Miracle-dz/UniFAR-FTUs huggingface dataset:
GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis

Truncating mutations in Gli3, an intracellular effector in the SHH-SMO-GLI signaling pathway, cause renal aplasia/dysplasia in humans and mice. Yet, the pathogenic mechanisms are undefined. Here, we report the effect of decreased SHH-SMO signaling on renal morphogenesis, the expression of SHH target genes and GLI binding to Shh target genes. Shh deficiency or cyclopamine-mediated SMO inhibition disrupted renal organogenesis, decreased expression of GLI1 and GLI2 proteins, but increased expression of GLI3 repressor relative to GLI3 activator. Shh deficiency decreased expression of kidney patterning genes (Pax2 and Sall1) and cell cycle regulators (cyclin D1 and MYCN). Elimination of Gli3 in Shh–/– mice rescued kidney malformation and restored expression of Pax2, Sall1, cyclin D1, MYCN, Gli1 and Gli2. To define mechanisms by which SHH-SMO signaling controls gene expression, we determined the binding of GLI proteins to 5′ flanking regions containing GLI consensus binding sequences in Shh target genes using chromatin immunoprecipitation. In normal embryonic kidney tissue, GLI1 and/or GLI2 were bound to each target gene. By contrast, treatment of embryonic kidney explants with cyclopamine decreased GLI1 and/or GLI2 binding, and induced binding of GLI3. However, cyclopamine failed to decrease Gli1 and Gli2 expression and branching morphogenesis in Gli3-deficient embryonic kidney tissue. Together, these results demonstrate that SHH-SMO signaling controls renal morphogenesis via transcriptional control of Gli, renal patterning and cell cycle regulator genes in a manner that is opposed by GLI3.
Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia.

PURPOSE For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC). METHODS We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with "B" symptoms or bulky [> 10 cm] disease) DLBCL. RESULTS A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age. CONCLUSION The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.
How effective is human video surveillance performance?

In surveillance situations, computer vision systems are often deployed to help humans perform their tasks more effectively. In a typical installation human observers are required to simultaneously monitor a number of video signals. Psychophysical research indicates that there are severe limitations in the ability of humans to monitor simultaneous signals. Do these same limitations extend to surveillance? We present a method for evaluating human surveillance performance in a situation that mimics demands of real world surveillance. A single computer monitor contained either nine display cells or four display cells. Each cell contained a stream of 2 to 4 moving objects. Observers were instructed to signal when a target event occurred - - when one of the objects entered a small square ldquoforbiddenrdquo region in the center of the display. Target events could occur individually or in groups of 2 or 3 temporally close events. The results indicate that the observers missed many targets (60%) when required to monitor 9 displays and many fewer when monitoring 4 displays (20%). Further, there were costs associated with target events occurring in close temporal succession. Understanding these limitations would help computer visions researchers to design algorithms and human-machine interfaces that result in improved overall performance.
Visual information processing dysfunction across the developmental course of early psychosis

Background Patients with schizophrenia consistently demonstrate information processing abnormalities assessed with visual masking (VM) tasks, and these deficits have been linked to clinical and functional severity. It has been suggested that VM impairments may be a vulnerability marker in individuals at risk for developing psychosis. Method Forward and backward VM performance was assessed in 72 first-episode (FE) psychosis patients, 98 subjects at risk (AR) for psychosis and 98 healthy controls (HC) using two identification tasks (with either a high- or low-energy mask) and a location task. VM was examined for stability in a subgroup (FE, n=15; AR, n=35; HC, n=21) and assessed relative to clinical and functional measures. Results In the identification tasks, backward VM deficits were observed in both FE and AR relative to HC whereas forward VM deficits were only present in FE patients compared to HC. In the location task, AR subjects demonstrated superior performance in forward VM relative to HC. VM performance was stable over time, and VM deficits were associated with baseline functional measures and predicted future negative symptom severity in AR subjects. Conclusions Visual information processing deficits, as indexed by backward VM, are present before and after the onset of frank psychosis, and probably represent a stable vulnerability marker that is associated with negative symptoms and functional decline. Additionally, the paradoxically better performance of AR subjects in select forward tasks suggests that early compensatory changes may characterize an emerging psychotic state.
Impact of the PDE4D gene polymorphism and additional SNP–SNP and gene–smoking interaction on ischemic stroke risk in Chinese Han population

Abstract Aims: To investigate the association between phosphodiesterase 4D gene (PDE4D) gene single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) risk, and impact of additional SNP- SNP and gene- smoking interaction on IS risk in Chinese population. Methods: A total of 1228 subjects (666 males, 562 females) were selected, including 610 IS patients and 618 control subjects. Logistic regression model was used to examine the association between SNPs in PDE4D gene and IS risk. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the SNP- SNP and gene- smoking interaction. Results: IS risks were significantly higher in carriers of A allele of rs12188950 polymorphism than those with GG genotype (GA + AA vs. GG), adjusted OR (95%CI) = 1.61 (1.26–2.19), and also significantly higher in carriers of T allele of rs966221 polymorphism than those with CC (CT + TT vs. CC), adjusted OR (95%CI) = 1.82 (1.39–2.23). We found that there was a significant SNP- SNP interaction between rs966221 and rs12188950. Subjects with CT or TT of rs966221 and GA or AA of rs12188950 genotype have the highest IS risk, compared to subjects with CC of rs966221 and GG of rs12188950 genotype, OR (95%CI) was 3.52 (2.68–4.69). We also found a significant gene–environment interaction between rs966221 and smoking. Smokers with CT or TT of rs966221 genotype have the highest IS risk, compared to never smokers with CC of rs966221 genotype, OR (95%CI) was 3.97 (2.25–5.71). Conclusions: Our results support an important association of rs966221 and rs12188950 minor allele and its interaction with increased risk of IS risk, and additional interaction between rs966221 and smoking.
Derandomizing Polynomial Identity Testing for Multilinear Constant-Read Formulae

We present a polynomial-time deterministic algorithm for testing whether constant-read multilinear arithmetic formulae are identically zero. In such a formula each variable occurs only a constant number of times and each subformula computes a multilinear polynomial. Before our work no subexponential-time deterministic algorithm was known for this class of formulae. We also present a deterministic algorithm that works in a blackbox fashion and runs in quasi-polynomial time in general, and polynomial time for constant depth. Finally, we extend our results and allow the inputs to be replaced with sparse polynomials. Our results encompass recent deterministic identity tests for sums of a constant number of read-once formulae, and for multilinear depth-four circuits.
Self-Resemblance and Social Rejection

Humans perceive and treat self-resembling others in ways that suggest that self-resemblance is a cue of kinship. However, we know little about how individuals respond to treatment by self-resembling others. Here we approach this problem by connecting facial self-resemblance to social rejection. Given that individuals should expect to cooperate with kin, we hypothesized that (1) social inclusion by perceived kin should elicit lesser feelings of rejection and (2) social exclusion by perceived kin should elicit greater feelings of rejection relative to inclusion or exclusion, respectively, by nonkin. To test these hypotheses, we recruited 90 participants to play two games of Cyberball, a virtual ball-tossing game, with separate pairs of ostensible partners. In one game, the ostensible partners were programed to fully include the participants in group play and, in the other game, they were programed to exclude the participants after a few rounds; the order of inclusion and exclusion was counterbalanced across participants. Partner faces were digitally manipulated to be either self- or nonself-resembling, and these conditions were also counterbalanced. Rejection feelings differed significantly as a function of self-resemblance between the inclusion and exclusion conditions, but only for participants who experienced inclusion first. Moreover, for these individuals, inclusion by self-resembling partners led to significantly lesser feelings of rejection than did inclusion by nonself-resembling partners. To explain this effect, we explore potential mechanisms of kin recognition and social rejection. Although nuanced, our results suggest that perceptions of kinship can moderate psychological responses to the actions of others.
Facial Expression Recognition from Image Sequences Based on Feature Points and Canonical Correlations

In this paper, we present a framework to recognize facial expressions from image sequences. Our method uses optical flow to track feature points in sequential facial frames, and computes normalized displacements of key feature points and certain standardized geometric distances to form a matrix, called facial-expression-arising-dataset (FEAD). Each FEAD represents an expression image sequence (from neutral to peak). We use canonical correlations to classify an FEAD into one of the six basic facial expressions, and utilize a linear discriminant function to optimize the learning and recognition process. Our method formulates the facial expression recognition as data sets matching problem to fully utilize the dynamic information in expression emerging process, and achieves a recognition accuracy of beyond 90%. Experimental results demonstrate the robustness and effectiveness of this method.
Measure-transformed Gaussian quasi score test

