Miracle-dz/UniFAR-FTUs huggingface dataset:
Confirmation of a dyslexia susceptibility locus on chromosome 1p34‐p36 in a set of 100 Canadian families

Dyslexia is a common and genetically complex trait that manifests primarily as a reading disability independent of general intelligence and educational opportunity. Strong evidence for a dyslexia susceptibility locus on chromosome 1p34‐p36 (near marker D1S199) was recently reported, and an earlier study found suggestive evidence for linkage to the same region. We tested for the presence of a dyslexia gene in this region in a sample of 100 Canadian families using both qualitative and quantitative definitions of the phenotype. Using a qualitative definition of dyslexia (affected, unaffected, or uncertain), the largest multipoint Genehunter Maximum LOD‐Score (MLS) in 100 core nuclear families was 3.65 at D1S507, distal to D1S199. Quantitative trait locus (QTL) linkage analysis was performed for four measures of dyslexia (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) employing the variance components approach implemented in Genehunter. Using a model with QTL additive and dominance variance and polygenic additive variance, the multipoint LOD scores maximized proximal to D1S199 (between D1S552 and D1S1622), with peaks of 4.01 for spelling and 1.65 for phonological coding (corresponding LOD scores under 1 degree of freedom were 3.30 and 1.13, respectively). In conclusion, our study confirms and strengthens recent findings of a dyslexia susceptibility gene on chromosome 1p34‐p36 (now designated DYX8). © 2003 Wiley‐Liss, Inc.
X-band interferometric SAR sensor for the Japanese altimetry mission, COMPIRA

COMPIRA (Coastal and Ocean Measurement mission with Precise and Innovative Radar Altimeter) is a new Japanese altimetry mission with X-band interferometric synthetic aperture radar (SHIOSAI; SAR Height Imaging Oceanic Sensor with Advanced Interferometry). We will use a wide-swath altimeter to maximize the spatial coverage of the altimetry measurements and to reduce errors in the tidal model in shallow marginal seas. We are now working on a conceptual study of the X-band interferometric synthetic aperture radar. In parallel, to demonstrate the sea surface height measurement with X-band interferometric SAR and obtain some parameters for design of SHIOSAI, we conducted aircraft experiments of the sea surface height measurement with an airborne interferometric SAR. In the paper, we will present current status of conceptual study of the SHIOSAI sensor and the airborne experiments.
c‐myc‐induced hepatocarcinogenesis in the absence of IGF‐I receptor

Numerous tumours, including hepatocarcinomas, produce IGFs, and some depend on these growth factors in a paracrine or autocrine fashion. We have shown that c‐myc‐induced experimental hepatocarcinogenesis is associated with enhanced production of IGF‐II. To assess the role of the IGF‐I receptor (IGF‐IR) in hepatocarcinogenesis, we generated conditional mutant mice that overexpressed c‐myc and were knocked out for IGF‐IR specifically in the liver. We compared these mice with littermate controls that also overexpressed c‐myc but had wild‐type IGF‐IR alleles. We found that the pretumoral phase, induced by early c‐myc expression and characterised by increased cell proliferation, was largely unaffected by the lack of IGF‐IR. To our further surprise, hepatocellular carcinomas (HCCs) lacking IGF‐IR readily developed and progressed at the same rate as control HCCs. At 9 months, all c‐myc transgenic mice displayed well‐differentiated multifocal tumours, regardless of whether their livers—and their tumours—were able to produce IGF‐IR. Levels of IRS‐1 and IRS‐2 were elevated in all tumours in the presence or absence of IGF‐IR, suggesting that the signalling pathway downstream of IGF‐IR is activated via IGF‐IR‐independent mechanisms in HCC. In conclusion, the deregulation of IGF signalling pathways, which often occurs during liver tumorigenesis, does not necessarily require IGF‐IRs, and hepatic IGF‐IR alone may not play a determinant role in c‐myc‐induced hepatocarcinogenesis. © 2004 Wiley‐Liss, Inc.
General and Conditional Replacement of Connexin43-Coding DNA by a lacZ Reporter Gene for Cell-Autonomous Analysis of Expression

