Occupational status of graduates who completed all the vocational agriculture offered by Washington County high schools

Call number: LD2668 .R4 1966 K1

Enlarged magnetic focusing radius of photoinduced ballistic currents

We exploit GaAs-based quantum point contacts as mesoscopic detectors to analyze the ballistic flow of photogenerated electrons in a two-dimensional electron gas at a perpendicular magnetic field. Whereas charge transport experiments always measure the classical cyclotron radius, we show that this changes dramatically when detecting the photoinduced non-equilibrium current in magnetic fields. The experimentally determined radius of the trajectories surprisingly exceeds the classical cyclotron value by far. Monte Carlo simulations suggest electron-electron scattering as the underlying reason.Comment: pdf-file includes both main article and supplementary informatio

Control of prostate cancer associated with withdrawal of a supplement containing folic acid, L-methyltetrahydrofolate and vitamin B12: a case report

<p>Abstract</p> <p>Introduction</p> <p>This is the first report of possible direct stimulation of hormone-resistant prostate cancer or interference of docetaxel cytotoxicity of prostate cancer in a patient with biochemical relapse of prostatic-specific antigen. This observation is of clinical and metabolic importance, especially at a time when more than 80 countries have fortified food supplies with folic acid and some contemplate further fortification with vitamin B₁₂.</p> <p>Case presentation</p> <p>Our patient is a 71-year-old Caucasian man who had been diagnosed in 1997 with prostate cancer, stage T1c, and Gleason score 3+4 = 7. His primary treatment included intermittent androgen deprivation therapy including leuprolide + bicalutamide + deutasteride, ketoconazole + hydrocortisone, nilandrone and flutamide to resistance defined as biochemical relapse of PSA. While undergoing docetaxel therapy to treat a continually increasing prostate-specific antigen level, withdrawal of 10 daily doses of a supplement containing 500 μg of vitamin B₁₂as cyanocobalamin, as well as 400 μg of folic acid as pteroylglutamic acid and 400 μg of L-5-methyltetrahydrofolate for a combined total of 800 μg of mixed folates, was associated with a return to a normal serum prostatic-specific antigen level.</p> <p>Conclusion</p> <p>This case report illustrates the importance of the effects of supplements containing large amounts of folic acid, L-5-methyltetrahydrofolate, and cyanocobalamin on the metabolism of prostate cancer cells directly and/or B vitamin interference with docetaxel efficacy. Physicians caring for patients with prostate cancer undergoing watchful waiting, hormone therapy, and/or chemotherapy should consider the possible acceleration of tumor growth and/or metastasis and the development of drug resistance associated with supplement ingestion. We describe several pathways of metabolic and epigenetic interactions that could affect the observed changes in serum levels of prostate-specific antigen.</p

Effects of drought on nitrogen turnover and abundances of ammonia-oxidizers in mountain grassland

Future climate scenarios suggest an increased frequency of summer drought periods in the European Alpine Region. Drought can affect soil nitrogen (N) cycling, by altering N transformation rates, as well as the abundances of ammonia-oxidizing bacteria and archaea. However, the extent to which drought affects N cycling under in situ conditions is still controversial. The goal of this study was to analyse effects of drought on soil N turnover and ammoniaoxidizer abundances in soil without drought history. To this end we conducted rain-exclusion experiments at two differently managed mountain grassland sites, an annually mown and occasionally fertilized meadow and an abandoned grassland. Soils were sampled before, during and after drought and were analysed for potential gross rates of N mineralization, microbial uptake of inorganic N, nitrification, and the abundances of bacterial and archaeal ammonia-oxidizers based on gene copy numbers of the amoA gene (AOB and AOA, respectively). Drought induced different responses at the two studied sites. At the managed meadow drought increased NH+/4 immobilization rates and NH+/4 concentrations in the soil water solution, but led to a reduction of AOA abundance compared to controls. At the abandoned site gross nitrification and NO-/3 immobilization rates decreased during drought, while AOB and AOA abundances remained stable. Rewetting had only minor, short-term effects on the parameters that had been affected by drought. Seven weeks after the end of drought no differences to control plots could be detected. Thus, our findings demonstrated that in mountain grasslands drought had distinct transient effects on soil nitrogen cycling and ammonia-oxidizers, which could have been related to a niche differentiation of AOB and AOA with increasing NH+/4 levels. However, the effect strength of drought was modulated by grassland management

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Trastuzumab Produces Therapeutic Actions by Upregulating miR-26a and miR-30b in Breast Cancer Cells

OBJECTIVE: Trastuzumab has been used for the treatment of HER2-positive breast cancer (BC). However, a subset of BC patients exhibited resistance to trastuzumab therapy. Thus, clarifying the molecular mechanism of trastuzumab treatment will be beneficial to improve the treatment of HER2-positive BC patients. In this study, we identified trastuzumab-responsive microRNAs that are involved in the therapeutic effects of trastuzumab. METHODS AND RESULTS: RNA samples were obtained from HER2-positive (SKBR3 and BT474) and HER2-negetive (MCF7 and MDA-MB-231) cells with and without trastuzumab treatment for 6 days. Next, we conducted a microRNA profiling analysis using these samples to screen those microRNAs that were up- or down-regulated only in HER2-positive cells. This analysis identified miR-26a and miR-30b as trastuzumab-inducible microRNAs. Transfecting miR-26a and miR-30b induced cell growth suppression in the BC cells by 40% and 32%, respectively. A cell cycle analysis showed that these microRNAs induced G1 arrest in HER2-positive BC cells as trastuzumab did. An Annexin-V assay revealed that miR-26a but not miR-30b induced apoptosis in HER2-positive BC cells. Using the prediction algorithms for microRNA targets, we identified cyclin E2 (CCNE2) as a target gene of miR-30b. A luciferase-based reporter assay demonstrated that miR-30b post-transcriptionally reduced 27% (p = 0.005) of the gene expression by interacting with two binding sites in the 3'-UTR of CCNE2. CONCLUSION: In BC cells, trastuzumab modulated the expression of a subset of microRNAs, including miR-26a and miR-30b. The upregulation of miR-30b by trastuzumab may play a biological role in trastuzumab-induced cell growth inhibition by targeting CCNE2

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment