Developing a Common Global Baseline for Nucleic Acid Synthesis Screening

Introduction: Nucleic acid synthesis is a powerful tool that has revolutionized the life sciences. However, the misuse of synthetic nucleic acids could pose a serious threat to public health and safety. There is a need for international standards for nucleic acid synthesis screening to help prevent the misuse of this technology.Methods: We outline current barriers to the adoption of screening, which include the cost of developing screening tools and resources, adapting to existing commercial practices, internationalizing screening, and adapting screening to benchtop nucleic acid synthesis devices. To address these challenges, we then introduce the Common Mechanism for DNA Synthesis Screening, which was developed in consultation with a technical consortium of experts in DNA synthesis, synthetic biology, biosecurity, and policy, with the aim of addressing current barriers. The Common Mechanism software uses a variety of methods to identify sequences of concern, identify taxonomic best matches to regulated pathogens, and identify benign genes that can be cleared for synthesis. Finally, we describe outstanding challenges in the development of screening practices.Results: The Common Mechanism is a step toward ensuring the safe and responsible use of synthetic nucleic acids. It provides a baseline capability that overcomes challenges to nucleic acid synthesis screening and provides a solution for broader international adoption of screening practices.Conclusion: The Common Mechanism is a valuable tool for preventing the misuse of synthetic nucleic acids. It is a critical step toward ensuring the safe and responsible use of this powerful technology

Functional Evidence for Complement-activating Immune Complexes in the Skin of Patients with Bullous Pemphigoid

Previous immunofluorescent studies showing deposits of immunoglobulin and complement at the cutaneous basement membrane zone have provided evidence supporting a role for immune complexes in the pathogenesis of bullous pemphigoid. In this study the functional activity of the deposits has been examined using leukocyte attachment, a method for detecting and quantitating the biological activity of complement-activating immune complexes in tissues. When peripheral blood leukocytes suspended in serum complement were incubated with cryostat sections of lesional and adjacent normal-appearing skin from 9 patients with pemphigoid, skin from 11 normal controls and lesional skin from 14 nonpemphigoid disease controls there was significantly greater attachment of leukocytes to the basement membrane zone of lesional bullous pemphigoid skin compared to normal-appearing pemphigoid skin and skin of both control groups. A significant reduction in attachment in the absence of serum complement suggested the reaction was dependent on activation of complement by tissue-deposited complexes. Although leukocyte attachment was greater in lesional than normal-appearing pemphigoid skin, a comparison of the incidence and intensity of cutaneous IgG and complement immunofluorescence between the 2 groups showed no significant differences. Furthermore, no correlation between leukocyte attachment and serum titers of immunoglobulin G or complement-binding anti-basement membrane zone antibodies was observed. These results suggest that immune reactants in lesional pemphigoid skin are functional complement-activating immune complexes, that differences exist between the activity of complexes in lesional and normal-appearing pemphigoid skin and may explain why lesions develop at some sites and not others

A Single Phase Hybrid Multiport Microinverter for Photovoltaic Energy Controlled by Exact Linearization

Solar energy can be captured by Photovoltaics (PV) and converted into electrical power. This electrical power can then be connected to grids by power electronic converters, which can also operate the PV panels at around their maximum power point (MPP), maximizing the harvested energy. When the PV panels are connected in an array, the partial shading effect generates a distortion of the power curve can result in a power loss since tracking algorithms might not be able to detect the MPP. To solve this issue microinverters have been proposed, with a small power electronic converter being connected to each PV panel, this arrangement enables independence for maximum power point tracking and electrical isolation. This paper presents a double output multiport microinverter capable of feeding DC and AC loads or providing connection to a single-phase AC grid and energy storage. The proposed structure can be operated in grid-connected and islanded modes. This paper describes the microinverter controlled with the exact linearization technique on both the DC and AC sides, obtaining a lineal transfer function representation of the nonlinear and coupled power electronic converters. The operation of the proposed topology and its control strategy is validated using a laboratory proof-of-concept prototype

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories:Findings From the CANVAS Program

Rationale & Objective: Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio. Study Design: Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. Settings & Participants: The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR ≥ 30 mL/min/1.73 m2 to treatment with canagliflozin or placebo. Intervention(s): Canagliflozin or matching placebo. Outcomes: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes. Results: Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high–risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (P trend = 0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P trend = 0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend = 0.06) and for chronic eGFR slope (P trend = 0.04). Limitations: Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR < 30 mL/min/1.73 m2. Conclusions: Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin. Funding: This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical. Trial Registration: The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754

Compendium of Single Event Effects Test Results for Commercial Off-The-Shelf and Standard Electronics for Low Earth Orbit and Deep Space Applications

We present the results of Single Event Effects (SEE) testing with high energy protons and with low and high energy heavy ions for electrical components considered for Low Earth Orbit (LEO) and for deep space applications

Microgrid Power Sharing Framework for Software Defined Networking and Cybersecurity Analysis

Hierarchical control is a widely used strategy that can increase resilience and improve the reliability of the electrical network based on microgrid global variables. Large amounts of data required during transitions prompt the use of more reliable and flexible communications to achieve the control objectives. Such communications can involve potential cyber vulnerabilities and latency restrictions, which cannot be always addressed in real-time. To accurately capture the system’s overall operation, this paper proposes a co-simulation framework driven by flexible communications and a resilient control algorithm to regulate the frequency and voltage deviations in a networked microgrids. Model-based predictive control has been implemented, to avoid slow transient response associated with linear hierarchical control. Software-Defined Networking (SDN) is responsible for increasing the communication intelligence during the power-sharing process. The effects of critical communications and overall system performance are reviewed and compared for different co-simulation scenarios. Graphical Network Simulator (GNS3) is used in combination with model-based predictive control and SDN, to provide latency below 100 ms, as defined in IEC 61850. Testing of the proposed system under different cyber attack scenarios demonstrate its excellent performance. The novel control architecture presented in the paper provides a reference framework for future cloud computing-based microgrids

Airborne S-Band SAR for forest biophysical retrieval in temperate mixed forests of the UK

Radar backscatter from forest canopies is related to forest cover, canopy structure and aboveground biomass (AGB). The S-band frequency (3.1–3.3 GHz) lies between the longer L-band (1–2 GHz) and the shorter C-band (5–6 GHz) and has been insufficiently studied for forest applications due to limited data availability. In anticipation of the British built NovaSAR-S satellite mission, this study evaluates the benefits of polarimetric S-band SAR for forest biophysical properties. To understand the scattering mechanisms in forest canopies at S-band the Michigan Microwave Canopy Scattering (MIMICS-I) radiative transfer model was used. S-band backscatter was found to have high sensitivity to the forest canopy characteristics across all polarisations and incidence angles. This sensitivity originates from ground/trunk interaction as the dominant scattering mechanism related to broadleaved species for co-polarised mode and specific incidence angles. The study was carried out in the temperate mixed forest at Savernake Forest and Wytham Woods in southern England, where airborne S-band SAR imagery and field data are available from the recent AirSAR campaign. Field data from the test sites revealed wide ranges of forest parameters, including average canopy height (6–23 m), diameter at breast-height (7–42 cm), basal area (0.2–56 m2/ha), stem density (20–350 trees/ha) and woody biomass density (31–520 t/ha). S-band backscatter-biomass relationships suggest increasing backscatter sensitivity to forest AGB with least error between 90.63 and 99.39 t/ha and coefficient of determination (r2) between 0.42 and 0.47 for the co-polarised channel at 0.25 ha resolution. The conclusion is that S-band SAR data such as from NovaSAR-S is suitable for monitoring forest aboveground biomass less than 100 t/ha at 25 m resolution in low to medium incidence angle rang

Steering a Tractor by Means of an EMG-Based Human-Machine Interface

An electromiographic (EMG)-based human-machine interface (HMI) is a communication pathway between a human and a machine that operates by means of the acquisition and processing of EMG signals. This article explores the use of EMG-based HMIs in the steering of farm tractors. An EPOC, a low-cost human-computer interface (HCI) from the Emotiv Company, was employed. This device, by means of 14 saline sensors, measures and processes EMG and electroencephalographic (EEG) signals from the scalp of the driver. In our tests, the HMI took into account only the detection of four trained muscular events on the driver’s scalp: eyes looking to the right and jaw opened, eyes looking to the right and jaw closed, eyes looking to the left and jaw opened, and eyes looking to the left and jaw closed. The EMG-based HMI guidance was compared with manual guidance and with autonomous GPS guidance. A driver tested these three guidance systems along three different trajectories: a straight line, a step, and a circumference. The accuracy of the EMG-based HMI guidance was lower than the accuracy obtained by manual guidance, which was lower in turn than the accuracy obtained by the autonomous GPS guidance; the computed standard deviations of error to the desired trajectory in the straight line were 16 cm, 9 cm, and 4 cm, respectively. Since the standard deviation between the manual guidance and the EMG-based HMI guidance differed only 7 cm, and this difference is not relevant in agricultural steering, it can be concluded that it is possible to steer a tractor by an EMG-based HMI with almost the same accuracy as with manual steering

National Prevalence and Trends of HIV Transmitted Drug Resistance in Mexico

BACKGROUND: Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access. METHODOLOGY/PRINCIPAL FINDINGS: We designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naïve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2∶8.8) and 6.8% (95% CI, 5.7∶8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (p = 0.0456) and PI (p = 0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects. CONCLUSIONS: TDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed

State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event

The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P &gt; 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field