Elliptical-core two mode fiber sensors and devices incorporating photoinduced refractive index gratings

Results of experiments performed using germanium-doped, elliptical core, two-mode optical fibers whose sensitivity to strain was spatially varied through the use of chirped, refractive-index gratings permanently induced into the core using Argon-ion laser light are presented. This type of distributed sensor falls into the class of eighted-fiber sensors which, through a variety of means, weight the strain sensitivity of a fiber according to a specified spatial profile. We describe results of a weighted-fiber vibration mode filter which successfully enhances the particular vibration mode whose spatial profile corresponds to the profile of the grating chirp. We report on the high temperature survivability of such grating-based sensors and discuss the possibility of multiplexing more than one sensor within a single fiber

Environmental Effects in Clusters: Modified Far-Infrared--Radio Relations within Virgo Cluster Galaxies

(abridged) We present a study on the effects of the intracluster medium (ICM) on the interstellar medium (ISM) of 10 Virgo cluster spiral galaxies using {\it Spitzer} far-infrared (FIR) and VLA radio continuum imaging. Relying on the FIR-radio correlation within normal galaxies, we use our infrared data to create model radio maps which we compare to the observed radio images. For 6 of our sample galaxies we find regions along their outer edges that are highly deficient in the radio compared with our models. We believe these observations are the signatures of ICM ram pressure. For NGC 4522 we find the radio deficit region to lie just exterior to a region of high radio polarization and flat radio spectral index, although the total 20 cm radio continuum in this region does not appear strongly enhanced. These characteristics seem consistent for other galaxies with radio polarization data in the literature. The strength of the radio deficit is inversely correlated with the time since peak pressure as inferred from stellar population studies and gas stripping simulations, suggesting the strength of the radio deficit is good indicator of the strength of the current ram pressure. We also find that galaxies having {\it local} radio {\it deficits} appear to have {\it enhanced global} radio fluxes. Our preferred physical picture is that the observed radio deficit regions arise from the ICM wind sweeping away cosmic-ray (CR) electrons and the associated magnetic field, thereby creating synchrotron tails as observed for some of our galaxies. We propose that CR particles are also re-accelerated by ICM-driven shocklets behind the observed radio deficit regions which in turn enhances the remaining radio disk brightness.Comment: 19 pages, 10 figures; Astrophysical Journa

Blood and tissue biomarker analysis in dogs with osteosarcoma treated with palliative radiation and intra-tumoral autologous natural killer cell transfer.

We have previously reported radiation-induced sensitization of canine osteosarcoma (OSA) to natural killer (NK) therapy, including results from a first-in-dog clinical trial. Here, we report correlative analyses of blood and tissue specimens for signals of immune activation in trial subjects. Among 10 dogs treated with palliative radiotherapy (RT) and intra-tumoral adoptive NK transfer, we performed ELISA on serum cytokines, flow cytometry for immune phenotype of PBMCs, and PCR on tumor tissue for immune-related gene expression. We then queried The Cancer Genome Atlas (TCGA) to evaluate the association of cytotoxic/immune-related gene expression with human sarcoma survival. Updated survival analysis revealed five 6-month survivors, including one dog who lived 17.9 months. Using feeder line co-culture for NK expansion, we observed maximal activation of dog NK cells on day 17-19 post isolation with near 100% expression of granzyme B and NKp46 and high cytotoxic function in the injected NK product. Among dogs on trial, we observed a trend for higher baseline serum IL-6 to predict worse lung metastasis-free and overall survival (P = 0.08). PCR analysis revealed low absolute gene expression of CD3, CD8, and NKG2D in untreated OSA. Among treated dogs, there was marked heterogeneity in the expression of immune-related genes pre- and post-treatment, but increases in CD3 and CD8 gene expression were higher among dogs that lived > 6 months compared to those who did not. Analysis of the TCGA confirmed significant differences in survival among human sarcoma patients with high and low expression of genes associated with greater immune activation and cytotoxicity (CD3e, CD8a, IFN-γ, perforin, and CD122/IL-2 receptor beta). Updated results from a first-in-dog clinical trial of palliative RT and autologous NK cell immunotherapy for OSA illustrate the translational relevance of companion dogs for novel cancer therapies. Similar to human studies, analyses of immune markers from canine serum, PBMCs, and tumor tissue are feasible and provide insight into potential biomarkers of response and resistance

Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.

Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project. The International Mouse Phenotyping Consortium (IMPC) database (data release 10.0) was interrogated for all mouse strains with integument abnormalities, which were then cross-referenced individually to identify knockouts with concomitant ocular abnormalities attributed to the same targeted gene deletion. The search yielded 307 knockout strains from unique genes with integument abnormalities, 226 of which have not been previously associated with oculocutaneous conditions. Of the 307 knockout strains with integument abnormalities, 52 were determined to have ocular changes attributed to the targeted deletion, 35 of which represent novel oculocutaneous genes. Some examples of various integument abnormalities are shown, as well as two examples of knockout strains with oculocutaneous phenotypes. Each of the novel genes provided here are potentially relevant to the pathophysiology of human integumentary, or oculocutaneous conditions, such as albinism, phakomatoses, or other multi-system syndromes. The novel genes reported here may implicate molecular pathways relevant to these human diseases and may contribute to the discovery of novel therapeutic targets

Limited Lifespan of Fragile Regions in Mammalian Evolution

An important question in genome evolution is whether there exist fragile regions (rearrangement hotspots) where chromosomal rearrangements are happening over and over again. Although nearly all recent studies supported the existence of fragile regions in mammalian genomes, the most comprehensive phylogenomic study of mammals (Ma et al. (2006) Genome Research 16, 1557-1565) raised some doubts about their existence. We demonstrate that fragile regions are subject to a "birth and death" process, implying that fragility has limited evolutionary lifespan. This finding implies that fragile regions migrate to different locations in different mammals, explaining why there exist only a few chromosomal breakpoints shared between different lineages. The birth and death of fragile regions phenomenon reinforces the hypothesis that rearrangements are promoted by matching segmental duplications and suggests putative locations of the currently active fragile regions in the human genome

Next Generation Very Large Array Memo No. 5 Science Working Groups Project Overview

We summarize the design, capabilities, and some of the priority science goals of a next generation Very Large Array (ngVLA). The ngVLA is an interferometric array with 10x larger effective collecting area and 10x higher spatial resolution than the current VLA and the Atacama Large Millimeter Array (ALMA), optimized for operation in the wavelength range 0.3cm to 3cm. The ngVLA opens a new window on the Universe through ultra-sensitive imaging of thermal line and continuum emission down to milliarcecond resolution, as well as unprecedented broad band continuum polarimetric imaging of non-thermal processes. The continuum resolution will reach 9mas at 1cm, with a brightness temperature sensitivity of 6K in 1 hour. For spectral lines, the array at 1" resolution will reach 0.3K surface brightness sensitivity at 1cm and 10 km s^(-1) spectral resolution in 1 hour. These capabilities are the only means with which to answer a broad range of critical scientific questions in modern astronomy, including direct imaging of planet formation in the terrestrial-zone, studies of dust-obscured star formation and the cosmic baryon cycle down to pc-scales out to the Virgo cluster, making a cosmic census of the molecular gas which fuels star formation back to first light and cosmic reionization, and novel techniques for exploring temporal phenomena from milliseconds to years. The ngVLA is optimized for observations at wavelengths between the superb performance of ALMA at submm wavelengths, and the future SKA1 at few centimeter and longer wavelengths. This memo introduces the project. The science capabilities are outlined in a parallel series of white papers. We emphasize that this initial set of science goals are simply a starting point for the project. We invite comment on these programs, as well as new ideas, through our public forum link on the ngVLA web page: https://science.nrao.edu/futures/ngvl

Interventions and approaches to integrating HIV and mental health services: a systematic review.

BACKGROUND: The frequency in which HIV and AIDS and mental health problems co-exist, and the complex bi-directional relationship between them, highlights the need for effective care models combining services for HIV and mental health. Here, we present a systematic review that synthesizes the literature on interventions and approaches integrating these services. METHODS: This review was part of a larger systematic review on integration of services for HIV and non-communicable diseases. Eligible studies included those that described or evaluated an intervention or approach aimed at integrating HIV and mental health care. We searched multiple databases from inception until October 2015, independently screened articles identified for inclusion, conducted data extraction, and assessed evaluative papers for risk of bias. RESULTS: Forty-five articles were eligible for this review. We identified three models of integration at the meso and micro levels: single-facility integration, multi-facility integration, and integrated care coordinated by a non-physician case manager. Single-site integration enhances multidisciplinary coordination and reduces access barriers for patients. However, the practicality and cost-effectiveness of providing a full continuum of specialized care on-site for patients with complex needs is arguable. Integration based on a collaborative network of specialized agencies may serve those with multiple co-morbidities but fragmented and poorly coordinated care can pose barriers. Integrated care coordinated by a single case manager can enable continuity of care for patients but requires appropriate training and support for case managers. Involving patients as key actors in facilitating integration within their own treatment plan is a promising approach. CONCLUSION: This review identified much diversity in integration models combining HIV and mental health services, which are shown to have potential in yielding positive patient and service delivery outcomes when implemented within appropriate contexts. Our review revealed a lack of research in low- and middle- income countries, and was limited to most studies being descriptive. Overall, studies that seek to evaluate and compare integration models in terms of long-term outcomes and cost-effectiveness are needed, particularly at the health system level and in regions with high HIV and AIDS burden

