Semiclassical Transition State Theory (SCTST) Rate Coefficients for the Unimolecular Decomposition of the Ethoxy (CHCHO) Radical.

The thermal unimolecular decay of ethoxy is important in high-temperature combustion environments where the ethoxy radical is a key reactive intermediate. Two dissociation pathways of ethoxy, including the β-C-C scission to yield CH + CHO and the H-elimination to make H + CHCHO, were characterized using a high-level coupled-cluster-based composite quantum chemical method (mHEAT-345(Q)). The former route is found to be dominant while the latter is insignificant, in agreement with previous experimental and theoretical studies.

Discovery and Optimization of N-Heteroaryl Indazole LRRK2 Inhibitors.

Inhibition of leucine-rich repeat kinase 2 is a genetically supported mechanism for the treatment of Parkinson's disease. We previously disclosed the discovery of an indazole series lead that demonstrated both safety and translational risks. The safety risks were hypothesized to be of unknown origin, so structural diversity in subsequent chemical matter was prioritized.

Accelerated flushing of contaminants from MSW landfill at the field scale using a fill-and-draw method.

A fill-and-draw flushing test on a landfill cell containing MSW waste was carried out to examine the operational viability of this method for accelerating the flushing of contaminants and landfill stabilisation. During the fill cycle, 800 m of water containing the tracer bromide was pumped into the base of a 0.44 ha landfill cell, resulting in the estimated saturation of 9,400 m of waste.

Antivesiculation and Complete Unbinding of Tail-Tethered Lipids.

We report the effect of tail-tethering on vesiculation and complete unbinding of bilayered membranes. Amphiphilic molecules of a bolalipid, resembling the tail-tethered molecular structure of archaeal lipids, with two identical zwitterionic phosphatidylcholine headgroups self-assemble into a large flat lamellar membrane, in contrast to the multilamellar vesicles (MLVs) observed in its counterpart, monopolar nontethered zwitterionic lipids. The antivesiculation is confirmed by small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cyro-TEM).

Pretreatment of Mesenchymal Stem Cells with Electrical Stimulation as a Strategy to Improve Bone Tissue Engineering Outcomes.

Electrical stimulation (EStim), whether used alone or in combination with bone tissue engineering (BTE) approaches, has been shown to promote bone healing. In our previous in vitro studies, mesenchymal stem cells (MSCs) were exposed to EStim and a sustained, long-lasting increase in osteogenic activity was observed. Based on these findings, we hypothesized that pretreating MSC with EStim, in 2D or 3D cultures, before using them to treat large bone defects would improve BTE treatments.

Structural insights into selective small molecule activation of PKG1α.

cGMP-dependent protein kinase I-α (PKG1α) is a target for pulmonary arterial hypertension due to its role in the regulation of smooth muscle function. While most work has focused on regulation of cGMP turnover, we recently described several small molecule tool compounds which were capable of activating PKG1α via a cGMP independent pathway. Selected molecules were crystallized in the presence of PKG1α and were found to bind to an allosteric site proximal to the low-affinity nucleotide binding domain.

Discovery of IACS-52825, a Potent and Selective DLK Inhibitor for Treatment of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major unmet medical need with limited treatment options. Despite different mechanisms of action, diverse chemotherapeutics can cause CIPN through a converged pathway─an active axon degeneration program that engages the dual leucine zipper kinase (DLK). DLK is a neuronally enriched kinase upstream in the MAPK-JNK cascade, and while it is dormant under physiological conditions, DLK mediates a core mechanism for neuronal injury response under stress conditions, making it an attractive target for treatment of neuronal injury and neurodegenerative diseases.

Facile polymerization in a bicellar template to produce polymer nano-rings.

Hypothesis: A well-defined discoidal bicelle composed of three lipids, specifically zwitterionic long-chain 1,2‑dipalmitoyl phosphocholine (DPPC) and short-chain 1,2‑dihexanoyl phosphocholine (DHPC) doped with anionic 1,2‑dipalmitoyl phosphoglycerol (DPPG) provides a generalized template for the synthesis of hydrophobic polymer nano-rings. The lipid molar ratio of DPPC/DHPC/DPPG is 0.71/0.

Optimization and Mechanistic Investigations of Novel Allosteric Activators of PKG1α.

Activation of PKG1α is a compelling strategy for the treatment of cardiovascular diseases. As the main effector of cyclic guanosine monophosphate (cGMP), activation of PKG1α induces smooth muscle relaxation in blood vessels, lowers pulmonary blood pressure, prevents platelet aggregation, and protects against cardiac stress. The development of activators has been mostly limited to cGMP mimetics and synthetic peptides.

Intensive hands-on microsurgery course provides a solid foundation for performing clinical microvascular surgery.

Purpose: Microvascular surgery requires highly specialized and individualized training; most surgical residency training programs are not equipped with microsurgery teaching expertise and/or facilities. The aim of this manuscript was to describe the methodology and clinical effectiveness of an international microsurgery course, currently taught year-round in eight countries.

Methods: In the 5-day microsurgery course trainees perform arterial and venous end-to-end, end-to-side, one-way-up, and continuous suture anastomoses and vein graft techniques in live animals, supported by video demonstrations and hands-on guidance by a full-time instructor.

