Quantum Channel Extreme Bandgap AlGaN HEMT.

An extreme bandgap AlGaN quantum channel HEMT with AlGaN top and back barriers, grown by MOCVD on a bulk AlN substrate, demonstrated a critical breakdown field of 11.37 MV/cm-higher than the 9.8 MV/cm expected for the channel's AlGaN material.

Jerks are Useful: Extracting pulse rate from wrist-placed accelerometry jerk during sleep in children.

Study Objectives: Evaluate wrist-placed accelerometry predicted heartrate compared to electrocardiogram (ECG) heartrate in children during sleep.

Methods: Children (n=82, 61% male, 43.9% Black) wore a wrist-placed Apple Watch Series 7 (AWS7) and ActiGraph GT9X during a polysomnogram.

Comparison of raw accelerometry data from ActiGraph, Apple Watch, Garmin, and Fitbit using a mechanical shaker table.

The purpose of this study was to evaluate the reliability and validity of the raw accelerometry output from research-grade and consumer wearable devices compared to accelerations produced by a mechanical shaker table. Raw accelerometry data from a total of 40 devices (i.e.

Development and Calibration of a PATCH Device for Monitoring Children's Heart Rate and Acceleration.

Introduction: Current wearables that collect heart rate and acceleration were not designed for children and/or do not allow access to raw signals, making them fundamentally unverifiable. This study describes the creation and calibration of an open-source multichannel platform (PATCH) designed to measure heart rate and acceleration in children ages 3-8 yr.

Methods: Children (N = 63; mean age, 6.

A Sliding Scale Signal Quality Metric of Photoplethysmography Applicable to Measuring Heart Rate across Clinical Contexts with Chest Mounting as a Case Study.

Unlabelled: Photoplethysmography (PPG) signal quality as a proxy for accuracy in heart rate (HR) measurement is useful in various public health contexts, ranging from short-term clinical diagnostics to free-living health behavior surveillance studies that inform public health policy. Each context has a different tolerance for acceptable signal quality, and it is reductive to expect a single threshold to meet the needs across all contexts. In this study, we propose two different metrics as sliding scales of PPG signal quality and assess their association with accuracy of HR measures compared to a ground truth electrocardiogram (ECG) measurement.

Chemical genomics with pyrvinium identifies C1orf115 as a regulator of drug efflux.

Pyrvinium is a quinoline-derived cyanine dye and an approved anti-helminthic drug reported to inhibit WNT signaling and have anti-proliferative effects in various cancer cell lines. To further understand the mechanism by which pyrvinium is cytotoxic, we conducted a pooled genome-wide CRISPR loss-of-function screen in the human HAP1 cell model. The top drug-gene sensitizer interactions implicated the malate-aspartate and glycerol-3-phosphate shuttles as mediators of cytotoxicity to mitochondrial complex I inhibition including pyrvinium.

Identification of Novel Regulators of Radiosensitivity Using High-Throughput Genetic Screening.

The biological impact of ionizing radiation (IR) on humans depends not only on the physical properties and absorbed dose of radiation but also on the unique susceptibility of the exposed individual. A critical target of IR is DNA, and the DNA damage response is a safeguard mechanism for maintaining genomic integrity in response to the induced cellular stress. Unrepaired DNA lesions lead to various mutations, contributing to adverse health effects.

Low-dose radiotherapy for COVID-19 pneumonia and cancer: summary of a recent symposium and future perspectives.

The lessons learned from the Coronavirus Disease 2019 (COVID-19) pandemic are numerous. Low dose radiotherapy (LDRT) was used in the pre-antibiotic era as treatment for bacterially/virally associated pneumonia. Motivated in part by these historic clinical and radiobiological data, LDRT for treatment of COVID-19-associated pneumonia was proposed in early 2020.

Heterometallic multinuclear nodes directing MOF electronic behavior.

Metal node engineering in combination with modularity, topological diversity, and porosity of metal-organic frameworks (MOFs) could advance energy and optoelectronic sectors. In this study, we focus on MOFs with multinuclear heterometallic nodes for establishing metal-property trends, , connecting atomic scale changes with macroscopic material properties by utilization of inductively coupled plasma mass spectrometry, conductivity measurements, X-ray photoelectron and diffuse reflectance spectroscopies, and density functional theory calculations. The results of Bader charge analysis and studies employing the Voronoi-Dirichlet partition of crystal structures are also presented.

Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration.

PLK4 has emerged as a prime target for cancer therapeutics, and its overexpression is frequently observed in various types of human cancer. Recent studies have further revealed an unexpected oncogenic activity of PLK4 in regulating cancer cell migration and invasion. However, the molecular basis behind the role of PLK4 in these processes still remains only partly understood.

Forward genetic screen in human podocytes identifies diphthamide biosynthesis genes as regulators of adhesion.

Podocyte function is tightly linked to the complex organization of its cytoskeleton and adhesion to the underlying glomerular basement membrane. Adhesion of cultured podocytes to a variety of substrates is reported to correlate with podocyte health. To identify novel genes that are important for podocyte function, we designed an in vitro genetic screen based on podocyte adhesion to plates coated with either fibronectin or soluble Fms-like tyrosine kinase-1 (sFLT1)/Fc.

Design, synthesis, anti-inflammatory, cytotoxic and cell based studies of some novel side chain analogues of myrrhanones A & B isolated from the gum resin of Commiphora mukul.

Myrrhanones A (1) and B (2), isolated from the gum resin of Commiphora mukul, were reported to exhibit anticancer and anti-inflammatory activities. In view of their interesting skeletal features and biological activities they have been chemically modified by exploiting their side chain functionalities to synthesise 29 diverse analogues. All the synthesized analogues were screened for their cytotoxic potential against a panel of five human cancer cell lines which include DU145 (Prostate), HT-29 (Colon), MCF-7 (Breast), Hela (Cervical) and U87MG (Glioblastoma) along with a normal cell line (L132).

