An understanding of the number and contribution of individual pluripotent hematopoietic stem cells (HSCs) to the formation of blood lineages has important clinical implications for gene therapy and ...stem cell transplantation. We have been able to efficiently mark rhesus macaque long-term repopulating stem and progenitor cells with retroviral vectors, and track their in vivo contributions to hematopoiesis using the linear amplification mediated–polymerase chain reaction (LAM-PCR) technique of insertion site analysis. We assessed the impact of busulfan on contributions of individual retrovirally marked clones to hematopoiesis. There were 2 macaques that received transplants of retrovirally transduced CD34+cells 2 years previously that were then treated with 4 mg/kg busulfan. Despite only transient and mild suppression of peripheral blood counts, the numbers of individual stem/progenitor clones contributing to granulocyte production decreased dramatically, by 80% in the first monkey and by 60% in the second monkey. A similar impact was seen on clones contributing to T cells. The clone numbers recovered gradually back toward baseline by 5 months following busulfan in the first monkey and by 3 months in the second monkey, and have remained stable for more than one year in both animals. Tracking of individual clones with insertion-site–specific primers suggested that clones contributing to hematopoiesis prior to busulfan accounted for the majority of this recovery, but that some previously undetected clones began to contribute during this recovery phase. These results indicate that even low-dose busulfan significantly affects stem and progenitor cell dynamics. The clonal diversity of hematopoiesis was significantly decreased after even a single, clinically well-tolerated dose of busulfan, with slow but almost complete recovery over the next several months, suggesting that true long-term repopulating stem cells were not permanently deleted. However, the prolonged period of suppression of many clones suggests that transplanted HSCs may have a marked competitive advantage if they can engraft and proliferate during this time period, and supports the use of this agent in nonmyeloablative regimens
Vibrationally resolved C and O 1s photoelectron spectra of carbon monoxide have been measured in the photon energy range between 300 and 440
eV and between 550 and 702
eV, respectively. The intensity ...ratios of the vibrational components vary slowly, approaching the sudden limit. From the spectra in the sudden limit, the information about the potential curves for the C 1s and O 1s ionized states are extracted. The experimental potential curves thus obtained are reproduced well by the present ab initio calculations based on the symmetry adapted cluster-configuration interaction method.
To evaluate antibody to hepatitis E virus (anti-HEV) seroreactivity, 5000 US blood donors were tested for anti-HEV by two EIAs: a mosaic protein assay (MPr-EIA) and a recombinant protein assay ...(RPr-EIA). Overall, 59 (1.2%) were seroreactive by MPr-EIA and 70 (1.4%) were seroreactive by RPr-EIA. The overall concordance between tests was 98.5% (4925/5000); the concordance among reactive sera by either test was only 27% (27/102). In a case-control study, seroreactive persons were more likely than seronegative persons to have traveled to countries in which HEV is endemic (odds ratio OR for MPr-EIA = 4.3, P < .001; OR for RPr-EIA = 2.5, P = .005), but 31% of MPr-EIA anti-HEV-reactive persons and 38% of RPr-EIA anti-HEV-reactive persons had no history of international travel. These findings suggest that travelers to regions in which HEV is endemic can acquire subclinical HEV infection. The significance of anti-HEV seroreactivity among persons without an international travel history needs to be determined.
Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is clinically used for fixation of implants such as artificial hip joints. However, it does not show ...bone-bonding ability, i.e., bioactivity. The lack of bioactivity would be one of factors which cause loosening between the cement and the implant. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with gamma-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the effects of the kinds of PMMA powder on setting time, apatite formation and compressive strength were investigated in a simulated body fluid (Kokubo solution). The cement modified with calcium acetate calcined at 220 degrees C could set within 15 min when the PMMA powder had an average molecular weight of 100,000 or less. The addition of calcium acetate calcined at 120 degrees C in the PMMA powder required a much longer period for setting. The modified cements formed an apatite layer after soaking in the Kokubo solution within 1 day for cement starting from PMMA powder with a molecular weight of 100,000 or less. Compressive strengths of the modified cements were more than 70 MPa for cements starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in molecular weight showed a smaller decrease in compressive strength than that consisting of 56,000 in molecular weight. These results indicate that bioactive PMMA cement can be produced with appropriate setting time and mechanical strength when PMMA powders with a suitable molecular weight are used. Such a type of design of bioactive PMMA bone cement leads to a novel development of bioactive material for bone substitutes.