The very small angle neutron scattering instrument at the National Institute of Standards and Technology.

A description and the performance of the very small angle neutron scattering diffractometer at the National Institute of Standards and Technology are presented. The measurement range of the instrument extends over three decades of momentum transfer from 2 × 10 to 0.7 Å.

CH + O: reaction mechanism, biradical and zwitterionic character, and formation of CHOO, the simplest Criegee intermediate.

The singlet and triplet potential surfaces for the title reaction were investigated using the CBS-QB3 level of theory. The wave functions for some species exhibited multireference character and required the CASPT2/6-31+G(d,p) and CASPT2/aug-cc-pVTZ levels of theory to obtain accurate relative energies. A Natural Bond Orbital Analysis showed that triplet CHOO (the simplest Criegee intermediate) and CHO (dioxirane) have mostly polar biradical character, while singlet CHOO has some zwitterionic character and a planar structure.

Discovery of Novel UDP--Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against .

This study describes a novel series of UDP--acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of LpxA with no activity against LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against LpxA (best half-maximal inhibitory concentration (IC) <5 nM) and cellular activity against (best minimal inhibitory concentration (MIC) of 4 μg/mL).

Mitigating background caused by extraneous scattering in small-angle neutron scattering instrument design.

Measurements, calculations and design ideas to mitigate background caused by extraneous scattering in small-angle neutron scattering (SANS) instruments are presented. Scattering includes processes such as incoherent scattering, inelastic scattering and Bragg diffraction. Three primary sources of this type of background are investigated: the beam stop located in front of the detector, the inside lining of the detector vessel and the environment surrounding the sample.

Quantum Transport in a Silicon Nanowire FET Transistor: Hot Electrons and Local Power Dissipation.

A review and perspective is presented of the classical, semiclassical and fully quantum routes to the simulation of electrothermal phenomena in ultrascaled silicon nanowire fieldeffect transistors. It is shown that the physics of ultrascaled devices requires at least a coupled electron quantum transport semiclassical heat equation model outlined here. The importance of the local density of states (LDOS) is discussed from classical to fully quantum versions.

Role of Bioelectricity During Cell Proliferation in Different Cell Types.

Most living organisms possess varying degrees of regenerative capabilities but how these regenerative processes are controlled is still poorly understood. Naturally occurring bioelectric voltages (like V) are thought to be playing instructive role in tissue regeneration, as well as embryonic development. The different distribution of ions on the either side of the cell membrane results in intra- and extra-cellular voltage differences, known as membrane potential or V.

Electrical Stimulation Decreases Dental Pulp Stem Cell Osteo-/Odontogenic Differentiation.

Dental pulp stem cells (DPSCs) have great potential for use in tissue engineering (TE)-based dental treatments. Electrical stimulation (EStim) has been shown to influence cellular functions that could play an important role in the success of TE treatments. Despite many recent studies focused on DPSCs, few have investigated the effect EStim has on these cells.

Electrical stimulation in bone tissue engineering treatments.

Electrical stimulation (EStim) has been shown to promote bone healing and regeneration both in animal experiments and clinical treatments. Therefore, incorporating EStim into promising new bone tissue engineering (BTE) therapies is a logical next step. The goal of current BTE research is to develop combinations of cells, scaffolds, and chemical and physical stimuli that optimize treatment outcomes.

Effects of Electrical Stimulation on Stem Cells.

Recent interest in developing new regenerative medicine- and tissue engineering-based treatments has motivated researchers to develop strategies for manipulating stem cells to optimize outcomes in these potentially, game-changing treatments. Cells communicate with each other, and with their surrounding tissues and organs via electrochemical signals. These signals originate from ions passing back and forth through cell membranes and play a key role in regulating cell function during embryonic development, healing, and regeneration.

Bone Fracture Sensing Using Ultrasound Pitch-Catch Measurements: A Proof-of-Principle Study.

The most common imaging method used to diagnose and monitor bone fractures and healing is multiple radiographic images performed by highly trained professionals with expensive equipment that can expose patients to high levels of ionizing radiation. Here we introduce and illustrate proof-of-concept of a potential alternative method for measuring bone fractures: ultrasound pitch-catch measurement technique. Measurements are performed with two piezoelectric transducers, housed in standard orthopedic screws and fixed on either side of simulated fractures, with and without an orthopedic plate, in ex vivo pig limb bones.

Small and ultra-small angle neutron scattering studies of commercial milk.

Milk and milk products are an essential part of global nutrition and the world-wide food industry. Studies of milk components using scattering techniques are well documented in the literature. However, those studies focused on the scattering wavevector region .

Electrical stimulation-based bone fracture treatment, if it works so well why do not more surgeons use it?

Background: Electrical stimulation (EStim) has been proven to promote bone healing in experimental settings and has been used clinically for many years and yet it has not become a mainstream clinical treatment.

Methods: To better understand this discrepancy we reviewed 72 animal and 69 clinical studies published between 1978 and 2017, and separately asked 161 orthopedic surgeons worldwide about their awareness, experience, and acceptance of EStim for treating fracture patients.

Results: Of the 72 animal studies, 77% reported positive outcomes, and the most common model, bone, fracture type, and method of administering EStim were dog, tibia, large bone defects, and DC, respectively.