MCSH, a lock with the standard interface

The MCS lock of Mellor-Crummey and Scott (1991), 23 pages. is a very efficient first-come first-served mutual-exclusion algorithm that uses the atomic hardware primitives fetch-and-store and compare-and-swap. However, it has the disadvantage that the calling thread must provide a pointer to an allocated record. This additional parameter violates the standard locking interface, which has only the lock as a parameter. Hence, it is impossible to switch to MCS without editing and recompiling an application that uses locks.This article provides a variation of MCS with the standard interface, which remains FCFS, called MCSH. One key ingredient is to stack allocate the necessary record in the acquire procedure of the lock, so its life-time only spans the delay to enter a critical section. A second key ingredient is communicating the allocated record between the acquire and release procedures through the lock to maintain the standard locking interface. Both of these practices are known to practitioners, but our solution combines them in a unique way. Furthermore, when these practices are used in prior papers, their correctness is often argued informally. The correctness of MCSH is verified rigorously with the proof assistant PVS, and experiments are run to compare its performance with MCS and similar locks

Процесс фтороаммонийной переработки высокофтористых бериллиевых концентратов

В работе приведено научное обоснование способа фтороаммонийной переработки высокофтористого бериллиевого концентрата, предложены технологические режимы переработки бериллиевого концентрата. Исследование технологического процесса и определение режимов, обеспечивающих экономически эффективную переработку концентратов, проводили на специально изготовленной опытной установке. В результате работы создана и апробирована принципиальная схема переработки бериллиевых концентратов, разработано аппаратурное оформление процесса. Приведено технико-экономическое обоснование технологии.The scientific substantiation of the processing of high-fluoride beryllium concentrates by ammonium fluoride is given in graduation thesis. Technological conditions of beryllium concentrate processing are proposed. The research of the technological process and determination of the conditions providing cost-effective processing of concentrates was carried out on a specially manufactured pilot plant. As a result of the work, a basic scheme for the processing of beryllium concentrates was developed and approved, and the hardware design of the process was developed. The feasibility study of technology is shown

The BBCH system to coding the phenological growth stages of plants – history and publications –

Die Entwicklungsstadien der wichtigsten Kulturpflanzen wurden in den vergangenen 19 Jahren von zahlreichen Wissenschaftlern nach den Prinzipien der erweiterten BBCH-Skala beschrieben. Die BBCH-Skalen sind inzwischen weltweit bekannt und werden von Wissenschaft, Administration und Praxis in Landwirtschaft und Gartenbau ebenso genutzt, wie in der Phänologie als integrative Wissenschaft im Bereich Umwelt, Meteorologie und Klimatologie. Diese Tatsache weist darauf hin, dass Zielsetzung und Hoffnung, die seit dem Beginn der Arbeit damit verbunden waren, sich erfüllt haben. Die BBCH-Skalen haben sich als hilfreich und praktisch erwiesen. Das Ziel, die Harmonisierung in der Anwendung von Dezimalcodes für die Beschreibung der phänologischen Entwicklungsstadien von Kulturpflanzen und Unkräutern herbeizuführen, wurde erreicht. Sie erfüllten auch die Hoffnung der Initiatoren, damit zur Verbesserung der internationalen agrarwissenschaftlichen und interdisziplinären Kommunikation beizutragen. In der vorliegenden Arbeit soll die Geschichte der BBCH-Skalen aufgezeigt werden, weil diese Einblick in die Hintergründe ihrer Entstehung und Entwicklung erlaubt. Alle Original-Publikationen werden mit ihren Literaturquellen zusammenfassend dargelegt. Die Arbeit soll die unterschiedliche Nutzung der BBCH-Skalen in den verschiedenen wissenschaftlichen Disziplinen dokumentieren. Es soll deutlich werden, dass der weltweite Erfolg der BBCH-Skalen vielen Wissenschaftlern rund um den Globus zu verdanken ist.The growth stages of development of many cultivated plants have been described by numerous scientists according to the principles of the extended BBCH scale within the last 19 years. The BBCH scales are now well- known worldwide and are used by research, administration and practise in agriculture and horticulture, as in the phenology as an integrative science in environment, meteorology and climatology. This fact indicates that the basic objectives and hope have been reached, justifying the practical approach taken by the authors of this scale. The BBCH scale is a contribution to improve the communication between different groups of scientists and to allow the interchange of data and scientific results in a transparent way. The BBCH scales have turned out helpful and practical. The aim to cause the harmonisation in the application of decimal codes for the description of the phenological growth stages of plants and weeds was reached. They also fulfilled the hope of the initiators to contribute with it to the improvement of the international agrarian-scientific and interdisciplinary communication. This paper will describe the history and background of the BBCH scales. The original publications are described and explained with reference of the original literature sources. The paper will describe the different area of use of the scales and list the different scientific disciplines using them. The worldwide success of the BBCH scales is the work of many scientists around the globe

Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study

Background Patients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known. Methods The phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied. Results Patients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38–0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27–0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53–0.98], P = 0.04). Conclusion Apabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS

Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins

Cotranslational protein folding can facilitate rapid formation of functional structures. However, it might also cause premature assembly of protein complexes, if two interacting nascent chains are in close proximity. By analyzing known protein structures, we show that homomeric protein contacts are enriched towards the C-termini of polypeptide chains across diverse proteomes. We hypothesize that this is the result of evolutionary constraints for folding to occur prior to assembly. Using high-throughput imaging of protein homomers in vivo in E. coli and engineered protein constructs with N- and C-terminal oligomerization domains, we show that, indeed, proteins with C-terminal homomeric interface residues consistently assemble more efficiently than those with N-terminal interface residues. Using in vivo, in vitro and in silico experiments, we identify features that govern successful assembly of homomers, which have implications for protein design and expression optimization

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences and Countermeasures.

Circadian (∼ 24 hour) timing systems pervade all kingdoms of life, and temporally optimize behaviour and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behaviour and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these too are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally-driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioural and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The reference site collaborative network of the european innovation partnership on active and healthy ageing

Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs