julilili42/papers huggingface dataset:
Nomenclature for alleles of the thiopurine methyltransferase gene
2013-02-13

The drug-metabolizing enzyme thiopurine methyltransferase (TPMT) has become one of the best examples of pharmacogenomics to be translated into routine clinical practice. TPMT metabolizes the thiopurines 6-mercaptopurine, 6-thioguanine, and azathioprine, drugs that are widely used for treatment of acute leukemias, inflammatory bowel diseases, and other disorders of immune regulation. Since the discovery of genetic polymorphisms in the TPMT gene, many sequence variants that cause a decreased enzyme activity have been identified and characterized. Increasingly, to optimize dose, pretreatment determination of TPMT status before commencing thiopurine therapy is now routine in many countries. Novel TPMT sequence variants are currently numbered sequentially using PubMed as a source of information; however, this has caused some problems as exemplified by two instances in which authors' articles appeared on PubMed at the same time, resulting in the same allele numbers given to different polymorphisms. Hence, there is an urgent need to establish an order and consensus to the numbering of known and novel TPMT sequence variants. To address this problem, a TPMT nomenclature committee was formed in 2010, to define the nomenclature and numbering of novel variants for the TPMT gene. A website (http://www.imh.liu.se/tpmtalleles) serves as a platform for this work. Researchers are encouraged to submit novel TPMT alleles to the committee for designation and reservation of unique allele numbers. The committee has decided to renumber two alleles: nucleotide position 106 (G>A) from TPMT*24 to TPMT*30 and position 611 (T>C, rs79901429) from TPMT*28 to TPMT*31. Nomenclature for all other known alleles remains unchanged.
Prospective Isolation of Mesenchymal Stem Cells from Human Bone Marrow Using Novel Antibodies Directed Against Sushi Domain Containing 2
2013-02-13

Several strategies have been developed to facilitate the prospective isolation of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) based on the selective expression or absence of surface markers. Recently, we described the monoclonal antibodies W3D5 and W5C5, which selectively react with BM-MSCs, but not with hematopoietic cells. Both antibodies showed an identical reactivity pattern, indicating that they may recognize the same molecule. To identify the cognate antigen, cultured MSCs were sorted for cells expressing either very high levels of W5C5/W3D5 antigen or for cells which were negative for this antigen. Further processing of these cells for microarray analysis revealed a 20-fold enrichment of the type 1 integral membrane protein Sushi domain containing 2 (SUSD2) in the in W5C5(+) subset. To confirm the identity of the W5C5/W3D5 antigen to SUSD2, HEK293 cells were transfected with the full-length coding sequence of human SUSD2 followed by reactivity analysis of W5C5 and W3D5 antibodies with the transfected line. Flow cytometric analysis showed that both antibodies selectively recognized HEK293/huSUSD2 cells, but not the parental cell line. In line with this, SUSD2 siRNA treatment of SUSD2(+) WERI-RB-1 retinoblastoma cells reduced the expression levels of W3D5 and W5C5 antigens to ~39% and 37%, respectively. Finally, FACSorting and colony assays revealed that only SUSD2(+), but not SUSD2(-) BM cells give rise to colony-forming units-fibroblasts and are able to differentiate into osteoblasts, adipocytes, and chondrocytes. In conclusion, we identified SUSD2 as a novel and specific marker for the prospective isolation of BM-MSCs.
Bacteria Regulate Intestinal Epithelial Cell Differentiation Factors Both In Vitro and In Vivo
2013-02-13

Intestinal bacteria influence the intestinal epithelial differentiation factors Hes1, Hath1 and KLF4, as well as Muc1 and HBD2, in vitro and in vivo. The induction of Muc1 and HBD2 seems to be triggered directly by bacteria and not by Notch.
The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism
2013-02-13

