A convenient synthesis of 1,2-diphenyl-9H-[l]benzopyrano [3,2-b] pyrrol-9-ones utilizing hypervalent iodine reagent

536-53

Therapy of pancreatic cancer via an EphA2 receptor-targeted delivery of gemcitabine.

First line treatment for pancreatic cancer consists of surgical resection, if possible, and a subsequent course of chemotherapy using the nucleoside analogue gemcitabine. In some patients, an active transport mechanism allows gemcitabine to enter efficiently into the tumor cells, resulting in a significant clinical benefit. However, in most patients, low expression of gemcitabine transporters limits the efficacy of the drug to marginal levels, and patients need frequent administration of the drug at high doses, significantly increasing systemic drug toxicity. In this article we focus on a novel targeted delivery approach for gemcitabine consisting of conjugating the drug with an EphA2 targeting agent. We show that the EphA2 receptor is highly expressed in pancreatic cancers, and accordingly, the drug-conjugate is more effective than gemcitabine alone in targeting pancreatic tumors. Our preliminary observations suggest that this approach may provide a general benefit to pancreatic cancer patients and offers a comprehensive strategy for enhancing delivery of diverse therapeutic agents to a wide range of cancers overexpressing EphA2, thereby potentially reducing toxicity while enhancing therapeutic efficacy

Quantum Dynamics without the Wave Function

When suitably generalized and interpreted, the path-integral offers an alternative to the more familiar quantal formalism based on state-vectors, selfadjoint operators, and external observers. Mathematically one generalizes the path-integral-as-propagator to a {\it quantal measure} $\mu$ on the space $\Omega$ of all ``conceivable worlds'', and this generalized measure expresses the dynamics or law of motion of the theory, much as Wiener measure expresses the dynamics of Brownian motion. Within such ``histories-based'' schemes new, and more ``realistic'' possibilities open up for resolving the philosophical problems of the state-vector formalism. In particular, one can dispense with the need for external agents by locating the predictive content of $\mu$ in its sets of measure zero: such sets are to be ``precluded''. But unrestricted application of this rule engenders contradictions. One possible response would remove the contradictions by circumscribing the application of the preclusion concept. Another response, more in the tradition of ``quantum logic'', would accommodate the contradictions by dualizing $\Omega$ to a space of ``co-events'' and effectively identifying reality with an element of this dual space.Comment: plainTeX, 24 pages, no figures. To appear in a special volume of {\it Journal of Physics A: Mathematical and General} entitled ``The Quantum Universe'' and dedicated to Giancarlo Ghirardi on the occasion of his 70th birthday. Most current version is available at http://www.physics.syr.edu/~sorkin/some.papers/ (or wherever my home-page may be

Effectiveness of community-based health education and home support program to reduce blood pressure among patients with uncontrolled hypertension in Nepal : a cluster-randomized trial

Background Hypertension is a major global public health problem. Elevated blood pressure can cause cardiovascular and kidney diseases. We assessed the effectiveness of health education sessions and home support programs in reducing blood pressure among patients with uncontrolled hypertension in a suburban community of Nepal. Methods We conducted a community-based, open-level, parallel-group, cluster randomized controlled trial in Birendranagar municipality of Surkhet, Nepal. We randomly assigned four clusters (wards) into intervention and control arms. We provided four health education sessions, frequent home and usual care for intervention groups over six months. The participants of the control arm received only usual care from health facilities. The primary outcome of this study was the proportion of controlled systolic blood pressure (SBP). The analysis included all participants who completed follow-up at six months. Results 125 participants were assigned to either the intervention (n = 63) or the control (n = 62) group. Of them, 60 participants in each group completed six months follow-up. Theproportion of controlled SBP was significantly higher among the intervention participants compared to the control (58.3% vs. 40%). Odds ratio of this was 2.1 with 95% CI: 1.01–4.35 (p = 0.046) and that of controlled diastolic blood pressure (DBP) was 1.31 (0.63–2.72) (p = 0.600). The mean change (follow-up minus baseline) in SBP was significantly higher in the intervention than in the usual care (-18.7 mmHg vs. -11.2 mmHg, p = 0.041). Such mean change of DBP was also higher in the intervention (-10.95 mmHg vs. -5.53 mmHg, p = 0.065). The knowledge score on hypertension improved by 2.38 (SD 2.4) in the intervention arm, which was significantly different from that of the control group, 0.13 (1.8) (p<0.001). Conclusions Multiple health education sessions complemented by frequent household visits by health volunteers can effectively improve knowledge on hypertension and reduce blood pressure among uncontrolled hypertensive patients at the community level in Nepal

Brane Baldness vs. Superselection Sectors

The search for intersecting brane solutions in supergravity is a large and profitable industry. Recently, attention has focused on finding localized forms of known `delocalized' solutions. However, in some cases, a localized version of the delocalized solution simply does not exist. Instead, localized separated branes necessarily delocalize as the separation is removed. This phenomenon is related to black hole no-hair theorems, i.e. `baldness.' We continue the discussion of this effect and describe how it can be understood, in the case of Dirichlet branes, in terms of the corresponding intersection field theory. When it occurs, it is associated with the quantum mixing of phases and lack of superselection sectors in low dimensional field theories. We find surprisingly wide agreement between the field theory and supergravity both with respect to which examples delocalize and with respect to the rate at which this occurs.Comment: 26 pages, ReVTeX, 2 figures, reference added, version to appear in PR

The holographic superconductors in higher-dimensional AdS soliton

We explore the behaviors of the holographic superconductors at zero temperature for a charged scalar field coupled to a Maxwell field in higher-dimensional AdS soliton spacetime via analytical way. In the probe limit, we obtain the critical chemical potentials increase linearly as a total dimension $d$ grows up. We find that the critical exponent for condensation operator is obtained as 1/2 independently of $d$, and the charge density is linearly related to the chemical potential near the critical point. Furthermore, we consider a slightly generalized setup the Einstein-Power-Maxwell field theory, and find that the critical exponent for condensation operator is given as $1/(4-2n)$ in terms of a power parameter $n$ of the Power-Maxwell field, and the charge density is proportional to the chemical potential to the power of $1/(2-n)$.Comment: LaTeX, 16 pages, 5 figures, typos corrected, one reference added, version to appear in European Physical Journal

Localized Branes and Black Holes

We address the delocalization of low dimensional D-branes and NS-branes when they are a part of a higher dimensional BPS black brane, and the homogeneity of the resulting horizon. We show that the effective delocalization of such branes is a classical effect that occurs when localized branes are brought together. Thus, the fact that the few known solutions with inhomogeneous horizons are highly singular need not indicate a singularity of generic D- and NS-brane states. Rather, these singular solutions are likely to be unphysical as they cannot be constructed from localized branes which are brought together from a finite separation.Comment: 13 pages, RevTex, no figures, few references and comments adde

Introductory programming: a systematic literature review

As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research

IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, divergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8+ T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma