest of lateral diffusion (STALL; with a 0.57-s lifetime, occurring approximately every 2 s). Simultaneous single-molecule tracking of GFP-PLCγ2 and CD59 clusters revealed that PLCγ2 molecules are transiently (median = 0.25 s) recruited from the cytoplasm exclusively at the CD59 clusters undergoing STALL, producing the IP3–Ca2+ signal. Therefore, we propose that the CD59 cluster in STALL may be a key, albeit transient, platform for transducing the extracellular GPI-AR signal to the intracellular IP3–Ca2+ signal, via PLCγ2 recruitment. The prolonged, analogue, bulk IP3–Ca2+ signal, which lasts for more than several minutes, is likely generated by the sum of the short-lived, digital-like IP3 bursts, each created by the transient recruitment of PLCγ2 molecules to STALLed CD59.
Testing the ‘Extreme Female Brain’ Theory of Psychosis in Adults with Autism Spectrum Disorder with or without Co-Morbid Psychosis

Introduction Males and females in the general population differ, on average, in their drive for empathizing (higher in females) and systemizing (higher in males). People with autism spectrum disorder (ASD) show a drive for systemizing over empathizing, irrespective of sex, which led to the conceptualisation of ASD as an ‘extreme of the typical male brain’. The opposite cognitive profile, an ‘extreme of the typical female brain’, has been proposed to be linked to conditions such as psychosis and mania/hypomania. Methods We compared an empathizing-over-systemizing bias (for short ‘empathizing bias’) in individuals with ASD, who had experienced psychotic illness (N = 64) and who had not (N = 71). Results There were overall differences in the distribution of cognitive style. Adults with ASD who had experienced psychosis were more likely to show an empathizing bias than adults with ASD who had no history of psychosis. This was modulated by IQ, and the group-difference was driven mainly by individuals with above-average IQ. In women with ASD and psychosis, the link between mania/hypomania and an empathizing bias was greater than in men with ASD. Conclusions The bias for empathizing over systemizing may be linked to the presence of psychosis in people with ASD. Further research is needed in a variety of clinical populations, to understand the role an empathizing bias may play in the development and manifestation of mental illness.
The 2007 North Atlantic Hurricane Season A Climate Perspective

The 2007 North Atlantic Hurricane Season A Climate Perspective Gerald Bell1, Eric Blake2, Chris Landsea2, Stanley Goldenberg3, Richard Pasch2, Todd Kimberlain2, 1Climate Prediction Center/NOAA/NWS/NCEP 2National Hurricane Center/NOAA/NWS/NCEP 3Hurricane Research Division/NOAA/OAR/AOML
Covert Communication in Mobile Applications (T)

This paper studies communication patterns in mobile applications. Our analysis shows that 63% of the external communication made by top-popular free Android applications from Google Play has no effect on the user-observable application functionality. To detect such covert communication in an efficient manner, we propose a highly precise and scalable static analysis technique: it achieves 93% precision and 61% recall compared to the empirically determined "ground truth", and runs in a matter of a few minutes. Furthermore, according to human evaluators, in 42 out of 47 cases, disabling connections deemed covert by our analysis leaves the delivered application experience either completely intact or with only insignificant interference. We conclude that our technique is effective for identifying and disabling covert communication. We then use it to investigate communication patterns in the 500 top-popular applications from Google Play.
Divergent and Convergent Evolution of Fungal Pathogenicity

Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen–host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus–animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation.
Clinical Predictors of Transient Ischemic Attack, Stroke, or Death Within 30 Days of Carotid Angioplasty and Stenting

Background and Purpose— Carotid angioplasty and stenting (CAS) is currently being assessed in the treatment of severe carotid stenosis. However, little data are available concerning patient-related factors affecting the risk of CAS. The purpose of this study was to identify potential clinical risk factors for the development of postprocedural deficits after CAS. Methods— The clinical characteristics of 299 patients (217 men, 82 women; mean age 69±9 years) who underwent CAS for asymptomatic (n=129, 43%) or symptomatic (n=170, 57%) stenoses and the combined 30-day complication rates (any transient ischemic attack [TIA], minor stroke, major stroke, or death) were analyzed with logistic regression analysis. Results— The overall 30-day TIA rate was 3.7%; the minor stroke rate was 5.3%, the major stroke rate was 0.7%, and the death rate was 0.7%. Although patients presenting with a hemispherical TIA or minor stroke had a significantly higher risk than asymptomatic patients (odds ratio [OR] 5.69; 95% confidence interval [CI], 2.03 to 19.57; P<0.001), the complication rates between patients presenting with a retinal TIA and asymptomatic patients was comparable (OR, 1.42; 95% CI, 0.13 to 9.09; P=0.6). Multivariate regression analysis revealed advanced age (OR, 1.06; 95% CI, 1 to 1.11; P<0.05), stroke (OR, 8; 95% CI, 2.6 to 24.4; P<0.01) or hemispherical TIA (OR, 4.7; 95% CI, 1.6 to 13.3) as presenting symptoms as independent clinical predictors of the combined 30-day outcome measures any TIA, stroke, or death. Conclusion— Aside from advanced age and symptom status, the type of presenting event predicts postprocedural complications after CAS. When evaluating the outcome of CAS and comparing this treatment modality to surgery, patients should be stratified according to their presenting event.
Preoperative low dose NSAID treatment influences the genes for stemness, growth, invasion and metastasis in colorectal cancer

