Nucleon Structure and Parity-Violating Electron Scattering

We review the area of strange quark contributions to nucleon structure. In particular, we focus on current models of strange quark vector currents in the nucleon and the associated parity-violating elastic electron scattering experiments from which vector- and axial-vector currents are extractedComment: 40 pages including 7 figures; review article to be published in Int. J. Mod. Phys.

X-Ray Optics at NASA Marshall Space Flight Center

NASA's Marshall Space Flight Center (MSFC) engages in research, development, design, fabrication, coating, assembly, and testing of grazing-incidence optics (primarily) for x-ray telescope systems. Over the past two decades, MSFC has refined processes for electroformed-nickel replication of grazing-incidence optics, in order to produce high-strength, thin-walled, full-cylinder x-ray mirrors. In recent years, MSFC has used this technology to fabricate numerous x-ray mirror assemblies for several flight (balloon, rocket, and satellite) programs. Additionally, MSFC has demonstrated the suitability of this technology for ground-based laboratory applications-namely, x-ray microscopes and cold-neutron microscopes and concentrators. This mature technology enables the production, at moderately low cost, of reasonably lightweight x-ray telescopes with good (15-30 arcsecond) angular resolution. However, achieving arcsecond imaging for a lightweight x-ray telescope likely requires development of other technologies. Accordingly, MSFC is conducting a multi-faceted research program toward enabling cost-effective production of lightweight high-resolution x-ray mirror assemblies. Relevant research topics currently under investigation include differential deposition for post-fabrication figure correction, in-situ monitoring and control of coating stress, and direct fabrication of thin-walled full-cylinder grazing-incidence mirrors

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients

Rationale For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. Objectives To compare the safety and efficacy of a 28-day course of treatment with LIS 240 mg or placebo BID in persons ≥ 12 years old with CF and chronic P. aeruginosa infection. Methods A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28 days in CF patients ≥ 12 years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported quality of life were among secondary endpoints. Main results Baseline demographics for 330 subjects (LIS = 220) were similar although significantly more patients randomized to LIS had experienced multiple exacerbations in the year prior to study entry. There was no statistically significant difference in protocol-defined pulmonary exacerbations between treatment arms. Relative change in FEV1% predicted from baseline was significantly greater for patients randomized to LIS compared to those randomized to placebo (mean difference 1.31%, p = 0.01 [95% CI 0.27, 2.34%]). LIS was well-tolerated, with dysguesia the most frequent adverse event. Conclusions LIS did not demonstrate a difference in time to next exacerbation when compared to placebo. Reasons for this result are discussed but may be due to an imbalance in the frequency of prior pulmonary exacerbations between the two groups. An improvement in FEV1 (% predicted) at 28 days was observed and LIS was well tolerated. LIS is safe and has a potential role in the management of CF patients with chronic P. aeruginosa

Transoral resection of pharyngeal cancer: Summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6–7, 2011, Arlington, Virginia

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6–7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)–initiated oropharyngeal cancers, and in those with HPV‐unrelated disease. The proceedings of this meeting are summarized. © 2012 Wiley Periodicals, Inc. Head Neck, 2012Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94490/1/23136_ftp.pd

A phase 3, open-label, randomized trial to evaluate the safety and efficacy of levofloxacin inhalation solution (APT-1026) versus tobramycin inhalation solution in stable cystic fibrosis patients

Background: Inhaled antibiotics are standard of care for persons with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa airway infection. APT-1026 (levofloxacin inhalation solution, LIS) is fluoroquinolone in development. We compared the safety and efficacy of LIS to tobramycin inhalation solution (TIS) in persons ≥12 years old with CF and chronic P. aeruginosa infection. Methods: This multinational, randomized (2:1), non-inferiority study compared LIS and TIS over three 28-day on/off cycles. Day 28 FEV1 % predicted change was the primary endpoint. Time to exacerbation and patient-reported quality of life superiority were among secondary endpoints. Results: Baseline demographics for 282 subjects were comparable. Non-inferiority was demonstrated (1.86% predicted mean FEV1 difference [95% CI −0.66 to 4.39%]). LIS was well-tolerated, with dysguesia (taste distortion) the most frequent adverse event. Conclusions: LIS is a safe and effective therapy for the management of CF patients with chronic P. aeruginosa

Asian dust-storm activity dominated by Chinese dynasty changes since 2000 BP

The Asian monsoon (AM) played an important role in the dynastic history of China, yet it remains unknown whether AM-mediated shifts in Chinese societies affect earth surface processes to the point of exceeding natural variability. Here, we present a dust storm intensity record dating back to the first unified dynasty of China (the Qin Dynasty, 221–207 B.C.E.). Marked increases in dust storm activity coincided with unified dynasties with large populations during strong AM periods. By contrast, reduced dust storm activity corresponded to decreased population sizes and periods of civil unrest, which was co-eval with a weakened AM. The strengthened AM may have facilitated the development of Chinese civilizations, destabilizing the topsoil and thereby increasing the dust storm frequency. Beginning at least 2000 years ago, human activities might have started to overtake natural climatic variability as the dominant controls of dust storm activity in eastern China

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

X-Ray Optics at NASA Marshall Space Flight Center

NASA's Marshall Space Flight Center (MSFC) engages in research, development, design, fabrication, coating, assembly, and testing of grazing-incidence optics (primarily) for x-ray telescope systems. Over the past two decades, MSFC has refined processes for electroformed-nickel replication of grazing-incidence optics, in order to produce high-strength, thin-walled, full-cylinder x-ray mirrors. In recent years, MSFC has used this technology to fabricate numerous x-ray mirror assemblies for several flight (balloon, rocket, and satellite) programs. Additionally, MSFC has demonstrated the suitability of this technology for ground-based laboratory applications-namely, x-ray microscopes and cold-neutron microscopes and concentrators. This mature technology enables the production, at moderately low cost, of reasonably lightweight x-ray telescopes with good (15-30 arcsecond) angular resolution. However, achieving arcsecond imaging for a lightweight x-ray telescope likely requires development of other technologies. Accordingly, MSFC is conducting a multi-faceted research program toward enabling cost-effective production of lightweight high-resolution x-ray mirror assemblies. Relevant research topics currently under investigation include differential deposition for post-fabrication figure correction, in-situ monitoring and control of coating stress, and direct fabrication of thin-walled full-cylinder grazing-incidence mirrors

Noncanonical DNA Motifs as Transactivation Targets by Wild Type and Mutant p53

Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0–13 nucleotides (nt), originally defined by the consensus RRRCWWGYYY (n = 0–13) RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs) by wild type (WT) and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi–in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical ½-(a single decamer) and ¾-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of ½- and ¾-site REs greatly expands the p53 master regulatory network