Pooled Lentiviral CRISPR-Cas9 Screens for Functional Genomics in Mammalian Cells.

CRISPR-Cas9 technology provides a simple way to introduce targeted mutations into mammalian cells to induce loss-of-function phenotypes. The CRISPR-Cas9 system has now successfully been applied for genetic screens in many cell types, providing a powerful tool for functional genomics with manifold applications. Genome-wide guide-RNA (gRNA) libraries allow facile generation of a pool of cells, each harboring a gene knockout mutation that can be used for the study of gene function, pathway analysis or the identification of genes required for cellular fitness.

CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions.

The observation that BRCA1- and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in homologous recombination. The cytotoxicity of PARP inhibitors depends on PARP trapping, the formation of non-covalent protein-DNA adducts composed of inhibited PARP1 bound to DNA lesions of unclear origins. To address the nature of such lesions and the cellular consequences of PARP trapping, we undertook three CRISPR (clustered regularly interspersed palindromic repeats) screens to identify genes and pathways that mediate cellular resistance to olaparib, a clinically approved PARP inhibitor.

Corrigendum: Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors.

This corrects the article DOI: 10.1038/nm.4219.

Evaluation and Design of Genome-Wide CRISPR/SpCas9 Knockout Screens.

The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled-library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols.

CT- and MRI-based gross target volume comparison in vestibular schwannomas.

Aim: This study represents an enumeration and comparison of gross target volumes (GTV) as delineated independently on contrast-enhanced computed tomography (CT) and T1 and T2 weighted magnetic resonance imaging (MRI) in vestibular schwannomas (VS).

Background: Multiple imaging in radiotherapy improves target localization.

Methods And Materials: 42 patients of VS were considered for this prospective study with one patient showing bilateral tumor.

Electronic Properties of Bimetallic Metal-Organic Frameworks (MOFs): Tailoring the Density of Electronic States through MOF Modularity.

The development of porous well-defined hybrid materials (e.g., metal-organic frameworks or MOFs) will add a new dimension to a wide number of applications ranging from supercapacitors and electrodes to "smart" membranes and thermoelectrics.

Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors.

Forward genetic screens with CRISPR-Cas9 genome editing enable high-resolution detection of genetic vulnerabilities in cancer cells. We conducted genome-wide CRISPR-Cas9 screens in RNF43-mutant pancreatic ductal adenocarcinoma (PDAC) cells, which rely on Wnt signaling for proliferation. Through these screens, we discovered a unique requirement for a Wnt signaling circuit: engaging FZD5, one of the ten Frizzled receptors encoded in the human genome.

A comparative evaluation of two rotary Ni-Ti instruments in the removal of gutta-percha during retreatment.

Aim: The purpose of this study is to achieve an effective method to remove root canal filling material from the root canal system. The study, thus, aims to evaluate the efficacy of the cleaning ability of two different rotary Ni-Ti systems; ProTaper Retreatment files and RaCe System compared to hand instrumentation with Hedstrom files for the removal of gutta-percha during retreatment.

Materials And Methods: Thirty mandibular premolars with one single straight canal were decoronated and instrumented with ProTaper files and filled with thermoplastic gutta-percha.

Novel triazole hybrids of myrrhanone C, a natural polypodane triterpene: Synthesis, cytotoxic activity and cell based studies.

The 3-keto functionality in ring A of myrrhanone C, a natural bicyclic triterpene has been chemically modified and synthesized 27 novel triazole hybrids belonging to two different series in very good to excellent yields (66-83%). The synthesized compounds were thoroughly characterized by their spectroscopic data (IR, (1)H&(13)C NMR, HRMS). All the synthesized compounds were evaluated for their cytotoxic potential against a panel of five human cancer cell lines by employing MTT assay using doxorubicin as the standard.

Cytokinetic effects of Wee1 disruption in pancreatic cancer.

The Wee1 kinase, which is activated in response to DNA damage, regulates exit from G2 through inhibitory phosphorylation of Cdk1/Cdc2, and is an attractive drug target. However, recent work has highlighted effects of Cdk2 phosphorylation by Wee1 on movement through S-phase, suggesting the potential to sensitize to S-phase specific agents by Wee1 inhibitors. In this paper we applied multiparametric flow cytometry to patient-derived pancreatic cancer xenograft tumor cells to study the cell cycle perturbations of Wee1 disruption via the small molecule inhibitor MK-1775, and genetic knockdown.

High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities.

The ability to perturb genes in human cells is crucial for elucidating gene function and holds great potential for finding therapeutic targets for diseases such as cancer. To extend the catalog of human core and context-dependent fitness genes, we have developed a high-complexity second-generation genome-scale CRISPR-Cas9 gRNA library and applied it to fitness screens in five human cell lines. Using an improved Bayesian analytical approach, we consistently discover 5-fold more fitness genes than were previously observed.

Synthesis and anticancer activity of novel fused pyrimidine hybrids of myrrhanone C, a bicyclic triterpene of Commiphora mukul gum resin.

Myrrhanone C [8(R)-3-oxo-8-hydroxypolypoda-13E,17E,21-triene], a bicyclic triterpene isolated from the gum resin of Commiphora mukul, has been chemically transformed to synthesize a series of ten novel pyrimidine hybrids in good to excellent yields. The synthesized compounds (2-22) were evaluated for their anticancer potential against a panel of six cancer cell lines, namely A-549 (lung), Hela (cervical), MCF-7 (breast), ACHN (renal), Colo-205 (colon) and B-16 (mouse melanoma) by employing the MTT assay. In general, the synthesized compounds showed significant anticancer activity against all the cancer cell lines tested.