Miracle-dz/UniFAR-FTUs huggingface dataset:
Urothelial Defects from Targeted Inactivation of Exocyst Sec10 in Mice Cause Ureteropelvic Junction Obstructions

Most cases of congenital obstructive nephropathy are the result of ureteropelvic junction obstructions, and despite their high prevalence, we have a poor understanding of their etiology and scarcity of genetic models. The eight-protein exocyst complex regulates polarized exocytosis of intracellular vesicles in a large variety of cell types. Here we report generation of a conditional knockout mouse for Sec10, a central component of the exocyst, which is the first conditional allele for any exocyst gene. Inactivation of Sec10 in ureteric bud-derived cells using Ksp1.3-Cre mice resulted in severe bilateral hydronephrosis and complete anuria in newborns, with death occurring 6–14 hours after birth. Sec10FL/FL;Ksp-Cre embryos developed ureteropelvic junction obstructions between E17.5 and E18.5 as a result of degeneration of the urothelium and subsequent overgrowth by surrounding mesenchymal cells. The urothelial cell layer that lines the urinary tract must maintain a hydrophobic luminal barrier again urine while remaining highly stretchable. This barrier is largely established by production of uroplakin proteins that are transported to the apical surface to establish large plaques. By E16.5, Sec10FL/FL;Ksp-Cre ureter and pelvic urothelium showed decreased uroplakin-3 protein at the luminal surface, and complete absence of uroplakin-3 by E17.5. Affected urothelium at the UPJ showed irregular barriers that exposed the smooth muscle layer to urine, suggesting this may trigger the surrounding mesenchymal cells to overgrow the lumen. Findings from this novel mouse model show Sec10 is critical for the development of the urothelium in ureters, and provides experimental evidence that failure of this urothelial barrier may contribute to human congenital urinary tract obstructions.
Expression and Replication Studies to Identify New Candidate Genes Involved in Normal Hearing Function

Considerable progress has been made in identifying deafness genes, but still little is known about the genetic basis of normal variation in hearing function. We recently carried out a Genome Wide Association Study (GWAS) of quantitative hearing traits in southern European populations and found several SNPs with suggestive but none with significant association. In the current study, we followed up these SNPs to investigate which of them might show a genuine association with auditory function using alternative approaches. Firstly, we generated a shortlist of 19 genes from the published GWAS results. Secondly, we carried out immunocytochemistry to examine expression of these 19 genes in the mouse inner ear. Twelve of them showed distinctive cochlear expression patterns. Four showed expression restricted to sensory hair cells (Csmd1, Arsg, Slc16a6 and Gabrg3), one only in marginal cells of the stria vascularis (Dclk1) while the others (Ptprd, Grm8, GlyBP, Evi5, Rimbp2, Ank2, Cdh13) in multiple cochlear cell types. In the third step, we tested these 12 genes for replication of association in an independent set of samples from the Caucasus and Central Asia. Nine out of them showed nominally significant association (p<0.05). In particular, 4 were replicated at the same SNP and with the same effect direction while the remaining 5 showed a significant association in a gene-based test. Finally, to look for genotype-phenotype relationship, the audiometric profiles of the three genotypes of the most strongly associated gene variants were analyzed. Seven out of the 9 replicated genes (CDH13, GRM8, ANK2, SLC16A6, ARSG, RIMBP2 and DCLK1) showed an audiometric pattern with differences between different genotypes further supporting their role in hearing function. These data demonstrate the usefulness of this multistep approach in providing new insights into the molecular basis of hearing and may suggest new targets for treatment and prevention of hearing impairment.
This Work Is Licensed under a Creative Commons Attribution 3.0 Unported License Clinical and Functional Characterisation of the Combined Respiratory Chain Defect in Two Sisters Due to Autosomal Recessive Mutations in Mtfmt

functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations a b s t r a c t a r t i c l e i n f o Keywords: Mitochondrial encephalomyopathy Leigh syndrome Mitochondrial translation mt-tRNA modification Exome sequencing identified compound heterozygous mutations in the recently discovered mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene in two sisters with mild Leigh syndrome and combined respiratory chain deficiency. The mutations lead to undetectable levels of the MTFMT protein. Blue native polyacrylamide gel electrophoresis showed decreased complexes I and IV, and additional products stained with complex V antibodies, however the overall steady state level of mt-tRNA Met was normal. Our data illustrate that exome sequencing is an excellent diagnostic tool, and its value in clinical medicine is enormous, however it can only be optimally exploited if combined with detailed phenotyping and functional studies. Mitochondrial protein synthesis is very complex, and the pathway requires ribosomal proteins, ribosomal assembly proteins, aminoacyl-tRNA synthetases, tRNA modifying enzymes, tRNA methylating enzymes and several initiation, elongation and termination factors of translation (Rötig, 2011; Smits et al., 2010). About 150 different proteins are involved in the translation of the 13 mitochondrial-encoded proteins, illustrating the importance of mitochondrial translation in human mitochondrial disease (Chrzanowska-Lightowlers et al., 2011; Rötig, 2011). Most of these gene defects result in cytochrome c oxidase (COX) deficient or ragged red fibres and biochemical multiple respiratory chain (RC) defect in affected organs. The clinical phenotypes are very variable, however most presentations are early-onset, severe, and often fatal, implying the importance of mitochondrial translation from birth (Kemp et al., 2011). Some of these conditions affect multiple tissues, however tissue specific manifestations have been reported for several mt-tRNA aminoacyl synthetase or mt-tRNA modifying genes Due to the rapid increase in the number of nuclear genes and the widely varying phenotypes associated with combined RC deficiency, it is extremely difficult to select specific candidate genes for diagnostic screening. As a consequence, sequencing the known nuclear genes affecting mitochondrial protein synthesis has not been efficient in an earlier study (Kemp et al., 2011). However, next generation sequencing (NGS) has proven to be a very powerful tool in identifying nuclear disease genes in combined RC deficiency (Calvo et al., 2010). Either analysing ~1000 genes predicted to encode mitochondrial proteins (MitoExome) (Calvo et al., 2010; Tucker et al., 2011) or studying the whole exome has successfully detected the causative …
Effects of Bicycle Helmet Laws on Children&Apos;S Injuries

In recent years, many states and localities in the USA have enacted bicycle helmet laws. We estimate the effects of these laws on injuries requiring emergency department treatment. Using hospital-level panel data and triple difference models, we find helmet laws are associated with reductions in bicycle-related head injuries among children. However, laws also are associated with decreases in non-head cycling injuries, as well as increases in head injuries from other wheeled sports. Thus, the observed reduction in bicycle-related head injuries may be due to reductions in bicycle riding induced by the laws.
PCU: the programmable culling unit

Culling techniques have always been a central part of computer graphics, but graphics hardware still lack efficient and flexible support for culling. To improve the situation, we introduce the programmable culling unit, which is as flexible as the fragment program unit and capable of quickly culling entire blocks of fragments. Furthermore, it is very easy for the developer to use the PCU as culling programs can be automatically derived from fragment programs containing a discard instruction. Our PCU can be integrated into an existing fragment program unit with a modest hardware overhead of only about 10%. Using the PCU, we have observed shader speedups between 1.4 and 2.1 for relevant scenes.
Methionine Biosynthesis is Essential for Infection in the Rice Blast Fungus Magnaporthe oryzae

Methionine is a sulfur amino acid standing at the crossroads of several biosynthetic pathways. In fungi, the last step of methionine biosynthesis is catalyzed by a cobalamine-independent methionine synthase (Met6, EC 2.1.1.14). In the present work, we studied the role of Met6 in the infection process of the rice blast fungus, Magnaporthe oryzae. To this end MET6 null mutants were obtained by targeted gene replacement. On minimum medium, MET6 null mutants were auxotrophic for methionine. Even when grown in presence of excess methionine, these mutants displayed developmental defects, such as reduced mycelium pigmentation, aerial hypha formation and sporulation. They also displayed characteristic metabolic signatures such as increased levels of cysteine, cystathionine, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine while methionine and glutathione levels remained unchanged. These metabolic perturbations were associated with the over-expression of MgCBS1 involved in the reversed transsulfuration pathway that metabolizes homocysteine into cysteine and MgSAM1 and MgSAHH1 involved in the methyl cycle. This suggests a physiological adaptation of M. oryzae to metabolic defects induced by the loss of Met6, in particular an increase in homocysteine levels. Pathogenicity assays showed that MET6 null mutants were non-pathogenic on both barley and rice leaves. These mutants were defective in appressorium-mediated penetration and invasive infectious growth. These pathogenicity defects were rescued by addition of exogenous methionine and S-methylmethionine. These results show that M. oryzae cannot assimilate sufficient methionine from plant tissues and must synthesize this amino acid de novo to fulfill its sulfur amino acid requirement during infection.
Reward Dependence and Harm Avoidance among Patients with Binge‐Purge Type Eating Disorders

INTRODUCTION The Cloninger's Psychobiological Model of Temperament and Character includes temperamental dimensions such as reward dependence (RD) and harm avoidance (HA). Studies of RD differentiate between sensitivity to reward (SR) versus to punishment (SP). We investigated the interrelationship between HA and RD in acutely ill patients with binge/purge (B/P) type eating disorders (EDs) and following symptomatic stabilization. METHODS Fifty patients with B/P EDs were assessed at admission to inpatient treatment, 36 of whom were reassessed at discharge. Thirty-six controls were similarly assessed. Participants completed Tridimensional Personality Questionnaire (TPQ), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), and took the Gambling Task. RESULTS Patients with B/P EDs had higher TPQ-RD and lower TPQ-HA accompanied by lower SPSRQ-SR and SPSRQ-SP. SPSRQ-SP correlated positively and negatively with TPQ-HA and TPQ-RD, respectively. CONCLUSIONS Combination of lower TPQ-HA, lower SPSRQ-SP, and greater risk-taking inclination may maintain disordered eating in patients with B/P EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Max-margin analysis based patch sampling for discovery of mid-level parts

Discovering representative, discriminative mid-level parts is crucial for visual recognition models such as Bag-Of-Parts. We present a weakly-supervised approach to learn class-specific mid-level parts from a database. In our approach, only the image-level labels but no additional human annotations are used. As a start, we employ a SVM-like model to sample discriminant patches from each image. The employed SVM-like model corresponds to a max-margin analysis between a specific image patch and other patches from the whole training set, which can be easily solved in a closed form. For each class, the sampled patches are then clustered in an agglomerative manner to generate the final semantic parts, in the meantime the less-representative patches are discarded. The proposed approach is effective since it sequentially discards the non-discriminative and non-representative patches. The approach is also efficient since the clustering operation only needs to handle a small number of discriminant patches. The state-of-the-art results are observed in scene classification benchmarks when using the learned parts as a visual codebook.
Examining Adolescent Suicidal Behaviors in Relation to Gun Carrying and Bullying

ABSTRACT Guided by the interpersonal theory of suicide, this study examines the associations between gun carrying, bullying, and suicidal behaviors among high school students. Arizona Youth Risk Behavior Surveys were completed by 2,677 students in 2011; 9.0% reported suicide attempt in the past year, 5.5% carried a gun in the past 30 days, 8.5% were involved in school bullying, and 3.9% in cyberbullying. After accounting for depressive symptoms and self-harm, multiple linear regression results demonstrate that youth who carried a gun in the past 30 days were 3.98 times more likely to attempt suicide. Bullying was not associated with suicide attempt; however, youth report being 1.55 times more likely to make a suicide plan if they were bullied in school, 1.89 times more likely if cyberbullied, and . 48 less likely if a cyberbully/victim. Results support the interpersonal theory of suicide; implications for school policies on gun carrying and bullying are discussed.
Unbiased, adaptive stochastic sampling for rendering inhomogeneous participating media

Realistic rendering of participating media is one of the major subjects in computer graphics. Monte Carlo techniques are widely used for realistic rendering because they provide unbiased solutions, which converge to exact solutions. Methods based on Monte Carlo techniques generate a number of light paths, each of which consists of a set of randomly selected scattering events. Finding a new scattering event requires free path sampling to determine the distance from the previous scattering event, and is usually a time-consuming process for inhomogeneous participating media. To address this problem, we propose an adaptive and unbiased sampling technique using kd-tree based space partitioning. A key contribution of our method is an automatic scheme that partitions the spatial domain into sub-spaces (partitions) based on a cost model that evaluates the expected sampling cost. The magnitude of performance gain obtained by our method becomes larger for more inhomogeneous media, and rises to two orders compared to traditional free path sampling techniques.
Relating Pupil Dilation and Metacognitive Confidence during Auditory Decision-Making

The sources of evidence contributing to metacognitive assessments of confidence in decision-making remain unclear. Previous research has shown that pupil dilation is related to the signaling of uncertainty in a variety of decision tasks. Here we ask whether pupil dilation is also related to metacognitive estimates of confidence. Specifically, we measure the relationship between pupil dilation and confidence during an auditory decision task using a general linear model approach to take into account delays in the pupillary response. We found that pupil dilation responses track the inverse of confidence before but not after a decision is made, even when controlling for stimulus difficulty. In support of an additional post-decisional contribution to the accuracy of confidence judgments, we found that participants with better metacognitive ability – that is, more accurate appraisal of their own decisions – showed a tighter relationship between post-decisional pupil dilation and confidence. Together our findings show that a physiological index of uncertainty, pupil dilation, predicts both confidence and metacognitive accuracy for auditory decisions.
Discrete Chebyshev transform. A natural modification of the DCT

