An AGN Identification for 3EG J2006-2321

We present a multiwavelength analysis of the high-energy gamma-ray source 3EG J2006-2321. The flux of this source above 100 MeV is shown to be variable on time scales of days and months. Optical observations and careful examination of archived radio data indicate that its radio counterpart is PMN J2005-2310, a flat-spectrum radio quasar with a 5-GHz flux density of 260 mJy. Study of the $V=18.7$ optical counterpart indicates a redshift of 0.833 and variable linear polarization. No X-ray source has been detected near the position of PMN J2005-2310, but an X-ray upper limit is derived from ROSAT data. This upper limit provides for a spectral energy distribution with global characteristics similar to those of known gamma-ray blazars. Taken together, these data indicate that 3EG J2006-2321, listed as unidentified in the 3rd EGRET Catalog, is a member of the blazar class of AGN. The 5-GHz radio flux density of this blazar is the lowest of the 68 EGRET-detected AGN. The fact that EGRET has detected such a source has implications for unidentified EGRET sources, particularly those at high latitudes ($|b|>30^{\circ}$), many of which may be blazars.Comment: 22 pages, 6 figures. To appear in ApJ v569 n1, 10 April 200

Feedback inhibition of L1 and alu retrotransposition through altered double strand break repair kinetics

<p>Abstract</p> <p>Background</p> <p>Cells adapt to various chronic toxic exposures in a multitude of ways to minimize further damage and maximize their growth potential. Expression of L1 elements in the human genome can be greatly deleterious to cells, generating numerous double strand breaks (DSBs). Cells have been reported to respond to chronic DSBs by altering the repair of these breaks, including increasing the rate of homology independent DSB repair. Retrotransposition is strongly affected by proteins involved in DSB repair. Therefore, L1 expression has the potential to be a source of chronic DSBs and thus bring about the changes in cellular environment that could ultimately restrict its own retrotransposition.</p> <p>Results</p> <p>We demonstrate that constitutive L1 expression leads to quicker DSB repair and decreases in the retrotransposition potential of L1 and other retrotransposons dependent on L1 expression for their mobility. This cellular adaptation results in reduced sensitivity to L1 induced toxicity. These effects can be induced by constitutive expression of the functional L1 ORF2 alone, but not by the constitutive expression of an L1 open reading frame 2 with mutations to its endonuclease and reverse transcriptase domains. This adaptation correlates with the relative activity of the L1 introduced into the cells.</p> <p>Conclusions</p> <p>The increased number of DSBs resulting from constitutive expression of L1 results in a more rapid rate of repair. The cellular response to this L1 expression also results in attenuation of retrotransposition and reduced sensitivity of the cells to negative consequences of L1 ORF2 expression. The influence does not appear to be through RNA interference. We believe that the increased rate of DSB repair is the most likely cause of the attenuation of retrotransposition. These alterations act as a fail safe mechanism that allows cells to escape the toxicity associated with the unchecked L1 expression. This gives cells that overexpress L1, such as tumor cells, the ability to survive the high levels of expression. However, the increased rate of break repair may come at the cost of accuracy of repair of the lesion, resulting in increased genomic instability.</p

Anomalous thermal expansion in 1D transition-metal cyanides: what makes the novel trimetallic cyanide Cu1/3Ag1/3Au1/3CN behave differently?

The structural dynamics of a quasi-one-dimensional (1D) mixed-metal cyanide, Cu1/3Ag1/3Au1/3CN, with intriguing thermal properties is explored. All the current known related compounds with straight-chain structures, such as group 11 cyanides CuCN, AgCN, AuCN and bimetallic cyanides MxM’1-xCN (M, M’ = Cu, Ag, Au), exhibit 1D negative thermal expansion (NTE) along the chains and positive thermal expansion (PTE) perpendicular to them. Cu1/3Ag1/3Au1/3CN exhibits similar PTE perpendicular to the chains, however PTE, rather than NTE, is also observed along the chains. In order to understand the origin of this unexpected behavior, inelastic neutron scattering (INS) measurements were carried out, underpinned by lattice-dynamical density-functional-theory (DFT) calculations. Synchrotron-based pair-distribution-function (PDF) analysis and 13C solid-state nuclear-magnetic-resonance (SSNMR) measurements were also performed to build an input structural model for the lattice dynamical study. The results indicate that transverse motions of the metal ions are responsible for the PTE perpendicular to the chains, as is the case for the related group 11 cyanides. However NTE along the chain due to the tension effect of these transverse motions is not observed. As there are different metal-to-cyanide bond lengths in Cu1/3Ag1/3Au1/3CN, the metals in neighboring chains cannot all be truly co-planar in a straight-chain model. For this system, DFT-based phonon calculations predict small PTE along the chain due to low-energy chain-slipping modes induced by a bond-rotation effect on the weak metallophilic bonds. However the observed PTE is greater than that predicted with the straight-chain model. Small bends in the chain to accommodate truly co-planar metals provide an alternative explanation for thermal behavior. These would mitigate the tension effect induced by the transverse motions of the metals and, as temperature increases and the chains move further apart, a straightening could occur resulting in the observed PTE. This hypothesis is further supported by unusual evolution in the phonon spectra, which suggest small changes in local symmetry with temperature

A cost-reducing extracorporeal membrane oxygenation (ECMO) program model: a single institution experience.

BACKGROUND: The worldwide demand for ECMO support has grown. Its provision remains limited due to several factors (high cost, complicated technology, lack of expertise) that increase healthcare cost. Our goal was to assess if an intensive care unit (ICU)-run ECMO model without continuous bedside perfusionists would decrease costs while maintaining patient safety and outcomes. METHOD: A new ECMO program was implemented in 2010, consisting of dedicated ICU multidisciplinary providers (ICU-registered nurses, mid-level providers and intensivists). In year one, we introduced an education platform, new technology and dedicated space. In year two, continuous bedside monitoring by perfusionists was removed and new management algorithms designating multidisciplinary providers as first responders were established. The patient safety and cost benefit from the removal of the continuous bedside monitoring of the perfusionists of this new ECMO program was retrospectively reviewed and compared. RESULTS: During the study period, 74 patients (28 patients in year 1 and 46 patients in year 2) were placed on ECMO (mean days: 8 ± 5.7). The total annual hospital expenditure for the ECMO program was significantly reduced in the new model ($234,000 in year 2 vs.$600,264 in year 1), showing a 61% decrease in cost. This cost decrease was attributed to a decreased utilization of perfusion services and the introduction of longer lasting and more efficient ECMO technology. We did not find any significant changes in registered nurse ratios or any differences in outcomes related to ICU safety events. CONCLUSION: We demonstrated that the ICU-run ECMO model managed to lower hospital cost by reducing the cost of continuous bedside perfusion support without a change in outcomes

Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect mRNA expression of hundreds of putative myokines that may underlie the endocrine functions of skeletal muscle. We identify candidate genes that may drive tissue specialization, including Smarca4, Vegfa, and Myostatin. By demonstrating the intrinsic diversity of skeletal muscles, these data provide a resource for studying the mechanisms of tissue specialization

Privacy Side Channels in Machine Learning Systems

Most current approaches for protecting privacy in machine learning (ML) assume that models exist in a vacuum, when in reality, ML models are part of larger systems that include components for training data filtering, output monitoring, and more. In this work, we introduce privacy side channels: attacks that exploit these system-level components to extract private information at far higher rates than is otherwise possible for standalone models. We propose four categories of side channels that span the entire ML lifecycle (training data filtering, input preprocessing, output post-processing, and query filtering) and allow for either enhanced membership inference attacks or even novel threats such as extracting users' test queries. For example, we show that deduplicating training data before applying differentially-private training creates a side-channel that completely invalidates any provable privacy guarantees. Moreover, we show that systems which block language models from regenerating training data can be exploited to allow exact reconstruction of private keys contained in the training set -- even if the model did not memorize these keys. Taken together, our results demonstrate the need for a holistic, end-to-end privacy analysis of machine learning

Last interglacial (MIS 5e) sea-level determined from a tectonically stable, far-field location, Eyre Peninsula, southern Australia

The last interglacial maximum (Marine Isotope Substage 5e [MIS 5e], 128¿116 ka) is a distinctive event in recent Earth history. Shoreline successions of this age are important for calibrating climate models and defining the overall behaviour of the crust¿mantle system to fluctuating ice and ocean-water volumes. In a global context, the recently intensified interest in last interglacial shoreline successions has revealed considerable variability in the magnitude of sea-level rise during this time interval and highlighted the need to examine paleosea-level evidence from tectonically stable, far-field settings. Situated in the far-field of continental ice sheets and on the tectonically stable Gawler Craton, the 300 km coastal sector of western Eyre Peninsula between Fowlers Bay and Lake Newland in southern Australia represents an important region for defining the glacio-eustatic (ice-equivalent) sea-level attained during the last interglacial maximum based on the relative sea-level observations from this region. Low-energy, shoaling upward, peritidal bioclastic carbonate successions of the last interglacial (locally termed Glanville Formation) formed within back-barrier, estuarine¿lagoonal environments in the lee of eolianite barrier complexes (locally termed Bridgewater Formation) along this coastline. The well-preserved shelly successions (coquinas) contain diverse molluscan fossil assemblages including species no longer living in the coastal waters of South Australia (e.g. the Sydney cockle Anadara trapezia and the benthic foraminifer Marginopora vertebralis). The extent of amino acid racemisation (a measure of fossil age based on increasing d/l value) in a range of species, and in particular A. trapezia and Katelysia sp., confirms the time equivalence of the isolated embayment-fill successions, correlated with the informal type section of the Glanville Formation at Dry Creek, north of Adelaide. Preliminary U-series analyses on A. trapezia also suggest a correlation with the last interglacial maximum, but further highlight the complexity in dating fossil molluscs by the U-series method in view of their open-system behaviour. The shelly successions of the Glanville Formation occur at elevations higher than attained by sea-level in the current, Holocene interglacial. A higher sea-level of between 2.1 ± 0.5 and 4 ± 0.5 m above present sea-level is inferred for the last interglacial maximum (MIS 5e) along this coastline based on the elevation of sedimentary successions host to the shallow subtidal¿intertidal fossil molluscs Katelysia sp., and Anadara trapezia. The paleosea-level observations place a lower limit on the sea-level attained during the last interglacial maximum and suggest that caution be exercised in the definition of the upper limit of sea-level during this interglacial

Comparing plasma and faecal measures of steroid hormones in Adelie penguins Pygoscelis adeliae

Physiological measurements of both stress and sex hormones are often used to estimate the consequences of natural or human-induced change in ecological studies of various animals. Different methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross-validated to ensure that they correlate. We directly compared faecal and plasma hormone measurements for the first time in a wild free-living species, the Adelie penguin (Pygoscelis adeliae). Blood and faecal samples were simultaneously collected from individual penguins for comparison and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher mean corticosterone concentrations than females, but the difference was only statistically significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males, perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma ‘snapshot’ concentration. Our data indicate that faecal sampling appears more suitable for assessing baseline hormone concentrations, whilst plasma sampling may best define immediate responses to environmental events. Consequently, future studies should ensure that they select the most appropriate matrix and method of hormone measurement to answer their research questions

Use of Heart Rate Index to Predict Oxygen Uptake – A Validation Study

International Journal of Exercise Science 13(7): 1705-1717, 2020. An equation that uses heart rate index (HRI) defined as HR/HRrest to predict oxygen uptake (VO2) in METs (e.g., METs = 6 × HRI ‒ 5) has been developed retrospectively from aggregate data of 60 published studies. However, the prediction error of this model as used by an individual has not been established. Therefore, the purpose of this study was to examine the predictive validity of the HRI equation by comparing submaximal and maximal VO2 predicted by the equation (VO2-Pred) with that measured by indirect calorimetry (VO2-Meas). Sixty healthy adults (age 20.5 ± 2.4 yr., body mass 69.4 ± 13.4 kg, height 1.7 ± 0.1 m) underwent a VO2max test and an experimental trial consisting of a 15-min resting measurement and three successive 10-min treadmill exercise bouts performed at 40%, 60% and 80% of VO2max. VO2 and HR were recorded during both the submaximal and maximal exercises and used to obtain VO2-Pred and VO2-Meas for each intensity and for VO2max. Validation was carried out by paired t-test, regression analysis, and Bland-Altman plots. A modest but significant (p \u3c 0.05) correlation was observed between VO2-Meas and VO2-Pred at 40% (r = 0.58), 60% (r = 0.53), and 80% of VO2max (r = 0.56) and at VO2max (r = 0.50). No differences between VO2-Pred and VO2-Meas were found at 40% (5.53 ± 1.21 vs. 5.28 ± 0.98 METs, respectively) of VO2max, but VO2-Pred was higher (p \u3c 0.05) than VO2-Meas at 60% (8.42 ± 1.77 vs. 7.96 ± 1.39 METs, respectively) and 80% (10.79 ± 2.13 vs. 10.29 ± 1.81 METs, respectively) of VO2max. In contrast, VO2-Pred was lower (p \u3c 0.05) than VO2-Meas at VO2max (12.32 ± 2.30 vs. 13.38 ± 2.24 METs, respectively). Standard errors of the estimate were 0.81, 1.20, 1.54, and 1.97 METs at 40%, 60%, 80% of VO2max and at VO2max, respectively. These results suggest that further investigation aimed to establish the accuracy of using HRI to predict VO2 is warranted

Fluid intake and clinicopathological characteristics of bladder cancer:the West Midlands Bladder Cancer Prognosis Programme (BCPP)

Objective Between 10 and 20% of bladder cancer patients who are diagnosed with nonmuscle-invasive bladder cancer will progress to muscle-invasive disease. Risk of progression depends on several factors at diagnosis including age, tumour stage, grade, size and number, and the presence or absence of carcinoma in situ. Fluid intake may be related to these factors. Methods Data of 1123 participants from the West Midlands Bladder Cancer Prognosis Programme were used. Data collection was via a semistructured questionnaire, and case report forms were used to collect clinicopathological data. Fluid intake was measured for six main categories: alcoholic fluids, hot fluids, fruit fluids, milk, fizzy drinks, and water, and converted into quintile variables. Multilevel mixed-effects linear regression was performed for every beverage category per clinicopathological variable and corrected for age, gender, and smoking status. Results Age at diagnosis was distributed differently amongst those in different total fluid intake quintiles (predicted means 71.5, 70.9, 71.5, 69.9, and 67.4, respectively) and showed a significant inverse linear trend in alcohol (P <0.01), hot fluids (P <0.01), and total fluids intake (P <0.01), in nonmuscle-invasive bladder cancer patients. Conclusion Our results suggest an inverse association for alcohol intake and total fluid intake with age at diagnosis. These results should be confirmed by future studies, alongside a possible (biological) mechanism that could influence tumour growth, and the effect of micturition frequency