Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics.

Recent genome-wide studies conducted in European Whites have identified novel susceptibility genes for childhood acute lymphoblastic leukemia (ALL). We sought to examine whether these loci are susceptibility genes among Hispanics, whose reported incidence of childhood ALL is the highest of all ethnic groups in California, and whether their effects differ between Hispanics and non-Hispanic Whites (NHWs). We genotyped 13 variants in these genes among 706 Hispanic (300 cases, 406 controls) and 594 NHW (225 cases, 369 controls) participants in a matched population-based case-control study in California. We found significant associations for the five studied ARID5B variants in both Hispanics (p values of 1.0 × 10(-9) to 0.004) and NHWs (p values of 2.2 × 10(-6) to 0.018). Risk estimates were in the same direction in both groups (ORs of 1.53-1.99 and 1.37-1.84, respectively) and strengthened when restricted to B-cell precursor high-hyperdiploid ALL (>50 chromosomes; ORs of 2.21-3.22 and 1.67-2.71, respectively). Similar results were observed for the single CEBPE variant. Hispanics and NHWs exhibited different susceptibility loci at CDKN2A. Although IKZF1 loci showed significant susceptibility effects among NHWs (p < 1 × 10(-5)), their effects among Hispanics were in the same direction but nonsignificant, despite similar minor allele frequencies. Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors

Off-Highway Gasoline Consuption Estimation Models Used in the Federal Highway Administration Attribution Process: 2008 Updates

This report is designed to document the analysis process and estimation models currently used by the Federal Highway Administration (FHWA) to estimate the off-highway gasoline consumption and public sector fuel consumption. An overview of the entire FHWA attribution process is provided along with specifics related to the latest update (2008) on the Off-Highway Gasoline Use Model and the Public Use of Gasoline Model. The Off-Highway Gasoline Use Model is made up of five individual modules, one for each of the off-highway categories: agricultural, industrial and commercial, construction, aviation, and marine. This 2008 update of the off-highway models was the second major update (the first model update was conducted during 2002-2003) after they were originally developed in mid-1990. The agricultural model methodology, specifically, underwent a significant revision because of changes in data availability since 2003. Some revision to the model was necessary due to removal of certain data elements used in the original estimation method. The revised agricultural model also made use of some newly available information, published by the data source agency in recent years. The other model methodologies were not drastically changed, though many data elements were updated to improve the accuracy of these models. Note that components in the Public Use of Gasoline Model were not updated in 2008. A major challenge in updating estimation methods applied by the public-use model is that they would have to rely on significant new data collection efforts. In addition, due to resource limitation, several components of the models (both off-highway and public-us models) that utilized regression modeling approaches were not recalibrated under the 2008 study. An investigation of the Environmental Protection Agency's NONROAD2005 model was also carried out under the 2008 model update. Results generated from the NONROAD2005 model were analyzed, examined, and compared, to the extent that is possible on the overall totals, to the current FHWA estimates. Because NONROAD2005 model was designed for emission estimation purposes (i.e., not for measuring fuel consumption), it covers different equipment populations from those the FHWA models were based on. Thus, a direct comparison generally was not possible in most sectors. As a result, NONROAD2005 data were not used in the 2008 update of the FHWA off-highway models. The quality of fuel use estimates directly affect the data quality in many tables published in the Highway Statistics. Although updates have been made to the Off-Highway Gasoline Use Model and the Public Use Gasoline Model, some challenges remain due to aging model equations and discontinuation of data sources

GENERATING TRAINING DATABASES USED IN VECTOR BASED OBJECT RECOGNITION IN HYBRID CLOUD USING PUBLIC PROFILES

Techniques are provided herein for generating a face data set which contains badge identifier photos and photos from social media. The faces are automatically tagged using facial recognition, text recognition, and human relationship mining

Cardiometabolic risk factors and mental health status among truck drivers : a systematic review

The first author (AG) has received funding for their PhD Studentship from the Colt Foundation. The Colt Foundation had no role in study design; election, synthesis and interpretation of data; writing of the report; or the decision to submit the manuscript for publication. SC and JAK are in receipt of funding from the NIHR Public Health Research Programme (reference: NIHR PHR 15/190/42) for the evaluation of a multi-component health behaviour intervention in truck drivers. They are also supported by the NIHR Leicester Biomedical Research Centre – Lifestyle theme. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.Peer reviewedPublisher PD

Structure and Magnetotransport Properties of Epitaxial Nanocomposite La0.67Ca0.33MnO3:SrTiO3 Thin Films Grown by a Chemical Solution Approach

Epitaxial La0.67Ca0.33MnO3:SrTiO3 (LCMO:STO) composite thin films have been grown on single crystal LaAlO3(001) substrates by a cost effective polymer-assisted deposition method. Both x-ray diffraction and high-resolution transmission electron microscopy confirm the growth of epitaxial films with an epitaxial relationship between the films and the substrates as (002)film||(002)sub and [202]film||[202]sub. The transport property measurement shows that the STO phase significantly increases the resistivity and enhances the magnetoresistance (MR) effect of LCMO and moves the metal-insulator transition to lower temperatures. For example, the MR values measured at magnetic fields of 0 and 3 T are −44.6% at 255 K for LCMO, −94.2% at 125 K for LCMO:3% STO, and −99.4% at 100 K for LCMO:5% STO, respectively