The catechol-O-methyltranferase (COMT) is one of the main enzymes that metabolise dopamine in the brain. The Val158Met polymorphism in the COMT gene (rs4680) causes a trimodal distribution of high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzyme activity. We tested whether the Val158Met polymorphism is a modifier of the age at onset (AAO) in Parkinson's disease (PD). The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin (5886 patients with PD and 10 723 healthy controls). The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression, with gender, age and cohort origin included in the initial model. The multivariate analysis of the AAO was a mixed linear model, with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as random effects. COMT genotype was coded as a quantitative variable, assuming a codominant genetic effect. The distribution of the COMT polymorphism was not significantly different in patients and controls (p=0.22). The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val (57.1±13.9, p=0.03) than the Val/Met (57.4±13.9) and the Met/Met genotypes (58.3±13.5). The difference was greater in men (1.9 years between Val/Val and Met/Met, p=0.007) than in women (0.2 years, p=0.81). Thus, the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism: the Val allele is associated with a younger AAO in men with idiopathic PD.
The Maternal Transcriptome of the Crustacean Parhyale hawaiensis Is Inherited Asymmetrically to Invariant Cell Lineages of the Ectoderm and Mesoderm
2013-02-13

In contrast to Drosophila, the four primary germ layer cell lineages in Parhyale are specified during the maternal control phase of the embryo. A key step in this process is the asymmetric distribution of a large number of maternal RNAs to the germ layer progenitor cells.
Targeting Cancer Stem Cells with Defined Compounds and Drugs
2013-02-13

Abstract : Cancer stem cells (CSCs) are a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of cancer cells that comprise the tumor. CSCs possess numerous intrinsic mechanisms of resistance to chemotherapeutic drugs, novel tumor-targeted drugs and radiation therapy, allowing them to survive current cancer therapies and to initiate tumor recurrence and metastasis. Recently, different pathways that confer resistance and survival of CSCs, but also compounds and drugs that selectively target some of these pathways in CSCs have been identified. Such compounds and drugs include antibiotics like salinomycin, phytochemicals such as parthenolide, cyclopamine, EGCG, resveratrol, curcumin, sulforaphane and oxymatrine, the small molecule inhibitors vismodegib and repertaxin, monoclonal antibodies and antibody constructs raised against cell surface proteins expressed by CSCs, and, surprisingly, some classical drugs such as metformin, tranilast and thioridazine. These agents exhibit significant anti-CSC activity, alone or in combination with cytostatic drugs or tumor-targeted drugs, as recently shown in vitro and in human xenograft mice. Since current cancer therapies fail to eliminate CSCs, leading to cancer recurrence and progression, selective targeting of CSCs with compounds and drugs introduced herein may represent a novel therapeutic strategy to eradicate cancer.
Experimental Sensitivity Analysis of Oxygen Transfer in the Capillary Fringe
2013-02-13

Abstract Oxygen transfer in the capillary fringe (CF) is of primary importance for a wide variety of biogeochemical processes occurring in shallow groundwater systems. In case of a fluctuating groundwater table two distinct mechanisms of oxygen transfer within the capillary zone can be identified: vertical predominantly diffusive mass flux of oxygen, and mass transfer between entrapped gas and groundwater. In this study, we perform a systematic experimental sensitivity analysis in order to assess the influence of different parameters on oxygen transfer from entrapped air within the CF to underlying anoxic groundwater. We carry out quasi two‐dimensional flow‐through experiments focusing on the transient phase following imbibition to investigate the influence of the horizontal flow velocity, the average grain diameter of the porous medium, as well as the magnitude and the speed of the water table rise. We present a numerical flow and transport model that quantitatively represents the main mechanisms governing oxygen transfer. Assuming local equilibrium between the aqueous and the gaseous phase, the partitioning process from entrapped air can be satisfactorily simulated. The different experiments are monitored by measuring vertical oxygen concentration profiles at high spatial resolution with a noninvasive optode technique as well as by determining oxygen fluxes at the outlet of the flow‐through chamber. The results show that all parameters investigated have a significant effect and determine different amounts of oxygen transferred to the oxygen‐depleted groundwater. Particularly relevant are the magnitude of the water table rise and the grain size of the porous medium.
X-ray photoelectron diffraction study of dopant effects in La0.7X0.3MnO3 (X = La, Sr, Ca, Ce) thin films
2013-02-13

