Wear behaviour of laser cladded Ni-based WC composite coating for Inconel hot extrusion : practical challenges and effectiveness

In forging, tooling costs make up a significant percentage of the total manufacturing cost. To combat tool failure, forging dies can be manufactured using or including layers of high wear-resistant alloys. The present work compares the manufacturing process challenges and wear response of traditional Nitriding to laser cladding using Ni-based WC on an H13 substrate for IN718 extrusion. The results have shown that machining of NiCrSiB + WC matrix material is problematic, both with regards to cutting tool wear and achievable surface finish. Assessment of pre- and post-extrusion Nitrided H13 and NiCrSiB + 30%WC laser clad dies shows more significant wear features in the case of the additively coated die. Crack formation and surface discontinuities attributed to the effects of material porosity and die heating are also discussed

An Analysis of Load Imbalance in Scale-out Data Serving

Despite the natural parallelism across lookups, performance of distributed key-value stores is often limited due to load imbalance induced by heavy skew in the popularity distribution of the dataset. To avoid violating service level objectives expressed in terms of tail latency, systems tend to keep server utilization low and organize the data in micro-shards, which in turn provides units of migration and replication for the purpose of load balancing. These techniques reduce the skew, but incur additional monitoring, data replication and consistency maintenance overheads. This work shows that the trend towards extreme scale-out will further exacerbate the skew-induced load imbalance, and hence the overhead of migration and replication

ParaLog: enabling and accelerating online parallel monitoring of multithreaded applications

Instruction-grain lifeguards monitor the events of a running application at the level of individual instructions in order to identify and help mitigate application bugs and security exploits. Because such lifeguards impose a 10-100X slowdown on existing platforms, previous studies have proposed hardware designs to accelerate lifeguard processing. However, these accelerators are either tailored to a specific class of lifeguards or suitable only for monitoring singlethreaded programs. We present ParaLog, the first design of a system enabling fast online parallel monitoring of multithreaded parallel applications. ParaLog supports a broad class of software-defined lifeguards. We show how three existing accelerators can be enhanced to support online multithreaded monitoring, dramatically reducing lifeguard overheads. We identify and solve several challenges in monitoring parallel applications and/or parallelizing these accelerators, including (i) enforcing inter-thread data dependences, (ii) dealing with inter-thread effects that are not reflected in coherence traffic, (iii) dealing with unmonitored operating system activity, and (iv) ensuring lifeguards can access shared metadata with negligible synchronization overheads. We present our system design for both Sequentially Consistent and Total Store Ordering processors. We implement and evaluate our design on a 16 core simulated CMP, using benchmarks from SPLASH-2 and PARSEC and two lifeguards: a data-flow tracking lifeguard and a memory-access checker lifeguard. Our results show that (i) our parallel accelerators improve performance by 2-9X and 1.13-3.4X for our two lifeguards, respectively, (ii) we are 5-126X faster than the time-slicing approach required by existing techniques, and (iii) our average overheads for applications with eight threads are 51% and 28% for the two lifeguards, respectively

In vitro effects of zinc on the cytokine production from peripheral blood mononuclear cells in patients with zinc allergy.

Metals, such as nickel, cobalt, chromium and zinc, are ubiquitous in the environment. Systemic reactions, including hand dermatitis and generalized eczematous reactions, can be caused by the dietary ingestion of metals. In this study, we aimed to determine whether the cytokine production from peripheral blood mononuclear cells (PBMCs) obtained from zinc allergy patients can be used as a sensitive marker to investigate zinc-allergic contact dermatitis. The diagnosis of sensitivity to metal was made based on the results of a metal patch test. The PBMCs were stimulated with various concentrations (5-100 μM) of zinc sulfate (ZnSO4) for 24 h. The culture supernatants were collected and analyzed using ELISA for measurement of the cytokine production. The levels of IFN-γ, TNF-α, IL-1β, IL-5, IL-13 and MIF were significantly higher in the zinc-allergic patients (n = 5) than in the healthy controls (n = 5) at 100 μM of ZnSO4 stimulation. Although, patch testing is considered as standard test to diagnose metal allergy but false-positive and -negative reactions may limit its use in conditions of existing dermatitis. Therefore, this study suggest that in support of patch testing the determination of cytokine production using PBMCs cultures would be helpful for making an early diagnosis of such conditions

Scopolamine Administration Modulates Muscarinic, Nicotinic and NMDA Receptor Systems

Studies on the effect of scopolamine on memory are abundant but so far only regulation of the muscarinic receptor (M1) has been reported. We hypothesized that levels of other cholinergic brain receptors as the nicotinic receptors and the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory formation, would be modified by scopolamine administration

Effectiveness of self-compassion related therapies:A systematic review and meta-analysis

This systematic review and meta-analysis investigated whether self-compassion-related therapies, including compassion-focussed therapy, mindfulness-based cognitive therapy and acceptance and commitment therapy, are effective in promoting self-compassion and reducing psychopathology in clinical and subclinical populations. A total of 22 randomised controlled trials met inclusion criteria, with data from up to 1172 individuals included in each quantitative analysis. Effect sizes were the standardised difference in change scores between intervention and control groups. Results indicated that self-compassion-related therapies produced greater improvements in all three outcomes examined: self-compassion (g = 0.52, 95% CIs [0.32, 0.71]), anxiety (g = 0.46, 95% CIs [0.25, 0.66]) and depressive symptoms (g = 0.40, 95% CIs [0.23, 0.57]). However, when analysis was restricted to studies that compared self-compassion-related therapies to active control conditions, change scores were not significantly different between the intervention and control groups for any of the outcomes. Patient status (clinical vs. subclinical) and type of therapy (explicitly compassion-based vs. other compassion-related therapies, e.g. mindfulness) were not moderators of outcome. There was some evidence that self-compassion-related therapies brought about greater improvements in the negative than the positive subscales of the Self-Compassion Scale, although a statistical comparison was not possible. The methodological quality of studies was generally good, although risk of performance bias due to a lack of blinding of participants and therapists was a concern. A narrative synthesis found that changes in self-compassion and psychopathology were correlated in several studies, but this relationship was observed in both intervention and control groups. Overall, this review presents evidence that third-wave therapies bring about improvements in self-compassion and psychopathology, although not over and beyond other interventions

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric