Commercial Cargo Derivative Study of the Advanced Hybrid Wing Body Configuration with Over-Wing Engine Nacelles

LM has leveraged our partnership with the Air Force Research Laboratory (AFRL) and NASA on the advanced hybrid wing body (HWB) concept to develop a commercial freighter which addresses the NASA Advanced Air Transport Technology (AATT) Project goals for improved efficiency beyond 2025. The current Air Force Research Laboratory (AFRL) Revolutionary Configurations for Energy Efficiency (RCEE) program established the HWB configuration and technologies needed for military transports to achieve aerodynamic and fuel efficiencies well beyond the commercial industry's most modern designs. This study builds upon that effort to develop a baseline commercial cargo aircraft and two HWB derivative commercial cargo aircraft to quanitify the benefit of the HWB and establish a technology roadmap for further development

Well-differentiated Papillary Mesothelioma With Invasive Foci

Well-differentiated papillary mesotheliomas (WDPMs) are usually encountered as incidental findings in the peritoneal cavity in women. Most WDPMs are benign, and the histologic features that indicate a more aggressive course are controversial. We report 20 cases of WDPM, which contained invasive foci. Thirteen cases arose in the peritoneal cavity, 1 in a hernia sac, 3 in the pleural cavity, and 3 in hydroceles. The female:male ratio was 16:4, and age range was 7 to 74 years. Tumor was multifocal in 15 cases. Some tumors showed back-to-back papillae, a pattern mimicking invasion but discernible on pan-keratin stain as compressive crowding. True invasive patterns ranged from simple bland-appearing glands invading the stalks of the papillae to solid foci of invasive tumor of higher cytologic grade than the original WDPM. All 5 tested cases were negative for p16 deletion by fluorescence in situ hybridization, but 2/3 had abnormal karyotypes. Recurrences were seen in 8 patients, and in 4 multiple recurrences were documented. Of 16 patients with follow-up, 14 are alive from periods of 6 months to 6 years (average 3.5 y), and 2 have known recurrent disease. One patient died of disseminated tumor at 8 years but without histologic confirmation of the nature of the tumor. We conclude that WDPM with invasive foci in the papillae appear to be prone to multifocality and recurrence, but that they rarely give rise to life-threatening disease. We suggest that these lesions be called WDPM with invasive foci to alert clinicians to the possibility of recurrence

Sea surface temperature signatures of oceanic internal waves in low winds

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): C06014, doi:10.1029/2006JC003947.In aerial surveys conducted during the Tropical Ocean–Global Atmosphere Coupled Ocean-Atmosphere Response Experiment and the low-wind component of the Coupled Boundary Layer Air-Sea Transfer (CBLAST-Low) oceanographic field programs, sea surface temperature (SST) variability at relatively short spatial scales (O(50 m) to O(1 km)) was observed to increase with decreasing wind speed. A unique set of coincident surface and subsurface oceanic temperature measurements from CBLAST-Low is used to investigate the subsurface expression of this spatially organized SST variability, and the SST variability is linked to internal waves. The data are used to test two previously hypothesized mechanisms for SST signatures of oceanic internal waves: a modulation of the cool-skin effect and a modulation of vertical mixing within the diurnal warm layer. Under conditions of weak winds and strong insolation (which favor formation of a diurnal warm layer), the data reveal a link between the spatially periodic SST fluctuations and subsurface temperature and velocity fluctuations associated with oceanic internal waves, suggesting that some mechanism involving the diurnal warm layer is responsible for the observed signal. Internal-wave signals in skin temperature very closely resemble temperature signals measured at a depth of about 20 cm, indicating that the observed internal-wave SST signal is not a result of modulation of the cool-skin effect. Numerical experiments using a one-dimensional upper ocean model support the notion that internal-wave heaving of the warm-layer base can produce alternating bands of relatively warm and cool SST through the combined effects of surface heating and modulation of wind-driven vertical shear.We gratefully acknowledge funding for this research from the Office of Naval Research through the CBLAST Departmental Research Initiative (grants N00014-01-1-0029, N00014-05-10090, N00014-01-1-0081, N00014-04-1-0110, N00014-05-1-0036, N00014-01-1-0080) and the Secretary of the Navy/Chief of Naval Operations Chair (grant N00014-99-1-0090)

Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection

Vaccines that elicit protective cytotoxic T lymphocytes (CTL) may improve on or augment those designed primarily to elicit antibody responses. However, we have little basis for estimating the numbers of CTL required for sterilising immunity at an infection site. To address this we begin with a theoretical estimate obtained from measurements of CTL surveillance rates and the growth rate of a virus. We show how this estimate needs to be modified to account for (i) the dynamics of CTL-infected cell conjugates, and (ii) features of the virus lifecycle in infected cells. We show that provided the inoculum size of the virus is low, the dynamics of CTL-infected cell conjugates can be ignored, but knowledge of virus life-histories is required for estimating critical thresholds of CTL densities. We show that accounting for virus replication strategies increases estimates of the minimum density of CTL required for immunity over those obtained with the canonical model of virus dynamics, and demonstrate that this modeling framework allows us to predict and compare the ability of CTL to control viruses with different life history strategies. As an example we predict that lytic viruses are more difficult to control than budding viruses when net reproduction rates and infected cell lifetimes are controlled for. Further, we use data from acute SIV infection in rhesus macaques to calculate a lower bound on the density of CTL that a vaccine must generate to control infection at the entry site. We propose that critical CTL densities can be better estimated either using quantitative models incorporating virus life histories or with in vivo assays using virus-infected cells rather than peptide-pulsed targets

The Resource Curse and Rentier States in the Caspian Region : A Need for Context Analysis

Although much attention is paid to the Caspian region with regard to energy issues, the domestic consequences of the region’s resource production have so far constituted a neglected field of research. A systematic survey of the latest research trends in the economic and political causalities of the resource curse and of rentier states reveals that there is a need for context analysis. In reference to this, the paper traces any shortcomings and promising approaches in the existent body of literature on the Caspian region. Following on from this, the paper then proposes a new approach; specifically, one in which any differences and similarities in the context conditions are captured. This enables a more precise exploration of the exact ways in which they form contemporary post-Soviet Caspian rentier states.Obwohl der Region am Kaspischen Meer im Zuge von Energiediskursen große Aufmerksamkeit zuteil wird, stellen die innerstaatlichen Folgen der Ressourcenproduktion in der Region ein bislang vernachlässigtes Forschungsfeld dar. Ein systematischer Überblick über die jüngsten Forschungstrends zu wirtschaftlichen und politischen Kausalzusammenhängen des Ressourcenfluchs und zu Rentierstaaten offenbart die Notwendigkeit von Kontextanalysen. Hierauf Bezug nehmend, analysiert der Aufsatz sowohl die Mängel als auch viel versprechende Ansätze in der betreffenden Literatur zur Region am Kaspischen Meer. Der Aufsatz stellt letztendlich einen neuen Ansatz vor, der Unterschiede und Gemeinsamkeiten in den Kontextbedingungen erfasst, um zu erforschen, wie diese die gegenwärtigen post-sowjetischen Rentierstaaten in der Region am Kaspischen Meer tatsächlich prägen

A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Purpose: To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent glioblastoma with homozygous phosphatase and tensin homolog (PTEN) deletion, mutation or protein loss. Methods: This multicenter, open-label, Phase Ib/II study included adult patients with glioblastoma with mesenchymal-epithelial transcription factor (c-Met) amplification. In Phase Ib, patients received INC280 as capsules or tablets in combination with buparlisib. In Phase II, patients received INC280 only. Response was assessed centrally using Response Assessment in Neuro-Oncology response criteria for high-grade gliomas. All adverse events (AEs) were recorded and graded. Results: 33 patients entered Phase Ib, 32 with altered PTEN. RP2D was not declared due to potential drug–drug interactions, which may have resulted in lack of efficacy; thus, Phase II, including 10 patients, was continued with INC280 monotherapy only. Best response was stable disease in 30% of patients. In the selected patient population, enrollment was halted due to limited activity with INC280 monotherapy. In Phase Ib, the most common treatment-related AEs were fatigue (36.4%), nausea (30.3%) and increased alanine aminotransferase (30.3%). MTD was identified at INC280 Tab 300 mg twice daily + buparlisib 80 mg once daily. In Phase II, the most common AEs were headache (40.0%), constipation (30.0%), fatigue (30.0%) and increased lipase (30.0%). Conclusion: The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. More stringent molecular selection strategies might produce better outcomes. Trial registration: NCT01870726

ARIA 2016:Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Diffractive Dijet Production in Antiproton-Proton Collisions at s\sqrt{s}=1.96 TeV

We report on a study of diffractive dijet production in $\bar{p}p$ collisions at $\sqrt{s}=1.96$ TeV using the CDF II detector at the Fermilab Tevatron $\bar{p}p$ collider. A data sample from 310 pb$^{-1}$ of integrated luminosity collected by triggering on a high transverse energy jet, $E_T^{jet}$, in coincidence with a recoil antiproton detected in a Roman pot spectrometer is used to measure the ratio of single-diffractive to inclusive-dijet event rates as a function of $x^{\bar p}$ of the interacting parton in the antiproton, the Bjorken-$x$, $x^{\bar p}_{Bj}$, and a $Q^2\approx (E_T^{jet})^2$ in the ranges $10^{-3}<x^{\bar p}_{Bj}<10^{-1}$ and $10^2<Q^2 <10^4$ GeV$^2$, respectively. Results are presented for the region of $\bar p$-momentum-loss fraction $0.03-4$ GeV$^2$. The $t_{\bar p}$ dependence is measured as a function of $Q^2$ and $x_{Bj}^{\bar p}$ and compared with that of inclusive single diffraction dissociation. We find weak $x^{\bar p}_{Bj}$ and $Q^2$ dependencies in the ratio of single diffractive to inclusive event rates, and no significant $Q^2$ dependence in the diffractive $t_{\bar p}$ distributions.Comment: 22 pages, 23 figures; published versio