Diagnostic and prognostic capabilities of a biomarker and EMR-based machine learning algorithm for sepsis.

Sepsis is a major cause of mortality among hospitalized patients worldwide. Shorter time to administration of broad-spectrum antibiotics is associated with improved outcomes, but early recognition of sepsis remains a major challenge. In a two-center cohort study with prospective sample collection from 1400 adult patients in emergency departments suspected of sepsis, we sought to determine the diagnostic and prognostic capabilities of a machine-learning algorithm based on clinical data and a set of uncommonly measured biomarkers.

Oligonucleotides and G-quadruplex stabilizers: targeting telomeres and telomerase in cancer therapy.

Cancer is a leading cause of death worldwide and an estimated 1 in 4 deaths in the United States is due to cancer. Despite recent advances in cancer treatment, adverse effects related to cancer therapy remain a limiting factor for many patients. The ideal cancer treatment would selectively target cancerous cells while sparing normal, healthy cells to offer maximal therapeutic benefit while minimizing toxicity.

T-oligo as an anticancer agent in colorectal cancer.

In the United States, there will be an estimated 96,830 new cases of colorectal cancer (CRC) and 50,310 deaths in 2014. CRC is often detected at late stages of the disease, at which point there is no effective chemotherapy. Thus, there is an urgent need for effective novel therapies that have minimal effects on normal cells.

Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization.

Objectives: To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR).

Methods: Susceptibility testing by broth microdilution was performed on 30 MRSA clinical isolates. For four of these isolates, the presence or absence of mutations in the QRDR was characterized.

R chi-01, a new family of oxazolidinones that overcome ribosome-based linezolid resistance.

New and improved antibiotics are urgently needed to combat the ever-increasing number of multidrug-resistant bacteria. In this study, we characterized several members of a new oxazolidinone family, R chi-01. This antibiotic family is distinguished by having in vitro and in vivo activity against hospital-acquired, as well as community-acquired, pathogens.

Recombineering with tolC as a selectable/counter-selectable marker: remodeling the rRNA operons of Escherichia coli.

This work describes the novel use of tolC as a selectable/counter-selectable marker for the facile modification of DNA in Escherichia coli. Expression of TolC (an outer membrane protein) confers relative resistance to toxic small molecules, while its absence renders the cell tolerant to colicin E1. These features, coupled with the lambdaredgam recombination system, allow for selection of tolC insertions/deletions anywhere on the E.

Structure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches.

We report three crystal structures of the Mycobacterium tuberculosis cell division protein FtsZ, as the citrate, GDP, and GTPgammaS complexes, determined at 1.89, 2.60, and 2.

Cysteinyl-tRNA(Cys) formation in Methanocaldococcus jannaschii: the mechanism is still unknown.

Most organisms form Cys-tRNA(Cys), an essential component for protein synthesis, through the action of cysteinyl-tRNA synthetase (CysRS). However, the genomes of Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus, and Methanopyrus kandleri do not contain a recognizable cysS gene encoding CysRS. It was reported that M.

Exploring the structure and function of the mycobacterial KatG protein using trans-dominant mutants.

In order to probe the structure and function of the mycobacterial catalase-peroxidase enzyme (KatG), we employed a genetic approach using dominant-negative analysis of katG merodiploids. Transformation of Mycobacterium bovis BCG with various katG point mutants (expressed from low-copy-number plasmids) resulted in reductions in peroxidase and catalase activities as measured in cell extracts. These reductions in enzymatic activity usually correlated with increased resistance to the antituberculosis drug isoniazid (INH).

Regulated expression of the Escherichia coli lepB gene as a tool for cellular testing of antimicrobial compounds that inhibit signal peptidase I in vitro.

Escherichia coli under-expressing lepB was utilized to test cellular inhibition of signal peptidase I (SPase). For the construction of a lepB regulatable strain, the E. coli lepB gene was cloned into pBAD, with expression dependent on L-arabinose.

An array of target-specific screening strains for antibacterial discovery.

As the global threat of drug- and antibiotic-resistant bacteria continues to rise, new strategies are required to advance the drug discovery process. This work describes the construction of an array of Escherichia coli strains for use in whole-cell screens to identify new antimicrobial compounds. We used the recombination systems from bacteriophages lambda and P1 to engineer each strain in the array for low-level expression of a single, essential gene product, thus making each strain hypersusceptible to specific inhibitors of that gene target.