Human motor performance assessment with lower limb exoskeletons as a potential strategy to support healthy aging-a perspective article.

With increasing age, motor performance declines. This decline is associated with less favorable health outcomes such as impaired activities of daily living, reduced quality of life, or increased mortality. Through regular assessment of motor performance, changes over time can be monitored, and targeted therapeutic programs and interventions may be informed.

Respiratory Disease Surveillance in the Middle East and Latin America during the COVID-19 Pandemic, 2020-2022.

Characterizing the epidemiology of circulating respiratory pathogens during the COVID-19 pandemic could clarify the burden of acute respiratory infections and monitor outbreaks of public health and military relevance. The US Department of Defense supported 2 regions for influenza-like illness and severe acute respiratory infections surveillance, one in the Middle East through US Naval Medical Research Unit EURAFCENT, and another in Latin America through US Naval Medical Research Unit SOUTH. During 2020‒2022, coinciding with the COVID-19 pandemic, we collected a total of 16,146 nasopharyngeal and oropharyngeal swab samples from sentinel sites in Jordan (n = 11,305) and Latin America (n = 4,841).

Analysis of the Effects of Ionic Liquid Properties on Electrospray Thruster Performance.

Ionic liquids (ILs) have proven extremely useful for a wide variety of roles, including as propellants for electrospray thrusters (ETs), due to their unique physical and chemical properties, as well as the potential tunability of those properties, through chemical engineering. However, there is a lack of literature exploring the effects of IL properties on ET operation. This paper presents experimental results investigating key physical properties of the common ILs 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMI-TFSI), 1-butyl-3-methylimidazolium trifluoromethanesulfonate (BMI-TFO), EAN, and Bmpyr-DCA not provided by manufacturers or reported in the literature, namely, their electrochemical stability windows (ESWs) and contact angles.

RSVP for VPSA : A Meta Design Study on Rapid Suggestive Visualization Prototyping for Visual Parameter Space Analysis.

Visual Parameter Space Analysis (VPSA) enables domain scientists to explore input-output relationships of computational models. Existing VPSA applications often feature multi-view visualizations designed by visualization experts for a specific scenario, making it hard for domain scientists to adapt them to their problems without professional help. We present RSVP, the Rapid Suggestive Visualization Prototyping system encoding VPSA knowledge to enable domain scientists to prototype custom visualization dashboards tailored to their specific needs.

Profiling Germinal Center-like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids.

Glycoengineered bacteria have emerged as a cost-effective platform for rapid and controllable biosynthesis of designer conjugate vaccines. However, little is known about the engagement of such conjugates with naïve B cells to induce the formation of germinal centers (GC), a subanatomical microenvironment that converts naïve B cells into antibody-secreting plasma cells. Using a three-dimensional biomaterials-based B-cell follicular organoid system, we demonstrate that conjugates triggered robust expression of hallmark GC markers, B cell receptor clustering, intracellular signaling, and somatic hypermutation.

Use of Lower Limb Exoskeletons as an Assessment Tool for Human Motor Performance: A Systematic Review.

Exoskeletons are a promising tool to support individuals with a decreased level of motor performance. Due to their built-in sensors, exoskeletons offer the possibility of continuously recording and assessing user data, for example, related to motor performance. The aim of this article is to provide an overview of studies that rely on using exoskeletons to measure motor performance.

A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways in Hypnozoites.

Radical cure of malaria must include elimination of quiescent 'hypnozoite' forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors against liver stages. From both libraries, we identified inhibitors targeting epigenetics pathways as selectively active against and hypnozoites.

A modular vaccine platform enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens.

Engineered outer membrane vesicles (OMVs) derived from Gram-negative bacteria are a promising technology for the creation of non-infectious, nanoparticle vaccines against diverse pathogens. However, antigen display on OMVs can be difficult to control and highly variable due to bottlenecks in protein expression and localization to the outer membrane of the host cell, especially for bulky and/or complex antigens. Here, we describe a universal approach for avidin-based vaccine antigen crosslinking (AvidVax) whereby biotinylated antigens are linked to the exterior of OMVs whose surfaces are remodeled with multiple copies of a synthetic antigen-binding protein (SNAP) comprised of an outer membrane scaffold protein fused to a biotin-binding protein.

Effects of Upper-Limb Exoskeletons Designed for Use in the Working Environment-A Literature Review.

Many employees report high physical strain from overhead work and resulting musculoskeletal disorders. The consequences of these conditions extend far beyond everyday working life and can severely limit the quality of life of those affected. One solution to this problem may be the use of upper-limb exoskeletons, which are supposed to relieve the shoulder joint in particular.

Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.

As a common protein modification, asparagine-linked (linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins. However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation. To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.

On-demand biomanufacturing of protective conjugate vaccines.

Conjugate vaccines are among the most effective methods for preventing bacterial infections. However, existing manufacturing approaches limit access to conjugate vaccines due to centralized production and cold chain distribution requirements. To address these limitations, we developed a modular technology for in vitro conjugate vaccine expression (iVAX) in portable, freeze-dried lysates from detoxified, nonpathogenic Upon rehydration, iVAX reactions synthesize clinically relevant doses of conjugate vaccines against diverse bacterial pathogens in 1 hour.

Ivor-Lewis oesophagectomy: A standardized operative technique in 11 steps.

Synopsis: Standardization of robotic oesophagectomy can benefit both patients and surgeons by decreasing complications, shortening the learning curve and improving surgical training.

Background: Thoraco-abdominal oesophagectomy with lymphadenectomy is the cornerstone of curative therapy for oesophageal carcinoma. To reduce post-operative morbidity, minimally invasive technology has become increasingly established.

Activity-Selectivity Trends in the Electrochemical Production of Hydrogen Peroxide over Single-Site Metal-Nitrogen-Carbon Catalysts.

Nitrogen-doped carbon materials featuring atomically dispersed metal cations (M-N-C) are an emerging family of materials with potential applications for electrocatalysis. The electrocatalytic activity of M-N-C materials toward four-electron oxygen reduction reaction (ORR) to HO is a mainstream line of research for replacing platinum-group-metal-based catalysts at the cathode of fuel cells. However, fundamental and practical aspects of their electrocatalytic activity toward two-electron ORR to HO, a future green "dream" process for chemical industry, remain poorly understood.

NFκB- and MAP-Kinase Signaling Contribute to the Activation of Murine Myeloid Dendritic Cells by a Flagellin A:Allergen Fusion Protein.

Fusion proteins incorporating the TLR5-ligand flagellin are currently undergoing clinical trials as vaccine candidates for many diseases. We recently reported a flagellin:allergen fusion protein containing the TLR5-ligand flagellin A (FlaA) from and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) to prevent allergic sensitization in an experimental mouse model. This study analyzes the signaling pathways contributing to rFlaA:Betv1-mediated pro- and anti-inflammatory cytokine secretion and cell metabolism in myeloid dendritic cells (mDCs) in vitro.

Interplay of Carbohydrate and Carrier in Antibacterial Glycoconjugate Vaccines.

Bacterial infections are a serious health concern and are responsible for millions of illnesses and deaths each year in communities around the world. Vaccination is an important public health measure for reducing and eliminating this burden, and regions with comprehensive vaccination programs have achieved significant reductions in infection and mortality. This is often accomplished by immunization with bacteria-derived carbohydrates, typically in conjunction with other biomolecules, which induce immunological memory and durable protection against bacterial human pathogens.

Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies.

Many microbial pathogens produce a β-(1→6)-linked poly--acetyl-d-glucosamine (PNAG) surface capsule, including bacterial, fungal, and protozoan cells. Broadly protective immune responses to this single conserved polysaccharide antigen in animals are possible but only when a deacetylated poly--acetyl-d-glucosamine (dPNAG; <30% acetate) glycoform is administered as a conjugate to a carrier protein. Unfortunately, conventional methods for natural extraction or chemical synthesis of dPNAG and its subsequent conjugation to protein carriers can be technically demanding and expensive.

Electrochemical processes on solid shaped nanoparticles with defined facets.

This 2007 Chemistry Nobel prize update covers scientific advances of the past decade in our understanding of electrocatalytic processes on surfaces of nanoscale shape-controlled polyhedral solids. It is argued that the field of chemical reaction processes on solid surfaces has recently been paying increasing attention to the fundamental understanding of electrified solid-liquid interfaces and toward the operando study of the minute fraction of catalytically active, structurally dynamic non-equilibrium Taylor-type surface sites. Meanwhile, despite mounting evidence of acting as structural proxies in some cases, the concept of catalytic structure sensitivity of well-defined nanoscale solid surfaces continues to be a key organizing principle for the science of shape-controlled nanocrystals and, hence, constitutes a central recurring theme in this review.

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies.

The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive.

SLC13A5 is a novel transcriptional target of the pregnane X receptor and sensitizes drug-induced steatosis in human liver.

The solute carrier family 13 member 5 (SLC13A5) is a sodium-coupled transporter that mediates cellular uptake of citrate, which plays important roles in the synthesis of fatty acids and cholesterol. Recently, the pregnane X receptor (PXR, NR1I2), initially characterized as a xenobiotic sensor, has been functionally linked to the regulation of various physiologic processes that are associated with lipid metabolism and energy homeostasis. Here, we show that the SLC13A5 gene is a novel transcriptional target of PXR, and altered expression of SLC13A5 affects lipid accumulation in human liver cells.

Spherical micelles assembled from variants of recombinant oleosin.

An emerging field in biomaterials is the creation and engineering of protein surfactants made by recombinant biotechnology. Protein surfactants made by recombinant biotechnology allow for complete control of the molecular weight and chemical sequence of the surfactant. The proteins are monodisperse in molecular weight, and functionalization with bioactive amino acid sequences is straightforwardly achieved through genetic engineering.

Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes.

Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fatty acid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH).

Aldehyde oxidase activity in donor-matched fresh and cryopreserved human hepatocytes and assessment of variability in 75 donors.

Studies were conducted to evaluate the impact of time and cryopreservation on aldehyde oxidase (AO) activity in human hepatocytes isolated from 10 donor livers, using O(6)-benzylguanine as a probe substrate. In addition, variability in activity was assessed using cryopreserved hepatocytes from 75 donors. Substantial donor-dependent loss in AO activity within 24 hours after isolation of hepatocytes was observed (average loss of 42%, range 15%-81%).

Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling.

Metformin is currently the most widely used drug for the treatment of type 2 diabetes. Mechanistically, metformin interacts with many protein kinases and transcription factors that alter the expression of numerous downstream target genes governing lipid metabolism, cell proliferation, and drug metabolism. The constitutive androstane receptor (CAR, NR1i3), a known xenobiotic sensor, has recently been recognized as a novel signaling molecule, in that its activation could be regulated by protein kinases in addition to the traditional ligand binding.

Analysis of a laminar-flow diffusional mixer for directed self-assembly of liposomes.

The present work describes the operation and simulation of a microfluidic laminar-flow mixer. Diffusive mixing takes place between a core solution containing lipids in ethanol and a sheath solution containing aqueous buffer, leading to self assembly of liposomes. Present device architecture hydrodynamically focuses the lipid solution into a cylindrical core positioned at the center of a microfluidic channel of 125 × 125-μm(2) cross-section.