A search for narrow resonances in the dijet mass spectrum is performed using data corresponding to an integrated luminosity of 2.9 pb⁻¹ collected by the CMS experiment at the Large Hadron Collider. Upper limits at the 95% confidence level are presented on the product of the resonance cross section, branching fraction into dijets, and acceptance, separately for decays into quark-quark, quark-gluon, or gluon-gluon pairs.
View Article and Find Full Text PDFEpigenetic therapy for solid tumors could benefit from an in vivo model that defines tumor characteristics of responsiveness and resistance to facilitate patient selection. Here we report that combining the histone deacetylase inhibitor entinostat with the demethylating agent vidaza profoundly affected growth of K-ras/p53 mutant lung adenocarcinomas engrafted orthotopically in immunocompromised nude rats by targeting and ablating pleomorphic cells that occupied up to 75% of the tumor masses. A similar reduction in tumor burden was seen with epigenetic therapy in K-ras or EGFR mutant tumors growing orthotopically.
View Article and Find Full Text PDFThis paper reports a precise, live cell-patterning method by means of patterning a silicon or glass substrate with alternating cytophilic and cytophobic self-assembled monolayers (SAMs) deposited via molecular vapor deposition. Specifically, a stack of hydrophobic heptadecafluoro-1,1,2,2-tetrahydrodecyltrichlorosilane SAMs and a silicon oxide adhesion layer were patterned on the substrate surface, and a hydrophilic SAM derived from 3-trimethoxysilyl propyldiethylenetriamine was coated on the remaining non-treated areas on the substrate surface to promote cell growth. The primary characteristics of the reported method include: (i) single-cell resolution; (ii) easy alignment of the patterns with the pre-existing patterns on the substrate; (iii) easy formation of nanoscale patterns (depending on the exposure equipment); (iv) long shelf life of the substrate pattern prior to cell culturing; (v) compatibility with conventional, inverted, optical microscopes for simple visualization of patterns formed on a glass wafer; and (vi) the ability to support patterned cell (osteoblast) networks for at least 2 weeks.
View Article and Find Full Text PDFPhosphoinositide 3-kinases have been targeted for therapeutic research because they are key components of a cell signaling cascade controlling proliferation, growth, and survival. Direct activation of the PI3Kalpha pathway contributes to the development and progression of solid tumors in breast, endometrial, colon, ovarian, and gastric cancers. In the context of a drug discovery effort, the availability of a robust crystallographic system is a means to understand the subtle differences between ATP competitive inhibitor interactions with the active site and their selectivity against other PI3Kinase enzymes.
View Article and Find Full Text PDFDeath-associated protein kinase (DAPK), a mediator of apoptotic systems, is silenced by promoter hypermethylation in lung and breast tumors. This gene has a CpG island extending 2500 bp from the translational start site; however, studies characterizing its transcriptional regulation have not been conducted. Two transcripts for DAPK were identified that code for a single protein, while being regulated by two promoters.
View Article and Find Full Text PDFThere is a critical need to identify efficacious chemopreventive agents for lung cancer that can be taken chronically with no side effects and whose mechanisms of action do not involve genotoxicity that could drive, rather than impede, cancer progression. We evaluated the ability of a chemopreventive cocktail that included selenium (antioxidant), rosiglitazone (peroxisome proliferator-activated receptor gamma agonist), sodium phenylbutyrate or valproic acid (histone deacetylase inhibitors) and hydralazine (cytosine-demethylating agent) to prevent the progression of lung cancer in A/J mice treated with NNK. Agents were administered alone or in various combinations.
View Article and Find Full Text PDFThe family Arenaviridae includes a number of highly pathogenic viruses that are responsible for acute hemorrhagic fevers in humans. Genetic diversity among arenavirus species in their respective rodent hosts supports the continued emergence of new pathogens. In the absence of available vaccines or therapeutic agents, the hemorrhagic fever arenaviruses remain a serious public health and biodefense concern.
View Article and Find Full Text PDFReceptor endocytosis is regulated by ligand binding, and receptors may signal after endocytosis in signaling endosomes. We hypothesized that signaling endosomes containing different types of receptors may be distinct from one another and have different physical characteristics. To test this hypothesis, we developed a high-resolution organelle fractionation method based on mass and density, optimized to resolve endosomes from other organelles.
View Article and Find Full Text PDFIn rats, dietary protein intake influences brain concentrations of tryptophan, tyrosine, and other large neutral amino acids (LNAAs) and the neurotransmitters to which they are linked. Few experiments have examined these dietary protein-amino acid relationships in nonhuman primates, in relation to time of day or dietary protein content. We therefore examined the effect in monkeys of changes in chronic protein intake on 24-hour plasma and cerebrospinal fluid (CSF) concentrations of LNAAs (tyrosine, phenylalanine, branched-chain amino acids) and basic amino acids.
View Article and Find Full Text PDFUsing parental FVB mice and their neu transgenic counterparts, FVBN202, we showed for the first time that dangerous hyperplasia of mammary epithelial cells coincided with breaking immunological tolerance to the neu "self" tumor antigen, though such immune responses failed to prevent formation of spontaneous neu-overexpressing mammary carcinoma (MMC) or reject transplanted MMC in FVBN202 mice. On the other hand, neu-specific immune responses appeared to be effective against MMC in parental FVB mice because of the fact that rat neu protein was seen as "nonself" antigen in these animals and the protein was dangerously overexpressed in MMC. Interestingly, low/intermediate expression of the neu "nonself" protein in tumors induced immune responses but such immune responses failed to reject the tumor in FVB mice.
View Article and Find Full Text PDFDual time point 2-deoxy-2-[18F] fluoro-d-glucose (FDG) positron emission tomography (PET) imaging has been shown to be useful in helping differentiate benign from malignant lesions. An enhancing mediastinal mass of fat and water density was incidentally detected on computed tomography (CT) in a patient being evaluated for thoracic trauma. He subsequently underwent dual time point FDG PET/CT imaging which revealed a significant rise in standard uptake value (SUV) within the lesion over time, favoring a malignant etiology.
View Article and Find Full Text PDFJ Deaf Stud Deaf Educ
January 2008
In this article we address "language approach" data as a key variable in quantitative, large-scale research on educational achievement, focusing on our work for the Achievements of Deaf Pupils in Scotland (ADPS) project. The complexity of approaches is addressed, with a particular focus on a "no-exclusion" model of service. In this context 3 years of language-related data are discussed, using constructions of language variables that take into account the variability in deaf pupils' hearing loss levels, types of provision, and professional practice.
View Article and Find Full Text PDFContext: The recent change in accreditation requirements for anatomic pathology and clinical pathology residency training from 5 to 4 years and the rapid advances in technologies for pathology services have sparked a renewed debate over the adequacy of pathology residency training. In particular, perceived deficiencies in training have been declared from a variety of sources, both in the form of recent editorial opinions and from surveys of community hospital pathologist employers in 1998, 2003, and 2005 by Dr Richard Horowitz.
Objective: To obtain more comprehensive data on the perceptions of strengths and weaknesses in pathology residency training.
The use of 5-methylcytosine demethylating agents in conjunction with inhibitors of histone deacetylation may offer a new therapeutic strategy for lung cancer. Monitoring the efficacy of gene demethylating treatment directly within the tumour may be difficult due to tumour location. This study determined the positive and negative predictive values of sputum and serum for detecting gene methylation in primary lung cancer.
View Article and Find Full Text PDFThe roles of beta-NER (beta-noradrenergic receptor), GR (glucocorticoid) and mineral corticoid receptors (MR) in the consolidation of anxiogenic effects of predator stress were studied. One minute after predator stress, different groups of rats were injected (ip) with vehicle, propranolol (beta-NER blocker, 5 and 10 mg/kg), mifepristone (RU486, GR blocker, 20 mg/kg), spironolactone (MR blocker, 50 mg/kg), propranolol (5 mg/kg) plus RU486 (20 mg/kg) or the anxiolytic, chloradiazepoxide (CPZ, 10 mg/kg). One week later, rodent anxiety was assessed in elevated plus maze, hole board, light/dark box, social interaction and acoustic startle.
View Article and Find Full Text PDFDiagnosticians recognize three subtypes of attention deficit/hyperactivity disorder (ADHD) if there are developmentally inappropriate levels (six or more symptoms) of Hyperactive-Impulsive behavior, or Inattentive behavior, or both (Combined), respectively. ADHD may partly reflect androgen dysfunction, and an arguable proxy for prenatal androgen exposure is the 2D:4D finger ratio set at least as early as week 9 in the fetus; this is lower in men than in women. We examined the relationship between digit ratios and ADHD symptoms representing the three phenotypes: ADHD/Combined as measured by "summarized" (Rasched) scales, i.
View Article and Find Full Text PDFThe neurotrophin receptor TrkA plays critical roles in the nervous system by recruiting signaling molecules that activate pathways required for the growth and survival of neurons. Here, we report APPL1 as a TrkA-associated protein. APPL1 and TrkA co-immunoprecipitated in sympathetic neurons.
View Article and Find Full Text PDFIn summary, early interception of Class III malocclusion is definitely warranted for many patients. A careful analysis of the patient's problem, and an analysis of the patient's airway is essential if one is to make the correct decision as to the amenability of early treatment of the patient's Class III malocclusion. The Class I patient, in most instances, especially if the crowding is severe, can be favorably impacted with guidance of occlusion.
View Article and Find Full Text PDFPrevious studies of postpartum amenorrhea (PPA) demonstrated distinct subgroups of women with short and long durations of amenorrhea. This phenomenon was attributed to cases where breastfeeding is absent because of pregnancy loss or infant death, or confusion of postpartum bleeding with resumption of menses. We explored these ideas using data from an 11-month prospective study in Bangladesh in which 858 women provided twice-weekly interviews and urine specimens for up to 9 months; 300 women were observed while experiencing PPA.
View Article and Find Full Text PDFLocalized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior. We report 23 new cases.
View Article and Find Full Text PDFAlthough cigarette smoke has been epidemiologically associated with lung cancer in humans for many years, animal models of cigarette smoke-induced lung cancer have been lacking. This study demonstrated that life time whole body exposures of female B6C3F1 mice to mainstream cigarette smoke at 250 mg total particulate matter/m(3) for 6 h per day, 5 days a week induces marked increases in the incidence of focal alveolar hyperplasias, pulmonary adenomas, papillomas and adenocarcinomas. Cigarette smoke-exposed mice (n = 330) had a 10-fold increase in the incidence of hyperplastic lesions, and a 4.
View Article and Find Full Text PDFGiven the same reproductive span, more children with shorter interbirth intervals and less parental attention per child should not do as well. There should be intermediate optima in family sizes, but only two studies have demonstrated optima. The goal here is to determine whether the relationship between fitness and fertility is linear and whether this relationship masks underlying variation in reproductive behaviors in a Mennonite congregation that lived in two disease settings, Prussia/Russia vs.
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