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\"Battling both inner and external demons, Stephanie must learn to balance school and crime-fighting or face the wrath of Barbara Gordon! With guest appearences from Batman and Robin and villains like Man-Bat and Clayface, Batgirl must step up to the mantle! Batgirl must battle the Calculator and stop his plan to unleash a nanovirus upon the citizens of Gotham City that will turn them into mindless techno-zombies, enter the FLOOD!\"-- Provided by publisher.

Accurate modelling of the weather’s temporal and spatial impacts on building energy demand is critical to decarbonizing energy systems. Here we introduce a customizable model for hourly heating and cooling demand applicable globally at all spatial scales. We validate against demand from ~5,000 buildings and 43 regions across four continents. The model requires limited data inputs and shows better agreement with measured demand than existing models. We use it first to demonstrate that a 1 °C reduction in thermostat settings across all buildings could reduce Europe’s gas consumption by 240 TWh yr −1 , approximately one-sixth of historical imports from Russia. Second, we show that service demand for cooling is increasing by up to 5% per year in some regions due to climate change, and 5 billion people experience >100 additional cooling degree days per year when compared with a generation ago. The model and underlying data are freely accessible to promote further research. Accurate modelling of the temporal and spatial impacts of weather on building energy demand is key to the decarbonization of energy systems. Now, Staffell et al. develop an openly available model for calculating hourly heating and cooling demand on a global scale.

Background Evidence for the efficacy of low-volume high-intensity interval training (HIIT) for the modulation of body composition is unclear. Objectives We examined the effect of low-volume HIIT versus a non-exercising control and moderate-intensity continuous training (MICT) on body composition and cardiorespiratory fitness in normal weight, overweight and obese adults. We evaluated the impact of low-volume HIIT (HIIT interventions where the total amount of exercise performed during training was ≤ 500 metabolic equivalent minutes per week [MET-min/week]) compared to a non-exercising control and MICT. Methods A database search was conducted in PubMed (MEDLINE), EMBASE, CINAHL, Web of Science, SPORTDiscus and Scopus from the earliest record to June 2019 for studies (randomised controlled trials and non-randomised controlled trials) with exercise training interventions with a minimum 4-week duration. Meta-analyses were conducted for between-group (low-volume HIIT vs. non-exercising control and low-volume HIIT vs. MICT) comparisons for change in total body fat mass (kg), body fat percentage (%), lean body mass (kg) and cardiorespiratory fitness. Results From 11,485 relevant records, 47 studies were included. No difference was found between low-volume HIIT and a non-exercising control on total body fat mass (kg) (effect size [ES]: − 0.129, 95% confidence interval [CI] − 0.468 to 0.210; p  = 0.455), body fat (%) (ES: − 0.063, 95% CI − 0.383 to 0.257; p  = 0.700) and lean body mass (kg) (ES: 0.050, 95% CI − 0.250 to 0.351; p  = 0.744), or between low-volume HIIT and MICT on total body fat mass (kg) (ES: − 0.021, 95% CI − 0.272 to 0.231; p  = 0.872), body fat (%) (ES: 0.005, 95% CI − 0.294 to 0.304; p  = 0.974) and lean body mass (kg) (ES: 0.030, 95% CI − 0.167 to 0.266; p  = 0.768). However, low-volume HIIT significantly improved cardiorespiratory fitness compared with a non-exercising control ( p  < 0.001) and MICT ( p  = 0.017). Conclusion These data suggest that low-volume HIIT is inefficient for the modulation of total body fat mass or total body fat percentage in comparison with a non-exercise control and MICT. A novel finding of our meta-analysis was that there appears to be no significant effect of low-volume HIIT on lean body mass when compared with a non-exercising control, and while most studies tended to favour improvement in lean body mass with low-volume HIIT versus MICT, this was not significant. However, despite its lower training volume, low-volume HIIT induces greater improvements in cardiorespiratory fitness than a non-exercising control and MICT in normal weight, overweight and obese adults. Low-volume HIIT, therefore, appears to be a time-efficient treatment for increasing fitness, but not for the improvement of body composition.

Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. We present DRIAD (Drug Repurposing In AD), a machine learning framework that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in lists of gene names. DRIAD is applied to lists of genes arising from perturbations in differentiated human neural cell cultures by 80 FDA-approved and clinically tested drugs, producing a ranked list of possible repurposing candidates. Top-scoring drugs are inspected for common trends among their targets. We propose that the DRIAD method can be used to nominate drugs that, after additional validation and identification of relevant pharmacodynamic biomarker(s), could be readily evaluated in a clinical trial. Clinical trials of novel therapeutics for Alzheimer’s Disease (AD) have provided largely negative results, so far. Here, the authors present a machine learning framework that quantifies potential associations between the pathology of AD severity and gene-based molecular mechanisms to enable drug repurposing.

A parasitic plant produces microRNAs that target host messenger RNAs, causing them to be processed into small interfering RNAs. miRNAs in plant parasitism Dodders are parasitic plants that obtain water and nutrients from the stems of their host plants, and exchange other material with their hosts, through structures called haustoria. Michael Axtell and colleagues report how haustoria mediate dodders' parasitism. Dodders accumulate many microRNAs (miRNAs) in their haustoria while infesting a host plant. These miRNAs seem to then transfer to the host, where they silence target messenger RNAs (mRNAs) through the production of secondary small interfering RNAs and mRNA cleavage. The authors also identify host proteins that are targeted by dodder miRNAs and provide evidence that such regulation of host gene expression through inter-species transfer of miRNAs is not limited to one host. Dodders ( Cuscuta spp.) are obligate parasitic plants that obtain water and nutrients from the stems of host plants via specialized feeding structures called haustoria. Dodder haustoria facilitate bidirectional movement of viruses, proteins and mRNAs between host and parasite 1 , but the functional effects of these movements are not known. Here we show that Cuscuta campestris haustoria accumulate high levels of many novel microRNAs (miRNAs) while parasitizing Arabidopsis thaliana . Many of these miRNAs are 22 nucleotides in length. Plant miRNAs of this length are uncommon, and are associated with amplification of target silencing through secondary short interfering RNA (siRNA) production 2 . Several A. thaliana mRNAs are targeted by 22-nucleotide C. campestris miRNAs during parasitism, resulting in mRNA cleavage, secondary siRNA production, and decreased mRNA accumulation. Hosts with mutations in two of the loci that encode target mRNAs supported significantly higher growth of C. campestris . The same miRNAs that are expressed and active when C. campestris parasitizes A. thaliana are also expressed and active when it infects Nicotiana benthamiana . Homologues of target mRNAs from many other plant species also contain the predicted target sites for the induced C. campestris miRNAs. These data show that C. campestris miRNAs act as trans-species regulators of host-gene expression, and suggest that they may act as virulence factors during parasitism.

Metabolic-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, affecting 25% of people globally and up to 80% of people with obesity. MAFLD is characterised by fat accumulation in the liver (hepatic steatosis) with varying degrees of inflammation and fibrosis. MAFLD is strongly linked with cardiometabolic disease and lifestyle-related cancers, in addition to heightened liver-related morbidity and mortality. This position statement examines evidence for exercise in the management of MAFLD and describes the role of the exercise professional in the context of the multi-disciplinary care team. The purpose of these guidelines is to equip the exercise professional with a broad understanding of the pathophysiological underpinnings of MAFLD, how it is diagnosed and managed in clinical practice, and to provide evidence- and consensus-based recommendations for exercise therapy in MAFLD management. The majority of research evidence indicates that 150–240 min per week of at least moderate-intensity aerobic exercise can reduce hepatic steatosis by ~ 2–4% (absolute reduction), but as little as 135 min/week has been shown to be effective. While emerging evidence shows that high-intensity interval training (HIIT) approaches may provide comparable benefit on hepatic steatosis, there does not appear to be an intensity-dependent benefit, as long as the recommended exercise volume is achieved. This dose of exercise is likely to also reduce central adiposity, increase cardiorespiratory fitness and improve cardiometabolic health, irrespective of weight loss. Resistance training should be considered in addition to, and not instead of, aerobic exercise targets. The information in this statement is relevant and appropriate for people living with the condition historically termed non-alcoholic fatty liver disease (NAFLD), regardless of terminology.

Elastocaloric cooling, a solid-state cooling technology, exploits the latent heat released and absorbed by stress-induced phase transformations. Hysteresis associated with transformation, however, is detrimental to efficient energy conversion and functional durability. We have created thermodynamically efficient, low-hysteresis elastocaloric cooling materials by means of additive manufacturing of nickel-titanium. The use of a localized molten environment and near-eutectic mixing of elemental powders has led to the formation of nanocomposite microstructures composed of a nickel-rich intermetallic compound interspersed among a binary alloy matrix. The microstructure allowed extremely small hysteresis in quasi-linear stress-strain behaviors—enhancing the materials efficiency by a factor of four to seven—and repeatable elastocaloric performance over 1 million cycles. Implementing additive manufacturing to elastocaloric cooling materials enables distinct microstructure control of high-performance metallic refrigerants with long fatigue life.

As the gravitational-wave (GW) detector network is upgraded and the sensitivity of the detectors improves, novel scientific avenues open for exploration. For example, tests of general relativity (GR) will become more accurate as smaller deviations can be probed. Additionally, the detection of lensed GWs becomes more likely. However, these new avenues could also interact with each other, and a GW event presenting deviations from GR could be mistaken for a lensed one. Here, we explore how phenomenological deviations from GR or binaries of exotic compact objects could impact those lensing searches focusing on a single event. We consider strong lensing, millilensing, and microlensing, and find that certain phenomenological deviations from GR may be mistaken for all of these types of lensing. Therefore, our study shows that future candidate lensing events would need to be carefully examined to avoid a false claim of lensing where instead a deviation from GR has been seen.

Small RNAs act as fungal pathogen effectors that silence host target genes to promote infection, a virulence mechanism termed cross-kingdom RNA interference (RNAi). The essential pathogen factors of cross-kingdom small RNA production are largely unknown. We here characterized the RNA-dependent RNA polymerase (RDR)1 in the fungal plant pathogen Botrytis cinerea that is required for pathogenicity and cross-kingdom RNAi. B . cinerea bcrdr1 knockout (ko) mutants exhibited reduced pathogenicity and loss of cross-kingdom small RNAs. We developed a \"switch-on\" GFP reporter to study cross-kingdom RNAi in real-time within the living plant tissue which highlighted that bcrdr1 ko mutants were compromised in cross-kingdom RNAi. Moreover, blocking seven pathogen cross-kingdom small RNAs by expressing a short-tandem target mimic RNA in transgenic Arabidopsis thaliana led to reduced infection levels of the fungal pathogen B . cinerea and the oomycete pathogen Hyaloperonospora arabidopsidis . These results demonstrate that cross-kingdom RNAi is significant to promote host infection and making pathogen small RNAs an effective target for crop protection.

Chimeric antigen receptor (CAR)-T cells have demonstrated clinical potential, but current receptors still need improvements to be successful against chronic HIV infection. In this study, we address some requirements of CAR motifs for strong surface expression of a novel anti-HIV CAR by evaluating important elements in the extracellular, hinge, and transmembrane (TM) domains. When combining a truncated CD4 extracellular domain and CD8α hinge/TM, the novel CAR did not express extracellularly but was detectable intracellularly. By shortening the CD8α hinge, CD4-CAR surface expression was partially recovered and addition of the LYC motif at the end of the CD8α TM fully recovered both intracellular and extracellular CAR expression. Mutation of LYC to TTA or TTC showed severe abrogation of CAR expression by flow cytometry and confocal microscopy. Additionally, we determined that CD4-CAR surface expression could be maximized by the removal of FQKAS motif at the junction of the extracellular domain and the hinge region. CD4-CAR surface expression also resulted in cytotoxic CAR T cell killing of HIV Env + target cells. In this study, we identified elements that are crucial for optimal CAR surface expression, highlighting the need for structural analysis studies to establish fundamental guidelines of CAR designs.