Wakeshield WSF-02 GPS Experiment

Shuttle mission STS-69 was launched on September 7, 1995, 10:09 CDT, carrying the Wake Shield Facility (WSF-02). The WSF-02 spacecraft included a set of payloads provided by the Texas Space Grant Consortium, known as TexasSat. One of the TexasSat payloads was a GPS TurboRogue receiver loaned by the University Corporation for Atmospheric Research. On September 11, the WSF-02 was unberthed from the Endeavour payload bay using the remote manipulator system. The GPS receiver was powered on prior to release and the WSF-02 remained in free-flight for three days before being retrieved on September 14. All WSF-02 GPS data, which includes dual frequency pseudorange and carrier phase, were stored in an on-board recorder for post-flight analysis, but "snap- shots" of data were transmitted for 2-3 minutes at intervals of several hours, when permitted by the telemetry band- widdl The GPS experiment goals were: (1) an evaluation of precision orbit determination in a low altitude environment (400 km) where perturbations due to atmospheric drag and the Earth's gravity field are more pronounced than for higher altitude satellites with high precision orbit requirements, such as TOPEX/POSEIDON; (2) an assessment of relative positioning using the WSF GPS receiver and the Endeavour Collins receiver; and (3) determination of atmospheric temperature profiles using GPS signals passing through the atmosphere. Analysis of snap-shot telemetry data indicate that 24 hours of continuous data were stored on board, which includes high rate (50 Hz) data for atmosphere temperature profiles. Examination of the limited number of real-time navigation solutions show that at least 7 GPS satellites were tracked simultaneously and the on-board clock corrections were at the microsec level, as expected. Furthermore, a dynamical consistency test provided a further validation of the on-board navigation solutions. Complete analysis will be conducted in post-flight using the data recorded on-board

Adiponectin Decreases Pulmonary Arterial Remodeling in Murine Models of Pulmonary Hypertension

Remodeling of the pulmonary arteries is a common feature among the heterogeneous disorders that cause pulmonary hypertension. In these disorders, the remodeled pulmonary arteries often demonstrate inflammation and an accumulation of pulmonary artery smooth muscle cells (PASMCs) within the vessels. Adipose tissue secretes multiple bioactive mediators (adipokines) that can influence both inflammation and remodeling, suggesting that adipokines may contribute to the development of pulmonary hypertension. We recently reported on a model of pulmonary hypertension induced by vascular inflammation, in which a deficiency of the adipokine adiponectin (APN) was associated with the extensive proliferation of PASMCs and increased pulmonary artery pressures. Based on these data, we hypothesize that APN can suppress pulmonary hypertension by directly inhibiting the proliferation of PASMCs. Here, we tested the effects of APN overexpression on pulmonary arterial remodeling by using APN-overexpressing mice in a model of pulmonary hypertension induced by inflammation. Consistent with our hypothesis, mice that overexpressed APN manfiested reduced pulmonary hypertension and remodeling compared with wild-type mice, despite developing similar levels of pulmonary vascular inflammation in the model. The overexpression of APN was also protective in a hypoxic model of pulmonary hypertension. Furthermore, APN suppressed the proliferation of PASMCs, and reduced the activity of the serum response factor–serum response element pathway, which is a critical signaling pathway for smooth muscle cell proliferation. Overall, these data suggest that APN can regulate pulmonary hypertension and pulmonary arterial remodeling through its direct effects on PASMCs. Hence, the activation of APN-like activity in the pulmonary vasculature may be beneficial in pulmonary hypertension

Lucro líquido do franqueado: um sinal para a escolha de franquia em época de crise

Este artículo aborda desde la perspectiva de la Teoría de Señales la elección de una franquicia por un potencial franquiciado que elige este canal de distribución por primera vez. El objetivo es analizar la relación entre algunas señales enviadas por el franquiciador y la elección de una franquicia por el potencial franquiciado. Concluimos que los efectos de las variables macroeconómicas de España en el periodo 2006-2013 influyeron en los ingresos netos de los franquiciados para que se convirtiera en una señal empleada por éstos a la hora de elegir la franquicia donde abrir un establecimiento.This paper adopts the perspective of Theory of Signals to discuss how someone starting a business as a franchisee for the first time can choose a suitable franchise brand. The aim was to analyze the relationship between certain signals sent by the franchisor and the choice of a franchise brand by the prospective franchisee. Using panel data, we found that the effects of macroeconomic variables in Spain for the 2006-2013 crisis period influenced franchisees' net income, which thus became a relevant signal in their process of choosing a franchise brand to start a business.Sob a perspectiva da Teoria de Sinais, este artigo aborda a seleção de uma franquia por um franqueado que elege esse potencial canal de distribuição pela primeira vez. O objetivo é analisar a relação entre alguns sinais enviados pelo franqueador e a escolha de uma franquia pelo potencial franqueado. Usando a metodologia de dados em painel, os resultados obtidos nos permitiram concluir que os efeitos das variáveis macroeconômicas da Espanha no período de crise econômica (2006-2013) influenciaram as receitas líquidas dos franqueados, tornando-se um sinal para eles elegerem onde abrir um estabelecimento franqueado

