Electronic polarization in pentacene crystals and thin films

Electronic polarization is evaluated in pentacene crystals and in thin films on a metallic substrate using a self-consistent method for computing charge redistribution in non-overlapping molecules. The optical dielectric constant and its principal axes are reported for a neutral crystal. The polarization energies P+ and P- of a cation and anion at infinite separation are found for both molecules in the crystal's unit cell in the bulk, at the surface, and at the organic-metal interface of a film of N molecular layers. We find that a single pentacene layer with herring-bone packing provides a screening environment approaching the bulk. The polarization contribution to the transport gap P=(P+)+(P-), which is 2.01 eV in the bulk, decreases and increases by only ~ 10% at surfaces and interfaces, respectively. We also compute the polarization energy of charge-transfer (CT) states with fixed separation between anion and cation, and compare to electroabsorption data and to submolecular calculations. Electronic polarization of ~ 1 eV per charge has a major role for transport in organic molecular systems with limited overlap.Comment: 10 revtex pages, 6 PS figures embedde

NMR and NQR Fluctuation Effects in Layered Superconductors

We study the effect of thermal fluctuations of the s-wave order parameter of a quasi two dimensional superconductor on the nuclear spin relaxation rate near the transition temperature Tc. We consider both the effects of the amplitude fluctuations and the Berezinskii-Kosterlitz-Thouless (BKT) phase fluctuations in weakly coupled layered superconductors. In the treatment of the amplitude fluctuations we employ the Gaussian approximation and evaluate the longitudinal relaxation rate 1/T1 for a clean s-wave superconductor, with and without pair breaking effects, using the static pair fluctuation propagator D. The increase in 1/T1 due to pair breaking in D is overcompensated by the decrease arising from the single particle Green's functions. The result is a strong effect on 1/T1 for even a small amount of pair breaking. The phase fluctuations are described in terms of dynamical BKT excitations in the form of pancake vortex-antivortex (VA) pairs. We calculate the effect of the magnetic field fluctuations caused by the translational motion of VA excitations on 1/T1 and on the transverse relaxation rate 1/T2 on both sides of the BKT transitation temperature T(BKT)<Tc. The results for the NQR relaxation rates depend strongly on the diffusion constant that governs the motion of free and bound vortices as well as the annihilation of VA pairs. We discuss the relaxation rates for real multilayer systems where the diffusion constant can be small and thus increase the lifetime of a VA pair, leading to an enhancement of the rates. We also discuss in some detail the experimental feasibility of observing the effects of amplitude fluctuations in layered s-wave superconductors such as the dichalcogenides and the effects of phase fluctuations in s- or d-wave superconductors such as the layered cuprates.Comment: 38 pages, 12 figure

Spin asymmetry for the 16O(gamma,pi- p) reaction in the Delta(1232) region within an effective Lagrangian approach

The spin asymmetry of the photon in the exclusive A(gamma,pi N)A-1 reaction is computed employing a recently developed fully relativistic model based on elementary pion production amplitudes that include a consistent treatment of the spin-3/2 nucleon resonances. We compare the results of this model to the only available data on Oxygen [Phys. Rev. C 61 (2000) 054609] and find that, contrary to other models, the predicted spin asymmetry compares well to the available experimental data in the Delta(1232) region. Our results indicate that no major medium modifications in the Delta(1232) properties are needed in order to describe the measured spin asymmetries.Comment: 16 pages, 7 figures. To be published in Physics Letters

Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors

The Worldwide Network of Blood and Marrow Transplantation (WBMT) pursues the mission of promoting hematopoietic cell transplantation (HCT) for instance by evaluating activities through member societies, national registries and individual centers. In 2016, 82,718 first HCT were reported by 1,662 HCT teams in 86 of the 195 World Health Organization member states representing a global increase of 6.2% in autologous HCT and 7.0% in allogeneic HCT and bringing the total to 1,298,897 procedures. Assuming a frequency of 84,000/year, 1.5 million HCT were performed by 2019 since 1957. Slightly more autologous (53.5%) than allogeneic and more related (53.6%) than unrelated HCT were reported. A remarkable increase was noted in haploidentical related HCT for leukemias and lymphoproliferative diseases, but even more in non-malignant diseases. Transplant rates (TR; HCT/10 million population) varied according to region reaching 560.8 in North America, 438.5 in Europe, 76.7 in Latin America, 53.6 in South East Asia/Western Pacific (SEA/WPR) and 27.8 in African/East Mediterranean (AFR/EMR). Interestingly, haploidentical TR amounted to 32% in SEA/WPR and 26% in Latin America, but only 14% in Europe and EMR and 4.9% in North America of all allogeneic HCT. HCT team density (teams/10 million population) was highest in Europe (7.7) followed by North America (6.0), SEA/WPR (1.9), Latin America (1.6) and AFR/EMR (0.4). HCT are increasing steadily worldwide with narrowing gaps between regions and greater increase in allogeneic compared to autologous activity. While related HCT is rising, largely due to increase in haploidentical HCT, unrelated HCT is plateauing and cord blood HCT is in decline

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing

Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants