Status, Plans, and Initial Results for ARES 1 Crew Launch Vehicle Aerodynamics

Following the completion of NASA's Exploration Systems Architecture Study in August 2004 for the NASA Exploration Systems Mission Directorate (ESMD), the Exploration Launch Office at the NASA Marshall Space Flight Center was assigned project management responsibilities for the design and development of the first vehicle in the architecture, the Ares I Crew Launch Vehicle (CLV), which will be used to launch astronauts to low earth orbit and rendezvous with either the International Space Station or the ESMD s earth departure stage for lunar or other future missions beyond low Earth orbit. The primary elements of the Ares I CLV project are the first stage, the upper stage, the upper stage engine, and vehicle integration. Within vehicle integration is an effort in integrated design and analysis which is comprised of a number of technical disciplines needed to support vehicle design and development. One of the important disciplines throughout the life of the project is aerodynamics. This paper will present the status, plans, and initial results of Ares I CLV aerodynamics as the project was preparing for the Ares I CLV Systems Requirements Review. Following a discussion of the specific interactions with other technical panels and a status of the current activities, the plans for aerodynamic support of the Ares I CLV until the initial crewed flights will be presented

STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation

Signal transducer and activator of transcription (STAT) 4 is one of the seven members of the STAT family. STAT4 has a prominent role in mediating interleukin-12-induced T-helper cell type 1 lineage differentiation. T cells are key players in the maintenance of adipose tissue (AT) inflammation. The role of STAT4 in obesity and AT inflammation is unknown. We sought to determine the role of STAT4 in AT inflammation in obesity-induced insulin resistance. We studied STAT4-null mice on the C57Bl6/J background. We have found that STAT4(-/-)C57Bl6/J mice develop high-fat diet-induced obesity (DIO) similar to wild-type controls, but that they have significantly improved insulin sensitivity and better glucose tolerance. Using flow cytometry and real-time PCR, we show that STAT4(-/-) mice with DIO produce significantly reduced numbers of inflammatory cytokines and chemokines in adipocytes, have reduced numbers of CD8(+) cells, and display increased alternative (M2) macrophage polarization. CD8(+) cells, but not CD4(+) cells, from STAT4(-/-) mice displayed reduced in vitro migration. Also, we found that adipocyte inflammation is reduced and insulin signaling is improved in STAT4(-/-) mice with DIO. We have identified STAT4 as a key contributor to insulin resistance and AT inflammation in DIO. Targeting STAT4 activation could be a novel approach to reducing AT inflammation and insulin resistance in obesity

Claudin-11 decreases the invasiveness of bladder cancer cells

The expression of claudin-11 in benign and malignant bladder tissue and the effect of forced expression of claudin-11 on tight junction function and invasiveness of bladder cancer cells were studied. Claudin-11 expression was tested in bladder cancer cell lines (T24/83, RT 112/84 and EJ138) using reverse transcription-polymerase chain reaction (RT-PCR) and in benign and malignant bladder tissue by quantitative RT-PCR and immunohistochemistry. T24/83 cells were transfected with the pcDNA.1/NT-GFP-TOPO vector containing full-length human claudin-11 sequence. Stable-transfected cells overexpressing claudin-11 (T24Cl-11Ex), wild-type cells (T24WT) and the empty plasmid control clone (T24GFP) were compared using transurothelial resistance (TUR), in vitro adhesion, invasion and growth assays. Claudin-11 was strongly expressed in the non-invasive RT112/84 cell line compared to the invasive T24/83 and EJ138 TCC cell lines. Benign bladder tissue demonstrated equal expression of claudin-11 mRNA as carcinoma, but displayed more intense staining than malignant tissue on immunohistochemistry. Forced-expression of claudin-11 in T24/83 cells was confirmed by PCR, immunoprecipitation and by immunofluorescence, which demonstrated increased perinuclear claudin-11 staining. Forced expression of claudin-11 did not affect TUR (p=0.243), but significantly reduced invasion (p=0.001) while increasing cell matrix adhesion (p=0.001) and growth rates (p=0.001). The greater expression of claudin-11 in benign vs. malignant tissue and non-invasive vs. invasive cell lines, and its effect in reducing bladder cancer cell invasiveness suggests that claudin-11 may have a role in preventing cancer progression and may serve as a therapeutic target in reducing metastasis