Preclinical data, and an increasing list of clinical investigations, show anti-inflammatory agents to favourably influence the biology of colorectal tumor. We have earlier reported on re-expression of activated immune cells after three days preoperative treatment of patients with colorectal carcinoma, randomized to receive oral NSAID (indomethacin or celebrex). Antisecretory prophylaxis (esomeprasol) was provided to all patients and served as sham treatment. Concomittant to MHC locus activation, Prominin1/CD133, a marker associated with stemness and poor prognosis in several solid tumors, was downregulated. The aim of the present study was to evaluate expression of additional regulators belonging to the stem cell niche, OCT4, SOX2 and BMP7, as well as some microRNAs, reported to act as tumor suppressors or oncomiRs. Peroperative tumor biopsies were analyzed by microarrays, quantitative real-time PCR and immunohistochemistry (IHC). The stem cell master regulator SOX2 was increased by NSAIDs (p<0.01), as well as the tumor suppressor miR-630 (p<0.01), while BMP7, a marker for poor prognosis in CRC, was downregulated by NSAID (indomethacin, p<0.02). The upregulation of SOX2, but not of its heterodimer binding partner OCT4, could imply a negative feed-back loop, with a switch-off for stemness preservation of tumor cells. This is supported by the overall evaluation of gene expression profiles with subsequent events, indicating less aggressive tumors following NSAID treatment.
Use of standing low-field magnetic resonance imaging to assess oblique distal sesamoidean ligament desmitis in three Thoroughbred racehorses

Desmitis of the oblique distal sesamoidean ligaments (ODSL) is caused by hyperextension of the metacarpophalangeal/metatarsophalangeal joint and has been described as a significant cause of lameness in racehorses. In this study, three Thoroughbred racehorses (age range: 3–6 years) were diagnosed with desmitis of the forelimb ODSL using standing low-field magnetic resonance imaging (sMRI). Radiography and ultrasonography were inconclusive with regard to a definitive diagnosis. For all horses, the sMRI characteristics included increased signal intensity within the medial ODSL on T1-weighted gradient echo, T2-weighted fast spin echo and short tau inversion recovery fast spin echo images, which use a fat suppression technique. Effusion of the digital flexor tendon sheath was also clearly visible on sMRI. Following rest and controlled exercise for roughly 3 months, two horses successfully returned to racing within 5 months. Our findings support the use of sMRI for diagnosing ODSL injuries in Thoroughbred racehorses.
[PAX6 mutation caused brain abnormalities in humans].

OBJECTIVE To investigate the association between PAX6 mutation and brain abnormalities. METHODS The brain structures of 18 affected patients and 6 normal controls in a large pedigree with a PAX6 mutation (c1080C-->T)were scanned with MRI assessing. RESULTS Most of the affected patients showed brain abnormalities such as corpus callosum degeneration, broad cerebral ventricle grooves and broad olfactory grooves. CONCLUSION Genetic defect of PAX6 gene may result in brain abnormalities.
Decision Stages and Asymmetries in Regular Retail Price Pass-Through

We study the pass-through of wholesale price changes onto regular retail prices using an unusually detailed data set obtained from a major retailer. We model pass-through as a two-stage decision process that reflects both whether as well as how much to change the regular retail price. We show that pass-through is strongly asymmetric with respect to wholesale price increases versus decreases. Wholesale price increases are passed through to regular retail prices 70% of the time while wholesale price decreases are passed through only 9% of the time. Pass-through is also asymmetric with respect to the magnitude of the wholesale price change, with the magnitude affecting the response to wholesale price increases but not decreases. Finally, we show that covariates such as private label versus national brand, 99-cent price endings, and the time since the last wholesale price change have a much stronger impact on the first stage of the decision process (i.e., whether to change the regular retail price) than on the second stage (i.e., how much to change the regular retail price). Data, as supplemental material, are available at http://dx.doi. org/10.1287/mksc.2015. 0947 .