Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding

The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens

CacheZoom: How SGX Amplifies The Power of Cache Attacks

In modern computing environments, hardware resources are commonly shared, and parallel computation is widely used. Parallel tasks can cause privacy and security problems if proper isolation is not enforced. Intel proposed SGX to create a trusted execution environment within the processor. SGX relies on the hardware, and claims runtime protection even if the OS and other software components are malicious. However, SGX disregards side-channel attacks. We introduce a powerful cache side-channel attack that provides system adversaries a high resolution channel. Our attack tool named CacheZoom is able to virtually track all memory accesses of SGX enclaves with high spatial and temporal precision. As proof of concept, we demonstrate AES key recovery attacks on commonly used implementations including those that were believed to be resistant in previous scenarios. Our results show that SGX cannot protect critical data sensitive computations, and efficient AES key recovery is possible in a practical environment. In contrast to previous works which require hundreds of measurements, this is the first cache side-channel attack on a real system that can recover AES keys with a minimal number of measurements. We can successfully recover AES keys from T-Table based implementations with as few as ten measurements.Comment: Accepted at Conference on Cryptographic Hardware and Embedded Systems (CHES '17

Black Holes in Modified Gravity (MOG)

The field equations for Scalar-Tensor-Vector-Gravity (STVG) or modified gravity (MOG) have a static, spherically symmetric black hole solution determined by the mass $M$ with two horizons. The strength of the gravitational constant is $G=G_N(1+\alpha)$ where $\alpha$ is a parameter. A regular singularity-free MOG solution is derived using a nonlinear field dynamics for the repulsive gravitational field component and a reasonable physical energy-momentum tensor. The Kruskal-Szekeres completion of the MOG black hole solution is obtained. The Kerr-MOG black hole solution is determined by the mass $M$, the parameter $\alpha$ and the spin angular momentum $J=Ma$. The equations of motion and the stability condition of a test particle orbiting the MOG black hole are derived, and the radius of the black hole photosphere and the shadows cast by the Schwarzschild-MOG and Kerr-MOG black holes are calculated. A traversable wormhole solution is constructed with a throat stabilized by the repulsive component of the gravitational field.Comment: 14 pages, 3 figures. Upgraded version of paper to match published version in European Physics Journal

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

<p><b>Background:</b> Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.</p> <p><b>Methods and Findings:</b> Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.</p> <p><b>Conclusions:</b> Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.</p&gt

The role of ongoing dendritic oscillations in single-neuron dynamics

The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as temporally local, near-instantaneous mappings from the current input of the cell to its current output, brought about by somatic summation of dendritic contributions that are generated in spatially localized functional compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations, and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought

A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

Emotions in context: examining pervasive affective sensing systems, applications, and analyses

Pervasive sensing has opened up new opportunities for measuring our feelings and understanding our behavior by monitoring our affective states while mobile. This review paper surveys pervasive affect sensing by examining and considering three major elements of affective pervasive systems, namely; “sensing”, “analysis”, and “application”. Sensing investigates the different sensing modalities that are used in existing real-time affective applications, Analysis explores different approaches to emotion recognition and visualization based on different types of collected data, and Application investigates different leading areas of affective applications. For each of the three aspects, the paper includes an extensive survey of the literature and finally outlines some of challenges and future research opportunities of affective sensing in the context of pervasive computing

The relation of steady evaporating drops fed by an influx and freely evaporating drops

We discuss a thin film evolution equation for a wetting evaporating liquid on a smooth solid substrate. The model is valid for slowly evaporating small sessile droplets when thermal effects are insignificant, while wettability and capillarity play a major role. The model is first employed to study steady evaporating drops that are fed locally through the substrate. An asymptotic analysis focuses on the precursor film and the transition region towards the bulk drop and a numerical continuation of steady drops determines their fully non-linear profiles. Following this, we study the time evolution of freely evaporating drops without influx for several initial drop shapes. As a result we find that drops initially spread if their initial contact angle is larger than the apparent contact angle of large steady evaporating drops with influx. Otherwise they recede right from the beginning