Although the discrete cosine transform (DCT) is widely used for feature extraction in pattern recognition, it is shown that it converges slowly for most theoretically smooth functions. A modification of the DCT is described, based on a change of variable, which changes it to a new transform, called the discrete Chebyshev transform (DChT), which converges very rapidly for the same smooth functions. Although this rapid convergence is largely destroyed by the noise in real experimental data, the discrete Chebyshev transform is still generally better than the DCT when the sampling of the data can be selected at nonequidistant points. The improvement over the DCT gives a theoretical explanation for improved speech recognition obtained using Mel feature cepstral coefficients. These choose the sampling frequencies of a DCT to correspond to the human perception of pitch. It is shown that this sampling is similar to the sampling used in the discrete Chebyshev transform.
Teachers' Perceptions and Implementation of Professional Development in Writing Instruction

This mixed-methods study investigated teachers’ perceptions and implementation of professional development in writing instruction at a United States public high school campus. A layered approach to professional development was utilized: (1) one group received weekly professional development during a Professional Learning Community (PLC) and participated on a district writing team, (2) one group received weekly professional development during a PLC and received instructional coaching, and (3) one group received only weekly professional development during a PLC. Data were gathered on teachers’ responses to their perceptions of professional development received, teachers’ body and verbal language during PLCs and professional development, reflection notes documented by teachers receiving instructional coaching, and interviews of the teachers who received instructional coaching. Analyses of the data demonstrated application of the newly learned instructional practices in the classroom indicating the value teachers placed on learning during PLCs. While no significant differences were noted from the analysis of the pre-to post-observations for teachers in any group it was evidenced that the teachers who received instructional coaching became more aware of their instructional practices and had a greater sense of collaboration and collegiality as a result of the coaching process.
Enabling Low-Distortion Varactors for Adaptive Transmitters

A varactor diode configuration is presented for the implementation of low-distortion tunable matching networks, phase shifters, and filters. The configuration is based on varactors with an "exponential" C(V) relation in antiseries configuration with specific control voltage harmonic loading conditions. The resulting network combines a high capacitance tuning range with relatively low control voltages and excellent linearity. The linearity is independent of the applied control voltage and does not degrade at low tone spacing, which is ideal for the realization of adaptive transmitters and modulators. A specific Ndx-2 varactor doping profile is required for exact third-order intermodulation (IM3) cancellation. The remaining distortion is dominated by the much smaller fifth-order nonlinearities. The required impedance levels of the harmonic terminations are studied in terms of the maximum modulation bandwidth for which the proposed configuration remains linear. The doping profile optimization for quality factor, tuning range, and breakdown voltage is discussed. For experimental verification, the proposed varactor configuration has been implemented using a silicon-on-glass technology. The measurements demonstrate IM3 cancellation and indicate a superior linearity for modulated signals up to 10-MHz bandwidth.
Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant

OBJECTIVE Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND METHODS We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes. RESULTS We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: −0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: −0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant. CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.
Medically Unexplained and Explained Physical Symptoms in the General Population: Association with Prevalent and Incident Mental Disorders

Background Clinical studies have shown that Medically Unexplained Symptoms (MUS) are related to common mental disorders. It is unknown how often common mental disorders occur in subjects who have explained physical symptoms (PHY), MUS or both, in the general population, what the incidence rates are, and whether there is a difference between PHY and MUS in this respect. Aim To study the prevalence and incidence rates of mood, anxiety and substance use disorders in groups with PHY, MUS and combined MUS and PHY compared to a no-symptoms reference group in the general population. Method Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face-to-face survey of the general population aged 18-64 years. We selected subjects with explained physical symptoms only (n=1952), with MUS only (n=177), with both MUS and PHY (n=209), and a reference group with no physical symptoms (n=4168). The assessment of common mental disorders was through the Composite International Diagnostic Interview 3.0. Multivariate logistic regression analyses were used to examine the association between group membership and the prevalence and first-incidence rates of comorbid mental disorders, adjusted for socio-demographic characteristics. Results MUS were associated with the highest prevalence rates of mood and anxiety disorders, and combined MUS and PHY with the highest prevalence rates of substance disorder. Combined MUS and PHY were associated with a higher incidence rate of mood disorder only (OR 2.9 (95%CI:1.27,6.74)). Conclusion In the general population, PHY, MUS and the combination of both are related to mood and anxiety disorder, but odds are highest for combined MUS and PHY in relation to substance use disorder. Combined MUS and PHY are related to a greater incidence of mood disorder. These findings warrant further research into possibilities to improve recognition and early intervention in subjects with combined MUS and PHY.