Voluntary Wheel Running Reverses Age-Induced Changes in Hippocampal Gene Expression

Normal aging alters expression of numerous genes within the brain. Some of these transcription changes likely contribute to age-associated cognitive decline, reduced neural plasticity, and the higher incidence of neuropathology. Identifying factors that modulate brain aging is crucial for improving quality of life. One promising intervention to counteract negative effects of aging is aerobic exercise. Aged subjects that exercise show enhanced cognitive performance and increased hippocampal neurogenesis and synaptic plasticity. Currently, the mechanisms behind the anti-aging effects of exercise are not understood. The present study conducted a microarray on whole hippocampal samples from adult (3.5-month-old) and aged (18-month-old) male BALB/c mice that were individually housed with or without running wheels for 8 weeks. Results showed that aging altered genes related to chromatin remodeling, cell growth, immune activity, and synapse organization compared to adult mice. Exercise was found to modulate many of the genes altered by aging, but in the opposite direction. For example, wheel running increased expression of genes related to cell growth and attenuated expression of genes involved in immune function and chromatin remodeling. Collectively, findings show that even late-onset exercise may attenuate age-related changes in gene expression and identifies possible pathways through which exercise may exert its beneficial effects

CDZNTE ROOM-TEMPERATURE SEMICONDUCTOR GAMMA-RAY DETECTOR FOR NATIONAL-SECURITY APPLICATIONS.

One important mission of the Department of Energy's National Nuclear Security Administration is to develop reliable gamma-ray detectors to meet the widespread needs of users for effective techniques to detect and identify special nuclear- and radioactive-materials. Accordingly, the Nonproliferation and National Security Department at Brookhaven National Laboratory was tasked to evaluate existing technology and to develop improved room-temperature detectors based on semiconductors, such as CdZnTe (CZT). Our research covers two important areas: Improving the quality of CZT material, and exploring new CZT-based gamma-ray detectors. In this paper, we report on our recent findings from the material characterization and tests of actual CZT devices fabricated in our laboratory and from materials/detectors supplied by different commercial vendors. In particular, we emphasize the critical role of secondary phases in the current CZT material and issues in fabricating the CZT detectors, both of which affect their performance

High Spatial-Resolution Imaging of Te Inclusions in CZT Material.

We present new results from our studies of defects in current single-crystal CdZnTe material. Our previous measurements, carried out on thin ({approx}1 mm) and long (>12 mm) CZT detectors, indicated that small (1-20 {micro}m) Te inclusions can significantly degrade the device's energy resolution and detection efficiency. We are conducting detailed studies of the effects of Te inclusions by employing different characterization techniques with better spatial resolution, such as quantitative fluorescence mapping, X-ray micro-diffraction, and TEM. Also, IR microscopy and gamma-mapping with pulse-shape analysis with higher spatial resolution generated more accurate results in the areas surrounding the micro-defects (Te inclusions). Our results reveal how the performance of CdZnTe detectors is influenced by Te inclusions, such as their spatial distribution, concentration, and size. We also discuss a model of charge transport through areas populated with Te inclusions

Te Inclusions and Their Relationship to the Performance of CdZnTe Detectors.

Te-rich secondary phases existing in CdZnTe (CZT) single crystals degrade the spectroscopic performance of these detectors. An unpredictable number of charges are trapped, corresponding to the abundance of these microscopic defects, thereby leading to fluctuations in the total collected charge and strongly affecting the uniformity of charge-collection efficiency. These effects, observed in thin planar detectors, also were found to be the dominant cause of the low performance of thick detectors, wherein the fluctuations accumulate along the charge's drift path. Reducing the size of Te inclusions from a virtual diameter of 10-20 {micro}m down to less than 5 {micro}m already allowed us to produce Frisch-ring detectors with a resolution as good as {approx}0.8% FWHM at 662 keV: Understanding and modeling the mechanisms involving Te-rich secondary phases and charge loss requires systematic studies on a spatial scale never before realized. Here, we describe a dedicated beam-line recently established at BNL's National Synchrotron Light Source for characterizing semiconductor detectors along with a IR system with counting capability that permits us to correlate the concentration of defects with the devices' performances

Performance-Limiting Defects in CdZnTe Detectors.

We studied the effects of small, <20 {micro}m, Te inclusions on the energy resolution of CdZnTe gamma-ray detectors using a highly collimated X-ray beam and gamma-rays, and modeled them via a simplified geometrical approach. Previous reports demonstrated that Te inclusions of about a few microns in diameter degraded the charge-transport properties and uniformity of CdZnTe detectors. The goal of this work was to understand the extent to which randomly distributed Te-rich inclusions affect the energy resolution of CZT detectors, and to define new steps to overcome their deleterious effects. We used a phenomenological model, which depends on several adjustable parameters, to reproduce the experimentally measured effects of inclusions on energy resolution. We also were able to hound the materials-related problem and predict the enhancement in performance expected by reducing the size and number of Te inclusions within the crystals

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al

Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience

From 1990 to 1997, 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin (40 mg m–2), cisplatin (50 mg m–2) administered intravenously on day 1, vincristine (0.6 mg m–2) on day 2 and cyclophosphamide (700 mg m–2) on day 4 (ADOC). The courses were repeated every 3 weeks. The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate, per cent of patients radically resected, time to progression and overall survival. Two complete responses (one clinical and one pathological) and 11 partial responses were observed (overall response rate 81.2%); two patients had stable disease and one progressed. Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting. Nine patients were radically resected (five out of ten with stage III, and four out of six with stage IVa). Median time to progression and overall survival was 33.2 and 47.5 months respectively. Three patients were alive and disease free after more than 5 years. The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma. As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity. © 1999 Cancer Research Campaig