We present and discuss element-specific x-ray photoelectron diffraction (XPD) patterns of La, Mn, O and the dopant ions Ca, Sr and Ce of various La0.7X0.3MnO (LXMO) films grown epitaxially on SrTiO3(001) substrates. The recorded XPD polar scans are explained in the framework of multiple-scattering cluster calculations, where in general a very good agreement between experimental and theoretical data has been found. Results for all thin films are compatible with a tetragonally distorted cubic perovskite structure with similar MnO6 network. Strong evidence for Mn-site termination was found in all thin films. Dopant locations on A-type sites were clearly confirmed for Sr in LSMO and Ca in LCMO films by means of XPD polar scans. The absence of surface-sensitive Ce3d diffraction features for Ce in LCeMO points to non-equivalent Ce sites and related near-surface disorder.
Emergence of atomic semifluxons in optical Josephson junctions
2013-02-13

We propose to create pairs of semifluxons starting from a flat-phase state in\\nlong, optical 0-pi-0 Josephson junctions formed with internal electronic states\\nof atomic Bose-Einstein condensates. In this optical system, we can dynamically\\ntune the length of the pi-junction, the detuning of the optical transition, or\\nthe strength of the laser-coupling, to induce transitions from the flat-phase\\nstate to such a semifluxon-pair state. Similarly as in superconducting 0-pi-0\\njunctions, there are two, energetically degenerate semifluxon-pair states. A\\nlinear mean-field model with two internal electronic states explains this\\ndegeneracy and shows the distinct static field configuration in a phase-diagram\\nof the junction parameters. This optical system offers the possibility to\\ndynamically create a coherent superposition of the distinct semifluxon-pair\\nstates and observe macroscopic quantum oscillation.\\n
Electrophysiological properties of mouse and epitope-tagged human cardiac sodium channel Nav1.5 expressed in HEK293 cells
2013-02-13

Background: The pore-forming subunit of the cardiac sodium channel, Na v 1.5, has been previously found to be mutated in genetically determined arrhythmias. Na v 1.5 associates with many proteins that regulate its function and cellular localisation. In order to identify more in situ Na v 1.5 interacting proteins, genetically-modified mice with a high-affinity epitope in the sequence of Na v 1.5 can be generated. Methods: In this short study, we (1) compared the biophysical properties of the sodium current (I Na ) generated by the mouse Na v 1.5 (mNa v 1.5) and human Na v 1.5 (hNa v 1.5) constructs that were expressed in HEK293 cells, and (2) investigated the possible alterations of the biophysical properties of the human Na v 1.5 construct that was modified with specific epitopes. Results: The biophysical properties of mNa v 1.5 were similar to the human homolog. Addition of epitopes either up-stream of the N-terminus of hNa v 1.5 or in the extracellular loop between the S5 and S6 transmembrane segments of domain 1, significantly decreased the amount of I Na and slightly altered its biophysical properties. Adding green fluorescent protein (GFP) to the N-terminus did not modify any of the measured biophysical properties of hNa v 1.5. Conclusions: These findings have to be taken into account when planning to generate genetically-modified mouse models that harbour specific epitopes in the gene encoding mNa v 1.5.
ReProGlo: A New Stem‐Cell‐Based High‐Throughput Assay to Predict the Embryotoxic Potential of Chemicals
2013-02-13