CCAT-prime: a novel telescope for submillimeter astronomy

The CCAT-prime telescope is a 6-meter aperture, crossed-Dragone telescope, designed for millimeter and sub-millimeter wavelength observations. It will be located at an altitude of 5600 meters, just below the summit of Cerro Chajnantor in the high Atacama region of Chile. The telescope's unobscured optics deliver a field of view of almost 8 degrees over a large, flat focal plane, enabling it to accommodate current and future instrumentation fielding >100k diffraction-limited beams for wavelengths less than a millimeter. The mount is a novel design with the aluminum-tiled mirrors nested inside the telescope structure. The elevation housing has an integrated shutter that can enclose the mirrors, protecting them from inclement weather. The telescope is designed to co-host multiple instruments over its nominal 15 year lifetime. It will be operated remotely, requiring minimum maintenance and on-site activities due to the harsh working conditions on the mountain. The design utilizes nickel-iron alloy (Invar) and carbon-fiber-reinforced polymer (CFRP) materials in the mirror support structure, achieving a relatively temperature-insensitive mount. We discuss requirements, specifications, critical design elements, and the expected performance of the CCAT-prime telescope. The telescope is being built by CCAT Observatory, Inc., a corporation formed by an international partnership of universities. More information about CCAT and the CCAT-prime telescope can be found at www.ccatobservatory.org.Comment: Event: SPIE Astronomical Telescope + Instrumentation, 2018, Austin, Texas, USA; Proceedings Volume 10700, Ground-based and Airborne Telescopes VII; 107005X (2018

Inhibiting histone deacetylase 1 suppresses both inflammation and bone loss in arthritis

Objective. Histone deacetylase 1 (HDAC1) is highly expressed in the synovium of RA patients. Thus we aimed to investigate a novel HDAC inhibitor (HDACi), NW-21, designed to target HDAC1. The effect of NW-21 on osteoclast formation and activity, cytokine and chemokine expression in vitro and arthritis in mice was assessed

What Drives the Expansion of Giant HII Regions?: A Study of Stellar Feedback in 30 Doradus

Observations show that star formation is an inefficient and slow process. This result can be attributed to the injection of energy and momentum by stars that prevents free-fall collapse of molecular clouds. The mechanism of this stellar feedback is debated theoretically: possible sources of pressure include the classical warm HII gas, the hot gas generated by shock-heating from stellar winds and supernovae, direct radiation of stars, and the dust-processed radiation field trapped inside the HII shell. In this paper, we measure observationally the pressures associated with each component listed above across the giant HII region 30 Doradus in the Large Magellanic Cloud. We exploit high-resolution, multi-wavelengh images (radio, infrared, optical, and X-ray) to map these pressures as a function of position. We find that radiation pressure dominates within 75 pc of the central star cluster, R136, while the HII gas pressure dominates at larger radii. By contrast, the dust-processed radiation pressure and hot gas pressure are generally weak and not dynamically important, although the hot gas pressure may have played a more significant role at early times. Based on the low X-ray gas pressures, we demonstrate that the hot gas is only partially confined and must be leaking out the HII shell. Additionally, we consider the implications of a dominant radiation pressure on the early dynamics of 30 Doradus.Comment: 14 pages, 17 figures; ApJ in pres

Hypothalamic ERK Mediates the Anorectic and Thermogenic Sympathetic Effects of Leptin

OBJECTIVE—Leptin is an adipocyte hormone that plays a major role in energy balance. Leptin receptors in the hypothalamus are known to signal via distinct mechanisms, including signal transducer and activator of transcription-3 (STAT3) and phosphoinositol-3 kinase (PI 3-kinase). Here, we tested the hypothesis that extracellular signal–regulated kinase (ERK) is mediating leptin action in the hypothalamus