45 research outputs found
Quantum entanglement: The unitary 8-vertex braid matrix with imaginary rapidity
We study quantum entanglements induced on product states by the action of
8-vertex braid matrices, rendered unitary with purely imaginary spectral
parameters (rapidity). The unitarity is displayed via the "canonical
factorization" of the coefficients of the projectors spanning the basis. This
adds one more new facet to the famous and fascinating features of the 8-vertex
model. The double periodicity and the analytic properties of the elliptic
functions involved lead to a rich structure of the 3-tangle quantifying the
entanglement. We thus explore the complex relationship between topological and
quantum entanglement.Comment: 4 pages in REVTeX format, 2 figure
Sustained TL1A expression modulates effector and regulatory T-cell responses and drives intestinal goblet cell hyperplasia
The tumor necrosis factor (TNF) superfamily protein TNF-like 1A (TL1A) is the ligand for death receptor 3 (DR3). TL1A is induced on activated dendritic cells (DCs) and its expression has been linked to human inflammatory bowel disease. To address how TL1A might influence intestinal inflammation, we generated transgenic mice that constitutively express TL1A on DCs. TL1A transgenic mice developed striking goblet cell hyperplasia in the ileum that was associated with elevated interleukin (IL)-13 levels in the small intestine. IL-13- and IL-17-producing small intestinal lamina propria T cells were increased in TL1A transgenic mice. TL1A also enhanced regulatory T (Treg) cell turnover in vivo and directly stimulated Treg cell proliferation in vitro. The presence of TL1A attenuated the ability of Treg cells to suppress conventional T cells, an effect that required DR3 signaling in either conventional T cells or Treg cells. Our findings identify mechanisms by which chronic DR3 signaling could promote pathogenesis in inflammatory bowel disease.<br/
Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production
BACKGROUND: The co-inhibitory receptor Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) attenuates immune responses and prevent autoimmunity, however, tumors exploit this pathway to evade the host T-cell response. The T-cell co-stimulatory receptor 4-1BB is transiently upregulated on T-cells following activation and increases their proliferation and inflammatory cytokine production when engaged. Antibodies which block CTLA-4 or which activate 4-1BB can promote the rejection of some murine tumors, but fail to cure poorly immunogenic tumors like B16 melanoma as single agents.METHODOLOGY/PRINCIPAL FINDINGS: We find that combining ?CTLA-4 and ?4-1BB antibodies in the context of a Flt3-ligand, but not a GM-CSF, based B16 melanoma vaccine promoted synergistic levels of tumor rejection. 4-1BB activation elicited strong infiltration of CD8+ T-cells into the tumor and drove the proliferation of these cells, while CTLA-4 blockade did the same for CD4+ effector T-cells. Anti-4-1BB also depressed regulatory T-cell infiltration of tumors. 4-1BB activation strongly stimulated inflammatory cytokine production in the vaccine and tumor draining lymph nodes and in the tumor itself. The addition of CTLA-4 blockade further increased IFN-? production from CD4+ effector T-cells in the vaccine draining node and the tumor. Anti 4-1BB treatment, with or without CTLA-4 blockade, induced approximately 75% of CD8+ and 45% of CD4+ effector T-cells in the tumor to express the killer cell lectin-like receptor G1 (KLRG1). Tumors treated with combination antibody therapy showed 1.7-fold greater infiltration by these KLRG1+CD4+ effector T-cells than did those treated with ?4-1BB alone.CONCLUSIONS/SIGNIFICANCE: This study shows that combining T-cell co-inhibitory blockade with ?CTLA-4 and active co-stimulation with ?4-1BB promotes rejection of B16 melanoma in the context of a suitable vaccine. In addition, we identify KLRG1 as a useful marker for monitoring the anti-tumor immune response elicited by this therapy. These findings should aid in the design of future trials for the immunotherapy of melanoma
Cabozantinib in Chemotherapy-Pretreated Metastatic Castration-Resistant Prostate Cancer: Results of a Phase II Nonrandomized Expansion Study
Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC)
Brief Assessment of Schizotypal Traits: A Multinational Study
The Schizotypal Personality Questionnaire-Brief (SPQ-B) was
developed with the aim of examining variations in healthy trait
schizotypy, as well as latent vulnerability to psychotic-spectrum
disorders. No previous study has studied the cross-cultural validity of
the SPQ-B in a large cross-national sample. The main goal of the present
study was to analyze the reliability and the internal structure of SPQ-B
scores in a multinational sample of 28,426 participants recruited from 14
countries. The mean age was 22.63 years (SD = 7.08; range 16-68 years),
37.7% (n = 10,711) were men. The omega coefficients were high, ranging
from 0.86 to 0.92 for the total sample. Confirmatory factor analysis
revealed that SPQ-B items were grouped either in a theoretical structure
of three first-order factors (Cognitive-Perceptual, Interpersonal, and
Disorganized) or in a bifactor model (three first-order factors plus a
general factor of schizotypal personality). In addition, the results
supported configural but not strong measurement invariance of SPQ-B
scores across samples. These findings provide new information about the
factor structure of schizotypal personality, and support the validity and
utility of the SPQ-B, a brief and easy tool for assessing self-reported
schizotypal traits, in cross-national research. Theoretical and clinical
implications for diagnostic systems, psychosis models, and cross-national
mental health strategies are derived from these results
Bloodless Pediatric Cardiopulmonary Bypass for a 3.2-kg Patient Whose Parents are of Jehovah’s Witness Faith
Patients and parents of Jehovah’s Witness (JW) faith present multiple challenges to a medical team, especially in the neonatal and pediatric population. The medical team must balance honoring the parents’ request of not receiving blood products and fulfilling our commitment as advocates for the child’s wellbeing. A multidisciplinary approach to cardiac surgery must be embraced for bloodless cardiopulmonary bypass (CPB) to be successful. At our institution, we have developed strategies and techniques for blood conservation that are used preoperatively, intraoperatively, and postoperatively for every CPB case with the goal of a bloodless procedure. These protocols include: preoperative erythropoietin, preoperative iron administration, selection of a CPB circuit specific to the patient’s height and weight, acute normovolemic hemodilution, retrograde autologous prime and venous autologous prime, tranexamic acid administration, zerobalance ultrafiltration, flushing of the pump suckers post-CPB, modified ultrafiltration, and cell salvage. We present an 8-day-old, 3.2-kg patient of JW faith with aortic valve stenosis and regurgitation and a patent foramen ovale who underwent a bloodless left ventricle-to-aorta tunnel repair and aortic valve repair on CPB