The ReProGlo assay uses murine embryonic stem cells stably transfected with a reporter vector for the Wnt/beta-catenin pathway. The impact of test chemicals on the activity of this pathway is used as an endpoint to predict the embryotoxicity of test chemicals. The assay is relatively fast (48 h) and cost-effective. Automation of the assay as well as integration of a metabolic activation system was shown to be feasible.
Fluorescein Angiographic Findings in Eyes of Patients with a Subretinal Electronic Implant
2013-02-14

Subretinal visual implants lead to increased capillary microaneurysms, a possible compensatory mechanism following recovery of inner retinal activity. There were no significant changes in capillary loss, calibre alteration of the capillaries, retinal neovascularization and leakage at 4 months. Further study will determine whether and to what degree long-term vascular changes are affected by the surgical procedure, the implant itself and/or recovery of retinal neuronal activity.
Exotic structure and decay of medium mass nuclei near the drip lines
2013-02-14

Nuclei at or near the N=Z line are of particular interest as micro-laboratory for fundamental effects. The simulation of many astrophysical objects requires the knowledge of properties and decay rates of nuclei near the drip lines. The structure and dynamics of proton-rich A70 nuclei and neutron-rich A100 nuclei are influenced by shape coexistence and mixing. A realistic description of shape coexistence phenomena requires beyond-mean-field approaches. Results concerning the self-consistent description of exotic phenomena including anomalies in mirror energy differences of proton-rich nuclei, triple shape coexistence in neutron-rich N=58 Sr and Zr isotopes as well as Gamow-Teller β-decay strength distributions, half-lives, and β- delayed neutron emission probabilities of neutron-rich nuclei in the A100 mass region obtained in the frame of the complex Excited Vampir model using realistic effective interactions in large model spaces are presented.
Analysis of ice phenology of lakes on the Tibetan Plateau from MODIS data
2013-02-15

Abstract. The Tibetan Plateau includes a large system of endorheic (closed basin) lakes. Lake ice phenology, i.e. the timing of freeze-up and break-up and the duration of the ice cover may provide valuable information about climate variations in this region. The ice phenology of 59 large lakes on the Tibetan Plateau was derived from Moderate Resolution Imaging Spectroradiometer (MODIS) 8-day composite data for the period from 2001 to 2010. Ice cover duration appears to have a high variability in the studied region due to both climatic and local factors. Mean values for the duration of ice cover were calculated for three groups of lakes defined by clustering, resulting in relatively compact geographic regions. In each group several lakes showed anomalies in ice cover duration in the studied period. Possible reasons for such anomalous behaviour are discussed. Furthermore, many lakes do not freeze up completely during some seasons. This was confirmed by inspection of high resolution optical data. Mild winter seasons, large water volume and/or high salinity are the most likely explanations. Trends in the ice cover duration derived by linear regression for all the studied lakes show a high variation in space. A correlation of ice phenology variables with parameters describing climatic and local conditions showed a high thermal dependency of the ice regime. It appears that the freeze-up tends to be more thermally determined than break-up for the studied lakes.
Kinetic Energy of Throughfall in Subtropical Forests of SE China – Effects of Tree Canopy Structure, Functional Traits, and Biodiversity
2013-02-15

Throughfall kinetic energy (TKE) plays an important role in soil erosion in forests. We studied TKE as a function of biodiversity, functional diversity as well as structural stand variables in a secondary subtropical broad-leaved forest in the Gutianshan National Nature Reserve (GNNR) in south-east China, a biodiversity hotspot in the northern hemisphere with more than 250 woody species present. Using a mixed model approach we could identify significant effects of all these variables on TKE: TKE increased with rarefied tree species richness and decreased with increasing proportion of needle-leaved species and increasing leaf area index (LAI). Furthermore, for average rainfall amounts TKE was decreasing with tree canopy height whereas for high rainfall amounts this was not the case. The spatial pattern of throughfall was stable across several rain events. The temporal variation of TKE decreased with rainfall intensity and increased with tree diversity. Our results show that more diverse forest stands over the season have to cope with higher cumulative raindrop energy than less diverse stands. However, the kinetic energy (KE) of one single raindrop is less predictable in diverse stands since the variability in KE is higher. This paper is the first to contribute to the understanding of the ecosystem function of soil erosion prevention in diverse subtropical forests.
Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma
2013-02-15

