Report of the committee on a commercially developed space facility

Major facilities that could support significant microgravity research and applications activity are discussed. The ground-based facilities include drop towers, aircraft flying parabolic trajectories, and sounding rockets. Facilities that are intrinsically tied to the Space Shuttle range from Get-Away-Special canisters to Spacelab long modules. There are also orbital facilities which include recoverable capsules launched on expendable launch vehicles, free-flying spacecraft, and space stations. Some of these existing, planned, and proposed facilities are non-U.S. in origin, but potentially available to U.S. investigators. In addition, some are governmentally developed and operated whereas others are planned to be privately developed and/or operated. Tables are provided to show the facility, developer, duration, estimated gravity level, crew interaction, flight frequency, year available, power to payload, payload volume, and maximum payload mass. The potential of direct and indirect benefits of manufacturing in space are presented

Timing of ibuprofen use and musculoskeletal adaptations to exercise training in older adults

AbstractProstaglandins (PGs) increase in bone in response to mechanical loading and stimulate bone formation. Inhibition of cyclooxygenase (COX), the enzyme responsible for PG synthesis, by non-steroidal anti-inflammatory drugs (NSAIDs) impairs the bone formation response to loading in animals when administered before, but not after, loading. The aim was to determine whether the timing of ibuprofen use (400mg before versus after exercise sessions) is a significant determinant of the adaptive response of BMD to exercise training in older adults. We hypothesized that taking ibuprofen before exercise would attenuate the improvements in total hip and lumbar spine BMD in response to 36weeks of training when compared with placebo or with ibuprofen use after exercise. Untrained women and men (N=189) aged 60 to 75years were randomly assigned to 1 of 3 treatment arms: placebo before and after exercise (PP); ibuprofen before and placebo after exercise (IP); and placebo before and ibuprofen after exercise (PI).The difference between groups in the change in BMD was not significant when IP was compared with either PP (hip, −0.5% (−1.4, 0.4); spine, 0.1% (−0.9, 1.2)) or PI (hip, 0.3% (−0.6, 1.2); spine, 0.5% (−0.5, 1.5)). Ibuprofen use appeared to have more adverse effects on BMD in women than men. The study demonstrated that ibuprofen use did not significantly alter the BMD adaptations to exercise in older adults, but this finding should be interpreted cautiously. It had been expected that the inhibition of bone formation by ibuprofen would be more robust in men than in women, but this did not appear to be the case and may have limited the power to detect the effects of ibuprofen. Further research is needed to understand whether NSAID use counteracts, in part, the beneficial effects of exercise on bone

An AMPKa2-specific phospho-switch controls lysosomal targeting for activation

AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are metabolic kinases that co-ordinate nutrient supply with cell growth. AMPK negatively regulates mTORC1, and mTORC1 reciprocally phosphorylates S345/7 in both AMPK α-isoforms. We report that genetic or torin1-induced loss of α2-S345 phosphorylation relieves suppression of AMPK signaling; however, the regulatory effect does not translate to α1-S347 in HEK293T or MEF cells. Dephosphorylation of α2-S345, but not α1-S347, transiently targets AMPK to lysosomes, a cellular site for activation by LKB1. By mass spectrometry, we find that α2-S345 is basally phosphorylated at 2.5-fold higher stoichiometry than α1-S347 in HEK293T cells and, unlike α1, phosphorylation is partially retained after prolonged mTORC1 inhibition. Loss of α2-S345 phosphorylation in endogenous AMPK fails to sustain growth of MEFs under amino acid starvation conditions. These findings uncover an α2-specific mechanism by which AMPK can be activated at lysosomes in the absence of changes in cellular energy

Employing Plant Functional Groups to Advance Seed Dispersal Ecology and Conservation

Seed dispersal enables plants to reach hospitable germination sites and escape natural enemies. Understanding when and how much seed dispersal matters to plant fitness is critical for understanding plant population and community dynamics. At the same time, the complexity of factors that determine if a seed will be successfully dispersed and subsequently develop into a reproductive plant is daunting. Quantifying all factors that may influence seed dispersal effectiveness for any potential seed-vector relationship would require an unrealistically large amount of time, materials and financial resources. On the other hand, being able to make dispersal predictions is critical for predicting whether single species and entire ecosystems will be resilient to global change. Building on current frameworks, we here posit that seed dispersal ecology should adopt plant functional groups as analytical units to reduce this complexity to manageable levels. Functional groups can be used to distinguish, for their constituent species, whether it matters (i) if seeds are dispersed, (ii) into what context they are dispersed and (iii) what vectors disperse them. To avoid overgeneralization, we propose that the utility of these functional groups may be assessed by generating predictions based on the groups and then testing those predictions against species-specific data. We suggest that data collection and analysis can then be guided by robust functional group definitions. Generalizing across similar species in this way could help us to better understand the population and community dynamics of plants and tackle the complexity of seed dispersal as well as its disruption

Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704

Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT

Exercise testing three days after onset of acute myocardial infarction

To determine the feasibility and predictive value of early exercise testing 72 hours after acute myocardial infarction, 109 consecutive patients who received reperfusion therapy were prospectively evaluated. In the group studied, in 87 (80%) the course was uncomplicated 3 days after admission, as defined by a lack of congestive heart failure, arrhythmias and angina, and 53 patients (49%) performed heart rate-limited (140 beats/min) treadmill exercise. These patients exercised for 7.9 +/- 3.4 minutes, achieving a heart rate of 129 +/- 11 beats/min and a systolic blood pressure of 151 +/- 27 mm Hg. The exercise test was not accompanied by any protracted ischemia, infarction or significant arrhythmias. Accompanying tomographic thallium-201 scintigraphy demonstrated a reversible perfusion defect in 14 patients (26%), no evidence for ischemia in 36 patients (69%) and an equivocal result in 3 patients (6%). Of the 14 patients with a positive exercise-thallium test result, 4 had an adverse clinical outcome of either reinfarctipn, postinfarction angina or ventricular tachycardia during hospital days 4 to 10; an adverse in-hospital outcome was not seen in the 40 patients with a negative exercise-thallium test result (p = 0.009). Thus, early exercise testing after acute myocardial infarction is safe in selected patients with an uncomplicated course and the test is predictive of in-hospital clinical outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26528/1/0000067.pd

LAVA: An Open-Source Approach To Designing LAMP (Loop-Mediated Isothermal Amplification) DNA Signatures

<p>Abstract</p> <p>Background</p> <p>We developed an extendable open-source Loop-mediated isothermal AMPlification (LAMP) signature design program called LAVA (LAMP Assay Versatile Analysis). LAVA was created in response to limitations of existing LAMP signature programs.</p> <p>Results</p> <p>LAVA identifies combinations of six primer regions for basic LAMP signatures, or combinations of eight primer regions for LAMP signatures with loop primers, which can be used as LAMP signatures. The identified primers are conserved among target organism sequences. Primer combinations are optimized based on lengths, melting temperatures, and spacing among primer sites. We compare LAMP signature candidates for <it>Staphylococcus aureus </it>created both by LAVA and by PrimerExplorer. We also include signatures from a sample run targeting all strains of <it>Mycobacterium tuberculosis</it>.</p> <p>Conclusions</p> <p>We have designed and demonstrated new software for identifying signature candidates appropriate for LAMP assays. The software is available for download at <url>http://lava-dna.googlecode.com/</url>.</p