Phase Ib pharmacodynamic study of the MNK inhibitor Tomivosertib (eFT508) combined with paclitaxel in patients with refractory metastatic breast cancer.

Purpose: Preclinical data motivate clinical evaluation of inhibitors of mitogen-activated protein kinase-interacting kinases 1 and 2 (MNK1/2). We conducted a phase 1b clinical trial to study target engagement and safety of tomivosertib, a MNK1/2 inhibitor, alone and in combination with paclitaxel.

Methods: Eligible patients had metastatic breast cancer resistant to standard of care treatments.

Dynamic Electrode-Electrolyte Intermixing in Solid-State Sodium Nano-Batteries.

Nanostructured solid-state batteries (SSBs) are poised to meet the demands of next-generation energy storage technologies by realizing performance competitive to their liquid-based counterparts while simultaneously offering improved safety and expanded form factors. Atomic layer deposition (ALD) is among the tools essential to fabricate nanostructured devices with challenging aspect ratios. Here, we report the fabrication and electrochemical testing of the first nanoscale sodium all-solid-state battery (SSB) using ALD to deposit both the VO cathode and NaPON solid electrolyte followed by evaporation of a thin-film Na metal anode.

The Effects of Incline Level on Optimized Lower-Limb Exoskeleton Assistance: A Case Series.

For exoskeletons to be successful in real-world settings, they will need to be effective across a variety of terrains, including on inclines. While some single-joint exoskeletons have assisted incline walking, recent successes in level-ground assistance suggest that greater improvements may be possible by optimizing assistance of the whole leg. To understand how exoskeleton assistance should change with incline, we used human-in-the-loop optimization to find whole-leg exoskeleton assistance torques that minimized metabolic cost on a range of grades.

Nanoscale Li, Na, and K ion-conducting polyphosphazenes by atomic layer deposition.

A key trailblazer in the development of thin-film solid-state electrolytes has been lithium phosphorous oxynitride (LiPON), the success of which has led to recent progress in thin-film ion conductors. Here we compare the structural, electrochemical, and processing parameters between previously published LiPON and NaPON ALD processes with a novel ALD process for the K analogue potassium phosphorous oxynitride (KPON). In each ALD process, alkali -butoxides and diethylphosphoramidate are used as precursors.

Application of Blue Honeysuckle Powder Obtained by an Innovative Method of Low-Temperature Drying in Skincare Face Masks.

Traditional technologies applied for obtaining plant raw materials for cosmetic production are based primarily on high-level processing, which is reflected in the qualitative composition of the resulting materials. By using low-temperature drying, it is possible to retain in the raw materials a range of valuable ingredients. In this study, blue honeysuckle powder was used as an ingredient of cosmetic face masks.

Optimized hip-knee-ankle exoskeleton assistance reduces the metabolic cost of walking with worn loads.

Background: Load carriage is common in a wide range of professions, but prolonged load carriage is associated with increased fatigue and overuse injuries. Exoskeletons could improve the quality of life of these professionals by reducing metabolic cost to combat fatigue and reducing muscle activity to prevent injuries. Current exoskeletons have reduced the metabolic cost of loaded walking by up to 22% relative to walking in the device with no assistance when assisting one or two joints.

Atomic Layer Deposition of Sodium Phosphorus Oxynitride: A Conformal Solid-State Sodium-Ion Conductor.

The development of novel materials that are compatible with nanostructured architectures is required to meet the demands of next-generation energy-storage technologies. Atomic layer deposition (ALD) allows for the precise synthesis of new materials that can conformally coat complex 3D structures. In this work, we demonstrate a thermal ALD process for sodium phosphorus oxynitride (NaPON), a thin-film solid-state electrolyte (SSE), for sodium-ion batteries (SIBs).

Ectromelia Virus Affects Mitochondrial Network Morphology, Distribution, and Physiology in Murine Fibroblasts and Macrophage Cell Line.

