Direct observation of ultrafast exciton localization in an organic semiconductor with soft X-ray transient absorption spectroscopy.

The localization dynamics of excitons in organic semiconductors influence the efficiency of charge transfer and separation in these materials. Here we apply time-resolved X-ray absorption spectroscopy to track photoinduced dynamics of a paradigmatic crystalline conjugated polymer: poly(3-hexylthiophene) (P3HT) commonly used in solar cell devices. The π→π* transition, the first step of solar energy conversion, is pumped with a 15 fs optical pulse and the dynamics are probed by an attosecond soft X-ray pulse at the carbon K-edge. We observe X-ray spectroscopic signatures of the initially hot excitonic state, indicating that it is delocalized over multiple polymer chains. This undergoes a rapid evolution on a sub 50 fs timescale which can be directly associated with cooling and localization to form either a localized exciton or polaron pair.

[Characteristics of local human skeleton reactions to microgravity and drug treatment of osteoporosis in clinic].

Analysis of the results of long-term investigations of bones in cosmonauts flown on the orbital station MIR and International space station (n = 80) was performed. Theoretically predicted (evolutionary predefined) change in mass of different skeleton bones was found to correlate (r = 0.904) with position relatively the Earth's gravity vector. Vector dependence of bone loss ensues from local specificity of expression of bone metabolism genes which reflects mechanic prehistory of skeleton structures in the evolution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss attested by the dependence of bone loss rate on polymorphism of certain bone metabolism markers. Parameters of one and the other orbital vehicle did not modulate individual-specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus-unique spatial structure of distribution of noncollagenous proteins responsible for position regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotrophic intervention into areas of bustling resorption.

[Analysis of polymorphism of bone metabolism genes and evaluation of the risk of osteopenia in cosmonauts].

Densitometry of cosmonauts following long-duration missions shows reduction of bone mineral density (BMD). On the average, post-flight BMD remains within the normal range and the broad variability of individual BMD values sometimes is qualified as local osteopenia. Individual reactions are typed by similarity of amount and rate of BMD loss. At present, analysis of functionally significant polymorphism of bone metabolism genes is the most effective instrument for diagnostics of susceptibility to osteopenia and osteoporosis. The investigation was aimed to analyze polymorphism of genes of vitamin-D and (VDR) and calcitonin (CALCR) receptors, and of collagen-1 alpha-1-chain (Col1a-1) in candidate cosmonauts and cosmonauts returned from 5 to 7-mo. missions. According to the results of analysis, in the majority of cosmonauts rapid BMD loss correlated with TT genotype by VDR gene but not with genotypes Tt and tt and associated with carriage of incomplete s-allele in the Col1a1 gene. Yet, in several instances high BMD loss rates were personified with carriers of VDR gene alleles (homo- and heterozygote states--tt and Tt) and heterozygote by Col1a1 gene (Ss).

[Comparative analysis of cosmonauts skeleton changes after space flights on orbital station Mir and international space station and possibilities of prognosis for interplanetary missions].

A summary of investigations results of human bone tissue changes in space flight on the orbital station (OS) Mir and international space station (ISS) using dual energy X-ray absorptiometry (DXA) is given. Results comparative analysis revealed an absence of significant differences in bone mass (BM) changes on the both OS. Theoretically expected BM loss was observed in bone trabecular structure of skeleton low part after space flight lasting 5-7 month. The BM losses are qualified in some cases as quicly developed but reversible osteopenia and generally interpreted as evidence of bone functional adaptation to the alterating mechanical loading. It was demonstrated the high individual variability BM loss amplitudes. Simultaneously was observed the individual pattern of BM loss distribution across different segments of skeleton after repetitive flights independently upon type of OS. In according with the above mentioned individual peculiarities it was impossible to establish the dependence of BM changes upon duration of space missions. Therefore we have not sufficiently data for calculation of probability to achive the critical demineralization level by the augmentation the space mission duration till 1.5-2 years. It is more less possibility of the bone quality changes prognosis, which in the aggregate with BM losses determines the bone fracture risk. It become clearly that DXA technology is unsuffitiently for this purpose. It is considered the main direction which may optimized the elaboration of the interplanetary project meaning the perfectly safe of skeleton mechanical function.

Recovery of spaceflight-induced bone loss: bone mineral density after long-duration missions as fitted with an exponential function.

The loss of bone mineral in NASA astronauts during spaceflight has been investigated throughout the more than 40 years of space travel. Consequently, it is a medical requirement at NASA Johnson Space Center (JSC) that changes in bone mass be monitored in crew members by measuring bone mineral density (BMD), with dual-energy X-ray absorptiometry (DXA) before and after flight, of astronauts who serve on long-duration missions (4-6 months). We evaluated this repository of medical data to track whether there is recovery of bone mineral that was lost during spaceflight. Our analysis was supplemented by BMD data from cosmonauts (by convention, a space traveler formally employed by the Russia Aviation and Space Agency or by the previous Soviet Union) who had also flown on long-duration missions. Data from a total of 45 individual crew members - a small number of whom flew on more than one mission - were used in this analysis. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing). Plotted BMD changes were fitted to an exponential mathematical function that estimated: (i) BMD change on landing day (day 0) and (ii) the number of days after landing when 50% of the lost bone would be recovered ("50% recovery time") in the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. In sum, averaged losses of bone mineral after long-duration spaceflight ranged between 2% and 9% across all sites with our recovery model predicting a 50% restoration of bone loss for all sites to be within 9 months.

[On possible mechanisms of osteopenia in humans in microgravity and situations imitating its effects].

The review deals with the analysis of osteodensitometry data from the cosmonauts flown on Russian space station MIR and the International space station and suppositions about involvement of different levels of metabolism regulation in bone loss triggered by insufficient mechanic loading in microgravity attendant by redistribution of body liquids. It is surmised that the initial reactions are associated with the biomechanical factor and recruitment of local mechanisms, i.e. osteocyte osteolysis and inhibition of osteoblast histogenesis. Regulation on the level of tissues and organs is responsible for destabilization of calcium homeostasis (low calcium absorption in the intestine and readsorption in the kidney). Changes in the hierarchy of ion and volume regulation may provoke osteoclast resorption which further increases osteopenia.

[Characteristics and patterns of the human bone reactions to microgravity].

Hypothesized processes of changes found in spacecrew bones following 5 to 7 mo. orbital missions are reviewed. Selective osteopenia of trabecular bones in the lower skeleton is attributed to a greater weight loading at 1 g. Increased mineral content in the upper skeleton (dual energy X-ray adsoptiometry--DXA) and hypermineralization of the limbic spongious bone (computer tomography) appear to be secondary and reflect the body liquids redistribution headword including to the abdomen. The additional negative gradient of the lower skeleton mass during early readaptation (about 1.5 mo, after landing) can be explained by remodeling (resorption and bone formation) as a reaction to the "load return". Personal variability is probably a fingerprint of genetic determinism of bone mass and metabolic phenotype that may sometimes lead to an increased risk of fracture. The authors raise the discussion about practicality of the genetic osteopenia prediction for space flyers.

[Reactions of the human bone system in space flight: phenomenology].

Results of multi-year bone observations in crewmembers of long-term (6 to 14 mos.) Salyut and Mir missions have been summarized. The theoretical expectation of bone losses (mineral bone density, MBD) was consistent only in the trabecular of the lower skeleton (lumbar spine, femur proximal epiphysis, pelvis). The upper skeleton bones (skull, cervical spine) demonstrated a clears-defined trend toward an increase in mineral content. There is a direct dependence of MBD losses on a skeleton bone position relative to the gravity vector and bone structure. Post-flight MBD did not, as a rule, deviate from the WHO-defined limits (T-criterion); in several instances MBD loss was qualified as local osteopenia. Shifts in MBD, same as MBD recovery rate, vary with subjects and, therefore, deny their dependence on flight duration. By and large, MBD shifts are interpreted as a functional adaptation of bone tissue to changing mechanic demands.

Bone status and fracture prevalence in Russian adults with childhood-onset growth hormone deficiency.

The consequences of lifelong untreated childhood-onset GH deficiency (COGHD) on adult bone and especially fracture prevalence are largely unknown due to the lack of data on long-term outcome of untreated patients. Therefore, we studied adult Russian patients (n = 66; 28 females and 38 males) with idiopathic GH-untreated COGHD. Patients had isolated GH deficiency (IGHD; n = 18, age 23 +/- 10 yr) or multiple pituitary hormone deficiency (MPHD) with open (OMPHD; n = 27, age 23 +/- 5 yr) or closed growth plates (CMPHD; n = 21, age 55 +/- 12 yr). Bone mineral content (BMC) and bone mineral density (BMD) values were compared with 821 normal Russian controls. Fracture prevalence was ascertained from medical history and compared with similar data from 333 normal controls. Height sd score was -4.6 (range, -1.8 to -8.1). This represents 82% of the height of normal Russian adults. BMC of the lumbar spine, femoral neck, and total body of patients with IGHD was 54, 71, and 59%, respectively, of that of age- and sex-matched controls (all P < 0 0.001). A similarly decreased BMC (42-69% of expected values) was found for all bone regions of patients with both OMPHD and CMPHD. Mean areal BMD measurements (g/cm(2)) varied (Z scores between -1.8 and -3.0), but the calculated true bone density (g/cm(3)) was normal in patients with IGHD or CMPHD and only slightly decreased (Z score, -0.8) in patients with OMPHD. Lifetime low-energy fracture prevalence was normal in patients with IGHD but substantially exceeded the expected prevalence in OMPHD (odds ratio of fracture = 3.0; 0.6 fractures per patient; P < 0.0001) or CMPHD patients (odds ratio for fracture = 7.4; 2.2 fractures per patient; P < 0.0001). In conclusion, IGHD and MPHD of childhood onset very substantially impair adult height and BMC. Although areal BMD is frankly decreased, volumetric bone density is unaffected, but nevertheless, the fracture prevalence in patients with MPHD is markedly increased. These observations demonstrate that not only volumetric density but also bone mass and shape are major determinants of bone strength.

