Neutrino Interactions at Ultrahigh Energies

We report new calculations of the cross sections for deeply inelastic neutrino-nucleon scattering at neutrino energies between 10^{9}\ev and 10^{21}\ev. We compare with results in the literature and assess the reliability of our predictions. For completeness, we briefly review the cross sections for neutrino interactions with atomic electrons, emphasizing the role of the $W$-boson resonance in $\bar{\nu}_{e}e$ interactions for neutrino energies in the neighborhood of 6.3\pev. Adopting model predictions for extraterrestrial neutrino fluxes from active galactic nuclei, gamma-ray bursters, and the collapse of topological defects, we estimate event rates in large-volume water \v{C}erenkov detectors and large-area ground arrays.Comment: 32 pages, 11 figures, uses RevTeX and boxedep

The use of Taqman genotyping assays for rapid confirmation of B-thalassaemia mutations in the Malays: accurate diagnosis with low DNA concentrations

Introduction: In Malaysia, β-thalassaemia is a common inherited blood disorder in haemoglobin synthesis with a carrier rate of 4.5%. Currently, PCR-incorporating techniques such as amplification refractory mutation system (ARMS) or reverse dot blot hybridization (RDBH) are used in β-thalassaemia mutation detection. ARMS allows single-mutation identification using two reactions, one for wild type and another for mutant alleles. RDBH requires probe immobilization and optimization of hybridization and washing temperatures which is time consuming. The aim of our study was to investigate whether β-thalassaemia mutations can be identified in samples with low DNA concentrations. Methods: Genotype identification of common β-thalassaemia mutations in Malays was carried out using Taqman genotyping assays. Results: Results show that the Taqman assays allow mutation detection with DNA template concentrations as low as 2-100 ng. In addition, consistent reproducibility was observed in the Taqman assays when repeated eight times and at different time intervals. Conclusion: The developed sensitive Taqman assays allow molecular characterization of β-thalassaemia mutations in samples with low DNA concentrations. The Taqman genotyping assays have potential as a diagnostic tool for foetal blood, chorionic villi or pre-implantation genetic diagnosis where DNA is limited and precious

High Energy Neutrino Signals of Four Neutrino Mixing

We evaluate the upward shower and muon event rates for two characteristic four neutrino mixing models for extragalactic neutrinos, as well as for the atmospheric neutrinos, with energy thresholds of 1 TeV, 10 TeV and 100 TeV. We show that by comparing the shower to muon event rates, one can distinguish between oscillation and no-oscillation models. By measuring shower and muon event rates for energy thresholds of 10 TeV and 100 TeV, and by considering their ratio, it is possible to use extragalactic neutrino sources to determine the type of four-flavor mixing pattern. We find that one to ten years of data taking with kilometer-size detector has a very good chance of providing valuable information about the physics beyond the Standard Model.Comment: version accepted for publication in Phys. Rev.

On Black Hole Detection with the OWL/Airwatch Telescope

In scenarios with large extra dimensions and TeV scale gravity ultrahigh energy neutrinos produce black holes in their interactions with the nucleons. We show that ICECUBE and OWL may observe large number of black hole events and provide valuable information about the fundamental Planck scale and the number of extra dimensions. OWL is especially well suited to observe black hole events produced by neutrinos from the interactions of cosmic rays with the 3 K background radiation. Depending on the parameters of the scenario of large extra dimensions and on the flux model, as many as 28 events per year are expected for a Planck scale of 3 TeV.Comment: 8 pages, including 7 color figures, three figure captions corrected, minor changes for clarification, one reference adde

Tau Neutrinos Underground: Signals of νμ→ντ\nu_\mu \to \nu_\tau Oscillations with Extragalactic Neutrinos

The appearance of high energy tau neutrinos due to $\nu_\mu \to \nu_\tau$ oscillations of extragalactic neutrinos can be observed by measuring the neutrino induced upward hadronic and electromagnetic showers and upward muons. We evaluate quantitatively the tau neutrino regeneration in the Earth for a variety of extragalactic neutrino fluxes. Charged-current interactions of the upward tau neutrinos below and in the detector, and the subsequent tau decay create muons or hadronic and electromagnetic showers. The background for these events are muon neutrino and electron neutrino charged-current and neutral-current interactions, where in addition to extragalactic neutrinos, we consider atmospheric neutrinos. We find significant signal to background ratios for the hadronic/electromagnetic showers with energies above 10 TeV to 100 TeV initiated by the extragalactic neutrinos. We show that the tau neutrinos from point sources also have the potential for discovery above a 1 TeV threshold. A kilometer-size neutrino telescope has a very good chance of detecting the appearance of tau neutrinos when both muon and hadronic/electromagnetic showers are detected.Comment: section added and two new figs; accepted for publication in Physical Review

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter‐individual variability in associations between body weight and dairy consumption. Methods and results: A genome‐wide interaction study to discover genetic variants that account for variation in BMI in the context of low‐fat, high‐fat and total dairy intake in cross‐sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta‐analyzed. Twenty‐six genetic variants reached the selected significance threshold (p‐interaction \u3c10−7), and six independent variants (LINC01512‐rs7751666, PALM2/AKAP2‐rs914359, ACTA2‐rs1388, PPP1R12A‐rs7961195, LINC00333‐rs9635058, AC098847.1‐rs1791355) were evaluated meta‐analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p‐interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p‐interaction = 7.36 × 10−8) such that each serving of low‐fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2‐rs1388) approached interaction replication significance for low‐fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight

Optics and Quantum Electronics

Contains table of contents for Section 2 and reports on eighteen research projects.National Science Foundation (Grant EET 87-00474)Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAALO3-89-C-0001)Charles Stark Draper Laboratory (Grant DL-H-285408)Charles Stark Draper Laboratory (Grant DL-H-2854018)National Science Foundation (Grant EET 87-03404)National Science Foundation (Grant ECS 84-06290)U.S. Air Force - Office of Scientific Research (Contract F49620-88-C-0089)AT&T Bell FoundationNational Science Foundation (Grant ECS 85-52701)National Institutes of Health (Grant 5-RO1-GM35459)Massachusetts General Hospital (Office of Naval Research Contract N00014-86-K-0117)Lawrence Livermore National Laboratory (Subcontract B048704

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