A metastable nano-scale disordered precipitate with orthorhombic symmetry has been identified using high resolution scanning transmission electron microscopy. The phase, termed O′, is metastable, ...formed by a shuffle mechanism involving a 110<11̅0> transverse phonon wave in samples of Ti–26Nb–2Zr (at.%) quenched from the β phase. The addition of 2% Zr to Ti–26Nb appears to suppress significantly the stability of both the 112̅ shear and 2/3 longitudinal phonon wave but promotes the 110<11̅0> transverse shuffle. This results in the nano-size O′ phase being homogeneously formed in the parent β phase matrix rather than the massive α″ phase.
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The interfaces between the phase separated regions in the dendritic grains of laser-deposited samples of the high entropy alloy CoCrCuFeNiAl have been studied using aberration-corrected analytical ...(scanning) transmission electron microscopy ((S)TEM). The compositional variations have been determined using energy dispersive x-ray spectroscopy (EDS) in (S)TEM. It was found that between B2, consisting mainly of Al, Ni, Co, and Fe, and disordered bcc phase, consisting mainly of Cr and Fe, there is a transition region, approximately 1.5nm in width, over which the chemical composition changes from the B2 to that of the bcc phase. The crystal structure of this interfacial region is also B2, but with very different sublattice occupancy than that of the adjacent B2 compound. The structural aspects of the interface between the ordered B2 phase and the disordered bcc phase have been characterized using high angle annular dark-field (HAADF) imaging in STEM. It has been determined that the interfaces are essentially coherent, with the lattice parameters of the two B2 regions and the disordered bcc phase being more or less the same, the uncertainty arising from possible relaxations from the proximity of the surfaces of the thin foils used in imaging of the microstructures. Direct observations show that there is a planar continuity between all three constituent phases.
•In the dendritic grains, there are two dominant phases, one with the ordered B2 structure, and the other disordered bcc.•From the intensity ratios in HAADF, the B2 phase appears to have a stoichiometry of the form Al(Ni, Co, and Fe).•Energy dispersive x-ray spectroscopy reveals the presence of an ordered interface transition region between the two phases.•Nanodiffraction in the Titan shows that the interface region is also ordered with the B2 crystal structure based on C.
AbstractApproximately 80% of US centralized Small Water Resource Recovery Facilities (WRRFs) serve populations less than 10,000 and can be significantly less energy efficient (E2) relative to larger ...systems. This study’s purpose was to provide case studies of E2 in small WRRFs through documentation of unit process energy use (within four small WRRFs), E2 changes reported by operators following a project that provided E2 recommendations to 83 WRRFs, and investigate barriers to E2 through surveying of operators (including comparisons between systems of different size and E2 implementation). Aeration was the largest energy component (66%–73%) of total energy use and space heating can be significant (4%–35%). E2 changes were reported by 19 operators, and facilities with available bills exhibited energy reductions of 4%–35%. Variable frequency drive (VFD) installation and improved operations exhibited the largest savings. Application of an E2 benchmarking model for small WRRFs was effective for measuring E2 improvements in systems with varying flowrates. Responses from 66 operators expressed financial barriers and lack of time or other priorities as the largest barriers in making E2 improvements.
Sharks and other large predators are scarce on most coral reefs, but studies of their historical ecology provide qualitative evidence that predators were once numerous in these ecosystems. ...Quantifying density of sharks in the absence of humans (baseline) is, however, hindered by a paucity of pertinent time-series data. Recently researchers have used underwater visual surveys, primarily of limited spatial extent or nonstandard design, to infer negative associations between reef shark abundance and human populations. We analyzed data from 1607 towed-diver surveys (>1 ha transects surveyed by observers towed behind a boat) conducted at 46 reefs in the central-western Pacific Ocean, reefs that included some of the world's most pristine coral reefs. Estimates of shark density from towed-diver surveys were substantially lower (<10%) than published estimates from surveys along small transects (<0.02 ha), which is not consistent with inverted biomass pyramids (predator biomass greater than prey biomass) reported by other researchers for pristine reefs. We examined the relation between the density of reef sharks observed in towed-diver surveys and human population in models that accounted for the influence of oceanic primary productivity, sea surface temperature, reef area, and reef physical complexity. We used these models to estimate the density of sharks in the absence of humans. Densities of gray reef sharks (Carcharhinus amblyrhynchos), whitetip reef sharks (Triaenodon obesus), and the group "all reef sharks" increased substantially as human population decreased and as primary productivity and minimum sea surface temperature (or reef area, which was highly correlated with temperature) increased. Simulated baseline densities of reef sharks under the absence of humans were 1.1-2.4/ha for the main Hawaiian Islands, 1.2-2.4/ha for inhabited islands of American Samoa, and 0.9-2.1/ha for inhabited islands in the Mariana Archipelago, which suggests that density of reef sharks has declined to 3-10% of baseline levels in these areas. Los tiburones y otros depredadores mayores son escasos en la mayoría de