Effects of chair restraint on the strength of the tibia in rhesus monkeys.

To determine the effects of the relative inactivity and unloading on the strength of the tibias of monkeys, Macaca mulatta, we used a non-invasive test to measure bending stiffness, or EI (Nm2), a mechanical property. The technique was validated by comparisons of in vivo measurements with standard measures of EI in the same bones post-mortem (r2 = 0.95, P < 0.0001). Inter-test precision was 4.28+/-1.4%. Normative data in 24 monkeys, 3.0+/-0.7 years and 3.6+/-0.6 kg, revealed EI to be 16% higher in the right than left tibia (4.4+/-1.6 vs. 3.7+/-1.6 Nm2, P < 0.05). Five monkeys, restrained in chairs for 14 days, showed decreases in EI. There were no changes in EI in two chaired monkeys that lost weight during a 2-week space flight. The factors that account for both the decreases in bone mechanical properties after chair restraint at 1 g and lack of change after microgravity remain to be identified. Metabolic factors associated with body weight changes are suggested by our results.

Muscle volume, MRI relaxation times (T2), and body composition after spaceflight.

Postflight changes in muscle volume, calf muscle transverse relaxation time, and total body composition were measured in 4 crewmembers after a 17-day mission and in 14-16 crewmembers in multiple shuttle/Mir missions of 16- to 28-wk duration. During the 17-day mission, all muscle regions except the hamstrings significantly decreased 3-10% compared with baseline. During the shuttle/Mir missions, there were significant decreases in muscle volume (5-17%) in all muscle groups except the neck. These changes, which reached a new steady state by 4 mo of flight or less, were reversed within 30-60 days after landing. Postflight swelling and elevation of calf muscle transverse relaxation time persisted for several weeks after flight, which suggests possible muscle damage. In contrast to the 17-day flight, in which loss in fat, but not lean body mass, was found (25), losses in bone mineral content and lean body mass, but not fat, were seen after the longer shuttle/Mir missions. The percent losses in total body lean body mass and bone mineral content were similar at approximately 3.4-3.5%, whereas the pelvis demonstrated the largest regional bone loss at 13%.

Bone mineral and lean tissue loss after long duration space flight.

The loss of bone and muscle is a major concern for long duration space flight. In December of 1989, we established a collaboration with Russian colleagues to determine the bone and lean tissue changes in cosmonauts before and after flights on the Mir space station lasting 4-14.4 months. Eighteen crew members received a lumbar spine and hip DEXA scan (Hologic 1000W) before and after flight; 17 crew members received an additional whole body scan. All results were expressed as percent change from baseline per month of flight in order to account for the different flight times. The pre-and post-flight data were analyzed using Hotelling's T(2) for 3 groups of variables: spine, neck of femur, trochanter; whole body BMD and subregions; lean (total, legs, arms) and fat (total only). A paired t-test was used as a follow-up to the Hotelling's T(2) to identify the individual measurements that were significantly different. These data define the rate and extent of bone and lean tissue loss during long duration space flight and indicate that the current in-flight exercise program is not sufficient to completely ameliorate bone and muscle loss during weightlessness.

Change and recovery of bone mass and acoustic properties of rhesus monkeys after Bion 11 spaceflight.

Bone mineral density (BMD) of lumbar spine and tibia, as well as ultrasound propagation speed along the tibia, was measured in Bion 11 flight and control monkeys. The flight monkeys showed a delay in the growth-related (L-1) bone mass increase compared to the preflight period. Similar changes were detected in some control animals. The changes occurred primarily in metabolically active spongy bone, as shown by ultrasound data.

Fast imaging of hard x rays with a laboratory microscope.

An improved x-ray microscope with a fully electronic CCD detector system has been constructed that allows improved laboratory-based microstructural investigations of materials with hard x rays. It uses the Kirkpatrick-Baez multilayer mirror design to form an image that has a demonstrated resolution of 4 microm at 8 keV (Cu K(alpha) radiation). This microscope performs well with standard sealed-tube laboratory x-ray sources, producing digital images with 20-s exposure times for a 5-microm Au grid (a thickness of two absorption lengths).

[Clinical and physiological evaluation of bone changes among astronauts after long-term space flights]. / Kliniko-fiziologicheskaia otsenka izmenenii kostnoi tkani u kosmonavtov posle dlitel'nykh kosmicheskikh poletov.

Results of the joint Russian/US studies of the effect of microgravity on bone tissues in 18 cosmonauts on return from 4.5- to 14.5-month long missions are presented. Dual-energy x-ray gamma-absorbtiometry (QDR-1000 W, Hologic, USA) was used to measure bone mineral density (BMD, g/cm2) and mineral content (BMC, g) in the whole body, the scalp including cervical vertebra, arms, ribs, sternal and lumbar regions of the spinal column, pelvis and legs. A clearly defined dependence of topography of changes upon the position of a skeletal segment in the gravity vector was established. The greatest BMD losses have been observed in the skeleton of the lower body, i.e. in pelvic bones (-11.99 +/- 1.22%), lumbar vertebra (-5.63 +/- 0.817%), and in proximal femur, particularly in the femoral neck (-8.17 +/- 1.24%). Bones of the upper skeleton were either unchanged (insignificant) or showed a positive trend. Overall changes in bone mass of the whole skeleton of male cosmonauts during the period of about 6 months on mission made up -1.41 +/- 0.406% and suggest the mean balance of calcium over flight equal to -227 +/- 62.8 mg/day. Reasoning is given to qualify these states of cosmonauts' bone tissues as local osteopenia. On the literature and results of authors' clinical evidence, discussed is availability of the densitometric data for predicting risk of trauma. A biological nature of the changes under observation is hypothesized.

[Changes in bone tissue of women under condition of 120 days antiorthostatic hypokinesia]. / Izmenenie sostoiania kostnoí tkani u zhenshchin v usloviiakh 120-sutochnoí antiortostaticheskoí gipokinezii.

The state of bone tissue has been studied in 8 women subjected to a 120-day HDT. Four test subjects (Group A) performed physical exercises during the experiment. Mineral content (MC) in bone tissue and mineral density of the bones (MD) were determined with the help of dichromatic x-ray bone densitometer HOLOGIC QDR--100/W. The velocity of propagation of ultrasound in the shin bone was also determined. It is found that the hypokinesia-associated losses of bone mass in the lower segments of the skeleton of women were insignificant. In the control group (Group B, non-exercising subjects), there markedly increased MC in the bones of the upper body and there were the slight signs of hypomineralization of the segments of the lower body as well as the significant (in 2 test subjects) decrease of MC in the pelvic bones in the recovery period to the level lower than at the beginning of the experiment. In group A, the increase of MC in the upper skeleton was expressed to a lesser degree. At the recovery period the all changes were practically neutralized and there were no signs of bone mass loss. The velocity of ultrasound by the Day 90 of the experiment had the marked tendency for a decrease in group A persisting up to the end of experiment while in the group B its changes were oppositely directed. Within 2 months after the experiment in the majority of women the tendency for recovery of the initial state both by the absolute values of ultrasound velocity and by the profile of curves of their distribution over the anterior surface of the shinbone was noted. The results are discussed in comparison with findings obtained in the experiments with long-term hypokinesia in men and in the space missions.

Effects of spaceflight on bone mineralization in the rhesus monkey.

We combined dual-photon absorptiometry, iliac crest histomorphometry, and backscattered electrons analysis to characterize bone mineralization effects of a spaceflight on young monkeys. Two 4- to 5-kg male rhesus monkeys (Macaca mulatta) were flown during a 11.5-day spaceflight that took place onboard Cosmos 2229 biosatellite (Bion 10). Vivarium (n = 4) and Earth-based chair (n = 4) control situations were studied for comparison. Flight monkeys exhibited lower values of iliac cancellous bone volume, associated with nonsignificantly thinner trabeculae. Bone mineralization rate and the proportion of trabecular bone surface involved in mineralization processes were found markedly reduced after spaceflight. Analysis of embedded sections by backscattered electrons imaging showed a nonsignificant shift to lower mineralization in the flight biopsies vs. postflight mock-up biopsies. These results were in accordance with dual-photon absorptiometry evaluations showing a tendency for decreased bone mineral content during flight and recovery thereafter. The ground simulation experiment performed on the same monkeys more than 1 mo after landing suggests that the observed effects were specifically related to spaceflight and that the animals had only partially recovered. Additional animals on future flights will be required to confirm these findings.

Bone and body mass changes during space flight.

Body mass, calcium and skeletal changes occur in humans who have worked in microgravity. Physiologic changes are seen as early as one week and are still occurring 312 days into space flight. The physiologic changes in bone and mineral metabolism may be among those which limits long duration space flight if an adequate countermeasure is not developed. The purpose of this paper is to summarize what is known about calcium dynamics and bone mineral changes as well as associated changes of body mass induced by space flight. The data reported is from a variety of studies conducted in both actual and simulated space flight.