Using the Cre/loxP system, we have circumvented early postnatal lethality and possible pleiotropic effects of general Cx43 gene deletion, in order to determine the expression and function of connexin43 (Cx43) in defined cell types. General or cell type-specific, Cre-mediated deletion of the floxed (i.e. flanked by loxP sites) Cx43-coding region led to activation of the inserted lacZ reporter gene in cells with transcriptional activity of the Cx43 gene. As deduced from lacZ expression in mice with general deletion, transcriptional activity of the Cx43 gene was not only found in a broad range of cell types known to a express Cx43, but also in pancreatic duct cells and vascular cells of the gut and skeletal muscle. Cre-mediated deletion restricted to defined cell types led to lacZ activation highlighting corresponding subsets of cells expressing Cx43, such as vascular endothelial cells, hepatic duct cells and putative neural crest cells, which were otherwise masked by strong Cx43 expression in neighbouring cells. In Cx43 expressing cell types, the floxed Cx43 allele was useful as a Cre-excision reporter for the characterization of Cre transgenes.
Human Pulmonary 3D Models For Translational Research

Lung diseases belong to the major causes of death worldwide. Recent innovative methodological developments now allow more and more for the use of primary human tissue and cells to model such diseases. In this regard, the review covers bronchial air‐liquid interface cultures, precision cut lung slices as well as ex vivo cultures of explanted peripheral lung tissue and de‐/re‐cellularization models. Diseases such as asthma or infections are discussed and an outlook on further areas for development is given. Overall, the progress in ex vivo modeling by using primary human material could make translational research activities more efficient by simultaneously fostering the mechanistic understanding of human lung diseases while reducing animal usage in biomedical research.
A novel classification technique for cancer diagnostics based on microarray gene expression profiling (MGEP)

Pattern Recognition (PR) plays a vital role in the field of Bioinformatics. Various techniques of PR are used to analyze, segment and manipulate the high dimensional microarray gene expression data for classification. Microarray Gene Expression Profiling (MGEP) is an important domain of Bioinformatics that yields such high dimensional data used for various clinical applications such as cancer diagnostics and drug designing. In this study a novel scheme has been developed for the classification of unknown malignant tumors into known classes. The classification scheme includes the transformation of high dimensional microarray data on to the Mahalanobis space before classification, in order to compensate for the data spreads corresponding to each class and every gene. The efficiency of the proposed classification scheme has been proven on 10 publicly available cancer datasets containing both binary and multiclass data. To improve the performance of the classifier gene selection technique is applied on the datasets as a preprocessing/data extraction step.
Induction of Cell Death by Betulinic Acid through Induction of Apoptosis and Inhibition of Autophagic Flux in Microglia BV-2 Cells

Betulinic acid (BA), a natural pentacyclic triterpene found in many medicinal plants is known to have various biological activity including tumor suppression and anti-inflammatory effects. In this study, the cell-death induction effect of BA was investigated in BV-2 microglia cells. BA was cytotoxic to BV-2 cells with IC50 of approximately 2.0 μM. Treatment of BA resulted in a dose-dependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content. BA treatment triggered apoptosis by decreasing Bcl-2 levels, activation of capase-3 protease and cleavage of PARP. In addition, BA treatment induced the accumulation of p62 and the increase in conversion of LC3-I to LC3-II, which are important autophagic flux monitoring markers. The increase in LC3-II indicates that BA treatment induced autophagosome formation, however, accumulation of p62 represents that the downstream autophagy pathway is blocked. It is demonstrated that BA induced cell death of BV-2 cells by inducing apoptosis and inhibiting autophagic flux. These data may provide important new information towards understanding the mechanisms by which BA induce cell death in microglia BV-2 cells.
Neurofilament Light and Polyadenylated mRNA Levels Are Decreased in Amyotrophic Lateral Sclerosis Motor Neurons

The presence of large neurofilamentous accumulations in the perikaryon and proximal axon of motor neurons in amyotrophic lateral sclerosis (ALS) suggests that the expression of this abundant cytoskeletal protein may be altered. We performed quantitative in situ hybridization for the low molecular weight neurofilament subunit (NF-L) messenger RNA in six cases of sporadic ALS and six controls. We found a 41% decrease (p < 0.02) in the NF-L mRNA levels in anterior horn cells in ALS, with a 60% decrease (p > 0.01) in alpha motor neurons. This alteration may represent a non-specific response to axonal or neuronal injury or, alternatively, reflect the regenerative activity of residual normal motor neurons. NF-L mRNA levels were consistently low (in the third and fourth quartiles) in spheroid-bearing motor neurons, indicating that the neurofilamentous accumulations observed in ALS are not likely the result of overexpression of the NF-L gene. Total neuronal polyadenylated mRNA levels were also 50% lower (p = 0.02) in anterior horn cells and 48% lower (p > 0.05) in alpha motor neurons in ALS, possibly reflecting a decrease in selected mRNA species in diseased motor neurons.
Micropattern size‐dependent endothelial differentiation from a human induced pluripotent stem cell line

The multifaceted extracellular milieu presents biochemical and biophysical stimuli that influence stem cell differentiation. Two‐dimensional (2D) micropatterned substrates allow the presentation of these cues in spatially defined geometries that have been demonstrated to guide stem cell fate decisions. Leveraging stem cells to reconstruct microvasculature, made up of an inner lining of endothelial cells (ECs) supported by pericytes, is critical to tissue‐engineering advances; thus, methods to improve endothelial differentiation efficiency are vital to these efforts. In this study, we examine the hypothesis that the diameter of micropatterned islands influences endothelial differentiation from human induced pluripotent stem cells (hiPSCs). Comparing island diameters of 80, 140, 225 and 500 µm, we found that co‐cultures of control ECs and pericytes did not yield variable ratios of cell types; however, when hiPSCs were differentiated toward a bicellular population of ECs and pericytes on these varying micropattern feature sizes, we found that smaller islands promoted EC differentiation efficiency, yielding a derived population composed of 70% ECs, which exhibited a greater sprouting propensity. Differentiation on the largest feature size exhibited a smaller EC yield, similar to that on non‐patterned substrates. Taken together, these data demonstrate that micropatterned islands of varying diameters can be used to modulate EC differentiation efficiency. Copyright © 2015 John Wiley & Sons, Ltd.
Semantic Motion Signature for Segmentation of High Speed Large Displacement Objects

This paper presents a novel method for unsupervised segmentation of objects with large displacements in high speed video sequences. Our general framework introduces a new foreground object predicting method that finds object hypotheses by encoding both spatial and temporal features via a semantic motion signature scheme. More specifically, temporal cues of object hypotheses are captured by the motion signature proposed in this paper, which is derived from sparse saliency representation imposed on magnitude of optical flow field. We integrate semantic scores derived from deep networks with location priors that allows us to directly estimate appearance potentials of foreground hypotheses. A unified MRF energy functional is proposed to simultaneously incorporate the information from the motion signature and semantic prediction features. The functional enforces both spatial and temporal consistency and impose appearance constancy and spatio-temporal smoothness constraints directly on the object hypotheses. It inherently handles the challenges of segmenting ambiguous objects with large displacements in high speed videos. Our experiments on video object segmentation benchmarks demonstrate the effectiveness of the proposed method for segmenting high speed objects despite the complicated scene dynamics and large displacements. key words: video object segmentation, motion signature, semantic prediction, large displacement, high speed video
Renal disease related to Waldenström macroglobulinaemia: incidence, pathology and clinical outcomes

The incidence and prognostic impact of nephropathy related to Waldenström macroglobulinaemia (WM) is currently unknown. We performed a retrospective study to assess biopsy‐confirmed WM‐related nephropathy in a cohort of 1391 WM patients seen at a single academic institution. A total of 44 cases were identified, the estimated cumulative incidence was 5·1% at 15 years. There was a wide variation in kidney pathology, some directly related to the WM: amyloidosis (n = 11, 25%), monoclonal‐IgM deposition disease/cryoglobulinaemia (n = 10, 23%), lymphoplasmacytic lymphoma infiltration (n = 8, 18%), light‐chain deposition disease (n = 4, 9%) and light‐chain cast nephropathy (n = 4, 9%), and some probably related to the WM: thrombotic microangiopathy (TMA) (n = 3, 7%), minimal change disease (n = 2, 5%), membranous nephropathy (n = 1, 2%) and crystal‐storing tubulopathy (n = 1, 2%). The median overall survival in patients with biopsy‐confirmed WM‐related nephropathy was 11·5 years, shorter than for the rest of the cohort (16 years, P = 0·03). Survival was better in patients with stable or improved renal function after treatment (P = 0·05). Based on these findings, monitoring for renal disease in WM patients should be considered and a kidney biopsy pursued in those presenting with otherwise unexplained renal failure and/or nephrotic syndrome.
Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene

Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene.
ANIMAL BREEDING IN RELATION TO NUTRITION AND ENVIRONMENTAL CONDITIONS

1. The action of the gene on the characters of an animal is limited to those manifestations which are physiologically possible if the gene is to survive. Environmental conditions affecting the physiology of the animal will therefore have a selective action on those genes which give rise to characters in harmony with the environment concerned. The main problem in animal breeding is to be able to direct the course of evolution and to select genes giving rise to increased development of certain characters.
LetterEvidence of Association between FKBP1B and Thyroid Autoimmune Disorders in a Large Tunisian Family

