Initial Top-Level Characterization of the Air Force Sustainment System

This draft white paper presents an initial top-level characterization of the Air Force sustainment system. The first part of the paper gives an overview of the proposed conceptual framework for system characterization. The second part presents an initial top-level characterization of the system, by using this framework, and offers some preliminary suggestions or recommendations. Finally, next steps in the research process are outlined, placing the paper in the larger context of the task on system characterization and transformation

Active Transport of Peptides Across the Intact Human Tympanic Membrane.

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients

Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes. METHODS AND ANALYSIS: We will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes. ETHICS AND DISSEMINATION: The study has been approved by the North West-Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination

3C 295, a cluster and its cooling flow at z=0.46

We present ROSAT HRI data of the distant and X-ray luminous (L_x(bol)=2.6^ {+0.4}_{-0.2} 10^{45}erg/sec) cluster of galaxies 3C 295. We fit both a one-dimensional and a two-dimensional isothermal beta-model to the data, the latter one taking into account the effects of the point spread function (PSF). For the error analysis of the parameters of the two-dimensional model we introduce a Monte-Carlo technique. Applying a substructure analysis, by subtracting a cluster model from the data, we find no evidence for a merger, but we see a decrement in emission South-East of the center of the cluster, which might be due to absorption. We confirm previous results by Henry & Henriksen(1986) that 3C 295 hosts a cooling flow. The equations for the simple and idealized cooling flow analysis presented here are solely based on the isothermal beta-model, which fits the data very well, including the center of the cluster. We determine a cooling flow radius of 60-120kpc and mass accretion rates of dot{M}=400-900 Msun/y, depending on the applied model and temperature profile. We also investigate the effects of the ROSAT PSF on our estimate of dot{M}, which tends to lead to a small overestimate of this quantity if not taken into account. This increase of dot{M} (10-25%) can be explained by a shallower gravitational potential inferred by the broader overall profile caused by the PSF, which diminishes the efficiency of mass accretion. We also determine the total mass of the cluster using the hydrostatic approach. At a radius of 2.1 Mpc, we estimate the total mass of the cluster (M{tot}) to be (9.2 +/- 2.7) 10^{14}Msun. For the gas to total mass ratio we get M{gas}/M{tot} =0.17-0.31, in very good agreement with the results for other clusters of galaxies, giving strong evidence for a low density universe.Comment: 26 pages, 7 figures, accepted for publication in Ap

The Extended Star Formation History of the Andromeda Spheroid at 35 Kpc on the Minor Axis

Using the HST ACS, we have obtained deep optical images reaching well below the oldest main sequence turnoff in fields on the southeast minor-axis of the Andromeda Galaxy, 35 kpc from the nucleus. These data probe the star formation history in the extended halo of Andromeda -- that region beyond 30 kpc that appears both chemically and morphologically distinct from the metal-rich, highly-disturbed inner spheroid. The present data, together with our previous data for fields at 11 and 21 kpc, do not show a simple trend toward older ages and lower metallicities, as one might expect for populations further removed from the obvious disturbances of the inner spheroid. Specifically, the mean ages and [Fe/H] values at 11 kpc, 21 kpc, and 35 kpc are 9.7 Gyr and -0.65, 11.0 Gyr and -0.87, and 10.5 Gyr and -0.98, respectively. In the best-fit model of the 35 kpc population, one third of the stars are younger than 10 Gyr, while only ~10% of the stars are truly ancient and metal-poor. The extended halo thus exhibits clear evidence of its hierarchical assembly, and the contribution from any classical halo formed via early monolithic collapse must be small.Comment: Accepted for publication in The Astrophysical Journal Letters. 4 pages, latex, 2 color figure

The pH Low Insertion Peptide pHLIP Variant 3 as a Novel Marker of Acidic Malignant Lesions

Current strategies for early detection of breast and other cancers are limited in part because some lesions identified as potentially malignant do not develop into aggressive tumors. Acid pH has been suggested as a key characteristic of aggressive tumors that might distinguish aggressive lesions from more indolent pathology. We therefore investigated the novel class of molecules, pH low insertion peptides (pHLIPs), as markers of low pH in tumor allografts and of malignant lesions in a mouse model of spontaneous breast cancer, BALB/neu-T. pHLIP Variant 3 (Var3) conjugated with fluorescent Alexa546 was shown to insert into tumor spheroids in a sequence-specific manner. Its signal reflected pH in murine tumors. It was induced by carbonic anhydrase IX (CAIX) overexpression and inhibited by acetazolamide (AZA) administration. By using 31P magnetic resonance spectroscopy (MRS), we demonstrated that pHLIP Var3 was retained in tumors of pH equal to or less than 6.7 but not in tissues of higher pH. In BALB/neu-T mice at different stages of the disease, the fluorescent signal from pHLIP Var3 marked cancerous lesions with a very low false-positive rate. However, only ∼60% of the smallest lesions retained a pHLIP Var3 signal, suggesting heterogeneity in pH. Taken together, these results show that pHLIP can identify regions of lower pH, allowing for its development as a theranostic tool for clinical applications

Intracellular microrheology of motile Amoeba proteus

The motility of motile Amoeba proteus was examined using the technique of passive particle tracking microrheology, with the aid of newly-developed particle tracking software, a fast digital camera and an optical microscope. We tracked large numbers of endogeneous particles in the amoebae, which displayed subdiffusive motion at short time scales, corresponding to thermal motion in a viscoelastic medium, and superdiffusive motion at long time scales due to the convection of the cytoplasm. Subdiffusive motion was characterised by a rheological scaling exponent of 3/4 in the cortex, indicative of the semiflexible dynamics of the actin fibres. We observed shear-thinning in the flowing endoplasm, where exponents increased with increasing flow rate; i.e. the endoplasm became more fluid-like. The rheology of the cortex is found to be isotropic, reflecting an isotropic actin gel. A clear difference was seen between cortical and endoplasmic layers in terms of both viscoelasticity and flow velocity, where the profile of the latter is close to a Poiseuille flow for a Newtonian fluid

Chandra X-ray observations of the 3C295 cluster core

We examine the properties of the X-ray gas in the central regions of the distant (z=0.46), X-ray luminous cluster of galaxies surrounding the powerful radio source 3C 295, using observations made with the Chandra Observatory. Between radii of 50-500 kpc, the cluster gas is approximately isothermal with an emission-weighted temperature, kT ~5 keV. Within the central 50 kpc radius this value drops to kT ~3.7 keV. The spectral and imaging Chandra data indicate the presence of a cooling flow within the central 50 kpc radius of the cluster, with a mass deposition rate of approximately 280 solar masses per year. We estimate an age for the cooling flow of 1-2 Gyr, which is approximately one thousand times older than the central radio source. We find no evidence in the X-ray spectra or images for significant heating of the X-ray gas by the radio source. We report the detection of an edge-like absorption feature in the spectrum for the central 50 kpc region, which may be due to oxygen-enriched dust grains. The implied mass in metals seen in absorption could have been accumulated by the cooling flow over its lifetime. Combining the results on the X-ray gas density profile with radio measurements of the Faraday rotation measure in 3C295, we estimate the magnetic field strength in the region of the cluster core to be B ~12 \muG.Comment: 27 pages, 16 figs, 5 tables. Accepted for publication in MNRA

The Social Licence for Research:Why care.data Ran Into Trouble

In this article we draw on the concept of a social licence to explain public concern at the introduction of care.data, a recent English initiative designed to extract data from primary care medical records for commissioning and other purposes, including research. The concept of a social licence describes how the expectations of society regarding some activities may go beyond compliance with the requirements of formal regulation; those who do not fulfil the conditions for the social licence (even if formally compliant) may experience ongoing challenge and contestation. Previous work suggests that people's cooperation with specific research studies depends on their perceptions that their participation is voluntary and is governed by values of reciprocity, non-exploitation and service of the public good. When these conditions are not seen to obtain, threats to the social licence for research may emerge. We propose that care.data failed to adequately secure a social licence because of: (i) defects in the warrants of trust provided for care.data, (ii) the implied rupture in the traditional role, expectations and duties of general practitioners, and (iii) uncertainty about the status of care.data as a public good. The concept of a social licence may be useful in explaining the specifics of care.data, and also in reinforcing the more general lesson for policy-makers that legal authority does not necessarily command social legitimacy

Pancreas and islet cell transplantation

Currently, for the patient with type 1 diabetes, a definitive treatment without resorting to the use of exogenous insulin can be achieved only with pancreas or islet cell transplantation. These means of restoring β-cell mass can completely maintain essentially normal long-term glucose homeostasis, although the need for powerful immunosuppressive regimens limits their application to only a subgroup of adult patients. Apart from the shortage of donors that has limited all kinds of transplantation, however, the widespread use of β-cell replacement has been precluded until recently by the drawbacks associated with both organ and islet cell transplantation. Although the study of recurrence of diabetes has generated attention, the fundamental obstacle to pancreas and islet transplantation has been, and remains, the alloimmune response. With a better elucidation of the mechanisms of alloengraftment achieved during the last 3 years, the stage has been set for further advances