In this paper, we develop a robust generalization of the Gaussian quasi score test (GQST) for composite binary hypothesis testing. The proposed test, called measure-transformed GQST (MT-GQST), is based on a transformation applied to the probability distribution of the data. The considered transform is structured by a non-negative function, called MT-function, that weights the data points. By appropriate selection of the MT-function we show that, unlike the GQST, the proposed MT-GQST incorporates higher-order moments and can gain robustness to outliers. The MT-GQST is applied for testing the parameter of a non-linear model. Simulation example illustrates its advantages as compared to the standard GQST and other robust detectors.
A mixed integer SDP approach for the optimal placement of energy storage devices in power grids with renewable penetration

In power networks, Energy Storage Systems (ESS) can help to cope with intermittent availability of renewable sources. However, fixed, maintenance, and operating costs are a critical aspect that must be considered in the positioning and sizing of these devices. This paper addresses the problem of placing storage devices in order to achieve an Optimal Power Flow (OPF) in presence of renewable sources. The problem is addressed formulating a Mixed Integer Semidefinite Program (MI-SDP) that takes into account energy production and ESS costs. While this approach provides a solution that does not guarantee a physical meaning, this latter is recoverable from the dual solution of the MI-SDP with fixed storage devices locations. The approach is demonstrated on the IEEE 14 and 30 bus benchmark systems where power demand, renewable generation profiles and costs have been taken from real data.
Co-Sparse Textural Similarity for Image Segmentation

We propose an algorithm for segmenting natural images based on texture and color information, which leverages the co-sparse analysis model for image segmentation within a convex multilabel optimization framework. As a key ingredient of this method, we introduce a novel textural similarity measure, which builds upon the co-sparse representation of image patches. We propose a Bayesian approach to merge textural similarity with information about color and location. Combined with recently developed convex multilabel optimization methods this leads to an efficient algorithm for both supervised and unsupervised segmentation, which is easily parallelized on graphics hardware. The approach provides competitive results in unsupervised segmentation and outperforms state-of-the-art interactive segmentation methods on the Graz Benchmark.
True hermaphroditism with XX/XY sex chromosome mosaicism: Report of a case

A case of true hermaphroditism with 46, XX/46, XY karyotype is reported. The propositus, reared as a male, showed ambiguous external genitalia with perineoscrotal hypospadias, and internal genitalia represented by bilateral ovotestes, normal uterus and tubes. Periodic menstrual bleedings appeared at puberty. The endocrinologic data demonstrated the secretory activity of both the ovarian and the testicular tissue. The analysis of red cell, lymphocyte and serum markers, done on the propositus and on his parents, failed to show any evidence of double fertilization. On this basis, the origin of the XX/XY condition (mosaicism versus chimerism) and its developmental consequences are discussed.
Lymphotropic herpesviruses in allogeneic bone marrow transplantation.

Human herpesvirus-6 (HHV-6), human herpesvirus-7 (HHV-7), Epstein-Barr virus (EBV), and human cytomegalovirus (CMV) DNA were repeatedly assayed in peripheral blood leukocytes from 37 allogeneic bone marrow transplant (BMT) patients by polymerase chain reaction. Before BMT, HHV-6 DNA was detected in 8 (22%) patients. HHV-7, EBV, and CMV DNA were detected in 21 (57%), 10 (27%), and 1 (3%) patient, respectively. After BMT, HHV-6 DNA was detected in 26 (70%), HHV-7 in 21 (57%), EBV in 28 (76%), and CMV in 21 (57%) patients. Thirty-two (87%) patients were positive with more than one virus. HHV-6, HHV-7, and EBV DNA were found earlier than CMV DNA in most patients after BMT. The proportions of HHV-6-positive samples during the first 3 months after BMT were higher in the patients with either delayed granulocyte engraftment (P = .04, Fisher's exact test) or delayed platelet engraftment (P = .001, Fisher's exact test). The HHV-6 DNA in samples from the patients with delayed engraftment was confirmed to be variant B. The detection of any lymphotropic herpesvirus was not related to the development of acute graft-versus-host disease (aGVHD). High-dose acyclovir (ACV) prophylaxis significantly (P < .01) reduced the proportion of HHV-6-positive samples and tended to lower HHV-6 DNA levels (P = .06). Our data indicate that HHV-6 variant B can inhibit marrow engraftment and that high-dose ACV may be beneficial to engraftment after BMT by preventing HHV-6 reactivation. No relation between the proportions of HHV-7-, EBV-, and CMV-positive samples in the first 3 months and engraftment or aGVHD was found.
Prediction of Early Breast Cancer Metastasis from DNA Microarray Data Using High-Dimensional Cox Regression Models

