Targeted Investigational Oncology Agents in the NCI-60: A Phenotypic Systems-based Resource.

The NCI-60 human tumor cell line panel has proved to be a useful tool for the global cancer research community in the search for novel chemotherapeutics. The publicly available cell line characterization and compound screening data from the NCI-60 assay have significantly contributed to the understanding of cellular mechanisms targeted by new oncology agents. Signature sensitivity/resistance patterns generated for a given chemotherapeutic agent against the NCI-60 panel have long served as fingerprint presentations that encompass target information and the mechanism of action associated with the tested agent.

Fiber Optic Sensing Textile for Strain Monitoring in Composite Substrates.

Composite polymers have become widely used in industries such as the aerospace, automobile, and civil construction industries. Continuous monitoring is essential to optimize the composite components' performance and durability. This paper describes the concept of a distributed fiber optic smart textile (DFOST) embedded into a composite panel that can be implemented during the fabrication process of bridges, planes, or vehicles without damaging the integrity of the composite.

Correction to "An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with Efficacy against Drug-Resistant Gram-Negative Infections".

[This corrects the article DOI: 10.1021/acscentsci.2c00598.

An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with Efficacy against Drug-Resistant Gram-Negative Infections.

Genomic studies and experiments with permeability-deficient strains have revealed a variety of biological targets that can be engaged to kill Gram-negative bacteria. However, the formidable outer membrane and promiscuous efflux pumps of these pathogens prevent many candidate antibiotics from reaching these targets. One such promising target is the enzyme FabI, which catalyzes the rate-determining step in bacterial fatty acid biosynthesis.

Pentostatin antagonizes the antiviral activity of MBX-2168 by inhibiting the biosynthesis of the active compound.

MBX-2168 has a mechanism of action similar to that of acyclovir (ACV) and ganciclovir (GCV), but two unique steps differentiate this drug from ACV/GCV. First, MBX-2168 is, at least partially, phosphorylated by the endogenous cellular kinase TAOK3 to a monophosphate. The second involves the removal of a moiety at the 6-position of MBX-2168-MP by adenosine deaminase like protein-1 (ADAL-1).

A Structure-Function-Inhibition Analysis of the Type III Secretion Needle Protein PscF.

The type III secretion system (T3SS) needle comprised of multiple PscF subunits is essential for the translocation of effector toxins into human cells, facilitating the establishment and dissemination of infection. Mutations in the gene provide resistance to the phenoxyacetamide (PhA) series of T3SS inhibitory chemical probes. To better understand PscF functions and interactions with PhA, alleles of with 71 single mutations altering 49 of the 85 residues of the encoded protein were evaluated for their effects on T3SS phenotypes.

Biosynthesis and half-life of MBX-2168-triphosphate in herpes virus-infected cells.

The third generation of methylenecyclopropane nucleoside analogs (MCPNAs) elicit an anti-viral effect against all three sub-classes of herpes viruses without inducing cytotoxicity in vitro. It has been previously established that the mechanism of action of MCPNAs is similar to that of ganciclovir (GCV) or acyclovir (ACV). However, the activation of MBX-2168, a third generation MCPNA, involves additional and unique enzymatic steps and this process has not been examined in virus-infected cells.

Recurrent acute kidney injury: predictors and impact in a large population-based cohort.

Background: This study examined the impact of recurrent episodes of acute kidney injury (AKI) on patient outcomes.

Methods: The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients ≥18 years of age between April 2015 and September 2018. Patients were grouped according to the number of AKI episodes they experienced with each patient's first episode described as their index episode.

Activation of 6-Alkoxy-Substituted Methylenecyclopropane Nucleoside Analogs Requires Enzymatic Modification by Adenosine Deaminase-Like Protein 1.

To determine the mechanism of action of third-generation methylenecyclopropane nucleoside analogs (MCPNAs), DNA sequencing of herpes simplex virus 1 (HSV-1) isolates resistant to third-generation MCPNAs resulted in the discovery of G841S and N815S mutations in HSV-1 UL30. Purified HSV-1 UL30 or human cytomegalovirus (HCMV) UL54 was then subjected to increasing concentrations of MBX-2168-triphosphate (TP), with results demonstrating a 50% inhibitory concentration (IC) of ∼200 μM, indicating that MBX-2168-TP does not inhibit the viral DNA polymerase. Further metabolic studies showed the removal of a moiety on the guanine ring of MBX-2168.

Acute Kidney Injury, Age, and Socioeconomic Deprivation: Evaluation of a National Data Set.

Introduction: This study examined the relationship among age, measures of social deprivation, and incidence and outcome of acute kidney injury (AKI).

Methods: The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients 18 years or older between March 2015 and January 2017. Socioeconomic classification of patients was derived from the Welsh Index of Multiple Deprivation (WIMD).

Utility of electronic AKI alerts in intensive care: A national multicentre cohort study.

Background: Electronic AKI alerts highlight changes in serum creatinine compared to the patient's own baseline. Our aim was to identify all AKI alerts and describe the relationship between electronic AKI alerts and outcome for AKI treated in the Intensive Care Unit (ICU) in a national multicentre cohort.

Methods: A prospective cohort study was undertaken between November 2013 and April 2016, collecting data on electronic AKI alerts issued.

Understanding Electronic AKI Alerts: Characterization by Definitional Rules.

Introduction: Automated acute kidney injury (AKI) electronic alerts are based on comparing creatinine with historic results.

Methods: We report the significance of AKI defined by 3 "rules" differing in the time period from which the baseline creatinine is obtained, and AKI with creatinine within the normal range.

Results: A total of 47,090 incident episodes of AKI occurred between November 2013 and April 2016.

