Nondestructive, high-resolution, chemically specific 3D nanostructure characterization using phase-sensitive EUV imaging reflectometry.

Next-generation nano- and quantum devices have increasingly complex 3D structure. As the dimensions of these devices shrink to the nanoscale, their performance is often governed by interface quality or precise chemical or dopant composition. Here, we present the first phase-sensitive extreme ultraviolet imaging reflectometer.

Fluorescence Anisotropy-Based Tethering for Discovery of Protein-Protein Interaction Stabilizers.

Protein-protein interaction (PPI) networks are fundamental for cellular processes. Small-molecule PPI enhancers have been shown to be powerful tools to fundamentally study PPIs and as starting points for potential new therapeutics. Yet, systematic approaches for their discovery are not widely available, and the design prerequisites of "molecular glues" are poorly understood.

Inducible nitric oxide synthase: Regulation, structure, and inhibition.

A considerable number of human diseases have an inflammatory component, and a key mediator of immune activation and inflammation is inducible nitric oxide synthase (iNOS), which produces nitric oxide (NO) from l-arginine. Overexpressed or dysregulated iNOS has been implicated in numerous pathologies including sepsis, cancer, neurodegeneration, and various types of pain. Extensive knowledge has been accumulated about the roles iNOS plays in different tissues and organs.

Disinfection of Blood Pressure Cuffs and Electrocardiographic Telemetry Leads With 0.5% Hydrogen Peroxide Wipes.

Background: Disinfection of frequently touched surfaces in the hospital is critical for providing safe care. Because of their complex intricate surfaces, blood pressure cuffs and electrocardiographic telemetry leads may be harder than other equipment to disinfect.

Objective: To determine the effectiveness of 0.

Door openings in the operating room are associated with increased environmental contamination.

Door openings in the operating room (OR) have been hypothesized to increase OR environmental contamination. This study measured average colony-forming units (CFU) in the OR as a function of door openings and other potentially important variables. Bacterial settle plates were placed inside and outside of laminar airflow (LAF) by both exit doors, on the instrument table, and on the back instrument table (if applicable) for 48 orthopedic and general surgery procedures.

Total Synthesis of Tambromycin Enabled by Indole C-H Functionalization.

The total synthesis of tambromycin (1), a recently isolated tetrapeptide, is reported. This unusual natural product possesses a highly modified tryptophan-derived indole fragment fused to an α-methylserine-derived oxazoline ring, and a unique noncanonical amino acid residue named tambroline (11). A convergent synthesis of tambromycin was achieved by a 13-step route that leveraged recent developments in the field of C-H functionalization to prepare the complex indole fragment, as well as an efficient synthesis of tambroline that featured a diastereoselective amination of homoproline.

Interrogation of Benzomalvin Biosynthesis Using Fungal Artificial Chromosomes with Metabolomic Scoring (FAC-MS): Discovery of a Benzodiazepine Synthase Activity.

The benzodiazepine benzomalvin A/D is a fungally derived specialized metabolite and inhibitor of the substance P receptor NK1, biosynthesized by a three-gene nonribosomal peptide synthetase cluster. Here, we utilize fungal artificial chromosomes with metabolomic scoring (FAC-MS) to perform molecular genetic pathway dissection and targeted metabolomics analysis to assign the in vivo role of each domain in the benzomalvin biosynthetic pathway. The use of FAC-MS identified the terminal cyclizing condensation domain as BenY-C and the internal C-domains as BenZ-C and BenZ-C.

A scalable platform to identify fungal secondary metabolites and their gene clusters.

The genomes of filamentous fungi contain up to 90 biosynthetic gene clusters (BGCs) encoding diverse secondary metabolites-an enormous reservoir of untapped chemical potential. However, the recalcitrant genetics, cryptic expression, and unculturability of these fungi prevent scientists from systematically exploiting these gene clusters and harvesting their products. As heterologous expression of fungal BGCs is largely limited to the expression of single or partial clusters, we established a scalable process for the expression of large numbers of full-length gene clusters, called FAC-MS.

Molecular gas in the halo fuels the growth of a massive cluster galaxy at high redshift.

The largest galaxies in the universe reside in galaxy clusters. Using sensitive observations of carbon monoxide, we show that the Spiderweb galaxy-a massive galaxy in a distant protocluster-is forming from a large reservoir of molecular gas. Most of this molecular gas lies between the protocluster galaxies and has low velocity dispersion, indicating that it is part of an enriched intergalactic medium.

SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane.

Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments.

Low dose compared to variable dose Warfarin and to Fondaparinux as prophylaxis for thromboembolism after elective hip or knee replacement surgery; a randomized, prospective study.

