CD8(+) tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling previously shown to result from inactivation of p56(lck) kinase. We identify a novel interacting partner for p56(lck) in nonlytic TIL, Protocadherin-18 ('pcdh18'), and show that pcdh18 is transcribed upon in vitro or in vivo activation of all CD8(+) central memory T cells (CD44(+)CD62L(hi)CD127(+)) coincident with conversion into effector memory cells (CD44(+)CD62L(lo)CD127(+)). Expression of pcdh18 in primary CD8(+) effector cells induces the phenotype of nonlytic TIL: defective proximal TCR signaling, cytokine secretion, and cytolysis, and enhanced AICD.
View Article and Find Full Text PDFStudy Objective: To investigate potential drug-drug interactions between clobazam and cytochrome P450 (CYP) isoenzyme substrates, inhibitors, and inducers.
Design: Two, prospective, open-label, single-center, drug-drug interaction (DDI) studies and a population pharmacokinetics analysis of seven multicenter phase II-III trials.
Setting: Clinical research unit.
Current models for molecular electrical doping of organic semiconductors are found to be at odds with other well-established concepts in that field, like polaron formation. Addressing these inconsistencies for prototypical systems, we present experimental and theoretical evidence for intermolecular hybridization of organic semiconductor and dopant frontier molecular orbitals. Common doping-related observations are attributed to this phenomenon, and controlling the degree of hybridization emerges as a strategy for overcoming the present limitations in the yield of doping-induced charge carriers.
View Article and Find Full Text PDFPurpose: Despite the exceptionally large population of young migrants in China, as well as increasing rates of HIV and sexually transmitted infections in recent years, condom use and contraceptive consistency among this population remains critically under-studied. This study examines the association between migration and condom use and contraceptive consistency.
Methods: A cross-sectional survey of 959 youth aged 15-24 years was conducted in rural and urban Shanghai.
Diplopia is a rare but well recognised complication following retrobulbar and peribulbar local anaesthesia but it has not been widely reported following sub-tenon's local anaesthesia (STLA). We report on a 76-year-old woman who developed vertical diplopia after left phacoemulsification. She had received a STLA.
View Article and Find Full Text PDFLOVAZA (omega-3-acid ethyl esters; eicosapentaenoic acid [EPA]/docosahexaenoic acid [DHA]), with diet, lowers very high triglycerides (≥500 mg/dL) in adults. This study evaluated whether an emulsion formulation (LEM) increases the bioavailability of EPA/DHA compared to the reference formulation (RF) in healthy volunteers. Following relative bioavailability assessment, LEM, RF, and placebo were dosed for 2 weeks.
View Article and Find Full Text PDFPurpose: The aim of our study was to show how using contrast inversion extends the diagnostic value of perineal ultrasound, in particular with regard to paraurethral pathologies.
Materials And Methods: To assess the practical value of contrast inversion in the daily routine, 42 women with urinary incontinence underwent perineal ultrasound examination. Pictures were converted to contrast inversion and then checked for the visibility of sonographic reference points for urogynecological measurements (urethra, meatus urethrae internus, vesical base) by two independent evaluators both in B-mode and contrast inversion.
Purpose: To identify risk and protective factors associated with adolescent sexual and reproductive health (ASRH) in the English-speaking Caribbean through a structured literature review.
Methods: Peer-reviewed articles published between January 1998 and December 2009 focused on the sexual and reproductive health of adolescents, aged 10-19 years, were included in this review. Articles were organized according to Bronfenbrenner's ecological systems theory.
Introduction: Violent acts in young people constitute one of the most serious forms of violence in any society. Violence by young people in schools, on the streets, and in their families has been documented in many studies worldwide. Homicide and non-fatal assaults involving young people have been reported as a great global burden of premature death, injury and disability.
View Article and Find Full Text PDFThe lumen of the endoplasmic reticulum (ER) contributes to the dynamics of Ca(2+) signaling by acting as a source or sink of signal Ca(2+). Despite its relevance for the understanding of the cell biology and pathophysiology of the luminal calcium store, the direct measurement of luminal Ca(2+) release and uptake is still critical when Ca(2+) homeostasis is analyzed in neural cells. For the analysis of Ca(2+)-dependent signaling, synthetic Ca(2+) indicators have become popular.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2011
We have examined changes in the chromatin landscape during muscle differentiation by mapping the genome-wide location of ten key histone marks and transcription factors in mouse myoblasts and terminally differentiated myotubes, providing an exceptionally rich dataset that has enabled discovery of key epigenetic changes underlying myogenesis. Using this compendium, we focused on a well-known repressive mark, histone H3 lysine 27 trimethylation, and identified novel regulatory elements flanking the myogenin gene that function as a key differentiation-dependent switch during myogenesis. Next, we examined the role of Polycomb-mediated H3K27 methylation in gene repression by systematically ablating components of both PRC1 and PRC2 complexes.
View Article and Find Full Text PDFBackground: Pseudoxanthoma elasticum (PXE) is a rare connective tissue disorder involving fragmentation and mineralization of elastic fibers predominantly in the skin, eyes, and cardiovascular system.
Objective: The objective of this study was to assess the efficacy of sevelamer hydrochloride on the reversal of elastic fiber calcification and clinical lesions of PXE.
Methods: This was a randomized, double-blind, placebo-controlled, two-part prospective study.
Objective: To investigate the feasibility and inter-investigator reproducibility of perineal ultrasonography in men with and without post-prostatectomy urinary incontinence (PPI).
Patients And Methods: This clinical pilot study involved 33 male patients, with a mean (range) age of 67.8 (51-76) years, who underwent radical prostatectomy (RP) ≥1 year ago.
Background: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab.
Patients And Methods: We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C.
Background: Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells.
View Article and Find Full Text PDFThe adsorption of the molecular acceptor hexaazatriphenylene-hexacarbonitrile on Ag(111) was investigated as function of layer density. We find that the orientation of the first molecular layer changes from a face-on to an edge-on conformation depending on layer density, facilitated through specific interactions of the peripheral molecular cyano groups with the metal. This is accompanied by a rehybridization of molecular and metal electronic states, which significantly modifies the interface and surface electronic properties, as rationalized by theoretical modeling.
View Article and Find Full Text PDFIEEE Trans Image Process
February 2011
This paper introduces a novel method to score how well proposed fused image quality measures (FIQMs) indicate the effectiveness of humans to detect targets in fused imagery. The human detection performance is measured via human perception experiments. A good FIQM should relate to perception results in a monotonic fashion.
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