A lunar base reference mission for the phased implementation of bioregenerative life support system components

Previous design efforts of a cost effective and reliable regenerative life support system (RLSS) provided the foundation for the characterization of organisms or 'biological processors' in engineering terms and a methodology was developed for their integration into an engineered ecological LSS in order to minimize the mass flow imbalances between consumers and producers. These techniques for the design and the evaluation of bioregenerative LSS have now been integrated into a lunar base reference mission, emphasizing the phased implementation of components of such a BLSS. In parallel, a designers handbook was compiled from knowledge and experience gained during past design projects to aid in the design and planning of future space missions requiring advanced RLSS technologies. The lunar base reference mission addresses in particular the phased implementation and integration of BLS parts and includes the resulting infrastructure burdens and needs such as mass, power, volume, and structural requirements of the LSS. Also, operational aspects such as manpower requirements and the possible need and application of 'robotics' were addressed

Interfering with TGFβ-induced Smad3 nuclear accumulation differentially affects TGFβ-dependent gene expression

BACKGROUND: Transforming growth factor-β (TGFβ) plays an important role in late-stage carcinogenesis by stimulating invasive behavior of cancer cells, promoting neo-angiogenesis and by helping cancer cells to escape surveillance by the immune system. It also supports colonization of the bone by metastatic breast cancer cells by increasing expression of osteolytic parathyroid hormone-related protein (PTHrP). Interfering with TGFβ signalling may thus weaken the malignant properties of cancer cells. We investigated to what extent two inhibitors, SB-202190 and SB-203580, interfere with TGFβ-signalling in invasive MDA-MB-231 breast cancer cells. These compounds, formerly used as p38-MAPK-specific inhibitors, were recently also demonstrated to inhibit TGFβ type I receptor kinase. RESULTS: Our results show that these inhibitors delay the onset of TGFβ-induced nuclear accumulation of Smad3 and reduces its amplitude. This effect was accompanied by a strong reduction in TGFβ-responsivess of the slow-responder genes pthrp, pai-1 and upa, while the reactivity of the fast-responder gene smad7 to TGFβ remained almost unchanged. Neither was the TGFβ response of the fast-responder ese-1/esx gene, whose expression we found to be strongly downregulated by TGFβ, affected by the inhibitors. CONCLUSION: The data show that SB-202190 and SB-203580 suppress TGFβ-dependent activation of genes that are important for the acquisition of invasive behavior, while having no effect on the expression of the natural TGFβ inhibitor Smad7. This suggests that these compounds are potent inhibitors of malignant behavior of cancer cells

Der PMN Elastase-Plasmaspiegel, ein biochemischer Parameter der Traumaschwere

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Feasible alternatives to green growth

Climate change and increasing income inequality have emerged as twin threats to contemporary standards of living, peace and democracy. These two problems are usually tackled separately in the policy agenda. A new breed of radical proposals have been advanced to manage a fair low-carbon transition. In this spirit, we develop a dynamic macrosimulation model to investigate the long-term effects of three scenarios: green growth, policies for social equity, and degrowth. The green growth scenario, based on technological progress and environmental policies, achieves a significant reduction in greenhouse gas emissions at the cost of increasing income inequality and unemployment. The policies for social equity scenario adds direct labour market interventions that result in an environmental performance similar to green growth while improving social conditions at the cost of increasing public deficit. The degrowth scenario further adds a reduction in consumption and exports, and achieves a greater reduction in emissions and inequality with higher public deficit, despite the introduction of a wealth tax. We argue that new radical social policies can combine social prosperity and low-carbon emissions and are economically and politically feasible

The mean magnetic field of the sun: Observations at Stanford

A solar telescope was built at Stanford University to study the organization and evolution of large-scale solar magnetic fields and velocities. The observations are made using a Babcock-type magnetograph which is connected to a 22.9 m vertical Littrow spectrograph. Sun-as-a-star integrated light measurements of the mean solar magnetic field were made daily since May 1975. The typical mean field magnitude is about 0.15 gauss with typical measurement error less than 0.05 gauss. The mean field polarity pattern is essentially identical to the interplanetary magnetic field sector structure (seen near the earth with a 4 day lag). The differences in the observed structures can be understood in terms of a warped current sheet model

Evolution of the IBDM Structural Latch Development into a Generic Simplified Design

This paper presents the evolution in the development of the structural latch for the International Berthing Docking Mechanism (IBDM, see Figure 1). It reports on the lessons learned since completion of the test program on the engineering development unit of the first generation latching system in 2007. The initial latch design has been through a second generation concept in 2008, and now evolved into a third generation of this mechanism. Functional and structural testing on the latest latch hardware has recently been completed with good results. The IBDM latching system will provide the structural connection between two mated space vehicles after berthing or docking. The mechanism guarantees that the interface seals become compressed to form a leak-tight pressure system that creates a passageway for the astronauts

Bone quality changes as measured by Raman and FTIR spectroscopy in primiparous cows with humeral fracture from New Zealand.