Background: Deep vein thrombosis (DVT) and pulmonary emboli (PE), known together as venous thromboembolic (VTE) disease remain major complications following elective hip and knee surgery. This study compares three chemoprophylactic regimens for VTE following elective primary unilateral hip or knee replacement, one of which was designed to minimize risk of post-operative bleeding.

Methods: Patients were randomized and stratified for hip vs.

ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.

ELQ-300 is a preclinical candidate that targets the liver and blood stages of Plasmodium falciparum, as well as the forms that are crucial to transmission of disease: gametocytes, zygotes, and ookinetes. A significant obstacle to the clinical development of ELQ-300 is related to its physicochemical properties. Its relatively poor aqueous solubility and high crystallinity limit absorption to the degree that only low blood concentrations can be achieved following oral dosing.

Inhibition of cytochrome bc1 as a strategy for single-dose, multi-stage antimalarial therapy.

Single-dose therapies for malaria have been proposed as a way to reduce the cost and increase the effectiveness of antimalarial treatment. However, no compound to date has shown single-dose activity against both the blood-stage Plasmodium parasites that cause disease and the liver-stage parasites that initiate malaria infection. Here, we describe a subset of cytochrome bc1 (cyt bc1) inhibitors, including the novel 4(1H)-quinolone ELQ-400, with single-dose activity against liver, blood, and transmission-stage parasites in mouse models of malaria.

Charge on luminous bodies resembling natural ball lightning produced via electrical arcs through lump silicon.

A phenomenon resembling natural ball lightning can be produced via electrical arcing through silicon. We use lump silicon instead of silicon wafers to achieve higher production rates and larger, longer-lived luminous balls than previously reported. The luminous balls consist of a silicon core surrounded by a porous network of loosely bound silicon dioxide nanoparticles.

Discovery, synthesis, and optimization of antimalarial 4(1H)-quinolone-3-diarylethers.

The historical antimalarial compound endochin served as a structural lead for optimization. Endochin-like quinolones (ELQ) were prepared by a novel chemical route and assessed for in vitro activity against multidrug resistant strains of Plasmodium falciparum and against malaria infections in mice. Here we describe the pathway to discovery of a potent class of orally active antimalarial 4(1H)-quinolone-3-diarylethers.

Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery.

Background: Surgical site infection has been identified as one of the most important preventable sources of morbidity and mortality associated with medical treatment. The purpose of the present study was to evaluate the feasibility and efficacy of an institutional prescreening program for the preoperative detection and eradication of both methicillin-resistant and methicillin-sensitive Staphylococcus aureus in patients undergoing elective orthopaedic surgery.

Methods: Data were collected prospectively during a single-center study.

Magnetic field probes for use in radio frequency plasma.

An impedance analyzer has been used in the characterization of a magnetic induction probe (B-dot probe) for use in plasma. The role of the impedance analyzer was to determine the frequency response of a B-dot probe up to 100 MHz. The probe was specifically designed to take measurements in rf plasma driven at 13.

An alternative theory on relaxation rates in cuprate superconductors.

Transport properties of high transition temperature (high-T(c)) superconductors apparently demonstrate two distinct relaxation rates in the normal state. We propose that this superficial inconsistence can be resolved with an effective carrier (quasiparticle) density n almost linear in temperature T. Experimental evidence both for and against this explanation is analyzed and we conclude that this offers a clear yet promising scenario.

[Enhanced structural transformations in DNA macromolecules exposed to weak thermalized neutron field].

We examined now an ultraweak thermalized neutron field (UTNF) affects the structural transformation in DNA macromolecules at room temperature. IR-spectroscopy, electrophoresis, and filtration through nitrocellulose filter measurements revealed that UTNF irradiation with a fluence of F(n) - 1.0 - 3.

Identification of cis-regulatory elements from the C. elegans Hox gene lin-39 required for embryonic expression and for regulation by the transcription factors LIN-1, LIN-31 and LIN-39.

Expression of the Caenorhabditis elegans Hox gene lin-39 begins in the embryo and continues in multiple larval cells, including the P cell lineages that generate ventral cord neurons (VCNs) and vulval precursor cells (VPCs). lin-39 is regulated by several factors and by Wnt and Ras signaling pathways; however, no cis-acting sites mediating lin-39 regulation have been identified. Here, we describe three elements controlling lin-39 expression: a 338-bp upstream fragment that directs embryonic expression in P5-P8 and their descendants in the larva, a 247-bp intronic region sufficient for VCN expression, and a 1.

Identification of residues of the Caenorhabditis elegans LIN-1 ETS domain that are necessary for DNA binding and regulation of vulval cell fates.

LIN-1 is an ETS domain protein. A receptor tyrosine kinase/Ras/mitogen-activated protein kinase signaling pathway regulates LIN-1 in the P6.p cell to induce the primary vulval cell fate during Caenorhabditis elegans development.