Miracle-dz/UniFAR-FTUs huggingface dataset:
Detailed gene dose analysis reveals recurrent focal gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia

Abstract To identify copy number alterations (CNAs) in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL), array comparative genomic hybridization was performed on 50 cases; detected CNAs were validated in a cohort of 191 cases analyzed by single nucleotide polymorphism arrays. Apart from CNAs involving leukemia-associated genes, recurrent deletions targeting genes not previously implicated in BCP ALL, e.g. INIP, IRF1 and PDE4B, were identified. Deletions of the DNA repair gene INIP were exclusively found in cases with t(12;21), and deletions of SH2B3 were associated with intrachromosomal amplification of chromosome 21 (p < 0.001). A majority of BTLA deletions (7/11; 64%) affected samples with gain of 21q chromosome material, suggesting that BTLA deletions are associated with both germline and somatic gain of chromosome 21. In cases without known risk-associated cytogenetic markers, CNAs associated with adverse prognosis were identified in 50% (10/20), indicating that a majority of these cases could be assigned to distinct genetic subtypes.
Contact Graphs in Multibody Dynamics Simulation

In rigid body simulation contact graphs are used detecting contact groups. Contact graphs provide an efficient underlying data structure for keeping information about the entire configuration and in this paper we extend their usage to a new collision detection phase termed “Spatial-Temporal Coherence Analysis”. This paper will review contact graphs and demonstrate the performance impact in a typical constraint based multibody simulator. CR Categories: I.3. 5 [Computer Graphics]: Computational Geometry and Object Modeling—Physically based modeling; I.3. 7 [Computer Graphics]: Three-Dimensional Graphics and Realism—Animation;
Nosocomial Transmission of C. difficile in English Hospitals from Patients with Symptomatic Infection

Background Recent evidence suggests that less than one-quarter of patients with symptomatic nosocomial Clostridium difficile infections (CDI) are linked to other in-patients. However, this evidence was limited to one geographic area. We aimed to investigate the level of symptomatic CDI transmission in hospitals located across England from 2008 to 2012. Methods A generalized additive mixed-effects Poisson model was fitted to English hospital-surveillance data. After adjusting for seasonal fluctuations and between-hospital variation in reported CDI over time, possible clustering (transmission between symptomatic in-patients) of CDI cases was identified. We hypothesised that a temporal proximity would be reflected in the degree of correlation between in-hospital CDI cases per week. This correlation was modelled through a latent autoregressive structure of order 1 (AR(1)). Findings Forty-six hospitals (33 general, seven specialist, and six teaching hospitals) located in all English regions met our criteria. In total, 12,717 CDI cases were identified; seventy-five per cent of these occurred >48 hours after admission. There were slight increases in reports during winter months. We found a low, but statistically significant, correlation between successive weekly CDI case incidences (phi = 0.029, 95%CI: 0.009–0.049). This correlation was five times stronger in a subgroup analysis restricted to teaching hospitals (phi = 0.104, 95%CI: 0.048–0.159). Conclusions The results suggest that symptomatic patient-to-patient transmission has been a source of CDI-acquisition in English hospitals in recent years, and that this might be a more important transmission route in teaching hospitals. Nonetheless, the weak correlation indicates that, in line with recent evidence, symptomatic cases might not be the primary source of nosocomial CDI in England.
Effects of lactic acid bacteria isolated from fermented mustard on lowering cholesterol.

OBJECTIVE To evaluate the ability of lactic acid bacteria (LAB) strains isolated from fermented mustard to lower the cholesterol in vitro. METHODS The ability of 50 LAB strains isolated from fermented mustard on lowering cholesterol in vitro was determined by modified o-phtshalaldehyde method. The LAB isolates were analyzed for their resistance to acid and bile salt. Strains with lowering cholesterol activity, were determined adherence to Caco-2 cells. RESULTS Strain B0007, B0006 and B0022 assimilated more cholesterol than BCRC10474 and BCRC 17010. The isolated strains showed tolerance to pH 3.0 for 3 h despite variations in the degree of viability and bile-tolerant strains, with more than 10(8) CFU/mL after incubation for 24 h at 1% oxigall in MRS. In addition, strain B0007 and B0022 identified as Lactobacillus plantarum with 16S rDNA sequences were able to adhere to the Caco-2 cell lines. CONCLUSIONS These strains B0007 and B0022 may be potential functional sources for cholesterol-lowering activities as well as adhering to Caco-2 cell lines.
Catechol‐O‐methyltransferase (COMT) gene variants: Possible association of the Val158Met variant with opiate addiction in hispanic women

Catechol‐O‐methyltransferase (COMT) catalyzes the breakdown of catechol neurotransmitters, including dopamine, which plays a prominent role in drug reward. A common single nucleotide polymorphism (SNP), G472A, codes for a Val158Met substitution and results in a fourfold down regulation of enzyme activity. We sequenced exon IV of COMT gene in search for novel polymorphisms and then genotyped four out of five identified by direct sequencing, using TaqMan assay on 266 opioid‐dependent and 173 control subjects. Genotype frequencies of the G472A SNP varied significantly (P = 0.029) among the three main ethnic/cultural groups (Caucasians, Hispanics, and African Americans). Using a genotype test, we found a trend to point‐wise association (P = 0.053) of the G472A SNP in Hispanic subjects with opiate addiction. Further analysis of G472A genotypes in Hispanic subjects with data stratified by gender identified a point‐wise significant (P = 0.049) association of G/A and A/A genotypes with opiate addiction in women, but not men. These point‐wise significant results are not significant experiment‐wise (at P < 0.05) after correction for multiple testing. No significant association was found with haplotypes of the three most common SNPs. Linkage disequilibrium patterns were similar for the three ethnic/cultural groups. © 2008 Wiley‐Liss, Inc.
FDG kinetics in cells and tissues: a biochemically-driven compartmental approach.

The radioactive glucose analogue 2-deoxy-2-[18F]fluoro-D-glucose (FDG) is widely used to reconstruct glucose metabolism and other biological functions in cells and tissues. The analysis of data on the time course of FDG tracer distribution is performed by the use of appropriate compartmental models. Motivated by recent results in cell biochemistry, we describe a new compartmental model aiming at the reconstruction of tracer kinetics in cells and tissues, which emphasizes the different roles of the cytosol and of the endoplasmic reticulum. Two applications of the new model are examined, that are concerned with real data from cancer cell cultures in vitro, and cancer tissues in vivo. The results are compared with those obtained through application of more standard compartmental models against the same datasets and appear to be in a better agreement with respect to recent biochemical experimental evidence. In particular, it is shown that tracer tends to accumulate in the endoplasmic reticulum, rather than cytosol, and that the rate of phosphorylation is higher than predicted by current models.
Existence and Boundary Regularity for Degenerate Phase Transitions

We study the Cauchy--Dirichlet problem associated to a phase transition modeled upon the degenerate two-phase Stefan problem. We prove that weak solutions are continuous up to the parabolic boundary and quantify the continuity by deriving a modulus. As a byproduct, these a priori regularity results are used to prove the existence of a so-called physical solution.
Fast Sorting Algorithms using AVX-512 on Intel Knights Landing

This paper describes fast sorting techniques using the recent AVX-512 instruction set. Our implementations benefit from the latest possibilities offered by AVX-512 to vectorize a two-parts hybrid algorithm: we sort the small arrays using a branch-free Bitonic variant, and we provide a vectorized partitioning kernel which is the main component of the well-known Quicksort. Our algorithm sorts in-place and is straightforward to implement thanks to the new instructions. Meanwhile, we also show how an algorithm can be adapted and implemented with AVX-512. We report a performance study on the Intel KNL where our approach is faster than the GNU C++ sort algorithm for any size in both integer and double floating-point arithmetics by a factor of 4 in average.
Nanocomposite hydrogels for cartilage tissue engineering: a review

Abstract The loss of cartilaginous tissues is an important challenge to orthopaedic surgeons. Injury to cartilage tissue due to its properties is along with movement difficulties. Tissue engineering is a developing field that can be used for regeneration or replacement of damaged tissues. In this field, an appropriate scaffold that support the recruitment, adhesion, proliferation and differentiation of cells is necessary. Hydrogels recently considered as materials that resemble the extracellular matrix (ECM) and efficiently replace defective tissues, but they have limited mechanical strength. So nanomaterials are embedded in the hydrogel’s matrix to improve their properties. Nanoparticles, such as organic/polymeric and inorganic (hydroxyapatite, clay, graphene and metallic nanoparticles), can be used as fillers to reinforce the hydrogel matrix. Utilizing those nanocomposites could help in better performance of hydrogels applicable in cartilage regeneration practices. This review presents some of nanocomposite hydrogel (NCH) systems that used in cartilage tissue engineering.
The rate of contralateral proximal femoral fracture following closed reduction and percutaneous pinning compared with arthroplasty for the treatment of femoral neck fractures.

