Modal survey of the space shuttle solid rocket motor using multiple input methods

The ability to accurately characterize propellant in a finite element model is a concern of engineers tasked with studying the dynamic response of the Space Shuttle Solid Rocket Motor (SRM). THe uncertainties arising from propellant characterization through specimem testing led to the decision to perform a model survey and model correlation of a single segment of the Shuttle SRM. Multiple input methods were used to excite and define case/propellant modes of both an inert segment and, later, a live propellant segment. These tests were successful at defining highly damped, flexible modes, several pairs of which occured with frequency spacing of less than two percent

The mid-infrared Tully-Fisher relation: Spitzer Surface Photometry

The availability of photometric imaging of several thousand galaxies with the Spitzer Space Telescope enables a mid-infrared calibration of the correlation between luminosity and rotation in spiral galaxies. The most important advantage of the new calibration in the 3.6 micron band, IRAC ch.1, is photometric consistency across the entire sky. Additional advantages are minimal obscuration, observations of flux dominated by old stars, and sensitivity to low surface brightness levels due to favorable backgrounds. Through Spitzer cycle 7 roughly 3000 galaxies had been observed and images of these are available at the Spitzer archive. In cycle 8 a program called Cosmic Flows with Spitzer has been initiated that will increase by 1274 the available sample of spiral galaxies with inclinations greater than 45 degrees from face-on suitable for distance measurements. This paper describes procedures based on the photometry package Archangel that are being employed to analyze both the archival and the new data in a uniform way. We give results for 235 galaxies, our calibrator sample for the Tully-Fisher relation. Galaxy magnitudes are determined with uncertainties held below 0.05 mag for normal spiral systems. A subsequent paper will describe the calibration of the [3.6] luminosity-rotation relation.Comment: Accepted for publication in The Astronomical Journal, 12 pages, 9 figure

Cosmicflows-4

With Cosmicflows-4, distances are compiled for 55,877 galaxies gathered into 38,065 groups. Eight methodologies are employed, with the largest numbers coming from the correlations between the photometric and kinematic properties of spiral galaxies (TF) and elliptical galaxies (FP). Supernovae that arise from degenerate progenitors (SNIa) are an important overlapping component. Smaller contributions come from distance estimates from the surface brightness fluctuations of elliptical galaxies (SBF) and the luminosities and expansion rates of core collapse supernovae (SNII). Cepheid Period-Luminosity Relation (CPLR) and Tip of the Red Giant Branch (TRGB) observations founded on local stellar parallax measurements along with the geometric maser distance to NGC 4258 provide the absolute scaling of distances. The assembly of galaxies into groups is an important feature of the study in facilitating overlaps between methodologies. Merging between multiple contributions within a methodology and between methodologies is carried out with Bayesian Markov chain Monte Carlo procedures. The final assembly of distances is compatible with a value of the Hubble constant of $H_0=75.0$ km s$^{-1}$ Mpc$^{-1}$ with the small statistical error $\pm$ $0.8$ km s$^{-1}$ Mpc$^{-1}$ but a large potential systematic error ~3 km s$^{-1}$ Mpc$^{-1}$. Peculiar velocities can be inferred from the measured distances. The interpretation of the field of peculiar velocities is complex because of large errors on individual components and invites analyses beyond the scope of this study.Comment: 38 pages, 24 figures. catalogs available at edd.ifa.hawaii.edu. Accepted to Ap

The Fate of Firms: Explaining Mergers and Bankruptcies

Using a uniquely complete data set of more than 50,000 observations of approximately 16,000 corporations, we test theories that seek to explain which firms become merger targets and which firms go bankrupt. We find that merger activity is much greater during prosperous periods than during recessions. In bad economic times, firms in industries with high bankruptcy rates are less likely to file for bankruptcy than they are in better years, supporting the market illiquidity arguments made by Shleifer and Vishny (1992). At the firm level, we find that, among poorly performing firms, the likelihood of merger increases with poorer performance, but among better performing firms, the relation is reversed and chances of merger increase with better performance. Such a changing relation has not been detected in prior merger studies. We also find that low-growth, resource-rich firms are prime acquisition targets and that firms’ debt capacity relates negatively to the likelihood of a merger. Debt-related variables, leverage and secured debt, play an especially prominent role in distinguishing between which firms merge and which firms go bankrupt

Autonomous Application of Quantitative PCR in the Deep Sea: In Situ Surveys of Aerobic Methanotrophs Using the Deep-Sea Environmental Sample Processor

Recent advances in ocean observing systems and genomic technologies have led to the development of the deep-sea environmental sample processor (D-ESP). The DESP filters particulates from seawater at depths up to 4000 m and applies a variety of molecular assays to the particulates, including quantitative PCR (qPCR), to identify particular organisms and genes in situ. Preserved samples enable laboratory-based validation of in situ results and expanded studies of genomic diversity and gene expression. Tests of the D-ESP at a methane-rich mound in the Santa Monica Basin centered on detection of 16S rRNA and particulate methane monooxygenase (pmoA) genes for two putative aerobic methanotrophs. Comparison of in situ qPCR results with laboratory-based assays of preserved samples demonstrates the D-ESP generated high-quality qPCR data while operating autonomously on the seafloor. Levels of 16S rRNA and pmoA cDNA detected in preserved samples are consistent with an active community of aerobic methanotrophs near the methane-rich mound. These findings are substantiated at low methane sites off Point Conception and in Monterey Bay where target genes are at or below detection limits. Successful deployment of the D-ESP is a major step toward developing autonomous systems to facilitate a wide range of marine microbiological investigations

Primary brain calcification: an international study reporting novel variants and associated phenotypes.

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic

Airships: A New Horizon for Science

The "Airships: A New Horizon for Science" study at the Keck Institute for Space Studies investigated the potential of a variety of airships currently operable or under development to serve as observatories and science instrumentation platforms for a range of space, atmospheric, and Earth science. The participants represent a diverse cross-section of the aerospace sector, NASA, and academia. Over the last two decades, there has been wide interest in developing a high altitude, stratospheric lighter-than-air (LTA) airship that could maneuver and remain in a desired geographic position (i.e., "station-keeping") for weeks, months or even years. Our study found considerable scientific value in both low altitude (< 40 kft) and high altitude (> 60 kft) airships across a wide spectrum of space, atmospheric, and Earth science programs. Over the course of the study period, we identified stratospheric tethered aerostats as a viable alternative to airships where station-keeping was valued over maneuverability. By opening up the sky and Earth's stratospheric horizon in affordable ways with long-term flexibility, airships allow us to push technology and science forward in a project-rich environment that complements existing space observatories as well as aircraft and high-altitude balloon missions.Comment: This low resolution version of the report is 8.6 MB. For the high resolution version see: http://kiss.caltech.edu/study/airship

Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis

Proliferation of pancreatic acinar cells is a critical process in the pathophysiology of pancreatic diseases, because limited or defective proliferation is associated with organ dysfunction and patient morbidity. In this context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal to develop therapeutic interventions promoting the regenerative process of the organ.In this study we used genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones to elucidate their role in acinar proliferation following caerulein‐mediated acute pancreatitis in mice. In addition, molecular mechanisms mediating the effects of thyroid hormones were identified by genetic and pharmacological inactivation of selected signalling pathways.In this study we demonstrated that levels of the thyroid hormone 3,3’,5‐triodo‐L‐thyronine (T3) transiently increased in the pancreas during acute pancreatitis. Moreover, by using genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones, we showed that T3 was required to promote proliferation of pancreatic acinar cells, without affecting the extent of tissue damage or inflammatory infiltration.Finally, upon genetic and pharmacological inactivation of selected signalling pathways, we demonstrated that T3 exerted its mitogenic effect on acinar cells via a tightly controlled action on different molecular effectors, including histone deacetylase, AKT, and TGFβ signalling.In conclusion, our data suggest that local availability of T3 in the pancreas is required to promote acinar cell proliferation and provide the rationale to exploit thyroid hormone signalling to enhance pancreatic regeneration

Recent developments and strategies in pediatric pharmacology research in the USA

Research in pediatric pharmacology has undergone major changes in the last ten years, with an expansion in both publicly and privately funded activities. A number of pharmacokinetics studies and multi-site controlled efficacy trials have been conducted, so that treatment of children and adolescents can now be better informed and evidence-based. Regulatory financial incentives to industry in return for studies on drugs still covered by patent exclusivity have resulted in a substantial increase in pediatric research funded by pharmaceutical companies. In parallel, public funding has supported research on off-patent medications and other clinical important aspects of treatment, such as comparisons between active treatments, including non-pharmacological interventions. With greater interest by industry in pediatric research, the role of government funding agencies has been redefined to avoid duplication and ensure better integration of efforts and utilization of resources. The present review discusses some of the recent developments in pediatric pharmacology with focus on psychiatric medications

Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling

Prostaglandins, particularly prostaglandin E2 (PGE2), play an important role during inflammation. This is exemplified by the clinical use of cyclooxygenase 2 inhibitors, which interfere with PGE2 synthesis, as effective antiinflammatory drugs. Here, we show that PGE2 directly promotes differentiation and proinflammatory functions of human and murine IL-17–producing T helper (Th17) cells. In human purified naive T cells, PGE2 acts via prostaglandin receptor EP2- and EP4-mediated signaling and cyclic AMP pathways to up-regulate IL-23 and IL-1 receptor expression. Furthermore, PGE2 synergizes with IL-1β and IL-23 to drive retinoic acid receptor–related orphan receptor (ROR)-γt, IL-17, IL-17F, CCL20, and CCR6 expression, which is consistent with the reported Th17 phenotype. While enhancing Th17 cytokine expression mainly through EP2, PGE2 differentially regulates interferon (IFN)-γ production and inhibits production of the antiinflammatory cytokine IL-10 in Th17 cells predominantly through EP4. Furthermore, PGE2 is required for IL-17 production in the presence of antigen-presenting cells. Hence, the combination of inflammatory cytokines and noncytokine immunomodulators, such as PGE2, during differentiation and activation determines the ultimate phenotype of Th17 cells. These findings, together with the altered IL-12/IL-23 balance induced by PGE2 in dendritic cells, further highlight the crucial role of the inflammatory microenvironment in Th17 cell development and regulation