The occurrence of spontaneous humeral fractures in primiparous dairy cows from New Zealand prompted the study of bone material from affected cows to further characterize this condition and to outline a likely pathogenesis. Previous studies indicate that these cows developed osteoporosis due to periods of suboptimal bone formation followed by increased bone resorption during the period of lactation complicated by copper deficiency. We hypothesized that there are significant differences in the chemical composition/bone quality in bones from cows with spontaneous humeral fracture compared to cows without humeral fractures. In this study, Raman and Fourier transform infrared spectroscopy band ratios were, for the first time, measured, calculated, and compared in bone samples from 67 primiparous dairy cows that suffered a spontaneous fracture of the humerus and 14 age-matched post-calving cows without humeral fractures. Affected bone showed a significantly reduced mineral/matrix ratio, increased bone remodeling, newer bone tissue with lower mineralization and, lower carbonate substitution, and reduced crystallinity. As such, is likely that these have detrimentally impacted bone quality and strength in affected cows.Published onlin

The K1 Protein of Kaposi's Sarcoma-Associated Herpesvirus Augments Viral Lytic Replication

ABSTRACT The K1 gene product of Kaposi's sarcoma-associated herpesvirus (KSHV) is encoded by the first open reading frame (ORF) of the viral genome. To investigate the role of the K1 gene during the KSHV life cycle, we constructed a set of recombinant viruses that contained either wild-type (WT) K1, a deleted K1 ORF (KSHVΔK1), stop codons within the K1 ORF (KSHV-K1 5×STOP ), or a revertant K1 virus (KSHV-K1 REV ). We report that the recombinant viruses KSHVΔK1 and KSHV-K1 5×STOP displayed significantly reduced lytic replication compared to WT KSHV and KSHV-K1 REV upon reactivation from latency. Additionally, cells infected with the recombinant viruses KSHVΔK1 and KSHV-K1 5×STOP also yielded smaller amounts of infectious progeny upon reactivation than did WT KSHV- and KSHV-K1 REV -infected cells. Upon reactivation from latency, WT KSHV- and KSHV-K1 REV -infected cells displayed activated Akt kinase, as evidenced by its phosphorylation, while cells infected with viruses deleted for K1 showed reduced phosphorylation and activation of Akt kinase. Overall, our results suggest that K1 plays an important role during the KSHV life cycle. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of three human malignancies, and KSHV K1 is a signaling protein that has been shown to be involved in cellular transformation and to activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. In order to investigate the role of the K1 protein in the life cycle of KSHV, we constructed recombinant viruses that were deficient for K1. We found that K1 deletion viruses displayed reduced lytic replication compared to the WT virus and also yielded smaller numbers of infectious progeny. We report that K1 plays an important role in the life cycle of KSHV

Stac Proteins Suppress Ca2+-Dependent Inactivation of Neuronal L-type Ca2+ Channels

Stac protein (named for its SH3-and cysteine-rich domains) was first identified in brain 20 years ago and is currently known to have three isoforms. Stac2, Stac1, and Stac3 transcripts are found at high, modest, and very low levels, respectively, in the cerebellum and forebrain, but their neuronal functions have been little investigated. Here, we tested the effects of Stac proteins on neuronal, high-voltage-activated Ca2+ channels. Overexpression of the three Stac isoforms eliminated Ca2+-dependent inactivation (CDI) ofL-type current in rat neonatal hippocampal neurons (sex unknown), but not CDI of non-L-type current. Using heterologous expression in tsA201 cells (together with β and α2-δ1 auxiliary subunits), we found that CDI for CaV1.2 and CaV1.3 (the predominant, neuronalL-type Ca2+ channels) was suppressed by all three Stac isoforms, whereas CDI for the P/Q channel, CaV2.1, was not. For CaV1.2, the inhibition of CDI by the Stac proteins appeared to involve their direct interaction with the channel’s C terminus. Within the Stac proteins, a weakly conserved segment containing ~100 residues and linking the structurally conserved PKC C1 and SH3_1 domains was sufficient to fully suppress CDI. The presence of CDI forL-type current in control neonatal neurons raised the possibility that endogenous Stac levels are low in these neurons and Western blotting indicated that the expression of Stac2 was substantially increased in adult forebrain and cerebellum compared with neonate. Together, our results indicate that one likely function of neuronal Stac proteins is to tune Ca2+ entry via neuronal L-type channels. © 2018 the authors