This paper describes fuzzy damage extraction method for ultrasonic nondestructive testing images. In our experiment, we employ a piece of wind turbine blade as a specimen has artificial damages. We ...acquire ultrasonic waveforms from scanning lines on surface of the pecimen using an ultrasonic single probe. To extract the damages, we calculate fuzzy degrees of average difference data of all scanning lines, and make fuzzy images whose ntensities calculated by the fuzzy degrees. As the results, we found the line image with all damage portions, and we estimated depth of damage surface with high accuracy.
A high-power, ultralow-chirp electroabsorption modulator (EAM) integrated with a distributed-feedback laser diode (EML) having ultrashort lifetime of photogenerated holes in the EAM quantum-well (QW) ...structure is reported for the first time. A shallow QW structure having a small valence band offset to enhance the sweepout of photogenerated holes was employed as EAM absorption layer. The measured hole lifetimes were 7-11 ps, and the measured frequency chirp (/spl alpha/-parameter) was low or negative at low EAM reverse bias voltages even under high optical output power conditions. Successful 10-Gb/s 80-km normal-dispersion single-mode fiber transmission (chromatic dispersion D=1600 ps/nm) and the record average fiber optical output power (P/sub f/) of +5.3 dBm were achieved at 25/spl deg/C. In addition, semicooled operation of EML at enhanced bit rates has been demonstrated for application in small-form-factor protocol-agnostic optical transceivers. A 10.7-Gb/s 1600-ps/nm transmission was achieved at 45/spl deg/C and P/sub f/=+3.0 dBm.
Objective To define the cardiovascular effects of lowering blood pressure in people with chronic kidney disease.Design Collaborative prospective meta-analysis of randomised trials.Data sources and ...eligibility Participating randomised trials of drugs to lower blood pressure compared with placebo or each other or that compare different blood pressure targets, with at least 1000 patient years of follow-up per arm.Main outcome measures Major cardiovascular events (stroke, myocardial infarction, heart failure, or cardiovascular death) in composite and individually and all cause death.Participants 26 trials (152 290 participants), including 30 295 individuals with reduced estimated glomerular filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73m2.Data extraction Individual participant data were available for 23 trials, with summary data from another three. Meta-analysis according to baseline kidney function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure were estimated with a random effects model.Results Compared with placebo, blood pressure lowering regimens reduced the risk of major cardiovascular events by about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect (P=1.00 for homogeneity). The results were similar irrespective of whether blood pressure was reduced by regimens based on angiotensin converting enzyme inhibitors, calcium antagonists, or diuretics/β blockers. There was no evidence that the effects of different drug classes on major cardiovascular events varied between patients with different eGFR (all P>0.60 for homogeneity).Conclusions Blood pressure lowering is an effective strategy for preventing cardiovascular events among people with moderately reduced eGFR. There is little evidence from these overviews to support the preferential choice of particular drug classes for the prevention of cardiovascular events in chronic kidney disease.
In successful knee arthroplasty, the femur and the tibia must be shaped to fit an artificial joint. The recent trend towards MIS (Minimally Invasive Surgery) to decrease the length of the required ...incision in the skin has increased surgical difficulty, since the open access area is small. The developed system consists of (1) a preplanning system providing a CAD function, (2) a multi-axis CAM system which avoids cutting the skin and the ligament, and keeps the cutting time within acceptable limits, and (3) a 7-axis machine tool that assures the safety of the patient and the surgeon, and enables MIS.
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