Integrated payload and mission planning, phase 3. Volume 2: Logic/Methodology for preliminary grouping of spacelab and mixed cargo payloads

The logic and methodology for a preliminary grouping of Spacelab and mixed-cargo payloads is proposed in a form that can be readily coded into a computer program by NASA. The logic developed for this preliminary cargo grouping analysis is summarized. Principal input data include the NASA Payload Model, payload descriptive data, Orbiter and Spacelab capabilities, and NASA guidelines and constraints. The first step in the process is a launch interval selection in which the time interval for payload grouping is identified. Logic flow steps are then taken to group payloads and define flight configurations based on criteria that includes dedication, volume, area, orbital parameters, pointing, g-level, mass, center of gravity, energy, power, and crew time

Strong Connectivity in Real Directed Networks

In many real, directed networks, the strongly connected component of nodes which are mutually reachable is very small. This does not fit with current theory, based on random graphs, according to which strong connectivity depends on mean degree and degree-degree correlations. And it has important implications for other properties of real networks and the dynamical behaviour of many complex systems. We find that strong connectivity depends crucially on the extent to which the network has an overall direction or hierarchical ordering -- a property measured by trophic coherence. Using percolation theory, we find the critical point separating weakly and strongly connected regimes, and confirm our results on many real-world networks, including ecological, neural, trade and social networks. We show that the connectivity structure can be disrupted with minimal effort by a targeted attack on edges which run counter to the overall direction. And we illustrate with example dynamics -- the SIS model, majority vote, Kuramoto oscillators and the voter model -- how a small number of edge deletions can utterly change dynamical processes in a wide range of systems.Comment: 16 pages, 6 figure

A Plasma Membrane Localization Signal in the HIV-1 Envelope Cytoplasmic Domain Prevents Localization at Sites of Vesicular Stomatitis Virus Budding and Incorporation into VSV Virions

AbstractPrevious studies showed that the HIV-1 envelope (Env) protein was not incorporated into vesicular stomatitis virus (VSV) virions unless its cytoplasmic tail was replaced with that of the VSV glycoprotein (G). To determine whether the G tail provided a positive incorporation signal for Env, or if sequences in the Env tail prevented incorporation, we generated mutants of Env with its 150-amino-acid tail shortened to 29, 10, or 3 amino acids (Envtr mutants). Cells infected with VSV recombinants expressing these proteins or an Env-G tail hybrid showed similar amounts of Env protein at the surface. The Env-G tail hybrid or the Envtr3 mutant were incorporated at the highest levels into budding VSV virions. In contrast, the Envtr29 or Envtr10 mutants were incorporated poorly. These results defined a signal preventing incorporation within the 10 membrane-proximal amino acids of the Env tail. Confocal microscopy revealed that this signal functioned by causing localization of human immunodeficiency virus type 1 Env to plasma membrane domains distinct from the VSV budding sites, where VSV proteins were concentrated

The Assessment of the Intrasubject Variability in Digoxin Absorption in Man from Two Oral Dosage Forms

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97194/1/j.1552-4604.1981.tb01771.x.pd

Effects of national housing quality standards on hospital emergency admissions: a quasi-experiment using data-linkage

Background National housing quality standards are now being applied throughout the UK. The Welsh Government has introduced the Welsh Housing Quality Standards. A housing improvement programme in Wales has been delivered through one local authority to bring 9500 homes up to standard. Homes received multiple elements, including new kitchens, bathrooms, windows and doors, boilers, insulation, and wiring, through an 8 year rolling work programme. The study aimed to determine the impacts of the different housing improvements on hospital emergency admissions for residents over 60 years of age. Methods Intervention homes (council homes that received at least one element of work) were data linked to individual health records of residents. Counts of admissions for respiratory and cardiovascular conditions, and for falls and burns, were obtained retrospectively for each individual in a dynamic housing cohort (Jan 1, 2005, to March 31, 2015). The criterion for the intervention cohort was for someone to have lived in any one of the 9500 intervention homes for at least 3 months within the intervention period. Counts were captured for up to 123 consecutive months for 7054 individuals in the intervention cohort and analysed in a multilevel approach to account for repeated observations for individuals, nested within geographical areas. Negative binomial regression models were constructed to determine the effect on emergency admissions for those living in homes compliant for each element of work compared with those living in homes that were non-compliant at that time. We adjusted for background trends in the regional general population, and for other confounding factors. Findings For residents 60 years old and over there was a reduction in admissions for people with compliant boilers (rate ratio 0·71, 95% CI 0·67–0·76), loft insulation (0·87, 0·80–0·95), wall insulation (0·74, 0·69–0·80), and windows and doors (0·56, 0·52–0·61) compared with those living in homes that were non-compliant for those work elements. Interpretation Improving housing to national standards reduces the number of emergency admissions to hospital for older residents. Strengths of the data-linkage approach included the retrospective collection of complete baseline and follow-up data using routine data for a long-term intervention, and large scale regional adjustment

In-Line-Test of Variability and Bit-Error-Rate of HfOx-Based Resistive Memory

Spatial and temporal variability of HfOx-based resistive random access memory (RRAM) are investigated for manufacturing and product designs. Manufacturing variability is characterized at different levels including lots, wafers, and chips. Bit-error-rate (BER) is proposed as a holistic parameter for the write cycle resistance statistics. Using the electrical in-line-test cycle data, a method is developed to derive BERs as functions of the design margin, to provide guidance for technology evaluation and product design. The proposed BER calculation can also be used in the off-line bench test and build-in-self-test (BIST) for adaptive error correction and for the other types of random access memories.Comment: 4 pages. Memory Workshop (IMW), 2015 IEEE Internationa

Short-term health and social impacts of energy-efficiency investments in low-income communities: a controlled field study

Background During 2012–15, £45 million was invested to improve the energy-efficiency of 4800 houses in low-income areas across Wales. Houses received measures such as external wall insulation, new windows and doors, upgrades to the heating system, and connection to the gas network. This study aimed to establish the short-term health and social impacts of these investments. Methods A quasi-experimental field study with a controlled, before and after design was conducted (364 individuals in improved houses [intervention], 418 in houses with no improvements [control]). Any adult living in 24 selected intervention areas and matched control areas (n=23) was eligible for inclusion. Self-completed questionnaires, administered via a drop-off-and-collect method, were collected in the winter months (December to February) before and after installation of the energy efficiency measures. Health outcomes were mental health composite scale (MCS) and physical health composite scale (PCS) scores of the SF-12v2, SF-6D utility scores derived from the SF-12v2, self-reported respiratory symptoms, and subjective wellbeing. Social outcomes were financial difficulties and stress, food security, thermal comfort, housing conditions, and social isolation. The study used measures validated in previous research. Linear, ordered multinomial, and logistic multilevel models were constructed with measurement occasions nested within individuals. Findings After controlling for sex, age, housing benefit, household income, and smoking status, we found that investments were not associated with improvements in MCS (B=0·00, 95% CI −1·60 to 1·60) or PCS (0·98, −0·34 to 2·28) scores, SF-6D utilities (−0·01, −0·04 to 0·02), or self-reported respiratory symptoms (−0·14, −0·54 to 0·26). However, people who received energy-efficiency measures reported improved subjective wellbeing compared with controls (B=0·38, 95% CI 0·12 to 0·65), and fewer financial difficulties (−0·15, −0·25 to −0·05); they reported higher thermal comfort (odds ratio 3·83, 95% CI 2·40 to 5·90), higher satisfaction with the improvement of their homes (3·87, 2·51 to 5·96), and less reluctance to invite friends or family to their homes (0·32, 0·13 to 0·77). Interpretation Although there is no evidence that energy-efficiency investments provide physical health benefits in the short term, they improve social and economic conditions that are conducive to better health. Longer term studies are needed to establish the health impacts of energy-efficiency investments

Determination of steroid estrogens in wastewater by high performance liquid chromatography-tandem mass spectrometry

This paper discusses the requirement for, and presents an analytical procedure for, the determination of four unconjugated steroid hormones and a conjugated steroid (estrone-3-sulfate) in wastewaters. The method quantifies the steroids by LC/MS/MS following solid phase extraction and a two stage clean-up procedure. Samples were extracted using C18 cartridges and eluates were then purified by gel permeation chromatography, followed by a further clean-up step on an aminopropyl cartridge. The limits of detection achieved were 0.2 ng l-1 for estriol, 17β-estradiol and 17α-ethinylestradiol, and 0.1 ng l-1 for estrone and the conjugate. The robustness of the method was demonstrated by achieving recoveries of >83% for all steroids in settled sewage and final effluent samples with relative standard deviations of 0.5 - 12%. The method was used to analyse a range of samples from a wastewater treatment works in south east England which demonstrated a >80% removal for estrone, estradiol and estriol with little impact on concentrations of ethinylestradiol or the conjugate

Development of a physiologically based pharmacokinetic model of actinomycin D in children with cancer

AIMS: Use of the anti‐tumour antibiotic actinomycin D is associated with development of hepatotoxicity, particularly in young children. A paucity of actinomycin D pharmacokinetic data make it challenging to develop a sound rationale for defining dosing regimens in younger patients. The study aim was to develop a physiologically based pharmacokinetic (PBPK) model using a combination of data from the literature and generated from experimental analyses. METHODS: Assays to determine actinomycin D Log P, blood:plasma partition ratio and ABCB1 kinetics were conducted. These data were combined with physiochemical properties sourced from the literature to generate a compound file for use within the modelling‐simulation software Simcyp (version 14 release 1). For simulation, information was taken from two datasets, one from 117 patients under the age of 21 and one from 20 patients aged 16–48. RESULTS: The final model incorporated clinical renal and biliary clearance data and an additional systemic clearance value. The mean AUC(0‐26h) of simulated subjects was within 1.25‐fold of the observed AUC(0‐26h) (84 ng h ml(−1) simulated vs. 93 ng h ml(−1) observed). For the younger age ranges, AUC predictions were within two‐fold of observed values, with simulated data from six of the eight age/dose ranges falling within 15% of observed data. Simulated values for actinomycin D AUC(0‐26h) and clearance in infants aged 0–12 months ranged from 104 to 115 ng h ml(−1) and 3.5–3.8 l h(−1), respectively. CONCLUSIONS: The model has potential utility for prediction of actinomycin D exposure in younger patients and may help guide future dosing. However, additional independent data from neonates and infants is needed for further validation. Physiological differences between paediatric cancer patients and healthy children also need to be further characterized and incorporated into PBPK models

A Diffusion-Based Approach to Geminate Recombination of Heme Proteins with Small Ligands

A model of postphotodissociative monomolecular (geminate) recombination of heme proteins with small ligands (NO, O2 or CO) is represented. The non-exponential decay with time for the probability to find a heme in unbound state is interpreted in terms of diffusion-like migration of ligabs physics/0212040 and between protein cavities. The temporal behavior for the probability is obtained from numerical simulation and specified by two parameters: the time \tau_{reb} of heme-ligand rebinding for the ligand localized inside the heme pocket and the time \tau_{esc} of ligand escape from the pocket. The model is applied in the analysis of available experimental data for geminate reoxygenation of human hemoglobin HbA. Our simulation is in good agreement with the measurements. The analysis shows that the variation in pH of the solution (6.0<pH<9.4) results in considerable changes for \tau_{reb} from 0.36 ns (at pH=8.5) up to 0.5 ns (pH=6.0) but effects slightly on the time \tau_{esc} (\tau_{esc} ~ 0.88 ns).Comment: 8 pages with 4 figures, submitted to Chem. Phy