One-pot, three-component synthesis of novel δ-sultam scaffolds via N-sulfonylation—intramolecular Michael sequences.

The synthesis of novel δ-sultam scaffolds utilizing one-pot, three-component reactions of 1,3-dicarbonyl compounds, primary aliphatic amines and substituted styrenesulfonyl chlorides is reported. A variety of six-membered sultams are obtained in moderate to good yields presumably via N-sulfonylation—intramolecular Michael addition sequences

Probing Grand Unified Theories with Cosmic Ray, Gamma-Ray and Neutrino Astrophysics

We explore scenarios where the highest energy cosmic rays are produced by new particle physics near the grand unification scale. Using detailed numerical simulations of extragalactic nucleon, gamma-ray, and neutrino propagation, we show the existence of an interesting parameter range for which such scenarios may explain part of the data and are consistent with all observational constraints. A combination of proposed observatories for ultra-high energy cosmic rays, neutrino telescopes of a few kilometer scale, and gamma-ray astrophysics instruments should be able to test these scenarios. In particular, for neutrino masses in the eV range, exclusive neutrino decay modes of superheavy particles can give rise to neutrino fluxes comparable to those predicted in models of active galactic nuclei.Comment: 15 latex pages, 5 postscript figures included, uses revtex.sty and psfig.sty. Submitted to Physical Review

Engineering Support Systems for Industrial Machines and Plants

In the business of industrial machines and plants, rapid and detailed estimates for planning installation, replacement of equipment, or maintenance work are key requirements for meeting the demands for greater reliability, lower costs and for maintaining safe and secure operation. These demands have been addressed by developing technology driven by IT. When replacing equipment at complex building or plants with high equipment density, the existing state of the installation locations and transportation routes for old and new equipment need to be properly measured. We have met this need by developing parts recognition technology based on 3D measurement, and by developing high-speed calculation technology of optimal routes for installation parts. This chapter provides an overview of these development projects with some real business application results

Limits to the muon flux from WIMP annihilation in the center of the Earth with the AMANDA detector

A search for nearly vertical up-going muon-neutrinos from neutralino annihilations in the center of the Earth has been performed with the AMANDA-B10 neutrino detector. The data sample collected in 130.1 days of live-time in 1997, ~10^9 events, has been analyzed for this search. No excess over the expected atmospheric neutrino background is oberved. An upper limit at 90% confidence level on the annihilation rate of neutralinos in the center of the Earth is obtained as a function of the neutralino mass in the range 100 GeV-5000 GeV, as well as the corresponding muon flux limit.Comment: 14 pages, 11 figures. Version accepted for publication in Physical Review

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Scaling up integration: development and results of a participatory assessment of HIV/TB services, South Africa

<p>Abstract</p> <p>Background</p> <p>In South Africa the need to integrate HIV, TB and STI programmes has been recognised at a policy and organisation level; the challenge is now one of translating policies into relevant actions and monitoring implementation to ensure that the anticipated benefits of integration are achieved. In this research, set in public primary care services in Cape Town, South Africa, we set out to determine how middle level managers could be empowered to monitor the implementation of an effective, integrated HIV/TB/STI service.</p> <p>Methods</p> <p>A team of managers and researchers designed an evaluation tool to measure implementation of key components of an integrated HIV/TB/STI package with a focus on integration. They used a comprehensive health systems framework based on conditions for programme effectiveness and then identified and collected tracer indicators. The tool was extensively piloted in two rounds involving 49 clinics in 2003 and 2004 to identify data necessary for effective facility-level management. A subsequent evaluation of 16 clinics (2 per health sub district, 12% of all public primary care facilities) was done in February 2006.</p> <p>Results</p> <p>16 clinics were reviewed and 635 records sampled. Client access to HIV/TB/STI programmes was limited in that 50% of facilities routinely deferred clients. Whilst the physical infrastructure and staff were available, there was problem with capacity in that there was insufficient staff training (for example, only 40% of clinical staff trained in HIV care). Weaknesses were identified in quality of care (for example, only 57% of HIV clients were staged in accordance with protocols) and continuity of care (for example, only 24% of VCT clients diagnosed with HIV were followed up for medical assessment). Facility and programme managers felt that the evaluation tool generated information that was useful to manage the programmes at facility and district level. On the basis of the results facility managers drew up action plans to address three areas of weakness within their own facility.</p> <p>Conclusions</p> <p>This use of the tool which is designed to empower programme and facility managers demonstrates how engaging middle managers is crucial in translating policies into relevant actions.</p