Dose-Dependent Effects of Closed-Loop tACS Delivered During Slow-Wave Oscillations on Memory Consolidation

Sleep is critically important to consolidate information learned throughout the day. Slow-wave sleep (SWS) serves to consolidate declarative memories, a process previously modulated with open-loop non-invasive electrical stimulation, though not always effectively. These failures to replicate could be explained by the fact that stimulation has only been performed in open-loop, as opposed to closed-loop where phase and frequency of the endogenous slow-wave oscillations (SWOs) are matched for optimal timing. The current study investigated the effects of closed-loop transcranial Alternating Current Stimulation (tACS) targeting SWOs during sleep on memory consolidation. 21 participants took part in a three-night, counterbalanced, randomized, single-blind, within-subjects study, investigating performance changes (correct rate and F1 score) on images in a target detection task over 24 h. During sleep, 1.5 mA closed-loop tACS was delivered in phase over electrodes at F3 and F4 and 180° out of phase over electrodes at bilateral mastoids at the frequency (range 0.5–1.2 Hz) and phase of ongoing SWOs for a duration of 5 cycles in each discrete event throughout the night. Data were analyzed in a repeated measures ANOVA framework, and results show that verum stimulation improved post-sleep performance specifically on generalized versions of images used in training at both morning and afternoon tests compared to sham, suggesting the facilitation of schematization of information, but not of rote, veridical recall. We also found a surprising inverted U-shaped dose effect of sleep tACS, which is interpreted in terms of tACS-induced faciliatory and subsequent refractory dynamics of SWO power in scalp EEG. This is the first study showing a selective modulation of long-term memory generalization using a novel closed-loop tACS approach, which holds great potential for both healthy and neuropsychiatric populations

BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors

<p>Abstract</p> <p>Background</p> <p>The prognosis for patients with recurrent glioblastoma is still poor with a median survival between 3 and 6 months. Reports about the application of carmustine (BCNU), one of the standard chemotherapeutic drugs in the treatment of newly diagnosed glioblastoma, in the recurrent situation are rare.</p> <p>Methods</p> <p>We performed a retrospective analysis of 35 patients with recurrent or progressive glioblastoma treated with 80 mg/m²BCNU on days 1 on 3 intravenously at our department for efficacy, toxicity and prognostic factors. Progression free survival and overall survival were estimated by the Kaplan-Meier method. The influence of age, Karnofsky performance status (KPS), tumor burden, pretreatment with temozolomide (TMZ), type of surgery for initial diagnosis and number of previous relapses on outcome was analyzed in a proportional hazards regression model.</p> <p>Results</p> <p>The median age of the group was 53 years, median KPS was 70. Median progression free survival was 11 weeks (95% confidence interval [CI]: 8-15), median overall survival 22 weeks (95% CI: 18-27). The rate of adverse events, especially hematological toxicity, is relatively high, and in 3 patients treatment had to be terminated due to adverse events (one pulmonary embolism, one pulmonary fibrosis, and one severe bone marrow suppression). No influence of age, KPS, tumor burden, pre-treatment with TMZ and number of previous relapses on outcome could be demonstrated, while gross total resection prior to recurrence showed a borderline statistically significant negative impact on PFS and OS. These data compare well with historical survival figures. However prospective randomized studies are needed to evaluate BCNU efficacy against newer drugs like bevacizumab or the intensified temozolomide regime (one week on/one week off).</p> <p>Conclusion</p> <p>In summary, BCNU treatment appears to be a valuable therapeutic option for recurrent glioblastomas, where no other validated radio- and/or chemotherapy are available.</p

The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline

QUESTION: What evidence is available regarding the use of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), surgical resection or chemotherapy for the treatment of recurrent/progressive brain metastases? TARGET POPULATION: This recommendation applies to adults with recurrent/progressive brain metastases who have previously been treated with WBRT, surgical resection and/or radiosurgery. Recurrent/progressive brain metastases are defined as metastases that recur/progress anywhere in the brain (original and/or non-original sites) after initial therapy. RECOMMENDATION: Level 3 Since there is insufficient evidence to make definitive treatment recommendations in patients with recurrent/progressive brain metastases, treatment should be individualized based on a patient\u27s functional status, extent of disease, volume/number of metastases, recurrence or progression at original versus non-original site, previous treatment and type of primary cancer, and enrollment in clinical trials is encouraged. In this context, the following can be recommended depending on a patient\u27s specific condition: no further treatment (supportive care), re-irradiation (either WBRT and/or SRS), surgical excision or, to a lesser extent, chemotherapy. Question If WBRT is used in the setting of recurrent/progressive brain metastases, what impact does tumor histopathology have on treatment outcomes? No studies were identified that met the eligibility criteria for this question