Structure and Magnetotransport Properties of Epitaxial Nanocomposite La0.67Ca0.33MnO3:SrTiO3 Thin Films Grown by a Chemical Solution Approach

Epitaxial La0.67Ca0.33MnO3:SrTiO3 (LCMO:STO) composite thin films have been grown on single crystal LaAlO3(001) substrates by a cost effective polymer-assisted deposition method. Both x-ray diffraction and high-resolution transmission electron microscopy confirm the growth of epitaxial films with an epitaxial relationship between the films and the substrates as (002)film||(002)sub and [202]film||[202]sub. The transport property measurement shows that the STO phase significantly increases the resistivity and enhances the magnetoresistance (MR) effect of LCMO and moves the metal-insulator transition to lower temperatures. For example, the MR values measured at magnetic fields of 0 and 3 T are −44.6% at 255 K for LCMO, −94.2% at 125 K for LCMO:3% STO, and −99.4% at 100 K for LCMO:5% STO, respectively

A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts.Results: The variant (c.344T\u3eA; p.V115E) is rare and alters a conserved residue in UFSP2. Immunoblotting in patient-derived fibroblasts revealed reduced UFSP2 abundance and increased abundance of UFMylated targets, indicating the variant may impair de-UFMylation rather than UFMylation. Reconstituting patient-derived fibroblasts with wild-type UFSP2 reduced UFMylation marks. Analysis of UFSP2\u27s structure indicated that variants observed in skeletal disorders localize to the catalytic domain, whereas V115 resides in an N-terminal domain possibly involved in substrate binding.Conclusion: Different UFSP2 variants cause markedly different diseases, with homozygosity for V115E causing a severe syndrome of neurodevelopmental disability and epilepsy

Chronic IL-1β-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

Chronic inflammation facilitates tumor progression. We discovered that a subset of non-small cell lung cancer cells underwent a gradually progressing epithelial-to-mesenchymal (EMT) phenotype following a 21-day exposure to IL-1β, an abundant proinflammatory cytokine in the at-risk for lung cancer pulmonary and the lung tumor microenvironments. Pathway analysis of the gene expression profile and in vitro functional studies revealed that the EMT and EMT-associated phenotypes, including enhanced cell invasion, PD-L1 upregulation, and chemoresistance, were sustained in the absence of continuous IL-1β exposure. We referred to this phenomenon as EMT memory. Utilizing a doxycycline-controlled SLUG expression system, we found that high expression of the transcription factor SLUG was indispensable for the establishment of EMT memory. High SLUG expression in tumors of lung cancer patients was associated with poor survival. Chemical or genetic inhibition of SLUG upregulation prevented EMT following the acute IL-1β exposure but did not reverse EMT memory. Chromatin immunoprecipitation and methylation-specific PCR further revealed a SLUG-mediated temporal regulation of epigenetic modifications, including accumulation of H3K27, H3K9, and DNA methylation, in the CDH1 (E-cadherin) promoter following the chronic IL-1β exposure. Chemical inhibition of DNA methylation not only restored E-cadherin expression in EMT memory, but also primed cells for chemotherapy-induced apoptosis

Attenuated cardiovascular reactivity is related to higher anxiety and fatigue symptoms in truck drivers

ACKNOWLEDGEMENTS The authors would like to thank all the truck drivers who participated in this study. The data presented in this paper were collected as part of the baseline measures from the “Structured Health Intervention For Truckers (SHIFT)” randomized controlled trial, which is funded by the NIHR Public Health Research Programme (reference: NIHR PHR 15/190/42). SAC, JAK, AS and NJP are supported by the NIHR Leicester Biomedical Research Centre—Lifestyle theme. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The first author (AG) has received funding for their PhD Studentship from the Colt Foundation (reference: JD/618). The Colt Foundation had no role in study design; election, synthesis, and interpretation of data; writing of the report; or the decision to submit the manuscript for publicationPeer reviewedPublisher PD

The complement system and human autoimmune diseases

Genetic deficiencies of early components of the classical complement activation pathway (especially C1q, r, s, and C4) are the strongest monogenic causal factors for the prototypic autoimmune disease systemic lupus erythematosus (SLE), but their prevalence is extremely rare. In contrast, isotype genetic deficiency of C4A and acquired deficiency of C1q by autoantibodies are frequent among patients with SLE. Here we review the genetic basis of complement deficiencies in autoimmune disease, discuss the complex genetic diversity seen in complement C4 and its association with autoimmune disease, provide guidance as to when clinicians should suspect and test for complement deficiencies, and outline the current understanding of the mechanisms relating complement deficiencies to autoimmunity. We focus primarily on SLE, as the role of complement in SLE is well-established, but will also discuss other informative diseases such as inflammatory arthritis and myositis