Identification of proteins in the postsynaptic density fraction by mass spectrometry

Our understanding of the organization of postsynaptic signaling systems at excitatory synapses has been aided by the identification of proteins in the postsynaptic density (PSD) fraction, a subcellular fraction enriched in structures with the morphology of PSDs. In this study, we have completed the identification of most major proteins in the PSD fraction with the use of an analytical method based on mass spectrometry coupled with searching of the protein sequence databases. At least one protein in each of 26 prominent protein bands from the PSD fraction has now been identified. We found 7 proteins not previously known to be constituents of the PSD fraction and 24 that had previously been associated with the PSD by other methods. The newly identified proteins include the heavy chain of myosin-Va (dilute myosin), a motor protein thought to be involved in vesicle trafficking, and the mammalian homolog of the yeast septin protein cdc10, which is important for bud formation in yeast. Both myosin-Va and cdc10 are threefold to fivefold enriched in the PSD fraction over brain homogenates. Immunocytochemical localization of myosin-Va in cultured hippocampal neurons shows that it partially colocalizes with PSD-95 at synapses and is also diffusely localized in cell bodies, dendrites, and axons. Cdc10 has a punctate distribution in cell bodies and dendrites, with some of the puncta colocalizing with PSD-95. The results support a role for myosin-Va in transport of materials into spines and for septins in the formation or maintenance of spines

Spin Transfer Torque for Continuously Variable Magnetization

We report quantum and semi-classical calculations of spin current and spin-transfer torque in a free-electron Stoner model for systems where the magnetization varies continuously in one dimension.Analytic results are obtained for an infinite spin spiral and numerical results are obtained for realistic domain wall profiles. The adiabatic limit describes conduction electron spins that follow the sum of the exchange field and an effective, velocity-dependent field produced by the gradient of the magnetization in the wall. Non-adiabatic effects arise for short domain walls but their magnitude decreases exponentially as the wall width increases. Our results cast doubt on the existence of a recently proposed non-adiabatic contribution to the spin-transfer torque due to spin flip scattering.Comment: 11 pages, 9 figure

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival : an updated analysis of KEYNOTE-010 trial

Background: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. Patients and methods: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) 50% and 1%; pembrolizumab doses were pooled in this analysis. Results: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS 50%. For TPS 50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS 1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS 50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS 1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. Conclusion: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples

Sea anemones may thrive in a high CO2 world

Increased seawater pCO 2, and in turn 'ocean acidification' (OA), is predicted to profoundly impact marine ecosystem diversity and function this century. Much research has already focussed on calcifying reef-forming corals (Class: Anthozoa) that appear particularly susceptible to OA via reduced net calcification. However, here we show that OA-like conditions can simultaneously enhance the ecological success of non-calcifying anthozoans, which not only play key ecological and biogeochemical roles in present day benthic ecosystems but also represent a model organism should calcifying anthozoans exist as less calcified (soft-bodied) forms in future oceans. Increased growth (abundance and size) of the sea anemone (Anemonia viridis) population was observed along a natural CO 2 gradient at Vulcano, Italy. Both gross photosynthesis (P G) and respiration (R) increased with pCO 2 indicating that the increased growth was, at least in part, fuelled by bottom up (CO 2 stimulation) of metabolism. The increase of P G outweighed that of R and the genetic identity of the symbiotic microalgae (Symbiodinium spp.) remained unchanged (type A19) suggesting proximity to the vent site relieved CO 2 limitation of the anemones' symbiotic microalgal population. Our observations of enhanced productivity with pCO 2, which are consistent with previous reports for some calcifying corals, convey an increase in fitness that may enable non-calcifying anthozoans to thrive in future environments, i.e. higher seawater pCO 2. Understanding how CO 2-enhanced productivity of non- (and less-) calcifying anthozoans applies more widely to tropical ecosystems is a priority where such organisms can dominate benthic ecosystems, in particular following localized anthropogenic stress. © 2012 Blackwell Publishing Ltd

Time--Distance Helioseismology Data Analysis Pipeline for Helioseismic and Magnetic Imager onboard Solar Dynamics Observatory (SDO/HMI) and Its Initial Results

The Helioseismic and Magnetic Imager onboard the Solar Dynamics Observatory (SDO/HMI) provides continuous full-disk observations of solar oscillations. We develop a data-analysis pipeline based on the time-distance helioseismology method to measure acoustic travel times using HMI Doppler-shift observations, and infer solar interior properties by inverting these measurements. The pipeline is used for routine production of near-real-time full-disk maps of subsurface wave-speed perturbations and horizontal flow velocities for depths ranging from 0 to 20 Mm, every eight hours. In addition, Carrington synoptic maps for the subsurface properties are made from these full-disk maps. The pipeline can also be used for selected target areas and time periods. We explain details of the pipeline organization and procedures, including processing of the HMI Doppler observations, measurements of the travel times, inversions, and constructions of the full-disk and synoptic maps. Some initial results from the pipeline, including full-disk flow maps, sunspot subsurface flow fields, and the interior rotation and meridional flow speeds, are presented.Comment: Accepted by Solar Physics topical issue 'Solar Dynamics Observatory

Improving SIEM for critical SCADA water infrastructures using machine learning

Network Control Systems (NAC) have been used in many industrial processes. They aim to reduce the human factor burden and efficiently handle the complex process and communication of those systems. Supervisory control and data acquisition (SCADA) systems are used in industrial, infrastructure and facility processes (e.g. manufacturing, fabrication, oil and water pipelines, building ventilation, etc.) Like other Internet of Things (IoT) implementations, SCADA systems are vulnerable to cyber-attacks, therefore, a robust anomaly detection is a major requirement. However, having an accurate anomaly detection system is not an easy task, due to the difficulty to differentiate between cyber-attacks and system internal failures (e.g. hardware failures). In this paper, we present a model that detects anomaly events in a water system controlled by SCADA. Six Machine Learning techniques have been used in building and evaluating the model. The model classifies different anomaly events including hardware failures (e.g. sensor failures), sabotage and cyber-attacks (e.g. DoS and Spoofing). Unlike other detection systems, our proposed work helps in accelerating the mitigation process by notifying the operator with additional information when an anomaly occurs. This additional information includes the probability and confidence level of event(s) occurring. The model is trained and tested using a real-world dataset

Time-distance analysis of the emerging active region NOAA 10790

We investigate the emergence of Active Region NOAA 10790 by means of time – distance helioseismology. Shallow regions of increased sound speed at the location of increased magnetic activity are observed, with regions becoming deeper at the locations of sunspot pores. We also see a long-lasting region of decreased sound speed located underneath the region of the flux emergence, possibly relating to a temperature perturbation due to magnetic quenching of eddy diffusivity, or to a dense flux tube. We detect and track an object in the subsurface layers of the Sun characterised by increased sound speed which could be related to emerging magnetic-flux and thus obtain a provisional estimate of the speed of emergence of around 1 km s−1

Gauge Field Back-reaction on a Black Hole

The order $\hbar$ fluctuations of gauge fields in the vicinity of a blackhole can create a repulsive antigravity region extending out beyond the renormalized Schwarzschild horizon. If the strength of this repulsive force increases as higher orders in the back-reaction are included, the formation of a wormhole-like object could occur.Comment: 17 pages, three figures available on request, in RevTe