Background DNA microarray studies identified gene expression signatures predictive of metastatic relapse in early breast cancer. Standard feature selection procedures applied to reduce the set of predictive genes did not take into account the correlation between genes. In this paper, we studied the performances of three high-dimensional regression methods – CoxBoost, LASSO (Least Absolute Shrinkage and Selection Operator), and Elastic net – to identify prognostic signatures in patients with early breast cancer. Methods We analyzed three public retrospective datasets, including a total of 384 patients with axillary lymph node-negative breast cancer. The Amsterdam van't Veer's training set of 78 patients was used to determine the optimal gene sets and classifiers using sensitivity thresholds resulting in misclassification of no more than 10% of the poor-prognosis group. To ensure the comparability between different methods, an automatic selection procedure was used to determine the number of genes included in each model. The van de Vijver's and Desmedt's datasets were used as validation sets to evaluate separately the prognostic performances of our classifiers. The results were compared to the original Amsterdam 70-gene classifier. Results The automatic selection procedure reduced the number of predictive genes up to a minimum of six genes. In the two validation sets, the three models (Elastic net, LASSO, and CoxBoost) led to the definition of genomic classifiers predicting the 5-year metastatic status with similar performances, with respective 59, 56, and 54% accuracy, 83, 75, and 83% sensitivity, and 53, 52, and 48% specificity in the Desmedt's dataset. In comparison, the Amsterdam 70-gene signature showed 45% accuracy, 97% sensitivity, and 34% specificity. The gene overlap and the classification concordance between the three classifiers were high. All the classifiers added significant prognostic information to that provided by the traditional prognostic factors and showed a very high overlap with respect to gene ontologies (GOs) associated with genes overexpressed in the predicted poor-prognosis vs. good-prognosis classes and centred on cell proliferation. Interestingly, all classifiers reported high sensitivity to predict the 4-year status of metastatic disease. Conclusions High-dimensional regression methods are attractive in prognostic studies because finding a small subset of genes may facilitate the transfer to the clinic, and also because they strengthen the robustness of the model by limiting the selection of false-positive predictive genes. With only six genes, the CoxBoost classifier predicted the 4-year status of metastatic disease with 93% sensitivity. Selecting a few genes related to ontologies other than cell proliferation might further improve the overall sensitivity performance.
Does School Tracking Affect Equality of Opportunity? New International Evidence

This paper investigates whether at the interaction between family background and school tracking affects human capital accumulation. Our a priori view is that more tracking should reinforce the role of parental privilege, and thereby reduce equality of opportunity. Compared to the current literature, which focuses on early outcomes, such as test scores at 13 and 15, we look at later outcomes, including literacy, dropout rates, college enrolment, employability and earnings. While we do not confirm previous results that tracking reinforces family background effects on literacy, we do confirm our view when looking at educational attainment and labour market outcomes. When looking at early wages, we find that parental background effects are stronger when tracking starts earlier. We reconcile the apparently contrasting results on literacy, educational attainment and earnings by arguing that the signalling role of formal education – captured by attainment – matters more than actual skills – measured by literacy – in the early stages of labour market experience.
Nonlinear Partial Least Squares Modeling of Phenyl Alkylamines with the Monoamine Oxidase Inhibitory Activities

The nonlinear partial least squares (PLS) method is a nonlinear version of PLS. In this approach, a quadratic inner relation is used instead of the linear inner relation in PLS. Since the quadratic inner relation can be extended to a general form, it is said that the nonlinear PLS method has a high potential for nonlinear modelling. However, few applications of the method have been appeared in quantitative structure--activity relationships (QSAR) studies, because the mathematical descriptions underlying the algorithm were not so clear. In this paper, we have carried out the QSAR analysis of four monoamine oxidase (MAO) inhibitory activities using the nonlinear PLS method. The in vitro and in vivo MAO inhibitory activities were analyzed separately. From the PLS loadings, the structural requirements could be estimated and the utility of the nonlinear PLS method was demonstrated.