Low Utilization of Circulating Glucose after Food Withdrawal in Snell Dwarf Mice

Glucose metabolism is altered in long-lived people and mice. Although it is clear that there is an association between altered glucose metabolism and longevity, it is not known whether this link is causal or not. Our current hypothesis is that decreased fasting glucose utilization may increase longevity by reducing oxygen radical production, a potential cause of aging. We observed that whole body fasting glucose utilization was lower in the Snell dwarf, a long-lived mutant mouse. Whole body fasting glucose utilization may be reduced by a decrease in the production of circulating glucose. Our isotope labeling analysis indicated both gluconeogenesis and glycogenolysis were suppressed in Snell dwarfs. Elevated circulating adiponectin may contribute to the reduction of glucose production in Snell dwarfs. Adiponectin lowered the appearance of glucose in the media over hepatoma cells by suppressing gluconeogenesis and glycogenolysis. The suppression of glucose production by adiponectin in vitro depended on AMP-activated protein kinase, a cell mediator of fatty acid oxidation. Elevated fatty acid oxidation was indicated in Snell dwarfs by increased utilization of circulating oleic acid, reduced intracellular triglyceride content, and increased phosphorylation of acetyl-CoA carboxylase. Finally, protein carbonyl content, a marker of oxygen radical damage, was decreased in Snell dwarfs. The correlation between high glucose utilization and elevated oxygen radical production was also observed in vitro by altering the concentrations of glucose and fatty acids in the media or pharmacologic inhibition of glucose and fatty acid oxidation with 4-hydroxycyanocinnamic acid and etomoxir, respectively

Metallothionein (MT) -I and MT-II Expression Are Induced and Cause Zinc Sequestration in the Liver after Brain Injury

Experiments with transgenic over-expressing, and null mutant mice have determined that metallothionein-I and -II (MT-I/II) are protective after brain injury. MT-I/II is primarily a zinc-binding protein and it is not known how it provides neuroprotection to the injured brain or where MT-I/II acts to have its effects. MT-I/II is often expressed in the liver under stressful conditions but to date, measurement of MT-I/II expression after brain injury has focused primarily on the injured brain itself. In the present study we measured MT-I/II expression in the liver of mice after cryolesion brain injury by quantitative reverse-transcriptase PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) with the UC1MT antibody. Displacement curves constructed using MT-I/II knockout (MT-I/II−/−) mouse tissues were used to validate the ELISA. Hepatic MT-I and MT-II mRNA levels were significantly increased within 24 hours of brain injury but hepatic MT-I/II protein levels were not significantly increased until 3 days post injury (DPI) and were maximal at the end of the experimental period, 7 DPI. Hepatic zinc content was measured by atomic absorption spectroscopy and was found to decrease at 1 and 3 DPI but returned to normal by 7DPI. Zinc in the livers of MT-I/II−/− mice did not show a return to normal at 7 DPI which suggests that after brain injury, MT-I/II is responsible for sequestering elevated levels of zinc to the liver. Conclusion: MT-I/II is up-regulated in the liver after brain injury and modulates the amount of zinc that is sequestered to the liver

Sodium ion interactions with aqueous glucose: Insights from quantum mechanics, molecular dynamics, and experiment

In the last several decades, significant efforts have been conducted to understand the fundamental reactivity of glucose derived from plant biomass in various chemical environments for conversion to renewable fuels and chemicals. For reactions of glucose in water, it is known that inorganic salts naturally present in biomass alter the product distribution in various deconstruction processes. However, the molecular-level interactions of alkali metal ions and glucose are unknown. These interactions are of physiological interest as well, for example, as they relate to cation-glucose cotransport. Here, we employ quantum mechanics (QM) to understand the interaction of a prevalent alkali metal, sodium, with glucose from a structural and thermodynamic perspective. The effect on B-glucose is subtle: a sodium ion perturbs bond lengths and atomic partial charges less than rotating a hydroxymethyl group. In contrast, the presence of a sodium ion significantly perturbs the partial charges of α-glucose anomeric and ring oxygens. Molecular dynamics (MD) simulations provide dynamic sampling in explicit water, and both the QM and the MD results show that sodium ions associate at many positions with respect to glucose with reasonably equivalent propensity. This promiscuous binding nature of Na + suggests that computational studies of glucose reactions in the presence of inorganic salts need to ensure thorough sampling of the cation positions, in addition to sampling glucose rotamers. The effect of NaCl on the relative populations of the anomers is experimentally quantified with light polarimetry. These results support the computational findings that Na + interacts similarly with a- and B-glucose

Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

Gene networks are an efficient route for associating candidate genes with biological processes. Here, networks are used to discover more than 15 new genes for ribosomal subunit maturation, rRNA processing, and ribosomal export from the nucleus