Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles

Notch is a highly conserved transmembrane protein that is involved in cell fate decisions and is found in organisms ranging from Drosophila to humans. A human homologue of Notch, TAN1, was initially identified at the chromosomal breakpoint of a subset of T-cell lymphoblastic leukemias/lymphomas containing a t(7;9) chromosomal translocation; however, its role in oncogenesis has been unclear. Using a bone marrow reconstitution assay with cells containing retrovirally transduced TAN1 alleles, we analyzed the oncogenic potential of both nuclear and extranuclear forms of truncated TAN1 in hematopoietic cells. Although the Moloney leukemia virus long terminal repeat drives expression in most hematopoietic cell types, retroviruses encoding either form of the TAN1 protein induced clonal leukemias of exclusively immature T cell phenotypes in approximately 50% of transplanted animals. All tumors overexpressed truncated TAN1 of the size and subcellular localization predicted from the structure of the gene. These results show that TAN1 is an oncoprotein and suggest that truncation and overexpression are important determinants of transforming activity. Moreover, the murine tumors caused by TAN1 in the bone marrow transplant model are very similar to the TAN1-associated human tumors and suggest that TAN1 may be specifically oncotropic for T cells

Analisis Komponen Reverse Mean pada Harga Saham melalui Perspektif Ekonomi Makro di Bursa Efek Jakarta

Reverse mean reversion and predictability of stock return is probably the most well researched topic in the empirical research of financial economics. Numerous empirical studies have been unable to reject the hypothesis that return unpredictable and that stock price follows a random walk or martingale process. The essence of the mean-reversion hypothesis is that the stocks price contains a temporary component. Thus, the market value of stock deviates from the fundamental value but will revert to its mean. The objective of this study is to test the mean reversion hypothesis in Indonesian capital market, by investigate the size and significance of mean reversion component of stock prices at the Jakarta Stock Exchange, for the period of January 1990 through December 2003, and to investigate the size of the forecast error variance decomposition for real stock prices which is caused by permanent innovation and temporary innovation for a horizon of 2, 3, 4, 6, 12 and 24 months. By placing appropriate structural restrictions on a vector auto-regressive system estimated for the period of January 1990 through December 2003, it was found that the temporary component in the stock prices at the Jakarta Stock Exchange has significant size. From this, it can be inferred that the pattern of share price movements at the Jakarta Stock Exchange has a temporary component which will gradually disperse or undergo reverse mean. This evidence supports the mean reversion hypothesis that stock price are not pure random walks and predictability of stock return and reject the random walk hypothesis

A TV-Gaussian prior for infinite-dimensional Bayesian inverse problems and its numerical implementations

Many scientific and engineering problems require to perform Bayesian inferences in function spaces, in which the unknowns are of infinite dimension. In such problems, choosing an appropriate prior distribution is an important task. In particular we consider problems where the function to infer is subject to sharp jumps which render the commonly used Gaussian measures unsuitable. On the other hand, the so-called total variation (TV) prior can only be defined in a finite dimensional setting, and does not lead to a well-defined posterior measure in function spaces. In this work we present a TV-Gaussian (TG) prior to address such problems, where the TV term is used to detect sharp jumps of the function, and the Gaussian distribution is used as a reference measure so that it results in a well-defined posterior measure in the function space. We also present an efficient Markov Chain Monte Carlo (MCMC) algorithm to draw samples from the posterior distribution of the TG prior. With numerical examples we demonstrate the performance of the TG prior and the efficiency of the proposed MCMC algorithm

Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache

Publisher Copyright: © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Objective: Identifying common genetic variants that confer genetic risk for cluster headache. Methods: We conducted a case–control study in the Dutch Leiden University Cluster headache neuro-Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord-Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell-derived RNA-sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses. Results: An association was found with cluster headache for 4 independent loci (r2 < 0.1) with genomewide significance (p < 5 × 10−8), rs11579212 (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.33–1.72 near RP11-815 M8.1), rs6541998 (OR = 1.53, 95% CI = 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI = 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI = 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the variance of cluster headache. SNPs rs11579212, rs10184573, and rs976357, as proxy SNP for rs2499799 (r2 = 1.0), replicated in the Norwegian sample (p < 0.05). Gene-based mapping yielded ASZ1 as possible fifth locus. RNA-sequencing indicated differential expression of POLR1B and TMEM87B in cluster headache patients. Interpretation: This genomewide association study (GWAS) identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders. ANN NEUROL 2021;90:203–216.Peer reviewe

Discerning Developmental Dyscalculia and Neurodevelopmental Models of Numerical Cognition in a Disadvantaged Educational Context

Developmental Dyscalculia (DD) signifies a failure in representing quantities, which impairs the performance of basic math operations and schooling achievement during childhood. The lack of specificity in assessment measures and respective cut-offs are the most challenging factors to identify children with DD, particularly in disadvantaged educational contexts. This research is focused on a numerical cognition battery for children, designed to diagnose DD through 12 subtests. The aims of the present study were twofold: to examine the prevalence of DD in a country with generally low educational attainment, by comparing z-scores and percentiles, and to test three neurodevelopmental models of numerical cognition based on performance in this battery. Participants were 304 Brazilian school children aged 7-12 years of both sexes (143 girls), assessed by the Zareki-R. Performances on subtests and the total score increase with age without gender differences. The prevalence of DD was 4.6% using the fifth percentile and increased to 7.4% via z-score (in total 22 out of 304 children were diagnosed with DD). We suggest that a minus 1.5 standard deviation in the total score of the Zareki-R is a useful criterion in the clinical or educational context. Nevertheless, a percentile ≤ 5 seems more suitable for research purposes, especially in developing countries because the socioeconomic environment or/and educational background are strong confounder factors to diagnosis. The four-factor structure, based on von Aster and Shalev's model of numerical cognition (Number Sense, Number Comprehension, Number Production and Calculation), was the best model, with significant correlations ranging from 0.89 to 0.97 at the 0.001 level

Improved water and land management in the Ethiopian highlands and its impact on downstream stakeholders dependent on the Blue Nile

Improved water and land management in the Ethiopian highlands and its impact on downstream stakeholders dependent on the Blue Nile – short title Upstream-Downstream in Blue Nile River project is one of the projects in the Nile Basin supported by the CPWF. It was implemented during from 2007 to 2009 through a partnership of 8 institutions. The Blue Nile is the major tributary of the Nile River, contributing about 62% of the Nile flow at Aswan. About two thirds of the area of this densely populated basin is in the highlands and hence receives fairly high levels of annual rainfall of 800 to 2,200 mm. However, the rainfall is erratic in terms of both spatial and temporal distribution with prolonged dry spells and drought often leading to crop failures. Currently, water resources are only marginally exploited in the upper basin but are much more developed in the downstream reaches. The population, located in the downstream part of the Blue Nile, is dependent on the river water for supplementary irrigation and energy production. Canal and reservoir siltation is a major problem, adding the burdens of poor riparian farmers. This project was envisaged to improve the scientific understanding of the land and water resources of the basin, and hypothesized that with increased scientific knowledge of the hydrological, watershed, and institutional processes of the Blue Nile in Ethiopia (Abbay), constraints to up-scaling adaptable best practices and promising technologies (technical, socio-economic, institutional) could be overcome, which will result in significant positive impacts for both upstream and downstream communities and state

Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache

Cefalea; Estudio de asociación del genoma completoCefalea; Estudi de l'associació del genoma completHeadache; Genomewide Association StudyObjective Identifying common genetic variants that confer genetic risk for cluster headache. Methods We conducted a case–control study in the Dutch Leiden University Cluster headache neuro-Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord-Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell-derived RNA-sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses. Results An association was found with cluster headache for 4 independent loci (r2 < 0.1) with genomewide significance (p < 5 × 10−8), rs11579212 (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.33–1.72 near RP11-815 M8.1), rs6541998 (OR = 1.53, 95% CI = 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI = 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI = 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the variance of cluster headache. SNPs rs11579212, rs10184573, and rs976357, as proxy SNP for rs2499799 (r2 = 1.0), replicated in the Norwegian sample (p < 0.05). Gene-based mapping yielded ASZ1 as possible fifth locus. RNA-sequencing indicated differential expression of POLR1B and TMEM87B in cluster headache patients. Interpretation This genomewide association study (GWAS) identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders. ANN NEUROL 2021;90:203–21

Farmer access to irrigation scheduling advice leads to sustainable intensification of high value crops

United States Agency for International Developmen