1,072 research outputs found
A quantum group version of quantum gauge theories in two dimensions
For the special case of the quantum group we present an alternative approach to quantum gauge theories in
two dimensions. We exhibit the similarities to Witten's combinatorial approach
which is based on ideas of Migdal. The main ingredient is the Turaev-Viro
combinatorial construction of topological invariants of closed, compact
3-manifolds and its extension to arbitrary compact 3-manifolds as given by the
authors in collaboration with W. Mueller.Comment: 6 pages (plain TeX
Visual Motion Area MT+/V5 Responds to Auditory Motion in Human Sight-Recovery Subjects
Using functional magnetic resonance imaging, we found that cortical visual motion area MT+/V5 responded to auditory motion in two rare subjects who had been blind since early childhood and whose vision was partially recovered in adulthood. Visually normal control subjects did not show similar auditory responses. These auditory responses in MT+ were specific to motion compared with other complex auditory stimuli including frequency sweeps and speech. Thus, MT+ developed motion-specific responses to nonvisual input, suggesting that cross-modal plasticity can be influenced by the normal functional specialization of a cortical region. Regarding sight recovery after early blindness, our results further demonstate that cross-modal responses coexist with regained visual responses within the visual cortex
Steady improvement in renal allograft survival among North American children: A five year appraisal by the North American Pediatric Renal Transplant Cooperative Study
Steady improvement in renal allograft survival among North American children. From 1987 through 1994, the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has enrolled 1641 cadaver donor transplants. For this study, we have analyzed one and two year graft survival by annual cohorts for the years 1987 through 1991. For the 1987 cohort one and two year graft survival was 72% and 65%, respectively, and for the 1991 cohort it was 83% and 78%, respectively. Using a proportional hazards model, and comparing the 1987 cohort to the 1991 cohort, the relative risk for graft failure was 1.40 (P = 0.02). Analysis of practice patterns revealed the following changes which may have been associated with this improved graft survival: (1) use of T cell induction antibody, 38% in 1987 and 67% in 1991 (P ≤ 0.001); (2) the increased use of cyclosporine (CsA) post-transplant: in 1987, 87% were maintained on CsA at day 30 compared to 97% in 1991 (P < 0.001); (3) the mean higher daily maintenance CsA dose at 12 months post-transplant which in 1987 was 6.5 mg/kg compared to 7.5 mg/kg in 1991 (P = 0.03); (4) the decreased use of random transfusions, 54% receiving >5 transfusions in 1987 compared to 37% in 1991 (P < 0.001); and (5) decreased use of younger cadaver donors between 1987 and 1991 (P < 0.001)
All Finite Generalized Tetrahedron Groups
A generalized tetrahedron groups is defined to be a group admitting a
presentation
where l,m,n,p,q,r >= 2, each W_i(a,b) is a cyclically reduced word involving both a and b. These groups appear in many contexts, not least as fundamental groups of certain hyperbolic orbifolds or as subgroups of generalized triangle groups. In this paper, we build on previous work to give a complete classification of all finite generalized tetrahedron groups
Pan-cancer Analysis of Homologous Recombination Repair–associated Gene Alterations and Genome-wide Loss-of-Heterozygosity Score
Alteracions genètiques; CàncerGene alterations; CancerAlteraciones genéticas; CáncerPurpose:
To study associations across tumor types between genome-wide loss of heterozygosity (gLOH) and alterations in homologous recombination repair (HRR)-associated genes beyond BRCA1 and BRCA2.
Experimental Design:
Genomic profiling using a targeted next-generation sequencing assay examining 324–465 genes (FoundationOne, FoundationOne Heme, and FoundationOne CDx; Foundation Medicine, Inc.) was performed in a cohort of 160,790 samples across different tumor types. Zygosity predictions and gLOH status were calculated and linked with alterations in 18 HRR-associated genes (BRCA1, BRCA2, PALB2, BARD1, ATR, ATRX, ATM, BAP1, RAD51B, RAD51C, RAD51D, BRIP1, NBN, CHEK1, CHEK2, FANCA, FANCC, MRE11) and other genomic features, using Fisher's exact test and Mann–Whitney U tests.
Results:
We identified a strong correlation between elevated gLOH and biallelic alterations in a core set of HRR-associated genes beyond BRCA1 and BRCA2, such as BARD1, PALB2, FANCC, RAD51C, and RAD51D (particularly in breast, ovarian, pancreatic, and prostate cancer). Monoallelic/heterozygous alterations in HRR-associated genes were not associated with elevated gLOH. gLOH was also independently associated with TP53 loss. Co-occurrence of TP53 loss and alterations in HRR-associated genes, and combined loss of TP53-PTEN or TP53-RB1, was associated with a higher gLOH than each of the events separately.
Conclusions:
Biallelic alterations in core HRR-associated genes are frequent, strongly associated with elevated gLOH, and enriched in breast, ovarian, pancreatic, and prostate cancer. This analysis could inform the design of the next generation of clinical trials examining DNA repair–targeting agents, including PARP inhibitors
A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase
l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as the primary AEP cleavage site. Sole modification at this site rendered ASNase resistant to AEP cleavage and suggested a key role for the flexible active loop in determining ASNase activity. We therefore propose what we believe to be a novel mechanism of drug resistance to ASNase. Our results may help to identify alternative therapeutic strategies with the potential of further improving outcome in childhood ALL
Truthmakers and modality
This paper attempts to locate, within an actualist ontology, truthmakers for modal truths: truths of the form or . In section 1 I motivate the demand for substantial truthmakers for modal truths. In section 2 I criticise Armstrong’s account of truthmakers for modal truths. In section 3 I examine essentialism and defend an account of what makes essentialist attributions true, but I argue that this does not solve the problem of modal truth in general. In section 4 I discuss, and dismiss, a theistic account of the source of modal truth proposed by Alexander Pruss. In section 5 I offer a means of (dis)solving the problem
The integral homology of of imaginary quadratic integers with non-trivial class group
We show that a cellular complex described by Floege allows to determine the
integral homology of the Bianchi groups , where is the
ring of integers of an imaginary quadratic number field \rationals[\sqrt{-m}]
for a square-free natural number . We use this to compute in the cases m =
5, 6, 10, 13 and 15 with non-trivial class group the integral homology of
, which before was known only in the cases m = 1, 2, 3, 7 and 11
with trivial class group
Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain
SummaryStem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain
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