Electrophysiology of Epithelial Sodium Channel (ENaC) Embedded in Supported Lipid Bilayer Using a Single Nanopore Chip.

Nanopore-based technologies are highly adaptable supports for developing label-free sensor chips to characterize lipid bilayers, membrane proteins, and nucleotides. We utilized a single nanopore chip to study the electrophysiology of the epithelial Na channel (ENaC) incorporated in supported lipid membrane (SLM). An isolated nanopore was developed inside the silicon cavity followed by fusing large unilamellar vesicles (LUVs) of DPPS (1,2-dipalmitoyl-sn-glycero-3-phosphoserine) and DPPE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine) to produce a solvent-free SLM with giga-ohm (GΩ) sealed impedance.

Seasonal pattern of incidence and outcome of Acute Kidney Injury: A national study of Welsh AKI electronic alerts.

Objectives: To identify any seasonal variation in the occurrence of, and outcome following Acute Kidney Injury.

Methods: The study utilised the biochemistry based AKI electronic (e)-alert system established across the Welsh National Health Service to collect data on all AKI episodes to identify changes in incidence and outcome over one calendar year (1st October 2015 and the 30th September 2016).

Results: There were total of 48 457 incident AKI alerts.

Lipid Bilayer Membrane in a Silicon Based Micron Sized Cavity Accessed by Atomic Force Microscopy and Electrochemical Impedance Spectroscopy.

Supported lipid bilayers (SLBs) are widely used in biophysical research to probe the functionality of biological membranes and to provide diagnoses in high throughput drug screening. Formation of SLBs at below phase transition temperature () has applications in nano-medicine research where low temperature profiles are required. Herein, we report the successful production of SLBs at above-as well as below-the of the lipids in an anisotropically etched, silicon-based micro-cavity.

Perceived Intensity and Discrimination Ability for Lingual Electrotactile Stimulation Depends on Location and Orientation of Electrodes.

Malfunctioning sensory systems can severely impact quality of life and repair is not always possible. One solution, called sensory substitution, is to use another sensory system to bring lost information to the brain. This approach often involves the use of bioengineered devices that electrically stimulate somatosensory fibers.

The incidence of pediatric acute kidney injury is increased when identified by a change in a creatinine-based electronic alert.

A prospective national cohort study was undertaken to collect data on all cases of pediatric (under 18 yrs of age) acute kidney injury (AKI) identified by a biochemistry-based electronic alert using the Welsh National electronic AKI reporting system. Herein we describe the utility and limitation of using this modification of the KDIGO creatinine-based system data set to characterize pediatric AKI. Of 1,343 incident episodes over a 30-month period, 34.

Non-invasive Hall current distribution measurement in a Hall effect thruster.

A means is presented to determine the Hall current density distribution in a closed drift thruster by remotely measuring the magnetic field and solving the inverse problem for the current density. The magnetic field was measured by employing an array of eight tunneling magnetoresistive (TMR) sensors capable of milligauss sensitivity when placed in a high background field. The array was positioned just outside the thruster channel on a 1.

Acute Kidney Injury in the Era of the AKI E-Alert.

Background And Objectives: Our aim was to use a national electronic AKI alert to define the incidence and outcome of all episodes of community- and hospital-acquired adult AKI.

Design, Setting, Participants, & Measurements: A prospective national cohort study was undertaken in a population of 3.06 million.

Convallatoxin-Induced Reduction of Methionine Import Effectively Inhibits Human Cytomegalovirus Infection and Replication.

Unlabelled: Cytomegalovirus (CMV) is a ubiquitous human pathogen that increases the morbidity and mortality of immunocompromised individuals. The current FDA-approved treatments for CMV infection are intended to be virus specific, yet they have significant adverse side effects, including nephrotoxicity and hematological toxicity. Thus, there is a medical need for safer and more effective CMV therapeutics.

DNA Targeting as a Likely Mechanism Underlying the Antibacterial Activity of Synthetic Bis-Indole Antibiotics.

We previously reported the synthesis and biological activity of a series of cationic bis-indoles with potent, broad-spectrum antibacterial properties. Here, we describe mechanism of action studies to test the hypothesis that these compounds bind to DNA and that this target plays an important role in their antibacterial outcome. The results reported here indicate that the bis-indoles bind selectively to DNA at A/T-rich sites, which is correlated with the inhibition of DNA and RNA synthesis in representative Gram-positive () and Gram-negative () organisms.

Electrochemical impedance spectroscopy for black lipid membranes fused with channel protein supported on solid-state nanopore.

Black lipid membranes (BLMs) have been used for detecting single-channel activities of pore-forming peptides and ion channels. However, the short lifetimes and poor mechanical stability of suspended bilayers limit their applications in high throughput electrophysiological experiments. In this work, we present a synthetic solid-state nanopore functionalized with BLM fused with channel protein.

Surface Free Energy Determination of APEX Photosensitive Glass.

Surface free energy (SFE) plays an important role in microfluidic device operation. Photosensitive glasses such as APEX offer numerous advantages over traditional glasses for microfluidics, yet the SFE for APEX has not been previously reported. We calculate SFE with the Owens/Wendt geometric method by using contact angles measured with the Sessile drop technique.

Fabrication of Solid State Nanopore in Thin Silicon Membrane Using Low Cost Multistep Chemical Etching.

Nanopore-based analysis is currently an area of great interest in many disciplines with the potential for exceptionally versatile applications in medicine. This work presents a novel step towards fabrication of a single solid-state nanopore (SSSN) in a thin silicon membrane. Silicon nanopores are realized using multistep processes on both sides of n-type silicon-on-insulator (SOI) <100> wafer with resistivity 1-4 Ω·cm.