Lunar Lander Offloading Operations Using a Heavy-Lift Lunar Surface Manipulator System

This study investigates the feasibility of using a heavy-lift variant of the Lunar Surface Manipulator System (LSMS-H) to lift and handle a 12 metric ton payload. Design challenges and requirements particular to handling heavy cargo were examined. Differences between the previously developed first-generation LSMS and the heavy-lift version are highlighted. An in-depth evaluation of the tip-over risk during LSMS-H operations has been conducted using the Synergistic Engineering Environment and potential methods to mitigate that risk are identified. The study investigated three specific offloading scenarios pertinent to current Lunar Campaign studies. The first involved offloading a large element, such as a habitat or logistics module, onto a mobility chassis with a lander-mounted LSMS-H and offloading that payload from the chassis onto the lunar surface with a surface-mounted LSMS-H. The second scenario involved offloading small pressurized rovers with a lander-mounted LSMS-H. The third scenario involved offloading cargo from a third-party lander, such as the proposed ESA cargo lander, with a chassis-mounted LSMS-H. In all cases, the analyses show that the LSMS-H can perform the required operations safely. However, Chariot-mounted operations require the addition of stabilizing outriggers, and when operating from the Lunar surface, LSMS-H functionality is enhanced by adding a simple ground anchoring system

Modelling the spectral energy distribution of the red giant in RS Ophiuchi: Evidence for irradiation

We present an analysis of optical and infrared spectra of the recurrent nova RS Oph obtained during between 2006 and 2009. The best fit to the optical spectrum for 2006 September 28 gives Teff = 3900 K for log g = 2.0, while for log g = 0.0 we find Teff = 4700 K, and a comparison with template stellar spectra provides Teff ~ 4500 K. The observed spectral energy distribution (SED), and the intensities of the emission lines, vary on short (≲1 d) time-scales, due to disc variability. We invoke a simple one-component model for the accretion disc, and a model with a hot boundary layer, with high (~3.9 × 10-6M⊙ yr-1) and low (~2 × 10-8M⊙ yr-1) accretion rates, respectively. Fits to the accretion disc-extracted infrared spectrum (2008 July 15) yield effective temperatures for the red giant of Teff = 3800 ± 100 K (log g = 2.0) and Teff = 3700 ± 100 K (log g = 0.0). Furthermore, using a more sophisticated approach, we reproduced the optical and infrared SEDs of the red giant in the RS Oph system with a twocomponent model atmosphere, in which 90 per cent of the surface has Teff = 3600 K and 10 per cent has Teff = 5000 K. Such structure could be due to irradiation of the red giant by the white dwarf. © 2015 The Authors

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review

BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting

ASO Visual Abstract: FOLFIRINOX or Gemcitabine Based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-Institutional, Patient-Level Meta-Analysis and Systematic Review

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Orientation of the Calcium Channel β Relative to the α12.2 Subunit Is Critical for Its Regulation of Channel Activity

BACKGROUND: The Ca(v)beta subunits of high voltage-activated Ca(2+) channels control the trafficking and biophysical properties of the alpha(1) subunit. The Ca(v)beta-alpha(1) interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID) be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(1)2.2, then testing for Ca(v)beta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6). This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(v)beta with respect to alpha(1)2.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively). Again, the ability of Ca(v)beta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(v)beta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(v)beta subunit relative to the alpha(1)2.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(v)beta to regulate channel activity

Glial-derived neurotrophic factor is essential for blood-nerve barrier functional recovery in an experimental murine model of traumatic peripheral neuropathy.

There is emerging evidence that glial-derived neurotrophic factor (GDNF) is a potent inducer of restrictive barrier function in tight junction-forming microvascular endothelium and epithelium, including the human blood-nerve barrier (BNB) in vitro. We sought to determine the role of GDNF in restoring BNB function in vivo by evaluating sciatic nerve horseradish peroxidase (HRP) permeability in tamoxifen-inducible GDNF conditional knockout (CKO) adult mice following non-transecting crush injury via electron microscopy, with appropriate wildtype (WT) and heterozygous (HET) littermate controls. A total of 24 age-, genotype- and sex-matched mice >12 weeks of age were injected with 30 mg/kg HRP via tail vein injection 7 or 14 days following unilateral sciatic nerve crush, and both sciatic nerves were harvested 30 minutes later for morphometric assessment by light and electron microscopy. The number and percentage of HRP-permeable endoneurial microvessels were ascertained to determine the effect of GDNF in restoring barrier function in vivo. Following sciatic nerve crush, there was significant upregulation in GDNF protein expression in WT and HET mice that was abrogated in CKO mice. GDNF significantly restored sciatic nerve BNB HRP impermeability to near normal levels by day 7, with complete restoration seen by day 14 in WT and HET mice. A significant recovery lag was observed in CKO mice. This effect was independent on VE-Cadherin or claudin-5 expression on endoneurial microvessels. These results imply an important role of GDNF in restoring restrictive BNB function in vivo, suggesting a potential strategy to re-establish the restrictive endoneurial microenvironment following traumatic peripheral neuropathies