Translating the therapeutic potential of AZD4547 in FGFR1-amplified non-small cell lung cancer through the use of patient-derived tumor xenograft models.

Purpose: To investigate the incidence of FGFR1 amplification in Chinese non-small cell lung cancer (NSCLC) and to preclinically test the hypothesis that the novel, potent, and selective fibroblast growth factor receptor (FGFR) small-molecule inhibitor AZD4547 will deliver potent antitumor activity in NSCLC FGFR1-amplified patient-derived tumor xenograft (PDTX) models.

Experimental Design: A range of assays was used to assess the translational relevance of FGFR1 amplification and AZD4547 treatment including in vitro lung cell line panel screening and pharmacodynamic (PD) analysis, FGFR1 FISH tissue microarray (TMA) analysis of Chinese NSCLC (n = 127), and, importantly, antitumor efficacy testing and PD analysis of lung PDTX models using AZD4547.

Results: The incidence of FGFR1 amplification within Chinese patient NSCLC tumors was 12.

Effects of long-term high-fat/high-energy and high-protein diets on insulin and ghrelin expression in developing rats.

Objective: This study investigated the long-term effects of high-fat/high-energy and high-protein diets on insulin secretion and ghrelin expression.

Methods: Dams of Sprague-Dawley rats were fed a standard, high-fat/high-energy, or high-protein diet during pregnancy and lactation, and their pups were defined as control, high-fat and high-energy, and high-protein groups, respectively. The pups were fed the same diet as their dams after weaning.

Novel neutron sources at the Radiological Research Accelerator Facility.

Since the 1960s, the Radiological Research Accelerator Facility (RARAF) has been providing researchers in biology, chemistry and physics with advanced irradiation techniques, using charged particles, photons and neutrons.We are currently developing a unique facility at RARAF, to simulate neutron spectra from an improvised nuclear device (IND), based on calculations of the neutron spectrum at 1.5 km from the epicenter of the Hiroshima atom bomb.

Total serum bilirubin levels during the first 2 days of life and subsequent neonatal morbidity in very low birth weight infants: a retrospective review.

To determine the relationship between total serum bilirubin (TSB) during the first 2 days of life and subsequent neonatal morbidity in very low birth weight (VLBW, less than 1500 g) infants. We performed a prospective study of 582 VLBW infants born between July 1, 2005 and December 31, 2009. TSB was measured in umbilical cord blood (UCB), at 24 and 48 h after birth.

Total serum bilirubin level in umbilical cord blood and respiratory distress syndrome in very low birth weight infants.

Aims: To explore the association between total serum bilirubin (TSB) level in umbilical cord blood (UCB) and the occurrence and/or severity of respiratory distress syndrome (RDS) in very low birth weight (VLBW) infants.

Methods: We performed a prospective study of 579 VLBW infants. The mean TSB level in UCB (1.

NT-proBNP, but not ANP and C-reactive protein, is predictive of paroxysmal atrial fibrillation in patients undergoing pulmonary vein isolation.

Objective: The purpose of this study is to evaluate the relationship between plasma high-sensitivity C-reactive protein (hs-CRP), atrial natriuretic peptides (ANP), N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels, and the risk and recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (PAF).

Methods: Plasma ANP, NT-proBNP, and hs-CRP levels were measured before and 3 months after PVI in 33 patients with PAF and 30 control participants.

Results: (1) NT-proBNP levels at baseline were significantly elevated in subjects with PAF compared with control subjects (296.

Survey of polyphenol constituents in grapes and grape-derived products.

A rapid and comprehensive qualitative method has been developed to characterize the different classes of polyphenols, such as anthocyanins, flavonols, phenolic acids, and flavanols/proanthocyanidins, in grape products. The detection was achieved by two runs with the same LC gradient in different MS ionization modes and mobile phase modifiers (positive ionization mode and 0.4% trifluoroacetic acid for anthocyanins and flavonols; negative ionization mode and 0.

Predictors of late recurrence of atrial fibrillation after catheter ablation.

Background: To predict the recurrence of atrial fibrillation is important for selecting patients who will be undergoing catheter ablation, several studies respectively evaluated the risk factor of the recurrence of atrial fibrillation post-ablation.

Objective: To investigate the factors predicting the recurrence of atrial fibrillation (AF) after catheter ablation.

Methods: 186 patients (55.

Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth.

Most tumor cells take up more glucose than normal cells but metabolize glucose via glycolysis even in the presence of normal levels of oxygen, a phenomenon known as the Warburg effect. Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and tumorigenesis. Here we show that PKM2 is acetylated on lysine 305 and that this acetylation is stimulated by high glucose concentration.

The RABiT: a rapid automated biodosimetry tool for radiological triage. II. Technological developments.

Purpose: Over the past five years the Center for Minimally Invasive Radiation Biodosimetry at Columbia University has developed the Rapid Automated Biodosimetry Tool (RABiT), a completely automated, ultra-high throughput biodosimetry workstation. This paper describes recent upgrades and reliability testing of the RABiT.

Materials And Methods: The RABiT analyses fingerstick-derived blood samples to estimate past radiation exposure or to identify individuals exposed above or below a cut-off dose.

Ghrelin ameliorates hypoxia-induced pulmonary hypertension via phospho-GSK3 β/β-catenin signaling in neonatal rats.

Effective treatment and/or prevention strategies for neonatal persistent pulmonary hypertension of the newborn (PPHN) have been an important topic in neonatal medicine. However, mechanisms of impaired pulmonary vascular structure in hypoxia-induced PPHN are poorly understood and consequently limit the development of effective treatment. In this study, we aimed to explore the molecular signaling cascades in the lungs of a PPHN animal model and used primary cultured rat pulmonary microvascular endothelial cells to analyze the physiological benefits of ghrelin during the pathogenesis of PPHN.

Transfer printing of graphene strip from the graphene grown on copper wires.

A simple, cost-effective and lithography-free fabrication of graphene strips for device applications is demonstrated. The graphene thin layers were directly grown on Cu wires, followed by Cu etching and transfer printing to arbitrary substrates by a PDMS stamp. The Cu wires can be arranged on the PDMS stamp in a desired pattern; hence, the substrates can receive graphene strips with the same pattern.

PEG-rhGH therapy for small for gestational age rats and effects on their metabolic parameters.

Aims: To determine whether administration of long-acting polyethylene glycol moiety covalently linked to recombinant human growth hormone (PEG-rhGH) can be efficacious in the treatment of small for gestational age (SGA) rats and to characterize its effects on metabolic parameters.

Methods: 20 pregnant rats were randomly divided into undernourished and standard nourished groups. SGA or appropriate for gestational age (AGA) offspring from each were then randomly assigned to receive either PEG-rhGH or normal saline (NS).

High-quality thin graphene films from fast electrochemical exfoliation.

Flexible and ultratransparent conductors based on graphene sheets have been considered as one promising candidate for replacing currently used indium tin oxide films that are unlikely to satisfy future needs due to their increasing cost and losses in conductivity on bending. Here we demonstrate a simple and fast electrochemical method to exfoliate graphite into thin graphene sheets, mainly AB-stacked bilayered graphene with a large lateral size (several to several tens of micrometers). The electrical properties of these exfoliated sheets are readily superior to commonly used reduced graphene oxide, which preparation typically requires many steps including oxidation of graphite and high temperature reduction.

[Relative analysis of OPN and its related signal molecules in hepatocellular carcinoma].

Osteopontin (OPN) has close relationship with metastasis in hepatocellular carcinoma but its downstream signal pathways have not been well defined in hepatocellular carcinoma. The object of this study is to identify the associated signal pathways in human HCC tissues. The expressions of OPN, intergrin aV, CD44v6, P-FAK, FAK, P-Src, Src, P-ERK and P-AKT were assayed using TMA analysis.

PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ.

The Hippo pathway regulates organ size by controlling both cell proliferation and apoptosis. TAZ functions as a transcriptional co-activator downstream of the Hippo pathway and has been implicated in human cancer development. A key step in the Hippo-TAZ pathway is phosphorylation of TAZ by LATS kinase, which leads to TAZ inhibition by both cytoplasmic retention and degradation.

An accelerator-based neutron microbeam system for studies of radiation effects.

A novel neutron microbeam is being developed at the Radiological Research Accelerator Facility (RARAF) of Columbia University. The RARAF microbeam facility has been used for studies of radiation bystander effects in mammalian cells for many years. Now a prototype neutron microbeam is being developed that can be used for bystander effect studies.

The complete preventive effect of homologous tumor vaccines--based on a 5-year experimental study in mice.

By using a frozen-thaw method, we developed homologous and heterologous cell-based tumor vaccines, which were derived from mouse H22 hepatoma, S180 sarcoma and human A549 lung carcinoma, SK-OV-3 ovarian, and SMMC-7721 hepatoma cell lines. The prophylactic and therapeutic effects of those vaccines were evaluated in mice challenged with live H22 or S180 cells. The result demonstrated that homologous vaccines and heterologous vaccines had no therapeutic effect on tumor growth.

The levels of Pdx1/insulin, Cacna1c and Cacna1d, and β-cell mass in a rat model of intrauterine undernutrition.

Objective: To elucidate the underlying mechanisms responsible for β-cell mass and function in response to intrauterine growth restriction (IUGR).

Methods: Offspring from undernourished mother rats with birth weight < -2 SD (IUGR group) and from standard-nourished rats with birth weight between mean +/- 1SD normal birth weight (NBW group) were examined. Levels of fasting glucose, serum insulin, and insulin-like growth factor-1 (IGF-1) were analyzed.

Highly efficient restoration of graphitic structure in graphene oxide using alcohol vapors.

Solution-based processes involving the chemical oxidation of graphite and reduction of the obtained graphene oxide (GO) sheets have attracted much attention for preparing graphene films for printed electronics and biosensors. However, the low electrical conductivity of reduced GO is still hindering the development of electronic applications. This article presents that GO sheets reduced by high-temperature alcohol vapors exhibit highly graphitic structures and excellent electrical conductivity.

A shaker K+ channel with a miniature engineered voltage sensor.

Voltage-gated ion channels sense transmembrane voltage changes via a paddle-shaped motif that includes the C-terminal part of the third transmembrane segment (S3b) and the N-terminal part of the fourth segment ((NT)S4) that harbors voltage-sensing arginines. Here, we find that residue triplets in S3b and (NT)S4 can be deleted individually, or even in some combinations, without compromising the channels' basic voltage-gating capability. Thus, a high degree of complementarity between these S3b and (NT)S4 regions is not required for basic voltage gating per se.

Extracellular protons titrate voltage gating of a ligand-gated ion channel.

Cyclic nucleotide-gated channels mediate transduction of light into electric signals in vertebrate photoreceptors. These channels are primarily controlled by the binding of intracellular cyclic GMP (cGMP). Glutamate residue 363 near the extracellular end of the ion selectivity filter interacts with the pore helix and helps anchor the filter to the helix.