Continuous Deployment Transitions at Scale

Predictable, rapid, and data-driven feature rollout; lightning-fast; and automated fix deployment are some of the benefits most large software organizations worldwide are striving for. In the process, they are transitioning toward the use of continuous deployment practices. Continuous deployment enables companies to make hundreds or thousands of software changes to live computing infrastructure every day while maintaining service to millions of customers. Such ultra-fast changes create a new reality in software development. Over the past four years, the Continuous Deployment Summit, hosted at Facebook, Netflix, Google, and Twitter has been held. Representatives from companies like Cisco, Facebook, Google, IBM, Microsoft, Netflix, and Twitter have shared the triumphs and struggles of their transition to continuous deployment practices—each year the companies press on, getting ever faster. In this chapter, the authors share the common strategies and practices used by continuous deployment pioneers and adopted by newcomers as they transition and use continuous deployment practices at scale

The structure of the nuclear stellar cluster of the Milky Way

We present high-resolution seeing limited and AO NIR imaging observations of the stellar cluster within about one parsec of Sgr A*, the massive black hole at the centre of the Milky Way. Stellar number counts and the diffuse background light density were extracted from these observations in order to examine the structure of the nuclear stellar cluster.Our findings are as follows: (a) A broken-power law provides an excellent fit to the overall structure of the GC nuclear cluster. The power-law slope of the cusp is $\Gamma=0.19\pm0.05$, the break radius is $R_{\rm break} = 6.0'' \pm 1.0''$ or $0.22\pm0.04$ pc, and the cluster density decreases with a power-law index of $\Gamma=0.75\pm0.1$ outside of $R_{\rm break}$. (b) Using the best velocity dispersion measurements from the literature, we derive higher mass estimates for the central parsec than assumed until now. The inferred density of the cluster at the break radius is $2.8\pm1.3\times 10^{6} {\rm M_{\odot} pc^{-3}}$. This high density agrees well with the small extent and flat slope of the cusp. Possibly, the mass of the stars makes up only about 50% of the total cluster mass. (c) Possible indications of mass segregation in the cusp are found (d) The cluster appears not entirely homogeneous. Several density clumps are detected that are concentrated at projected distances of $R=3''$ and $R=7''$ from Sgr A*.(e) There appears to exist an under-density of horizontal branch/red clump stars near $R=5''$, or an over-density of stars of similar brightness at $R=3''$ and $R=7''$. (f) The extinction map in combination with cometary-like features in an L'-band image may provide support for the assumption of an outflow from Sgr A*.Comment: accepted for publication by A&A; please contact first author for higher quality figure

Transmission of toxigenic Corynebacterium diphtheriae by a fully immunised resident returning from a visit to West Africa, United Kingdom, 2017.

In early 2017, a United Kingdom (UK)-born person in their 20s presented with a skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last received a diphtheria-containing vaccine in 2013, completing the recommended course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae. Real-time PCR ascertained the species and presence of the diphtheria toxin gene. An Elek test confirmed toxigenicity. The isolate was macrolide sensitive and penicillin resistant. The local Public Health England (PHE) Health Protection Team obtained the patient's clinical history and traced contacts to inform appropriate public health action. One close contact (in their early 80s with uncertain immunisation status who had not recently travelled) had a positive throat swab for toxigenic C. diphtheriae and reported a history of mild coryzal symptoms. Multilocus sequence typing revealed that strains from the index case and contact had Sequence Type 463. Diphtheria is extremely rare in the UK due to high vaccine coverage and this is the first documented transmission in 30 years. Clinicians and laboratory staff should remain highly suspicious of lesions in overseas travellers, even when patients are fully vaccinated. Older individuals who might not have completed a full immunisation course may have higher diphtheria susceptibility