Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells

A critical determinant of tumor eradication by adoptive immunotherapy is the tumor associated antigen recognized by cytotoxic T lymphocytes. Here the authors generate ex vivo autologous cytotoxic T lymphocytes by exposure to antigens induced by DNA demethylation and report the results of a phase 1 trial of 25 patients with recurrent glioblastoma multiforme with tumor regression in three patients

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Synthesis and characterization of ceria-supported catalysts for carbon dioxide transformation to diethyl carbonate

Abstract The support materials Al₂O₃, SiO₂ and TiO₂ were modified with 16 wt% CeO₂, using two different preparation methods evaporation-impregnation and precipitation-deposition. The synthesized 16 wt% CeO₂-Al₂O₃, 16 wt% CeO₂-SiO₂ and 16 wt% CeO₂-TiO₂ materials were characterized by means of X-ray powder diffraction for the phase purity, scanning electron microscopy for the morphology, nitrogen physisorption to determine the specific surface area and X-ray photo electron spectroscopy for the oxidation state of the Ce in the TiO₂, Al₂O₃ and SiO₂ matrices. Transmission electron microscopy was used to study the particle size of CeO₂ whereas CO₂-temperature programmed desorption (TPD) was used to determine the basicity of ceria-modified TiO₂, Al₂O₃ and SiO₂ catalysts. Furthermore, the catalytic performance of the as prepared CeO₂-modified catalysts were compared in the synthesis of diethyl carbonate starting from ethanol and CO₂ using butylene oxide as the dehydrating agent. The physico-chemical characterization results were correlated with the catalytic activity results and discussed in detail

Oxidation-Induced Changes in the ALD-Al2O3/InAs(100) Interface and Control of the Changes for Device Processing

InAs crystals are emerging materials for various devices like radio frequency transistors and infrared sensors. Control of oxidation-induced changes is essential for decreasing amounts of the harmful InAs surface (or interface) defects because it is hard to avoid the energetically favored oxidation of InAs surface parts in device processing. We have characterized atomic-layer-deposition (ALD) grown Al2O3/InAs interfaces, preoxidized differently, with synchrotron hard X-ray photoelectron spectroscopy (HAXPES), low-energy electron diffraction, scanning tunneling microscopy, and time-of-flight elastic recoil detection analysis. The chemical environment and core-level shifts are clarified for well-embedded InAs interfaces (12 nm Al2O3) to avoid, in particular, effects of a significant potential change at the vacuum-solid interface. High-resolution As 3d spectra reveal that the Al2O3/InAs interface, which was sputter-cleaned before ALD, includes +1.0 eV shift, whereas As 3d of the preoxidized (3 × 1)-O interface exhibits a shift of −0.51 eV. The measurements also indicate that an As2O3 type structure is not crucial in controlling defect densities. Regarding In 4d measurements, the sputtered InAs interface includes only a +0.29 eV shift, while the In 4d shift around −0.3 eV is found to be inherent for the crystalline oxidized interfaces. Thus, the negative shifts, which have been usually associated with dangling bonds, are not necessarily an indication of such point defects as previously expected. In contrast, the negative shifts can arise from bonding with O atoms. Therefore, specific care should be directed in determining the bulk-component positions in photoelectron studies. Finally, we present an approach to transfer the InAs oxidation results to a device process of high electron mobility transistors (HEMT) using an As-rich III–V surface and In deposition. The approach is found to decrease a gate leakage current of HEMT without losing the gate controllability.peerReviewe

TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC

Intracellular factors are involved in and essential for hematopoiesis. HIV-1 Tat-interacting protein of 110 kDa (TIP110; p110nrb/SART3/p110) is an RNA-binding nuclear protein implicated in the regulation of HIV-1 gene and host gene transcription, pre-mRNA splicing, and cancer immunology. In the present study, we demonstrate a role for TIP110 in the regulation of hematopoiesis. TIP110 was expressed in human CD34+ cells and decreased with differentiation of CD34+ cells. TIP110 mRNA was also expressed in phenotyped mouse marrow hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Using TIP110 transgenic (TIP110TG) and haploinsufficient (TIP110+/−) mice, we found that increased TIP110 expression enhanced HPC numbers, survival, and cell cycling, whereas decreased TIP110 expression had the opposite effects. Moreover, TIP110+/− bone marrow HPCs responded more effectively, and TIP110TG HPCs less effectively, than those of wild-type control mice to recovery from the cell-cycle–active drug 5-fluorouracil (5-FU). Unexplained sex differences were noted in HSC competitive repopulating ability, but not HPC numbers, in TIP110TG mice. Intracellularly, TIP110 regulated CMYC and GATA2 expression at the transcriptional level, and TIP110 and CMYC reciprocally regulated the expression of each other. These results demonstrate a role for TIP110 in the regulation of hematopoiesis, effects that are likely linked to TIP110 regulation of CMYC