Modal Analysis of the Orion Capsule Two Parachute System

As discussed in Ref [1], it is apparent from flight tests that the system made up of two main parachutes and a capsule can undergo several distinct dynamical behaviors. The most significant and problematic of these is the pendulum mode in which the system develops a pronounced swinging motion with an amplitude of up to 24 deg. Large excursions away from vertical by the capsule could cause it to strike the ground at a large horizontal or vertical speed and jeopardize the safety of the astronauts during a crewed mission. In reference [1], Ali et al. summarized a series of efforts taken by the Capsule Parachute Assembly System (CPAS) Program to understand and mitigate the pendulum issue. The period of oscillation and location of the system's pivot point are determined from post-flight analysis. Other noticeable but benign modes include: 1) flyout (scissors) mode, where the parachutes move back and forth symmetrically with respect to the vertical axis similar to the motion of a pair of scissors; 2) maypole mode, where the two parachutes circle around the vertical axis at a nearly constant radius and period; and 3) breathing mode, in which deformation of the non-rigid canopies affects the axial acceleration of the system in an oscillatory manner. Because these modes are relatively harm- less, little effort has been devoted to analyzing them in comparison with the pendulum motion. Motions of the actual system made up of two parachutes and a capsule are extremely complicated due to nonlinearities and flexibility effects. Often it is difficult to obtain insight into the fundamental dynamics of the system by examining results from a multi-body simulation based on nonlinear equations of motion (EOMs). As a part of this study, the dynamics of each mode observed during flight is derived from first principles on an individual basis by making numerous simplifications along the way. The intent is to gain a better understanding into the behavior of the complex multi-body system by studying the reduced set of differential equations associated with each mode. This approach is analogous to the traditional modal analysis technique used to study airplane flight dynamics, in which the full nonlinear behavior of the airframe is decomposed into the phugoid and short period modes for the longitudinal dynamics and the spiral, roll-subsidence, and dutch-roll modes for the lateral dynamics. It is important to note that the study does not address the mechanisms that cause the system to transition from one mode to another, nor does it discuss motions during which two or more modes occur simultaneously

Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well

[Accepted Manuscript] Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2)

Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15-99years) diagnosed with ovarian cancer during 1995-2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). Survival from type I epithelial ovarian tumours for women diagnosed during 2005-09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20-45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology

[Accepted Manuscript] Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2)

Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15-99years) diagnosed with ovarian cancer during 1995-2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). Survival from type I epithelial ovarian tumours for women diagnosed during 2005-09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20-45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology

Observations of GRB 990123 by the Compton Gamma-Ray Observatory

GRB 990123 was the first burst from which simultaneous optical, X-ray and gamma-ray emission was detected; its afterglow has been followed by an extensive set of radio, optical and X-ray observations. We have studied the gamma-ray burst itself as observed by the CGRO detectors. We find that gamma-ray fluxes are not correlated with the simultaneous optical observations, and the gamma-ray spectra cannot be extrapolated simply to the optical fluxes. The burst is well fit by the standard four-parameter GRB function, with the exception that excess emission compared to this function is observed below ~15 keV during some time intervals. The burst is characterized by the typical hard-to-soft and hardness-intensity correlation spectral evolution patterns. The energy of the peak of the nu f_nu spectrum, E_p, reaches an unusually high value during the first intensity spike, 1470 +/- 110 keV, and then falls to \~300 keV during the tail of the burst. The high-energy spectrum above ~MeV is consistent with a power law with a photon index of about -3. By fluence, GRB 990123 is brighter than all but 0.4% of the GRBs observed with BATSE, clearly placing it on the -3/2 power-law portion of the intensity distribution. However, the redshift measured for the afterglow is inconsistent with the Euclidean interpretation of the -3/2 power-law. Using the redshift value of >= 1.61 and assuming isotropic emission, the gamma-ray fluence exceeds 10E54 ergs.Comment: Submitted to The Astrophysical Journal. 16 pages including 4 figure

The adipocyte differentiation protein APMAP is an endogenous suppressor of Aβ production in the brain

The deposition of amyloid-beta (Aβ) aggregates in the brain is a major pathological hallmark of Alzheimer's disease (AD). Aβ is generated from the cleavage of C-terminal fragments of the amyloid precursor protein (APP-CTFs) by γ-secretase, an intramembrane-cleaving protease with multiple substrates, including the Notch receptors. Endogenous modulation of γ-secretase is pointed to be implicated in the sporadic, age-dependent form of AD. Moreover, specifically modulating Aβ production has become a priority for the safe treatment of AD because the inhibition of γ-secretase results in adverse effects that are related to impaired Notch cleavage. Here, we report the identification of the adipocyte differentiation protein APMAP as a novel endogenous suppressor of Aβ generation. We found that APMAP interacts physically with γ-secretase and its substrate APP. In cells, the partial depletion of APMAP drastically increased the levels of APP-CTFs, as well as uniquely affecting their stability, with the consequence being increased secretion of Aβ. In wild-type and APP/ presenilin 1 transgenic mice, partial adeno-associated virus-mediated APMAP knockdown in the hippocampus increased Aβ production by ∼20 and ∼55%, respectively. Together, our data demonstrate that APMAP is a negative regulator of Aβ production through its interaction with APP and γ-secretase. All observed APMAP phenotypes can be explained by an impaired degradation of APP-CTFs, likely caused by an altered substrate transport capacity to the lysosomal/autophagic syste

Process development for manufacturing of cellular structures with controlled geometry and properties

This study presents experimental results on the behaviour of aluminium alloy metal structures and foams manufactured by lost-wax casting and using 3D printed components for internal structure definition. Results for tensile tests, metallurgical properties, surface quality and geometry tolerances were obtained and discussed. The analysis focused on development geometries, used for adjusting manufacturing parameters and prototype geometries intended for geometrical and mechanical validation. The results are indicative of the viability of the method for producing foam structures suitable for mechanical loading.The authors are grateful to the Portuguese Foundation for Science and Technology (FCT) who financially supported this work, through the project PTDC/EME-PME/115668/2009.info:eu-repo/semantics/publishedVersio

Influence of Exercise Modality on Cerebral-Ocular Hemodynamics and Pressures

Background: Moderate and high intensity aerobic or resistance exercise has clearly identified benefits for cardiac, muscle, and bone health. However, the impact of such exercise - either as a mitigating or an exacerbating factor - on the development of the visual impairment and intracranial pressure syndrome (VIIP) is unknown. Accordingly, our aim was to characterize the effect of an acute bout of resistance (RE), moderate-intensity continuous (CE), and high-intensity interval exercise (IE) during a cephalad fluid shift on cerebral-ocular hemodynamics and pressures. Methods: 10 male subjects (36 plus or minus 9 years) completed 4 testing days in a 15 degree head-down tilt (HDT): (1) assessment of maximum volume of O (sub 2), (2) RE session (4 sets of 12 repetition maximum leg press exercise), (3) CE session (30 minutes of cycling at 60 percent maximum volume of O (sub 2)), and (4) IE session (4 by 4-minute intervals of exercise at 85 percent maximum volume of O (sub 2) with 3-minute active rest periods). During each session, blood flow (Vivid-e, GE Healthcare) in extracranial arteries (common carotid artery, CCA; internal carotid artery, ICA; external carotid artery, ECA and vertebral artery, VA), and mean blood flow velocity in middle cerebral artery (MCA), internal jugular pressure (IJP; VeinPress), and intraocular pressure (IOP; Icare PRO) were measured at rest, at the end of each resistance or interval set, and every 5 minutes during continuous exercise. Translaminar pressure gradient (TLPG) was estimated by subtracting IJP from IOP. Results: There were no differences across days in pre-exercise resting blood flows or pressures. IOP decreased slightly from HDT rest (20.2 plus or minus 2.3 millimeters of mercury) to exercise (RE: 19.2 plus or minus 2.8 millimeters of mercury; CE: 18.9 plus or minus 3.2 millimeters of mercury; IE: 20.1 plus or minus 2.8 millimeters of mercury), while IJP decreased during CE (31.6 plus or minus 9.5 millimeters of mercury) and RE (32.0 plus or minus 8.1 millimeters of mercury), and increased during IE (35.1 plus or minus 9.5 millimeters of mercury) from HDT rest (33.3 plus or minus 6.5 millimeters of mercury). Estimated TLPG was increased during IE only. Compared to RE and CE, IE resulted in the greatest increase in MCA blood flow velocity and extracranial artery blood flow. Conclusions: These preliminary results suggest that high-intensity IE acutely increases cerebral blood flow, IJP, and TLPG. Alterations in TLPG is one mechanism that may contribute to optic nerve sheath edema in astronauts. Accordingly, acutely raising IOP and/or orbital pressure during exercise could optimize cerebral-ocular pressures during spaceflight