Results of Skylab medical experiment M171: Metabolic activity

The experiment was conducted to establish whether man's ability to perform mechanical work would be progressively altered as a result of exposure to the weightless environment of space flight. The Skylab crewmen exercised on a bicycle ergometer at workloads approximating 25, 50, and 75 percent of their maximum aerobic capacity. The physiological parameters monitored were respiratory gas exchange, blood pressure, and vectorcardiogram/heart rate. The results of these tests indicate that the crewmen had no significant decrement in their responses to exercise during their exposure to zero gravity. The results of the third manned Skylab mission (Skylab 4) are presented and a comparison is made of the overall results obtained from the three successively longer Skylab manned missions. The Skylab 4 crewmembers' 84-day in-flight responses to exercise were no worse and were probably better than the responses of the crewmen on the first two Skylab missions. Indications that exercise was an important contributing factor in maintaining this response are discussed

Assignment of the Human and Mouse Prion Protein Genes to Homologous Chromosomes

Purified preparations of scrapie prions contain one major macromolecule, designated prion protein (PrP). Genes encoding PrP are found in normal animals and humans but not within the infectious particles. The PrP gene was assigned to human chromosome 20 and the corresponding mouse chromosome 2 using somatic cell hybrids. In situ hybridization studies mapped the human PrP gene to band 20p12→pter. Our results should lead to studies of genetic loci syntenic with the PrP gene, which may play a role in the pathogenesis of prion diseases or other degenerative neurologic disorders

Rhodopsin Expression Level Affects Rod Outer Segment Morphology and Photoresponse Kinetics

Background: The retinal rod outer segment is a sensory cilium that is specialized for the conversion of light into an electrical signal. Within the cilium, up to several thousand membranous disks contain as many as a billion copies of rhodopsin for efficient photon capture. Disks are continually turned over, requiring the daily synthesis of a prodigious amount of rhodopsin. To promote axial diffusion in the aqueous cytoplasm, the disks have one or more incisures. Across vertebrates, the range of disk diameters spans an order of magnitude, and the number and length of the incisures vary considerably, but the mechanisms controlling disk architecture are not well understood. The finding that transgenic mice overexpressing rhodopsin have enlarged disks lacking an incisure prompted us to test whether lowered rhodopsin levels constrain disk assembly. Methodology/Principal Findings: The structure and function of rods from hemizygous rhodopsin knockout (R+/−) mice with decreased rhodopsin expression were analyzed by transmission electron microscopy and single cell recording. R+/− rods were structurally altered in three ways: disk shape changed from circular to elliptical, disk surface area decreased, and the single incisure lengthened to divide the disk into two sections. Photocurrent responses to flashes recovered more rapidly than normal. A spatially resolved model of phototransduction indicated that changes in the packing densities of rhodopsin and other transduction proteins were responsible. The decrease in aqueous outer segment volume and the lengthened incisure had only minor effects on photon response amplitude and kinetics. Conclusions/Significance: Rhodopsin availability limits disk assembly and outer segment girth in normal rods. The incisure may buffer the supply of structural proteins needed to form larger disks. Decreased rhodopsin level accelerated photoresponse kinetics by increasing the rates of molecular collisions on the membrane. Faster responses, together with fewer rhodopsins, combine to lower overall sensitivity of R+/− rods to light

Additive Laser Excitation of Giant Nonlinear Surface Acoustic Wave Pulses

The laser ultrasonics technique perfectly fits the needs for non-contact, non-invasive, non-destructive mechanical probing of samples of mm to nm sizes. This technique is however limited to the excitation of low-amplitude strains, below the threshold for optical damage of the sample. In the context of strain engineering of materials, alternative optical techniques enabling the excitation of high amplitude strains in a non-destructive optical regime are seeking. We introduce here a non-destructive method for laser-shock wave generation based on additive superposition of multiple laser-excited strain waves. This technique enables strain generation up to mechanical failure of a sample at pump laser fluences below optical ablation or melting thresholds. We demonstrate the ability to generate nonlinear surface acoustic waves (SAWs) in Nb:SrTiO$_3$ substrates, at typically 1 kHz repetition rate, with associated strains in the percent range and pressures close to 100 kbars. This study paves the way for the investigation of a host of high-strength SAW-induced phenomena, including phase transitions in conventional and quantum materials, plasticity and a myriad of material failure modes, chemistry and other effects in bulk samples, thin layers, or two-dimensional materials

Reconstructing palaeoclimate and hydrological fluctuations in the Fezzan Basin (southern Libya) since 130 ka: a catchment-based approach

We propose a novel method to evaluate regional palaeoclimate that can be used to alleviate the problems caused by the discontinuous nature of palaeoenvironmental data found in deserts. The technique involves processing satellite imagery and DEM’s to map past rivers, catchments and evaluate the areas and volumes of palaeolakes. This information is used to determine the new Lake Evaluation Index (LEI) that allows a qualitative estimate of the amount of sediment received by lakes and how long-lived those lakes are. Lakes with considerable longevity and large sediment stores are selected for study. Validation is performed using image interpretation of remote sensing data, UltraGPR surveys and fieldwork. These techniques are also used to identify and study spring deposits and fluvial landforms that provide valuable palaeoclimate information. The method is applied to the Fezzan Basin in southern Libya focusing on the Wadi ash Shati and Wadi el-Agial catchments. Results indicate that the palaeohydrology is accurately mapped except within dune fields. We analysed the sedimentology of the key deposits identified by this methodology, developing a chronology using optically stimulated luminescence (OSL) and radiocarbon dating. We find evidence for relatively humid conditions during MIS 5c/d and e, as well as during the early to middle Holocene. Larger lakes and more extensive river systems were present during MIS 5 than are found during the Holocene, suggestive of greater humidity. The Holocene humid period started at ~11 ka and continued until ~5 ka being interrupted by abrupt periods of aridity at ~8.2 ka and ~6 ka that coincide with North Atlantic cooling. After each of these arid events the climate was less humid than previously, suggesting that they were superimposed upon an overall drying trend. The termination of the Holocene humid period in the Sahara has received much scrutiny in recent years, and sediments of Palaeolake Shati provide a continuous record of this. We do not find evidence to support the hypothesis of either sudden or gradual aridification of the Sahara at ~5 ka, instead we find that that aridity started to develop at ~6.5 ka, whereupon the lake levels oscillated until finally drying-up by 5.3 ka. Most of the other lakes in the Fezzan also dried up at ~ 5ka. We suggest that thousands of years of aridification prior to 5 ka shrunk these lakes so that additional aridity at this time led to their final desiccation. Because lakes are prodigious dust sources this mechanism potentially explains the rapid rise in dust flux to the Atlantic at 5 ka, with this final drying being the culmination of longer term aridity, albeit overprinted with considerable climate variability

Understanding Anthropological Understanding: for a merological anthropology

In this paper I argue for a merological anthropology in which ideas of ‘partiality’ and ‘practical adequacy’ provide a way out of the impasse of relativism which is implied by post-modernism and the related abandonment of a concern with ‘truth’. Ideas such as ‘aptness’ and ‘faithfulness’ enable us to re-establish empirical foundations without having to espouse a simple realism which has been rightly criticised. Ideas taken from ethnomethodology, particularly the way we bootstrap from ‘practical adequacy’ to ‘warrants for confidence’ point to a merological anthropology in which we recognize that we do not and cannot know everything, but that we can have reasons for being confident in the little we know

Local IL-13 gene transfer prior to immune-complex arthritis inhibits chondrocyte death and matrix-metalloproteinase-mediated cartilage matrix degradation despite enhanced joint inflammation

During immune-complex-mediated arthritis (ICA), severe cartilage destruction is mediated by Fcγ receptors (FcγRs) (mainly FcγRI), cytokines (e.g. IL-1), and enzymes (matrix metalloproteinases (MMPs)). IL-13, a T helper 2 (Th2) cytokine abundantly found in synovial fluid of patients with rheumatoid arthritis, has been shown to reduce joint inflammation and bone destruction during experimental arthritis. However, the effect on severe cartilage destruction has not been studied in detail. We have now investigated the role of IL-13 in chondrocyte death and MMP-mediated cartilage damage during ICA. IL-13 was locally overexpressed in knee joints after injection of an adenovirus encoding IL-13 (AxCAhIL-13), 1 day before the onset of arthritis; injection of AxCANI (an empty adenoviral construct) was used as a control. IL-13 significantly increased the amount of inflammatory cells in the synovial lining and the joint cavity, by 30% to 60% at day 3 after the onset of ICA. Despite the enhanced inflammatory response, chondrocyte death was diminished by two-thirds at days 3 and 7. The mRNA level of FcγRI, a receptor shown to be crucial in the induction of chondrocyte death, was significantly down-regulated in synovium. Furthermore, MMP-mediated cartilage damage, measured as neoepitope (VDIPEN) expression using immunolocalization, was halved. In contrast, mRNA levels of MMP-3, -9, -12, and -13 were significantly higher and IL-1 protein, which induces production of latent MMPs, was increased fivefold by IL-13. This study demonstrates that IL-13 overexpression during ICA diminished both chondrocyte death and MMP-mediated VDIPEN expression, even though joint inflammation was enhanced

Quantum Maxwell-Bloch equations for spatially inhomogeneous semiconductor lasers

We present quantum Maxwell-Bloch equations (QMBE) for spatially inhomogeneous semiconductor laser devices. The QMBE are derived from fully quantum mechanical operator dynamics describing the interaction of the light field with the quantum states of the electrons and the holes near the band gap. By taking into account field-field correlations and field-dipole correlations, the QMBE include quantum noise effects which cause spontaneous emission and amplified spontaneous emission. In particular, the source of spontaneous emission is obtained by factorizing the dipole-dipole correlations into a product of electron and hole densities. The QMBE are formulated for general devices, for edge emitting lasers and for vertical cavity surface emitting lasers, providing a starting point for the detailed analysis of spatial coherence in the near field and far field patterns of such laser diodes. Analytical expressions are given for the spectra of gain and spontaneous emission described by the QMBE. These results are applied to the case of a broad area laser, for which the frequency and carrier density dependent spontaneous emission factor beta and the evolution of the far field pattern near threshold are derived.Comment: 22 pages RevTex and 7 figures, submitted to Phys.Rev.A, revisions in abstract and in the discussion of temporal coherenc

A protocol for manual segmentation of medial temporal lobe subregions in 7 Tesla MRI

Recent advances in MRI and increasing knowledge on the characterization and anatomical variability of medial temporal lobe (MTL) anatomy have paved the way for more specific subdivisions of the MTL in humans. In addition, recent studies suggest that early changes in many neurodegenerative and neuropsychiatric diseases are better detected in smaller subregions of the MTL rather than with whole structure analyses. Here, we developed a new protocol using 7 Tesla (T) MRI incorporating novel anatomical findings for the manual segmentation of entorhinal cortex (ErC), perirhinal cortex (PrC; divided into area 35 and 36), parahippocampal cortex (PhC), and hippocampus; which includes the subfields subiculum (Sub), CA1, CA2, as well as CA3 and dentate gyrus (DG) which are separated by the endfolial pathway covering most of the long axis of the hippocampus. We provide detailed instructions alongside slice-by-slice segmentations to ease learning for the untrained but also more experienced raters. Twenty-two subjects were scanned (19–32 yrs, mean age = 26 years, 12 females) with a turbo spin echo (TSE) T2-weighted MRI sequence with high-resolution oblique coronal slices oriented orthogonal to the long axis of the hippocampus (in-plane resolution 0.44 × 0.44 mm2) and 1.0 mm slice thickness. The scans were manually delineated by two experienced raters, to assess intra- and inter-rater reliability. The Dice Similarity Index (DSI) was above 0.78 for all regions and the Intraclass Correlation Coefficients (ICC) were between 0.76 to 0.99 both for intra- and inter-rater reliability. In conclusion, this study presents a fine-grained and comprehensive segmentation protocol for MTL structures at 7 T MRI that closely follows recent knowledge from anatomical studies. More specific subdivisions (e.g. area 35 and 36 in PrC, and the separation of DG and CA3) may pave the way for more precise delineations thereby enabling the detection of early volumetric changes in dementia and neuropsychiatric diseases