Mitochondria are multifunctional organelles that participate in numerous processes in response to viral infection, but they are also a target for viruses. The aim of this study was to define subcellular events leading to alterations in mitochondrial morphology and function during infection with ectromelia virus (ECTV). We used two different cell lines and a combination of immunofluorescence techniques, confocal and electron microscopy, and flow cytometry to address subcellular changes following infection.

Three-Dimensional Solid-State Lithium-Ion Batteries Fabricated by Conformal Vapor-Phase Chemistry.

Three-dimensional thin-film solid-state batteries (3D TSSB) were proposed by Long et al. in 2004 as a structure-based approach to simultaneously increase energy and power densities. Here, we report experimental realization of fully conformal 3D TSSBs, demonstrating the simultaneous power-and-energy benefits of 3D structuring.

Functional role of Hsp60 as a positive regulator of human viral infection progression.

Heat shock proteins (Hsps) are a family of proteins highly conserved in evolution. Members of the Hsp family are mainly responsible for proper protein folding, however they perform many other functions in living organisms. Hsp60 is a molecular chaperone that is present in mitochondria and cytosol of eukaryotic cells, as well as on their surface.

Nanoscale Protection Layers To Mitigate Degradation in High-Energy Electrochemical Energy Storage Systems.

In the pursuit of energy storage devices with higher energy and power, new ion storage materials and high-voltage battery chemistries are of paramount importance. However, they invite-and often enhance-degradation mechanisms, which are reflected in capacity loss with charge/discharge cycling and sometimes in safety problems. Degradation mechanisms are often driven by fundamentals such as chemical and electrochemical reactions at electrode-electrolyte interfaces, volume expansion and stress associated with ion insertion and extraction, and profound inhomogeneity of electrochemical behavior.

Spatiotemporal Parameters are not Substantially Influenced by Load Carriage or Inclination During Treadmill and Overground Walking.

Influences of load carriage and inclination on spatiotemporal parameters were examined during treadmill and overground walking. Ten soldiers walked on a treadmill and overground with three load conditions (00 kg, 20 kg, 40 kg) during level, uphill (6% grade) and downhill (-6% grade) inclinations at self-selected speed, which was constant across conditions. Mean values and standard deviations for double support percentage, stride length and a step rate were compared across conditions.

Phage Therapy in Bacterial Infections Treatment: One Hundred Years After the Discovery of Bacteriophages.

The therapeutic use of bacteriophages has seen a renewal of interest blossom in the last few years. This reversion is due to increased difficulties in the treatment of antibiotic-resistant strains of bacteria. Bacterial resistance to antibiotics, a serious problem in contemporary medicine, does not implicate resistance to phage lysis mechanisms.

African Swine Fever Virus: a new old enemy of Europe.

African swine fever (ASF) is a highly contagious viral disease of swine with a mortality rate approaching 100 percent. African Swine Fever Virus (ASFV) is a double-stranded DNA virus with a complex molecular structure. Its large genome, encoding multiple virulence factors, allows for efficient replication, which takes place predominantly in the cytoplasm of monocytes and macrophages.

Electrochemical Thin Layers in Nanostructures for Energy Storage.

Conventional electrical energy storage (EES) electrodes, such as rechargeable batteries, are mostly based on composites of monolithic micrometer sized particles bound together with polymeric and conductive carbon additives and binders. The kinetic limitations of these monolithic chunks of material are inherently linked to their electrical properties, the kinetics of ion insertion through their interface and ion migration in and through the composite phase. Redox chemistry of nanostructured materials in EES systems offer vast gains in power and energy.

Remodeling of the fibroblast cytoskeletal architecture during the replication cycle of Ectromelia virus: A morphological in vitro study in a murine cell line.

Ectromelia virus (ECTV, the causative agent of mousepox), which represents the same genus as variola virus (VARV, the agent responsible for smallpox in humans), has served for years as a model virus for studying mechanisms of poxvirus-induced disease. Despite increasing knowledge on the interaction between ECTV and its natural host-the mouse-surprisingly, still little is known about the cell biology of ECTV infection. Because pathogen interaction with the cytoskeleton is still a growing area of research in the virus-host cell interplay, the aim of the present study was to evaluate the consequences of ECTV infection on the cytoskeleton in a murine fibroblast cell line.

[MAVS protein and its interactions with hepatitis A, B and C viruses].

Mitochondrial antiviral signaling protein (MAVS) transmits activation signal of type I interferon (IFN) gene transcription in the molecular intracellular pathway, which depends on the protein encoded by retinoic acid inducible gene I (RIG-I) or melanoma differentiation-associated protein-5 (MDA-5). MAVS, as a signal molecule, performs an essential function in the development of an antiviral immune response. The molecule of MAVS consists of two domains: the N-terminal domain and the C-terminal domain.

Solid Electrolyte Lithium Phosphous Oxynitride as a Protective Nanocladding Layer for 3D High-Capacity Conversion Electrodes.

Materials that undergo conversion reactions to form different materials upon lithiation typically offer high specific capacity for energy storage applications such as Li ion batteries. However, since the reaction products often involve complex mixtures of electrically insulating and conducting particles and significant changes in volume and phase, the reversibility of conversion reactions is poor, preventing their use in rechargeable (secondary) batteries. In this paper, we fabricate and protect 3D conversion electrodes by first coating multiwalled carbon nanotubes (MWCNT) with a model conversion material, RuO2, and subsequently protecting them with conformal thin-film lithium phosphous oxynitride (LiPON), a well-known solid-state electrolyte.

Functionalization of Defect Sites in Graphene with RuO2 for High Capacitive Performance.

Graphene is an attractive material for its physicochemical properties, but for many applications only chemically synthesized forms such as graphene oxide (GO) and reduced graphene oxide (rGO) can be produced in sufficient amounts. If considered as electrode material, the intrinsic defects of GO or rGO may have negative influence on the conductivity and electrochemical properties. Such defects are commonly oxidized sites that offer the possibility to be functionalized with other materials in order to improve performance.

Biomechanical Effects of Stiffness in Parallel With the Knee Joint During Walking.

The human knee behaves similarly to a linear torsional spring during the stance phase of walking with a stiffness referred to as the knee quasi-stiffness. The spring-like behavior of the knee joint led us to hypothesize that we might partially replace the knee joint contribution during stance by utilizing an external spring acting in parallel with the knee joint. We investigated the validity of this hypothesis using a pair of experimental robotic knee exoskeletons that provided an external stiffness in parallel with the knee joints in the stance phase.

Ultrasensitive and label-free molecular-level detection enabled by light phase control in magnetoplasmonic nanoantennas.

Systems allowing label-free molecular detection are expected to have enormous impact on biochemical sciences. Research focuses on materials and technologies based on exploiting localized surface plasmon resonances in metallic nanostructures. The reason for this focused attention is their suitability for single-molecule sensing, arising from intrinsically nanoscopic sensing volume and the high sensitivity to the local environment.

Preliminary investigation of effects of a quasi-passive knee exoskeleton on gait energetics.

In this paper, we explain that the human knee behavior in the weight acceptance phase of gait (first ~40% of gait cycle) resembles that of a linear torsional spring. This led us to study the effects of the assistance provided by a pair of quasi-passive knee exoskeletons, which implement springs in parallel with the knee joints in the weight acceptance phase. Using the exoskeletons in a series of experiments on seven participants, we found that the exoskeleton mildly but non-significantly reduces the metabolic power of walking.

Fabrication of 3D core-shell multiwalled carbon nanotube@RuO2 lithium-ion battery electrodes through a RuO2 atomic layer deposition process.

Pushing lithium-ion battery (LIB) technology forward to its fundamental scaling limits requires the ability to create designer heterostructured materials and architectures. Atomic layer deposition (ALD) has recently been applied to advanced nanostructured energy storage devices due to the wide range of available materials, angstrom thickness control, and extreme conformality over high aspect ratio nanostructures. A class of materials referred to as conversion electrodes has recently been proposed as high capacity electrodes.