Abstract Background Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post‐relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. Methods Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS‐trials after achievement of a complete remission. Sufficient information about post‐relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. Results Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow‐up from relapse of 8 years, 20 patients were alive and disease‐free (5‐year post‐relapse survival [PROS] 21.3 ± 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection + radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 ± 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. Conclusion Post‐relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence‐based risk‐stratification for recurrent disease including relapse treatment. Pediatr Blood Cancer 2013;60:1267–1273. © 2013 Wiley Periodicals, Inc.
Analytical relationship between Gaussian and transformed‐Gaussian spatially distributed fields
2013-02-15

Key Points A transformation of random fields usually changes the spatial correlation. The correlation relationship can be expressed analytically. Correlation lengths of connected fields are 60% and 38% of underlying fields.
Synthesis and structure of a bis-glycosylated hexa-β-peptide
2013-02-17

The bis-glycosylated hexapeptide 12) under optimized conditions with the HBTU/HOBt reagent followed by deprotection of the intermediate fully protected hexapeptide.Hexapeptide 14 is shown to adopt a random coil structure in solution.
Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6
2013-02-18

Spinocerebellar ataxias are dominantly inherited disorders that are associated with progressive brain degeneration, mainly affecting the cerebellum and brainstem. As part of the multicentre European integrated project on spinocerebellar ataxias study, 37 patients with spinocerebellar ataxia-1, 19 with spinocerebellar ataxia-3 and seven with spinocerebellar ataxia-6 were clinically examined and underwent magnetic resonance imaging at baseline and after a 2-year follow-up. All patients were compared with age-matched and gender-matched healthy control subjects. Magnetic resonance imaging analysis included three-dimensional volumetry and observer-independent longitudinal voxel-based morphometry. Volumetry revealed loss of brainstem, cerebellar and basal ganglia volume in all genotypes. Most sensitive to change was the pontine volume in spinocerebellar ataxia-1, striatal volume in spinocerebellar ataxia-3 and caudate volume in spinocerebellar ataxia-6. Sensitivity to change, as measured by standard response mean, of the respective MRI measures was greater than that of the most sensitive clinical measure, the Scale for the Assessment and Rating of Ataxia. Longitudinal voxel-based morphometry revealed greatest grey matter loss in the cerebellum and brainstem in spinocerebellar ataxia-1, in the putamen and pallidum in spinocerebellar ataxia-3 and in the cerebellum, thalamus, putamen and pallidum in spinocerebellar ataxia-6. There was a mild correlation between CAG repeat length and volume loss of the bilateral cerebellum and the pons in spinocerebellar ataxia-1. Quantitative volumetry and voxel-based morphometry imaging demonstrated genotype-specific patterns of atrophy progression in spinocerebellar ataxias-1, 3 and 6, and they showed a high sensitivity to detect change that was superior to clinical scales. These structural magnetic resonance imaging findings have the potential to serve as surrogate markers, which might help to delineate quantifiable endpoints and non-invasive methods for rapid and reliable data acquisition, encouraging their use in clinical trials.
A Low‐Temperature Synthesis Route for CaAlSiN3 Doped with Eu2+
2013-02-18

Abstract A new low‐temperature synthesis route of the strongly red‐emitting Eu 2+ activated nitride phosphor CaAlSiN 3 is presented. The fluorides CaSiF 6 and AlF 3 were used as a source of metal ions and Li 3 N as a nitrogen source. A KCN/LiCl flux system was employed to lower the temperature of the reaction from 1100 to 750 °C. The course of the reaction was studied by differential thermal analysis, and the product of the reaction was inspected by X‐ray powder diffraction and luminescence measurements of CaAlSiN 3 :Eu.