SFTA2 - a novel secretory peptide highly expressed in the lung - is modulated by lipopolysaccharide but not hyperoxia

Tissue-specific transcripts are likely to be of importance for the corresponding organ. While attempting to define the specific transcriptome of the human lung, we identified the transcript of a yet uncharacterized protein, SFTA2. In silico analyses, biochemical methods, fluorescence imaging and animal challenge experiments were employed to characterize SFTA2. Human SFTA2 is located on Chr. 6p21.33, a disease-susceptibility locus for diffuse panbronchiolitis. RT-PCR verified the abundance of SFTA2-specific transcripts in human and mouse lung. SFTA2 is synthesized as a hydrophilic precursor releasing a 59 amino acid mature peptide after cleavage of an N-terminal secretory signal. SFTA2 has no recognizable homology to other proteins while orthologues are present in all mammals. SFTA2 is a glycosylated protein and specifically expressed in nonciliated bronchiolar epithelium and type II pneumocytes. In accordance with other hydrophilic surfactant proteins, SFTA2 did not colocalize with lamellar bodies but colocalized with golgin97 and clathrin-labelled vesicles, suggesting a classical secretory pathway for its expression and secretion. In the mouse lung, Sfta2 was significantly downregulated after induction of an inflammatory reaction by intratracheal lipopolysaccharides paralleling surfactant proteins B and C but not D. Hyperoxia, however, did not alter SFTA2 mRNA levels. We have characterized SFTA2 and present it as a novel unique secretory peptide highly expressed in the lung

The Robo-AO-2 facility for rapid visible/near-infrared AO imaging and the demonstration of hybrid techniques

We are building a next-generation laser adaptive optics system, Robo-AO-2, for the UH 2.2-m telescope that will deliver robotic, diffraction-limited observations at visible and near-infrared wavelengths in unprecedented numbers. The superior Maunakea observing site, expanded spectral range and rapid response to high-priority events represent a significant advance over the prototype. Robo-AO-2 will include a new reconfigurable natural guide star sensor for exquisite wavefront correction on bright targets and the demonstration of potentially transformative hybrid AO techniques that promise to extend the faintness limit on current and future exoplanet adaptive optics systems.Comment: 15 page

Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial

BACKGROUND: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. METHODS: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m(2) gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m(2) oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. FINDINGS: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5-31·5) compared with 25·5 months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68-0·98], p=0·032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group. INTERPRETATION: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma

The Robo-AO-2 facility for rapid visible/near-infrared AO imaging and the demonstration of hybrid techniques

We are building a next-generation laser adaptive optics system, Robo-AO-2, for the UH 2.2-m telescope that will deliver robotic, diffraction-limited observations at visible and near-infrared wavelengths in unprecedented numbers. The superior Maunakea observing site, expanded spectral range and rapid response to high-priority events represent a significant advance over the prototype. Robo-AO-2 will include a new reconfigurable natural guide star sensor for exquisite wavefront correction on bright targets and the demonstration of potentially transformative hybrid AO techniques that promise to extend the faintness limit on current and future exoplanet adaptive optics systems

Cartographies of Race and Class: Mapping the Class-Monopoly Rents of American Subprime Mortgage Capital

The worst global financial crisis since the Great Depression has drawn worldwide attention to America's subprime mortgage sector and its linkages with predatory exploitation in working-class and racially marginalized communities. During nearly two decades of expansion, agents of subprime capital fought regulation and reform by (1) using the doctrine of risk-based pricing to equate financial innovation with democratized access to capital, (2) appealing to the cultural myths of the 'American Dream' of homeownership, and (3) dismissing well-documented cases of racial discrimination and predatory abuse as anecdotal evidence of rare problems confined to a few lost-cause places in what is otherwise a benevolent free-market landscape. In this article, we challenge these three tactics. Properly adapted and updated, Harvey's (1974) theory of class-monopoly rent allows us to map and interpret the localized, neighborhood exploitations of class and race in several hundred US metropolitan areas as they were woven through Wall Street securitization conduits into global networks of debt and investment. Understanding the structural inequalities of class-monopoly rent is essential for analysis, organizing, and policy responses to the crisis. Copyright (c) 2009 The Authors. Journal Compilation (c) 2009 Joint Editors and Blackwell Publishing Ltd.

New insights into weather and stroke: influences of specific air masses and temperature changes on stroke incidence

Background/Objectives: Meteorological factors seem to influence stroke incidence, however, the complex association between weather and stroke remains unclear. Possible explanations from the literature do not categorize into subdivisions of ischemic strokes, only have small patient numbers, or refer to a selection of isolated weather elements without investigating weather changes and more. Method: In this exploratory trial, almost 18,000 stroke cases from a single stroke center in Southern Germany were analyzed from 2006 to 2015 and classified into the main subgroups of strokes and subdivisions of ischemic stroke etiologies applying the Trial of Org 10172 in Acute Stroke Treatment classification. For each stroke event, the air mass classification was determined from a subset of 7 air mass categories. Relative excess morbidities were derived for the 7 different air mass categories, taking into account the day of the event and up to 2 and 5 days preceding the stroke event. Results: Statistically significant findings (alpha <= 0.1) reveal that dry tropical air masses were associated with a lower/higher risk for hemorrhagic (HEM)/macroangiopathic strokes (MAS), respectively. Dry polar air masses were associated with a higher risk for intracerebral bleedings and lower risk for ischemic stroke subtypes. Moist air masses were associated with a reduced incidence of MAS. A strong temperature increase 5 days prior to the event was associated with a lower risk of HEM strokes. Temperature increases were associated with lower risks for MAS and cardio-embolic strokes. Significant temperature decreases were associated with a higher risk of MAS. Conclusions: Temperature effects were dependent on both air masses and temperature changes within 5 days prior to the event and were associated with statistically relevant changes in stroke incidence. Decisive factors such as etiology, age, sex, and risk factors were also taken into account

The Effect of Chemistry and 3D Microstructural Architecture on Corrosion of Biodegradable Mg–Ca–Zn Alloys

The development of biodegradable Mg–Ca–Zn alloys strongly relies on the understanding of the varying 3D microstructural architectures by means of high-density-resolution imaging, such as synchrotron radiation–based X-ray microtomography (SR-μCT). The development of useful strategies to control the degradation process, including the design of appropriate 3D microstructures, focusing on the type, fraction, morphology, distribution, connectivity, and interfaces of different phases, depends on a comprehensive understanding of the underlying corrosion processes. SR-μCT enables the nondestructive analysis of the same microstructure within a volume exposed to different immersion times in artificial physiological solutions, e.g., Hanks’ balanced salt solution without glucose (HBSS). In this work, quantitative 3D imaging via SR-μCT demonstrates the formation of a continuous 3D network of secondary phases for low-alloyed Mg–Ca–Zn. Furthermore, a change in the corrosion mechanism from very localized to uniform heterogeneous corrosion processes is observed. This mechanistic change is associated not exclusively with the electrochemical activity of the primary $α$-Mg$_{SS}$ and the secondary (Mg,Zn)$_2$Ca and Mg–Ca–Zn phases, but also with their volume fraction, distribution, 3D morphology, connectivity, and the formation of corrosion product layers

Keck and VLT AO observations and models of the uranian rings during the 2007 ring plane crossings

We present observations of the uranian ring system at a wavelength of 2.2 μm, taken between 2003 and 2008 with NIRC2 on the W.M. Keck telescope in Hawaii, and on 15–17 August 2007 with NaCo on the Very Large Telescope (VLT) in Chile. Of particular interest are the data taken around the time of the uranian ring plane crossing with Earth on 16 August 2007, and with the Sun (equinox) on 7 December 2007. We model the data at the different viewing aspects with a Monte Carlo model to determine: (1) the normal optical depth τ_0, the location, and the radial extent of the main rings, and (2) the parameter Aτ_0 (A is the particle geometric albedo), the location, and the radial plus vertical extent of the dusty rings. Our main conclusions are: (i) The brightness of the ∊ ring is significantly enhanced at small phase and ring inclination angles; we suggest this extreme opposition effect to probably be dominated by a reduction in interparticle shadowing. (ii) A broad sheet of dust particles extends inwards from the λ ring almost to the planet itself. This dust sheet has a vertical extent of ∼140 km, and Aτ_0 = 2.2 × 10^(−6). (iii) The dusty rings between ring 4 and the α ring and between the α and β rings are vertically extended with a thickness of ∼300 km. (iv) The ζ ring extends from ∼41,350 km almost all the way inwards to the planet. The main ζ ring, centered at ∼39,500 km from the planet, is characterized by Aτ_0 = 3.7 × 10^(−6); this parameter decreases closer to the planet. The ζ ring has a full vertical extent of order 800–900 km, with a pronounced density enhancement in the mid-plane. (v) The η_c ring is optically thin and less than several tens of km in the vertical direction. This ring may be composed of macroscopic material, surrounded by clumps of dust