Explore the vast range of titles available.

Atmospheric water is a resource equivalent to ~10% of all fresh water in lakes on Earth. However, an efficient process for capturing and delivering water from air, especially at low humidity levels (down to 20%), has not been developed. We report the design and demonstration of a device based on a porous metal-organic framework {MOF-801, [Zr₆O₄(OH)₄(fumarate)₆]} that captures water from the atmosphere at ambient conditions by using low-grade heat from natural sunlight at a flux of less than 1 sun (1 kilowatt per square meter). This device is capable of harvesting 2.8 liters of water per kilogram of MOFdaily at relative humidity levels as low as 20% and requires no additional input of energy.

Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, which are fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBMs), harbor highly recurrent TERT promoter mutations of unknown function but specific to two nucleotide positions. We identified the functional consequence of these mutations in GBMs to be recruitment of the multimeric GA-binding protein (GABP) transcription factor specifically to the mutant promoter. Allelic recruitment of GABP is consistently observed across four cancer types, highlighting a shared mechanism underlying TERT reactivation. Tandem flanking native E26 transformation-specific motifs critically cooperate with these mutations to activate TERT, probably by facilitating GABP heterotetramer binding. GABP thus directly links TERT promoter mutations to aberrant expression in multiple cancers.

Although there is anecdotal evidence of ageism occurring at both the structural level (in which societal institutions reinforce systematic bias against older persons) and individual level (in which older persons take in the negative views of aging of their culture), previous systematic reviews have not examined how both levels simultaneously influence health. Thus, the impact of ageism may be underestimated. We hypothesized that a comprehensive systematic review would reveal that these ageism levels adversely impact the health of older persons across geography, health outcomes, and time. A literature search was performed using 14 databases with no restrictions on region, language, and publication type. The systematic search yielded 13,691 papers for screening, 638 for full review, and 422 studies for analyses. Sensitivity analyses that adjusted for sample size and study quality were conducted using standardized tools. The study protocol is registered (PROSPERO CRD42018090857). Ageism led to significantly worse health outcomes in 95.5% of the studies and 74.0% of the 1,159 ageism-health associations examined. The studies reported ageism effects in all 45 countries, 11 health domains, and 25 years studied, with the prevalence of significant findings increasing over time (p < .0001). A greater prevalence of significant ageism-health findings was found in less-developed countries than more-developed countries (p = .0002). Older persons who were less educated were particularly likely to experience adverse health effects of ageism. Evidence of ageism was found across the age, sex, and race/ethnicity of the targeters (i.e., persons perpetrating ageism). The current analysis which included over 7 million participants is the most comprehensive review of health consequences of ageism to date. Considering that the analysis revealed that the detrimental impact of ageism on older persons' health has been occurring simultaneously at the structural and individual level in five continents, our systematic review demonstrates the pernicious reach of ageism.

This study aims at examining the impact of the interrelation between the adoption of Industry 4.0 technologies and the implementation of lean production (LP) practices on the improvement level of European manufacturers’ operational performance. To achieve that, we conducted a survey with 108 European manufacturers that have been implementing LP and initiated their Industry 4.0 adoption. The collected data was analyzed through multivariate techniques, allowing to identify the effect of this relationship according to different contextual factors deemed as influential by previous literature, such as company size, LP implementation experience, type of ownership, and business operating model. Results underpin the idea of a wide applicability of both approaches, indicating that higher adoption levels of Industry 4.0 may be easier to achieve when LP practices are extensively implemented in the company. In opposition, when processes are not robustly designed and continuous improvement practices are not established, companies’ readiness for adopting novel technologies may be lower. By comprehending that Industry 4.0 technologies are highly related to LP practices, disregarding the context, managers from EU manufacturers can address the implementation of both approaches in a more assertive way.

The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B1, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs.

Predictive coding is a key mechanism to understand the computational processes underlying brain functioning: in a hierarchical network, higher levels predict the activity of lower levels, and the unexplained residuals (i.e., prediction errors) are passed back to higher layers. Because of its recursive nature, we wondered whether predictive coding could be related to brain oscillatory dynamics. First, we show that a simple 2-level predictive coding model of visual cortex, with physiological communication delays between levels, naturally gives rise to alpha-band rhythms, similar to experimental observations. Then, we demonstrate that a multilevel version of the same model can explain the occurrence of oscillatory traveling waves across levels, both forward (during visual stimulation) and backward (during rest). Remarkably, the predictions of our model are matched by the analysis of 2 independent electroencephalography (EEG) datasets, in which we observed oscillatory traveling waves in both directions.

Search and Rescue (SAR) missions represent an important challenge in the robotics research field as they usually involve exceedingly variable-nature scenarios which require a high-level of autonomy and versatile decision-making capabilities. This challenge becomes even more relevant in the case of aerial robotic platforms owing to their limited payload and computational capabilities. In this paper, we present a fully-autonomous aerial robotic solution, for executing complex SAR missions in unstructured indoor environments. The proposed system is based on the combination of a complete hardware configuration and a flexible system architecture which allows the execution of high-level missions in a fully unsupervised manner (i.e. without human intervention). In order to obtain flexible and versatile behaviors from the proposed aerial robot, several learning-based capabilities have been integrated for target recognition and interaction. The target recognition capability includes a supervised learning classifier based on a computationally-efficient Convolutional Neural Network (CNN) model trained for target/background classification, while the capability to interact with the target for rescue operations introduces a novel Image-Based Visual Servoing (IBVS) algorithm which integrates a recent deep reinforcement learning method named Deep Deterministic Policy Gradients (DDPG). In order to train the aerial robot for performing IBVS tasks, a reinforcement learning framework has been developed, which integrates a deep reinforcement learning agent (e.g. DDPG) with a Gazebo-based simulator for aerial robotics. The proposed system has been validated in a wide range of simulation flights, using Gazebo and PX4 Software-In-The-Loop, and real flights in cluttered indoor environments, demonstrating the versatility of the proposed system in complex SAR missions.

Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. In this study, we have measured plasma and tissue levels of endogenous steroids in second trimester human fetuses using multidimensional and high-resolution mass spectrometry. Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (<1 ng/mL), while in female fetuses, there are significantly lower levels of androsterone and testosterone. In the male, intermediates in the backdoor pathway are found primarily in the placenta and fetal liver, with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are only present at very low levels in the fetal testes. This is consistent with transcript levels of enzymes involved in the alternate pathway (steroid 5α-reductase type 1 [SRD5A1], aldo-keto reductase type 1C2 [AKR1C2], aldo-keto reductase type 1C4 [AKR1C4], cytochrome P450 17A1 [CYP17A1]), as measured by quantitative PCR (qPCR). These data identify androsterone as the predominant backdoor androgen in the human fetus and show that circulating levels are sex dependent, but also that there is little de novo synthesis in the testis. Instead, the data indicate that placental progesterone acts as substrate for synthesis of backdoor androgens, which occurs across several tissues. Masculinization of the human fetus depends, therefore, on testosterone and androsterone synthesis by both the fetal testes and nongonadal tissues, leading to DHT formation at the genital tubercle. Our findings also provide a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans.

Phenylalanine hydroxylase (PAH) deficiency is an inborn error of metabolism that results in elevated phenylalanine levels in blood. The classical form of the disease with phenylalanine level > 1200 µmol/L in blood is called phenylketonuria (PKU) and is associated with severe intellectual disability when untreated. In addition, phenylalanine levels above the therapeutic range in pregnant female patients lead to adverse fetal effects. Lowering the plasma phenylalanine level prevents intellectual disability, maintaining the level in the therapeutic range of 120–360 µmol/L is associated with good outcome for patients as well as their pregnancies. Patient phenotypes are on a continuous spectrum from mild hyperphenylalaninemia to mild PKU, moderate PKU, and severe classic PKU. There is a good correlation between the biochemical phenotype and the patient’s genotype. For over four decades the only available treatment was a very restrictive low phenylalanine diet. This changed in 2007 with the approval of cofactor therapy which is effective in up to 55% of patients depending on the population. Cofactor therapy typically is more effective in patients with milder forms of the disease and less effective in classical PKU. A new therapy has just been approved that can be effective in all patients with PAH deficiency regardless of their degree of enzyme deficiency or the severity of their phenotype. This article reviews the mainstay therapy, adjunct enzyme cofactor therapy, and the newly available enzyme substitution therapy for hyperphenylalaninemia. It also provides an outlook on emerging approaches for hyperphenylalaninemia treatment such as recruiting the microbiome into the therapeutic endeavor as well as therapies under development such as gene therapy.

In 2011 a new Investment Framework was proposed that described how the scale-up of key HIV interventions could dramatically reduce new HIV infections and AIDS-related deaths in low and middle income countries by 2015. This framework included ambitious coverage goals for prevention and treatment services for 2015, resulting in a reduction of new HIV infections by more than half, in line with the goals of the declaration of the UN High Level Meeting in June 2011. However, the approach suggested a leveling in the number of new infections at about 1 million annually-far from the UNAIDS goal of ending AIDS by 2030. In response, UNAIDS has developed the Fast-Track approach that is intended to provide a roadmap to the actions required to achieve this goal. The Fast-Track approach is predicated on a rapid scale-up of focused, effective prevention and treatment services over the next 5 years and then maintaining a high level of programme implementation until 2030. Fast-Track aims to reduce new infections and AIDS-related deaths by 90% from 2010 to 2030 and proposes a set of biomedical, behavioral and enabling intervention targets for 2020 and 2030 to achieve that goal, including the rapid scale-up initiative for antiretroviral treatment known as 90-90-90. Compared to a counterfactual scenario of constant coverage for all services at early-2015 levels, the Fast-Track approach would avert 18 million HIV infections and 11 million deaths from 2016 to 2030 globally. This paper describes the analysis that produced these targets and the estimated resources needed to achieve them in low- and middle-income countries. It indicates that it is possible to achieve these goals with a significant push to achieve rapid scale-up of key interventions between now and 2020. The annual resources required from all sources would rise to US$7.4Bn in low-income countries, US$8.2Bn in lower middle-income countries and US$10.5Bn in upper-middle-income-countries by 2020 before declining approximately 9% by 2030.