los arrecifes de coral, pero estudios de su ecología histórica proporcionan evidencia cualitativa de que los depredadores una vez fueron numerosos en estos ecosistemas. Sin embargo, la cuantificación de la densidad de tiburones en ausencia de humanos (línea de base) es obstaculizada por la falta de datos de series de tiempo pertinentes. Recientemente, los investigadores han utilizado muestreos visuales submarinos, de extensión espacial limitada o de diseño no estándar, para inferir asociaciones negativas entre la abundancia de tiburones de arrecife y las poblaciones humanas. Analizamos datos de 1607 muestreos por remolque de buzos (transectos > muestreados por observadores remolcados por una lancha) realizados en 46 arrecifes en el Océano Pacífico centro-occidental, arrecifes que incluyeron algunos de los más prístinos del mundo. Las estimaciones de densidad de tiburones fue sustancialmente menor (<10%) que estimaciones publicadas a partir de muestreos a lo largo de transectos pequeños (<0.02 ha), lo cual no es consistente con las pirámides de biomasa invertidas (la biomasa de depredadores es mayor que la biomasa de presas) reportadas para arrecifes prístinos por otros autores. Examinamos la relación entre la densidad de tiburones de arrecife observados en los muestreos por remolque de buzos y la población humana en modelos y consideramos la influencia de la productividad oceánica primaria, la temperatura de la superficie del mar, la superficie del arrecife y su complejidad física. Utilizamos estos modelos para estimar la densidad de tiburones en ausencia de humanos. Las densidades de Carcharhinus amblyrhynchos, Triaenodon obesus y el grupo de "tiburones estrictamente arrecifales" incrementó sustancialmente a medida que disminuyó la población humana y que incrementó la productividad primaria y la temperatura de la superficie del mar (o superficie del arrecife, que estaba altamente correlacionada con la temperatura. Las densidades basales simuladas de tiburones arrecifales en ausencia de humanos fueron 1.1-2.4/ha para las Islas Hawaianas, 1.2-2.4/ha en islas deshabitadas de Samoa Americana y 0.9-2.1/ha e islas deshabitadas del Archipiélago Mariana, lo que sugiere que la densidad de tiburones arrecifales ha declinado entre 3 -10% en relación con los niveles basales en esas áreas.
This study examined whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance. As compared with placebo, pioglitazone reduced the conversion of ...IGT to diabetes by 72% but was associated with significant weight gain and edema.
Type 2 diabetes mellitus affects 21 million Americans,
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and its prevalence is increasing.
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Microvascular and macrovascular complications are common in type 2 diabetes mellitus and are related to both the severity and the duration of hyperglycemia.
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The natural history of type 2 diabetes mellitus has been well defined,
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starting with a genetic predisposition and progression from normal glucose tolerance with insulin resistance to impaired glucose tolerance and eventually type 2 diabetes mellitus with the superimposition of beta-cell failure.
Because hyperglycemia plays a central role in the microvascular and macrovascular complications of diabetes,
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,
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,
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it is possible that interventions that . . .
With the current explosion of knowledge on the role of mitochondrial dysfunction in the genesis of various human disease states, there is an increased interest in targeting mitochondrial processes, ...pathways, and proteins for drug discovery efforts in cancer and cardiovascular, metabolic, and central nervous system diseases, the latter including autism and neurodegenerative diseases. We provide an update on understanding the central role of the mitochondrion in ATP and reactive oxygen species production and in controlling cell death pathways.
A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart ...Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine Endorsed by the American College of Emergency Physicians In general, use of cardiac RNI for diagnosis and risk assessment in intermediate- and high-risk patients with coronary artery disease (CAD) was viewed favorably, while testing in low-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Given the iterative nature of the process, readers are counseled not to compare too closely individual appropriate use ratings among modalities rated at different times over the past 2 years. Since this process is iterative and evolving, readers are counseled that individual appropriate use ratings among modalities rated at different times over the past 2 years may not be consistent.\n Manesh R. Patel None None None None None None Dr. Eric D. Peterson None None None Bristol-Myers Squibb/Sanofi Aventis Merck Schering-Plough St. Jude None None Dr. Michael J. Wolk None None None None None None Cardiac Radionuclide Imaging Appropriate Use Criteria Indication Reviewers Dr. James Arrighi None None None None None None Dr. Robert O. Bonow Bristol-Myers Squibb Medical Imaging Edwards Lifesciences None None None None None Dr. Lee A. Fleisher None None None None None Preoperative potassium Preoperative potassium level Dr. Julius M. Gardin None CV Therapeutics Pfizer Takeda None Merck None None Dr. Raymond J. Gibbons Cardiovascular Clinical Studies (WOMEN study) Consumers Union TIMI 37A None None Kai Pharmaceuticals King Pharmaceuticals Radiant Medical TargeGen Ther Ox None None Dr. John A. Gillespie None None None None None None Dr. Bennett S. Greenspan None None None None None None Dr. Rory Hachamovitch Bristol-Myers Squibb Medical Imaging GE Healthcare None Astellas Bracco Diagnostics GE Healthcare Siemens None None Dr. Warren R. Janowitz None None None None None None Dr. Christopher M. Kramer Siemens None None Astellas GlaxoSmithKline Merck Siemens None None Dr. Michael H. Picard Acusphere None None Edwards Lifesciences None None Dr. Michael Poon None None None None None None Dr. Miguel A. Quinones None None None None None Diet pills and valve disease Dr. Raymond F. Stainback None None None None None None Dr. Mark I. Travin None None None None None Adding exercise to pharmacologic stress ECG stress testing and ordering nuclear studies Dr. Samuel Wann None None None None None None Dr. R. Parker Ward None None None Pfizer None None Dr. Neil J. Weissman Takeda Wyeth None None Acusphere Arena Pharmaceutical ATS Biotronik Boston Scientific Edwards Lifesciences Lipid Science Point Biomedical Sorin Carbomedics Spectranetics St. Jude Zilver None Anorexic agents Dr. Jack A. Ziffer Tyco Healthcare None CV Therapeutics Spectrum Dynamics Bristol-Myers Squibb CV Therapeutics None None Dr. William A. Zoghbi None None None None None None * ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM CARDIAC RADIONUCLIDE IMAGING APPROPRIATE USE CRITERIA WRITING GROUP, TECHNICAL PANEL, TASK FORCE, AND INDICATION REVIEWERS--RELATIONSHIPS WITH INDUSTRY AND OTHER ENTITIES (IN ALPHABETICAL ORDER) This table represents the relevant relationships of committee members with industry and other entities that were reported orally at the initial writing committee meeting and updated in conjunction with all meetings and conference calls of the writing committee during the document development process.
Small cell lung cancer Kalemkerian, Gregory P; Akerley, Wallace; Bogner, Paul ...
Journal of the National Comprehensive Cancer Network,
2013-Jan-01, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on ...extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.
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► Malaria transmission blocking candidates need to be prioritized to transfer the best to the field. ► SMFA analyses vary between laboratories and efficacy estimates are often ...underpowered and highly uncertain. ► The effectiveness of a TBI candidate to reduce mosquito infectivity depends on parasite exposure. ► We show that the relationship between oocyst prevalence and intensity is predictable. ► This will allow laboratory results to be extrapolated to different field situations.
The standard membrane feeding assay (SMFA) is currently considered to be the ‘gold standard’ for assessing the effectiveness of malaria transmission blocking interventions (TBIs) in vivo. The operation and analysis of SMFAs has varied between laboratories: field scientists often measure TBI efficacy as a reduction in the prevalence of infected mosquitoes whilst laboratory scientists are more likely to quote efficacy as a change in the number of oocysts within the mosquito. These metrics give outputs that differ widely, resulting in a need for greater understanding of how the SMFA informs TBI assessment. Using data from 536 different assays (conducted on Plasmodium falciparum and Plasmodium berghei, in either Anopheles gambiae or Anopheles stephensi) it is shown that the relationship between these metrics is complex, yet predictable. Results demonstrate that the distribution of oocysts between mosquitoes is highly aggregated, making efficacy estimates based on reductions in intensity highly uncertain. Analysis of 30 SMFAs carried out on the same TBI confirms that the observed reduction in prevalence depends upon the parasite exposure (as measured by oocyst intensity in the control group), with assays which have lower exposure appearing more effective. By contrast, if efficacy is estimated as a reduction in oocyst intensity, then this candidate demonstrated constant efficacy, irrespective of the exposure level. To report transmission-blockade efficacy accurately, the results of SMFAs should give both the prevalence and intensity of oocysts in both the control and intervention group. Candidates should be assessed against a range of parasite exposures to allow laboratory results to be extrapolated to different field situations. Currently, many studies assessing TBIs are underpowered and uncertainties in efficacy estimates rarely reported. Statistical techniques that account for oocyst over-dispersion can reduce the number of mosquitoes that need to be dissected and allow TBI candidates from different laboratories to be accurately compared.
The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3′-5′ nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) ...pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high homology with DDR proteins Topoisomerase 3α (TOP3α) and NEIL3 (Nei-like DNA glycosylase 3), as well as transcription and RNA regulatory proteins, such as TTF2 (transcription termination factor 2), TFIIS, and RPB9. Biochemical and NMR results establish the nucleic acid-binding activity of the Zf-GRF domain. Moreover, an APE2 Zf-GRF X-ray structure and small-angle X-ray scattering analyses show that the Zf-GRF fold is typified by a crescent-shaped ssDNA binding claw that is flexibly appended to an APE2 endonuclease/exonuclease/phosphatase (EEP) catalytic core. Structure-guided Zf-GRF mutations impact APE2 DNA binding and 3′-5′ exonuclease processing, and also prevent efficient APE2-dependent RPA recruitment to damaged chromatin and activation of the ATR-Chk1 DDR pathway in response to oxidative stress in Xenopus egg extracts. Collectively, our data unveil the APE2 Zf-GRF domain as a nucleic acid interaction module in the regulation of a key single-strand break resection function of APE2, and also reveal topologic similarity of the Zf-GRF to the zinc ribbon domains of TFIIS and RPB9.
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