FKBP1B belongs to immunophilins superfamily and functions as a cytosolic receptor protein of FK506. The role of FKBP1B in the immunosuppressive pathway of FK506 is well established. Previously, we reported a strong evidence of linkage between D2S171 microsatellite marker (located in vicinity of FKBP1B gene) and susceptibility to autoimmune thyroid diseases (AITDs). In this study, we report linkage disequilibrium between the dimorphism (C/T) in the 3′ untranslated region (3′ UTR) of FKBP1B gene and susceptibility to AITDs. DNAs were extracted from a large Tunisian family affected with Graves' disease (GD) and Hashimoto's thyroiditis (HT) and analysed by PCR–RFLP using DraIII restriction enzyme. Our results showed an excess of transmission of the allele C from heterozygous parents to affected offspring (transmission disequilibrium test (TDT)=4.76; p=0.012). This suggests a linkage disequilibrium of 3′ UTR (C/T) SNP with AITDs. Moreover, The FBAT analysis gives a significant association with the C allele under the recessive model (χ2=5.50; p=0.018). These results support the involvement of FKBP1B gene in the genetic susceptibility to the AITDs development in the studied family.
Robust Recovery of Heavily Degraded Depth Measurements

The revolution of RGB-D sensors is advancing towards mobile platforms for robotics, autonomous vehicles and consumer hand-held devices. Strong pressures on power consumption and system price require new powerful algorithms that can robustly handle very low quality raw data. In this paper we demonstrate the ability to reliably recover depth measurements from a variety of highly degraded depth modalities, coupled with standard RGB imagery. The method is based on a regularizer which fuses super-pixel information with the total-generalized-variation (TGV) functional. We examine our algorithm on several different degradations, including new Intel's RealSense hand-held device, LiDAR-type data and ultra-sparse random sampling. In all modalities which are heavily degraded, our robust algorithm achieves superior performance over the state-ofthe-art. Additionally, a robust error measure based on Tukey's biweight metric is suggested, which is better at ranking algorithm performance since it does not reward blurry non-physical depth results.
Cloud Microphysics Impact on Hurricane Track as Revealed in Idealized Experiments

Analyses of tropical cyclones created in an idealized environment reveal how and why cloud microphysical assumptions can influencestorm motion, including speed and direction. It is well known that in the absence of a mean flow, a leading factor in storm propagation is the establishment of ‘‘beta gyres’’ owing to planetary vorticity advection by the storm’s circulation. Previous research demonstrated that tangential winds well beyond the core influence storm motion by helping to determine the gyres’ orientation and intensity. Microphysical assumptions, especially involving average particle fall speeds, can strongly influence the winds at outer radius. More specifically, microphysics modulates the radial distribution of column-average virtual temperature, which largely determines the radial surface pressure gradient and therefore the winds because they tend to be in gradient balance beyond the core. Microphysics schemes can differ markedly with respect to average fall speed, depending on the complexity of the scheme and how interactions among condensation types are handled. Average fall speed controls the outward movement of particles produced in the eyewall into the anvil, where they can influence the environment through cloud‐radiative interactions and phase changes. With the assistance of some special sensitivity tests, the influence of microphysics and fall speed on radial temperature gradients, leading to different outer wind strengths and tracks, is shown. Among other things, this work demonstrates that the treatment of outer rainbands in operational models can potentially influence how simulated storms move, thus affecting position forecasts.
Directional Breeding of High Itaconic Acid Yielding Strain of Aspergillus terreus with a New Plate Technique

Itaconic acid is commercially produced by the cultivation of Aspergillus terreus using starch hydrolysate as carbon source. The degree of hydrolysis had a great influence on itaconic acid production which was suitable when corn starch was saccharified at 35 DE. The α-amylase was sufficient to drive the starch hydrolysis to the degree. The agar plate assay with LiCl treatment provided a rapid, simple and unequivocal method for screening large numbers of colonies for itaconic acid producing strains. It was learned by experience that the strains on the plates with thick hyphae and light-colored spores often accompanied high itaconic acid production. A strain, designated Ast165, producing itaconic acid with a high yield, was successfully obtained by directional breeding of metabolic end products resistant strains. The itaconic acid concentration produced by Ast165 was 53.8 g/l from 100 g/l of starch hydrolysate in shake flasks. The conversion rate was 61.3%, which was the highest value found in tests.