Towards optimising distributed data streaming graphs using parallel streams

Modern scientific collaborations have opened up the op-portunity of solving complex problems that involve multi-disciplinary expertise and large-scale computational experi-ments. These experiments usually involve large amounts of data that are located in distributed data repositories running various software systems, and managed by different organi-sations. A common strategy to make the experiments more manageable is executing the processing steps as a work-flow. In this paper, we look into the implementation of fine-grained data-flow between computational elements in a scientific workflow as streams. We model the distributed computation as a directed acyclic graph where the nodes rep-resent the processing elements that incrementally implement specific subtasks. The processing elements are connected in a pipelined streaming manner, which allows task executions to overlap. We further optimise the execution by splitting pipelines across processes and by introducing extra parallel streams. We identify performance metrics and design a mea-surement tool to evaluate each enactment. We conducted ex-periments to evaluate our optimisation strategies with a real world problem in the Life Sciences—EURExpress-II. The paper presents our distributed data-handling model, the op-timisation and instrumentation strategies and the evaluation experiments. We demonstrate linear speed up and argue that this use of data-streaming to enable both overlapped pipeline and parallelised enactment is a generally applicable optimisation strategy

A Systematic Review on the Effects of Different Types of Probiotics in Animal Alzheimer's Disease Studies

Alzheimer's disease (AD) is a global public health priority as with aging populations, its prevalence is expected to rise even further in the future. The brain and gut are in close communication through immunological, nervous and hormonal routes, and therefore, probiotics are examined as an option to influence AD hallmarks, such as plaques, tangles, and low grade inflammation. This study aimed to provide an overview of the available animal evidence on the effect of different probiotics on gut microbiota composition, short chain fatty acids (SCFAs), inflammatory markers, Amyloid-beta (A beta), and cognitive functioning in AD animal models. A systematic literature search was performed in PubMed, SCOPUS, and APA PsychInfo. Articles were included up to May 2021. Inclusion criteria included a controlled animal study on probiotic supplementation and at least one of the abovementioned outcome variables. Of the eighteen studies, most were conducted in AD male mice models (n = 9). Probiotics of the genera Lactobacillus and Bifidobacterium were used most frequently. Probiotic administration increased species richness and/or bacterial richness in the gut microbiota, increased SCFAs levels, reduced inflammatory markers, and improved cognitive functioning in AD models in multiple studies. The effect of probiotic administration on A beta remains ambiguous. B. longum (NK46), C. butyricum, and the mixture SLAB51 are the most promising probiotics, as positive improvements were found on almost all outcomes. The results of this animal review underline the potential of probiotic therapy as a treatment option in AD

Measurement of the conductance of a hydrogen molecule

Recent years have shown steady progress in research towards molecular electronics [1,2], where molecules have been investigated as switches [3-5], diodes [6], and electronic mixers [7]. In much of the previous work a Scanning Tunnelling Microscope was employed to address an individual molecule. As this arrangement does not provide long-term stability, more recently metal-molecule-metal links have been made using break junction devices [8-10]. However, it has been difficult to establish unambiguously that a single molecule forms the contact [11]. Here, we show that a single H2 molecule can form a stable bridge between Pt electrodes. In contrast to results for other organic molecules, the bridge has a nearly perfect conductance of one quantum unit, carried by a single channel. The H2-bridge provides a simple test system and a fundamental step towards understanding transport properties of single-molecule devices.Comment: 6 pages, 4 figure

Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies

Plus-strand RNA viruses are the largest group of viruses. Many are human pathogens that inflict a socio-economic burden. Interestingly, plus-strand RNA viruses share remarkable similarities in their replication. A hallmark of plus-strand RNA viruses is the remodeling of intracellular membranes to establish replication organelles (so-called “replication factories”), which provide a protected environment for the replicase complex, consisting of the viral genome and proteins necessary for viral RNA synthesis. In the current study, we investigate pan-viral similarities and virus-specific differences in the life cycle of this highly relevant group of viruses. We first measured the kinetics of viral RNA, viral protein, and infectious virus particle production of hepatitis C virus (HCV), dengue virus (DENV), and coxsackievirus B3 (CVB3) in the immuno-compromised Huh7 cell line and thus without perturbations by an intrinsic immune response. Based on these measurements, we developed a detailed mathematical model of the replication of HCV, DENV, and CVB3 and showed that only small virus-specific changes in the model were necessary to describe the in vitro dynamics of the different viruses. Our model correctly predicted virus-specific mechanisms such as host cell translation shut off and different kinetics of replication organelles. Further, our model suggests that the ability to suppress or shut down host cell mRNA translation may be a key factor for in vitro replication efficiency, which may determine acute self-limited or chronic infection. We further analyzed potential broad-spectrum antiviral treatment options in silico and found that targeting viral RNA translation, such as polyprotein cleavage and viral RNA synthesis, may be the most promising drug targets for all plus-strand RNA viruses. Moreover, we found that targeting only the formation of replicase complexes did not stop the in vitro viral replication early in infection, while inhibiting intracellular trafficking processes may even lead to amplified viral growth. Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Methane Formation in Cold Regions from Carbon Atoms and Molecular Hydrogen

Methane is typically thought to be formed in the solid state on top of cold interstellar icy grain mantles via the successive atomic hydrogenation of a carbon atom. In the current work we investigate the role of molecular hydrogen in the CH4 reaction network. We make use of an ultrahigh vacuum cryogenic setup combining an atomic carbon atom beam with atomic and/or molecular beams of hydrogen and deuterium on a water ice. These experiments lead to the formation of methane isotopologues detected in situ through reflection absorption infrared spectroscopy. Most notably, CH4 is experimentally formed by combining C atoms with only H2 on amorphous solid water, albeit more slowly than in experiments where H atoms are also present. Furthermore, CH2D2 is detected in an experiment involving C atoms with H2 and D2 on H2O ice. CD4, however, is only formed when D atoms are present in the experiment. These findings have been rationalized by means of computational and theoretical chemical insights. This leads to the following conclusions: (a) the reaction C + H2 → CH2 takes place, although it is not barrierless for all binding sites on water, (b) the reaction CH + H2 → CH3 is barrierless, but has not yet been included in astrochemical models, (c) the reactions CH2 + H2 → CH3 + H and CH3 + H2 → CH4 + H can take place only via a tunneling mechanism, and (d) molecular hydrogen possibly plays a more important role in the solid-state formation of methane than assumed so far. © 2022. The Author(s). Published by the American Astronomical Society.FEUZ-2020-0038; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, NWO: 722.017.008T.L. is grateful for support from NWO via a VENI fellowship (722.017.008). G.F. acknowledges financial support from the Russian Ministry of Science and Higher Education via the State Assignment Contract FEUZ-2020-0038. This research benefited from the financial support from the Dutch Astrochemistry Network II (DANII). Further support includes a VICI grant of NWO (the Netherlands Organization for Scientific Research). Funding by NOVA (the Netherlands Research School for Astronomy) is acknowledged

Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders

BACKGROUND: There is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders. METHODS: Ecological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels. RESULTS: Current depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant. CONCLUSIONS: Patients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation

Suramin Inhibits Chikungunya Virus Replication by Interacting with Virions and Blocking the Early Steps of Infection

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause a debilitating disease that is primarily characterized by persistent joint pain. CHIKV has been emerging globally, while neither a vaccine nor antiviral medication is available. The anti-parasitic drug suramin was previously shown to inhibit CHIKV replication. In this study we aimed to obtain more detailed insight into its mechanism of action. We found that suramin interacts with virions and can inhibit virus binding to cells. It also appeared to inhibit post-attachment steps of the infection process, likely by preventing conformational changes of the envelope glycoproteins required for fusion and the progression of infection. Suramin-resistant CHIKV strains were selected and genotyping and reverse genetics experiments indicated that mutations in E2 were responsible for resistance. The substitutions N5R and H18Q were reverse engineered in the E2 glycoprotein in order to understand their role in resistance. The binding of suramin-resistant viruses with these two E2 mutations was inhibited by suramin like that of wild-type virus, but they appeared to be able to overcome the post-attachment inhibitory effect of suramin. Conversely, a virus with a G82R mutation in E2 (implicated in attenuation of vaccine strain 181/25), which renders it dependent on the interaction with heparan sulfate for entry, was more sensitive to suramin than wild-type virus. Using molecular modelling studies, we predicted the potential suramin binding sites on the mature spikes of the chikungunya virion. We conclude that suramin interferes with CHIKV entry by interacting with the E2 envelope protein, which inhibits attachment and also interferes with conformational changes required for fusion

Honokiol inhibits SARS-CoV-2 replication in cell culture at a post-entry step

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019, and the resulting pandemic has already caused the death of over 6 million people. There are currently few antivirals approved for treatment of the 2019 coronavirus disease (COVID-19), and more options would be beneficial, not only now but also to increase our preparedness for future coronavirus outbreaks. Honokiol is a small molecule from magnolia trees for which several biological effects have been reported, including anticancer and anti-inflammatory activities. Honokiol has also been shown to inhibit several viruses in cell culture. In this study, we determined that honokiol protected Vero E6 cells from SARS-CoV-2-mediated cytopathic effect, with a 50% effective concentration of 7.8 mu M. In viral load reduction assays, honokiol decreased viral RNA copies as well as viral infectious progeny titers. The compound also inhibited SARS-CoV-2 replication in the more relevant human A549 cells expressing angiotensin converting enzyme 2 and transmembrane protease serine 2. Time-of-addition and other assays showed that honokiol inhibited virus replication at a post-entry step of the replication cycle. Honokiol was also effective against more recent variants of SARS-CoV-2, including Omicron, and it inhibited other human coronaviruses as well. Our study suggests that honokiol is an interesting molecule to be evaluated further in animal studies and, when successful, maybe even in clinical trials to investigate its effect on virus replication and pathogenic (inflammatory) host responses.IMPORTANCE Honokiol is a compound that shows both anti-inflammatory and antiviral effects, and therefore its effect on SARS-CoV-2 infection was assessed. This small molecule inhibited SARS-CoV-2 replication in various cell-based infection systems, with up to an similar to 1,000-fold reduction in virus titer. In contrast to earlier reports, our study clearly showed that honokiol acts on a postentry step of the replication cycle. Honokiol also inhibited different recent SARS-CoV-2 variants and other human coronaviruses (Middle East respiratory syndrome CoV and SARS-CoV), demonstrating its broad spectrum of antiviral activity. The anticoronavirus effect, combined with its anti-inflammatory properties, make honokiol an interesting compound to be further explored in animal coronavirus infection models.Molecular basis of virus replication, viral pathogenesis and antiviral strategie