Mild-to-wild plastic transition is governed by athermal screw dislocation slip in bcc Nb.

Plastic deformation in crystals is mediated by the motion of line defects known as dislocations. For decades, dislocation activity has been treated as a homogeneous, smooth continuous process. However, it is now recognized that plasticity can be determined by long-range correlated and intermittent collective dislocation processes, known as avalanches.

STING regulates peripheral nerve regeneration and colony stimulating factor 1 receptor (CSF1R) processing in microglia.

Inflammatory responses are crucial for regeneration following peripheral nerve injury (PNI). PNI triggers inflammatory responses at the site of injury. The DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream effector stimulator of interferon genes (STING) sense foreign and self-DNA and trigger type I interferon (IFN) immune responses.

A natural impact-resistant bicontinuous composite nanoparticle coating.

Nature utilizes the available resources to construct lightweight, strong and tough materials under constrained environmental conditions. The impact surface of the fast-striking dactyl club from the mantis shrimp is an example of one such composite material; the shrimp has evolved the capability to localize damage and avoid catastrophic failure from high-speed collisions during its feeding activities. Here we report that the dactyl club of mantis shrimps contains an impact-resistant coating composed of densely packed (about 88 per cent by volume) ~65-nm bicontinuous nanoparticles of hydroxyapatite integrated within an organic matrix.

Cost-effectiveness analysis of pre-ART HIV drug resistance testing in Kenyan women.

Background: The prevalence of pre-treatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitor (NNRTI) agents is increasing in sub-Saharan Africa, which may decrease the effectiveness of efavirenz-based antiretroviral therapy (ART) programs. However, due to recent safety concerns, there has been hesitancy to replace efavirenz-based ART with dolutegravir in women of reproductive potential. Our objective was to evaluate whether PDR testing for women not initiating dolutegravir-based ART would be a cost-effective strategy to address the challenges posed by PDR.

Control of wildfire-sourced PM2.5 in an office setting using a commercially available portable air cleaner.

A steady increase in wildfire event severity and season length has led to greater potential for exposure to fine particulate matter associated with wildfire smoke. Research has found fine particulate matter to be correlated with a myriad of health ailments and thus effective strategies for controlling exposures are needed. In this study, a correction factor associated with wildfire-sourced fine particulate matter was established for a TSI SidePak AM520 by conducting sampling with a co-located MetOne BAM 1020.

A microelectromechanical systems (MEMS) force-displacement transducer for sub-5 nm nanoindentation and adhesion measurements.

We present a highly sensitive force-displacement transducer capable of performing ultra-shallow nanoindentation and adhesion measurements. The transducer utilizes electrostatic actuation and capacitive sensing combined with microelectromechanical fabrication technologies. Air indentation experiments report a root-mean-square (RMS) force resolution of 1.

Piezoresistive Response of Quasi-One-Dimensional ZnO Nanowires Using an in Situ Electromechanical Device.

Quasi-one-dimensional structures from metal oxides have shown remarkable potentials with regard to their applicability in advanced technologies ranging from ultraresponsive nanoelectronic devices to advanced healthcare tools. Particularly due to the piezoresistive effects, zinc oxide (ZnO)-based nanowires showed outstanding performance in a large number of applications, including energy harvesting, flexible electronics, smart sensors, etc. In the present work, we demonstrate the versatile crystal engineering of ZnO nano- and microwires (up to centimeter length scales) by a simple flame transport process.

Mortality along the continuum of HIV care in Rwanda: a model-based analysis.

Background: HIV is the leading cause of death among adults in sub-Saharan Africa. However, mortality along the HIV care continuum is poorly described. We combine demographic, epidemiologic, and health services data to estimate where are people with HIV dying along Rwanda's care continuum.

High Cycle Fatigue in the Transmission Electron Microscope.

One of the most common causes of structural failure in metals is fatigue induced by cyclic loading. Historically, microstructure-level analysis of fatigue cracks has primarily been performed post mortem. However, such investigations do not directly reveal the internal structural processes at work near micro- and nanoscale fatigue cracks and thus do not provide direct evidence of active microstructural mechanisms.

Hunting, Exotic Carnivores, and Habitat Loss: Anthropogenic Effects on a Native Carnivore Community, Madagascar.

The wide-ranging, cumulative, negative effects of anthropogenic disturbance, including habitat degradation, exotic species, and hunting, on native wildlife has been well documented across a range of habitats worldwide with carnivores potentially being the most vulnerable due to their more extinction prone characteristics. Investigating the effects of anthropogenic pressures on sympatric carnivores is needed to improve our ability to develop targeted, effective management plans for carnivore conservation worldwide. Utilizing photographic, line-transect, and habitat sampling, as well as landscape analyses and village-based bushmeat hunting surveys, we provide the first investigation of how multiple forms of habitat degradation (fragmentation, exotic carnivores, human encroachment, and hunting) affect carnivore occupancy across Madagascar's largest protected area: the Masoala-Makira landscape.

Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates.

Purpose: To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS).

Methods: Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing.

Chemical genetic approach identifies microtubule affinity-regulating kinase 1 as a leucine-rich repeat kinase 2 substrate.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of autosomal-dominant forms of Parkinson's disease. LRRK2 is a modular, multidomain protein containing 2 enzymatic domains, including a kinase domain, as well as several protein-protein interaction domains, pointing to a role in cellular signaling. Although enormous efforts have been made, the exact pathophysiologic mechanisms of LRRK2 are still not completely known.

Using soil records with atmospheric dispersion modeling to investigate the effects of clean air regulations on 60 years of manganese deposition in Marietta, Ohio (USA).

Atmospheric emissions of metals from anthropogenic activities have led to deposition and contamination of soils worldwide. We quantified addition of manganese (Mn) to soils around the largest emitter of Mn in the United States (U.S.

Randomness in the evolution of cooperation.

Tag-based ethnocentric cooperation is a highly robust behavior which can evolve and prevail under a wide variety of conditions. Recent studies have demonstrated, however, that ethnocentrism can temporarily be suppressed by other competing strategies, especially in its early evolutionary stages. In a series of computational experiments, conducted with an agent-based evolutionary model of tag-mediated cooperation, we addressed the question of whether a stochastically established and once dominant non-ethnocentric strategy such as indiscriminate altruism can stably persist and permanently outweigh ethnocentrism.

An atomic charge model for graphene oxide for exploring its bioadhesive properties in explicit water.

Graphene Oxide (GO) has been shown to exhibit properties that are useful in applications such as biomedical imaging, biological sensors, and drug delivery. The binding properties of biomolecules at the surface of GO can provide insight into the potential biocompatibility of GO. Here we assess the intrinsic affinity of amino acids to GO by simulating their adsorption onto a GO surface.

Favorable adsorption of capped amino acids on graphene substrate driven by desolvation effect.

The use of graphene-based nanomaterials is being explored in the context of various biomedical applications. Here, we performed a molecular dynamics simulation of individual amino acids on graphene utilizing an empirical force field potential (Amber03). The accuracy of our force field method was verified by modeling the adsorption of amino acids on graphene in vacuum.

Discovery of novel indolinone-based, potent, selective and brain penetrant inhibitors of LRRK2.

Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). The most frequent kinase-enhancing mutation is the G2019S residing in the kinase activation domain. This opens up a promising therapeutic avenue for drug discovery targeting the kinase activity of LRRK2 in PD.

Estrogen Receptor α (ERα) and Estrogen Related Receptor α (ERRα) are both transcriptional regulators of the Runx2-I isoform.

Runx2 is a master regulator of bone development and has also been described as an oncogene. Estrogen Receptor α (ERα) and Estrogen Related Receptor α (ERRα), both implicated in bone metabolism and breast cancer, have been shown to share common transcriptional targets. Here, we show that ERα is a positive regulator of Runx2-I transcription.

High LRRK2 levels fail to induce or exacerbate neuronal alpha-synucleinopathy in mouse brain.

The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2) is one of the most frequently identified genetic causes of Parkinson's disease (PD). Clinically, LRRK2(G2019S) carriers with PD and idiopathic PD patients have a very similar disease with brainstem and cortical Lewy pathology (α-synucleinopathy) as histopathological hallmarks. Some patients have Tau pathology.

The PARP inhibitor PJ34 causes a PARP1-independent, p21 dependent mitotic arrest.

Poly(ADP)-ribose polymerase (PARP) inhibitors modify the enzymatic activity of PARP1/2. When certain PARP inhibitors are used either alone or in combination with DNA damage agents they may cause a G2/M mitotic arrest and/or apoptosis in a susceptible genetic context. PARP1 interacts with the cell cycle checkpoint proteins Ataxia Telangectasia Mutated (ATM) and ATM and Rad3-related (ATR) and therefore may influence growth arrest cascades.

An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression.

Mammalian DNA replication initiates at multiple sites along chromosomes at different times, following a temporal replication program. Homologous alleles typically replicate synchronously; however, mono-allelically expressed genes such as imprinted genes, allelically excluded genes and genes on the female X chromosome replicate asynchronously. We have used a chromosome engineering strategy to identify a human autosomal locus that controls this replication timing program in cis.