BACKGROUND As the population ages, the number of proximal femoral fractures seen each year is expected to increase. Subsequent contralateral hip fractures have been reported to occur in as many as 11.8% of patients after surgical fixation of the initial fracture, but it is unknown if this rate is similar among patients managed with different surgical procedures. METHODS A retrospective comparative study was performed at a single institution at which electronic medical records and digital radiographs were reviewed for 1177 patients who underwent closed reduction and percutaneous pinning or arthroplasty for the treatment of a proximal femoral fracture. For the primary outcome of subsequent fracture, logistic regression analysis was applied. RESULTS Four hundred and ninety-five patients were managed with closed reduction and percutaneous pinning, and 682 were managed with arthroplasty. Patients who underwent closed reduction and percutaneous pinning were two times more likely to have a subsequent contralateral femoral fracture in comparison with those who underwent arthroplasty, with contralateral fracture rates of 10.10% for the closed reduction and percutaneous pinning group and 5.57% for the arthroplasty group (p = 0.0035). CONCLUSIONS Patients undergoing closed reduction and percutaneous pinning as the initial treatment for a hip fracture had an increased risk of a subsequent contralateral hip fracture in comparison with those undergoing arthroplasty, after controlling for patient characteristics.
Revised Primordial Helium Abundance Based on New Atomic Data

We have derived a primordial helium abundance of Yp = 0.2477 ± 0.0029, based on new atomic physics computations of the recombination coefficients of He I and of the collisional excitation of the H I Balmer lines together with observations and photoionization models of metal-poor extragalactic H II regions. The new atomic data increase our previous determination of Yp by 0.0086, a very significant amount. By combining our Yp result with the predictions made by the standard big bang nucleosynthesis model, we find a baryon-to-photon ratio, η, in excellent agreement both with the η-value derived by the primordial deuterium abundance value observed in damped Lyα systems and with the one obtained from the WMAP observations.
Targeting the cyclin dependent kinase and retinoblastoma axis overcomes standard of care resistance in BRAFV600E-mutant melanoma

Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant BRAFV600E-mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression. The rationale for this is that the retinoblastoma protein (pRb) is 95% wildtype in BRAF mutant melanoma. We discovered that 77/77 stage IV metastatic melanoma tissues were positive for inactive phosphorylated pRb (pRb-Ser780). Rb is hyperphosphorylated and inactivated by CDK4/6:cyclin D1 and when restored to its hypophosphorylated active form blocks cell cycle progression. The addition of a CDK4/6 inhibitor to SOC therapy was superior to SOC. Importantly, triple therapy in an upfront treatment and salvage therapy setting provided sustained durable response. We also showed that CDK4/6 blockade resensitized drug resistant melanoma to SOC therapy. Durable response was associated with sustained suppression of pRb-Ser780. Thus, reactivation of pRb may prove to be a clinical biomarker of response and the mechanism responsible for durable response. In light of recent clinical trial data using this triple therapy against BRAFV600E-mutant melanoma, our findings demonstrating superior and prolonged durable response in PDTX models portend use of this therapeutic strategy against naïve and SOC resistant BRAF V600E-mutant metastatic melanoma coupled with pRB-Ser780 as a biomarker of response.
Children's academic attainment is linked to the global organization of the white matter connectome

Abstract Literacy and numeracy are important skills that are typically learned during childhood, a time that coincides with considerable shifts in large‐scale brain organization. However, most studies emphasize focal brain contributions to literacy and numeracy development by employing case‐control designs and voxel‐by‐voxel statistical comparisons. This approach has been valuable, but may underestimate the contribution of overall brain network organization. The current study includes children (N = 133 children; 86 male; mean age = 9.42, SD = 1.715; age range = 5.92–13.75y) with a broad range of abilities, and uses whole‐brain structural connectomics based on diffusion‐weighted MRI data. The results indicate that academic attainment is associated with differences in structural brain organization, something not seen when focusing on the integrity of specific regions. Furthermore, simulated disruption of highly‐connected brain regions known as hubs suggests that the role of these regions for maintaining the architecture of the network may be more important than specific aspects of processing. Our findings indicate that distributed brain systems contribute to the etiology of difficulties with academic learning, which cannot be captured using a more traditional voxel‐wise statistical approach.
Nkx2.2+ Progenitors Generate Somatic Motoneurons in the Chick Spinal Cord

Heterogeneous classes of neurons are present in the spinal cord and are essential for its function. Expression patterns of transcription factors in neural progenitor cells determine neuron subtypes during development. Nkx2.2 is expressed in the progenitor cell pool located just ventrally to the Olig2-positive pool and is indispensable for V3 interneuron generation in the spinal cord and also for visceral motoneuron generation in the hindbrain. However, whether Nkx2.2-positive progenitor cells generate diverse classes of neuron is not fully understood. Using a chick lineage tracing method in a genetically-defined manner, we found that Nkx2.2-expressing progenitor cells differentiate into general visceral motoneurons as well as sim1-positive V3 interneurons. Surprisingly, we further observed that Nkx2.2-expressing progenitors differentiate into somatic motoneuron. Our findings suggest that the different classes of motoneurons are derived from more complex sources than were previously expected in the chick spinal cord.
The Major Fusarium Species Causing Maize Ear and Kernel Rot and Their Toxigenicity in Chongqing, China

Fusarium verticillioides, F. proliferatum, and F. meridionale were identified as the predominant fungi among 116 Fusarium isolates causing maize ear and kernel rot, a destructive disease in Chongqing areas, China. The toxigenic capability and genotype were determined by molecular amplification and toxin assay. The results showed that the key toxigenic gene FUM1 was detected in 47 F. verticillioides and 19 F. proliferatum isolates. Among these, F. verticillioides and F. proliferatum isolates mainly produced fumonisin B1, ranging from 3.17 to 1566.44, and 97.74 to 11,100.99 µg/g for each gram of dry hyphal weight, with the averages of 263.94 and 3632.88 µg/g, respectively, indicating the F. proliferatum isolates on average produced about an order of magnitude more fumonisins than F. verticillioides did in these areas, in vitro. Only NIV genotype was detected among 16 F. meridionale and three F. asiaticum isolates. Among these, 11 F. meridionale isolates produced NIV, varying from 17.40 to 2597.34 µg/g. ZEA and DON toxins were detected in 11 and 4 F. meridionale isolates, with the toxin production range of 8.35–78.57 and 3.38–33.41 µg/g, respectively. Three F. asiaticum isolates produced almost no mycotoxins, except that one isolate produced a small amount of DON. The findings provide us with insight into the risk of the main pathogenic Fusarium species and a guide for resistance breeding in these areas.
A multi-component social skills intervention for children with Asperger syndrome: the Junior Detective Training Program.

BACKGROUND The study aimed to investigate the effectiveness of a new multi-component social skills intervention for children with Asperger syndrome (AS): The Junior Detective Training Program. This 7-week program included a computer game, small group sessions, parent training sessions and teacher handouts. METHOD Forty-nine children with AS were recruited to participate and randomly assigned to intervention (n = 26) or wait-list control (n = 23) conditions. RESULTS Relative to children in the wait-list group, program participants showed greater improvements in social skills over the course of the intervention, as indicated by parent-report measures. Teacher-report data also confirmed that children receiving the intervention made significant improvements in social functioning from pre- to post-treatment. Treatment group participants were better able to suggest appropriate emotion-management strategies for story characters at post-intervention than at pre-intervention, whereas control participants were not. However, there was no difference in the improvements made by children in the intervention and control conditions on facial expression and body-posture recognition measures. Follow-up data suggested that treatment gains were maintained by children at 5-months post-intervention. CONCLUSIONS The Junior Detective Training Program appeared to be effective in enhancing the social skills and emotional understanding of children with AS. Limitations and suggestions for future research are discussed.
Molecular Systematic of Three Species of Oithona (Copepoda, Cyclopoida) from the Atlantic Ocean: Comparative Analysis Using 28S rDNA

Species of Oithona (Copepoda, Cyclopoida) are highly abundant, ecologically important, and widely distributed throughout the world oceans. Although there are valid and detailed descriptions of the species, routine species identifications remain challenging due to their small size, subtle morphological diagnostic traits, and the description of geographic forms or varieties. This study examined three species of Oithona (O. similis, O. atlantica and O. nana) occurring in the Argentine sector of the South Atlantic Ocean based on DNA sequence variation of a 575 base-pair region of 28S rDNA, with comparative analysis of these species from other North and South Atlantic regions. DNA sequence variation clearly resolved and discriminated the species, and revealed low levels of intraspecific variation among North and South Atlantic populations of each species. The 28S rDNA region was thus shown to provide an accurate and reliable means of identifying the species throughout the sampled domain. Analysis of 28S rDNA variation for additional species collected throughout the global ocean will be useful to accurately characterize biogeographical distributions of the species and to examine phylogenetic relationships among them.
Pract ica l parallel coset enumerat ion

Coset enumeration is a most important procedure for investigating finitely presented groups. We present a practical parallel procedure for coset enumeration on shared memory processors. The shared memory architecture is particularly interesting because such parallel computation is both faster and cheaper. The lower cost comes when the program requires large amounts of memory, and additional CPU's allow us to lower the time that the expensive memory is being used. Rather than report on a suite of test cases, we take a single, typical case, and analyze the performance factors in-depth. The parallelization is achieved through a master-slave architecture. This results in an interesting phenomenon, whereby the CPU time is divided into a sequential and a parallel portion, and the parallel part demonstrates a speedup that is linear in the number of processors. We describe an early version for which only 40% of the program was parallelized, and we describe how this was modified to achieve 90% parallelization while using 15 slave processors and a master. In the latter case, a sequential time of 158 seconds was reduced to 29 seconds using 15 slaves. "Supported in part by NSF Grant CCR-9509783. tSupported in part by the Australian Research Council.