Soft x-ray Ar + 8 laser excited by low-voltage capillary discharge.

We demonstrated the operation of a 46.9-nm capillary discharge Ar + 8-laser excited by electrical pulses at a very low voltage (35 - 45 kV), which is approximately two times lower than previously reported. The decrease in pulse voltage not only allows for further reduction in the size of the laser's excitation part, but also a principal shift to the experimental methods, techniques, and technologies used in ordinary pulsed gas lasers operating in the ultraviolet, visible, and infrared regions of the spectra. In an argon-filled alumina capillary with an inner diameter of 3.1 mm and a length of 22 cm, laser pulses with an energy of 4 µJ and a duration of 1.6 ns were generated. The laser produces a beam with a Gaussian intensity distribution and an FWHM divergence of 1.9 mrad. The results could be particularly useful in the development of compact, practical soft x-ray capillary lasers for use in small laboratories at educational and research institutions.

Calcium scoring on coronary computed angiography tomography with photon-counting detector technology: Predictors of performance.

INTRODUCTION: Obtaining accurate coronary artery calcium (CAC) score measurements from CCTA datasets with virtual non-iodine (VNI) algorithms would reduce acquisition time and radiation dose. We aimed to assess the agreement of VNI-derived and conventional true non-contrast (TNC)-based CAC scores and to identify the predictors of accuracy. METHODS: CCTA datasets were acquired with either 120 or 140 â€‹kVp. CAC scores and volumes were calculated from TNC and VNI images in 197 consecutive patients undergoing CCTA. CAC density score, mean volume/lesion, aortic Hounsfield units and standard deviations were then measured. Finally, percentage deviation (VNI - TNC/TNC∗100) of CTA-derived CAC scores from non-enhanced scans was calculated for each patient. Predictors (including anthropometric and acquisition parameters, as well as CAC characteristics) of the degree of discrepancy were evaluated using linear regression analysis. RESULTS: While the agreement between TNC and VNI was substantial (mean bias, 6.6; limits of agreement, 178.5/145.3), a non-negligible proportion of patients (36/197, 18.3%) were falsely reclassified as CAC score â€‹= â€‹0 on VNI. The use of higher tube voltage significantly decreased the percentage deviation relative to TNC-based values (ߠ​= â€‹-0.21 [95%CI: 0.38 to -0.03], p â€‹= â€‹0.020) and a higher CAC density score also proved to be an independent predictor of a smaller difference (ߠ​= â€‹-0.22 [95%CI: 0.37 to -0.07], p â€‹= â€‹0.006). CONCLUSION: The performance of VNI-based calcium scoring may be improved by increased tube voltage protocols, while the accuracy may be compromised for calcified lesions of lower density. The implementation of VNI in clinical routine, however, needs to be preceded by a solution for detecting smaller lesions as well.

Effects of caffeine on central and peripheral fatigue following closed- and open-loop cycling exercises.

We examined whether endurance performance and neuromuscular fatigue would be affected by caffeine ingestion during closed- and open-loop exercises. Nine cyclists performed a closed-loop (4,000-m cycling time trial) and an open-loop exercise (work rate fixed at mean power of the closed-loop trial) 60 min after ingesting caffeine (CAF, 5 mg/kg) or placebo (PLA, cellulose). Central and peripheral fatigue was quantified via pre- to post-exercise decrease in quadriceps voluntary activation and potentiated twitch force, respectively. Test sensitivity for detecting caffeine-induced improvements in exercise performance was calculated as the mean change in time divided by the error of measurement. Caffeine ingestion reduced the time of the closed-loop trial (PLA: 375.1±14.5 s vs CAF: 368.2±14.9 s, P=0.024) and increased exercise tolerance during the open-loop trial (PLA: 418.2±99.5 s vs CAF: 552.5±106.5 s, P=0.001), with similar calculated sensitivity indices (1.5, 90%CI: 0.7-2.9 vs 2.8, 90%CI: 1.9-5.1). The reduction in voluntary activation was more pronounced (P=0.019) in open- (-6.8±8.3%) than in closed-loop exercises (-1.9±4.4%), but there was no difference between open- and closed-loop exercises for the potentiated twitch force reduction (-25.6±12.8 vs -26.6±12.0%, P>0.05). Caffeine had no effect on central and peripheral fatigue development in either mode of exercise. In conclusion, caffeine improved endurance performance in both modes of exercise without influence on post-exercise central and peripheral fatigue, with the open-loop exercise imposing a greater challenge to central fatigue tolerance.

Effects of caffeine on central and peripheral fatigue following closed- and open-loop cycling exercises

We examined whether endurance performance and neuromuscular fatigue would be affected by caffeine ingestion during closed- and open-loop exercises. Nine cyclists performed a closed-loop (4,000-m cycling time trial) and an open-loop exercise (work rate fixed at mean power of the closed-loop trial) 60 min after ingesting caffeine (CAF, 5 mg/kg) or placebo (PLA, cellulose). Central and peripheral fatigue was quantified via pre- to post-exercise decrease in quadriceps voluntary activation and potentiated twitch force, respectively. Test sensitivity for detecting caffeine-induced improvements in exercise performance was calculated as the mean change in time divided by the error of measurement. Caffeine ingestion reduced the time of the closed-loop trial (PLA: 375.1±14.5 s vs CAF: 368.2±14.9 s, P=0.024) and increased exercise tolerance during the open-loop trial (PLA: 418.2±99.5 s vs CAF: 552.5±106.5 s, P=0.001), with similar calculated sensitivity indices (1.5, 90%CI: 0.7-2.9 vs 2.8, 90%CI: 1.9-5.1). The reduction in voluntary activation was more pronounced (P=0.019) in open- (-6.8±8.3%) than in closed-loop exercises (-1.9±4.4%), but there was no difference between open- and closed-loop exercises for the potentiated twitch force reduction (-25.6±12.8 vs -26.6±12.0%, P>0.05). Caffeine had no effect on central and peripheral fatigue development in either mode of exercise. In conclusion, caffeine improved endurance performance in both modes of exercise without influence on post-exercise central and peripheral fatigue, with the open-loop exercise imposing a greater challenge to central fatigue tolerance.

Publisher Correction: Shedding new light on the Crab with polarized X-rays.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Shedding new light on the Crab with polarized X-rays.

Strong magnetic fields, synchrotron emission, and Compton scattering are omnipresent in compact celestial X-ray sources. Emissions in the X-ray energy band are consequently expected to be linearly polarized. X-ray polarimetry provides a unique diagnostic to study the location and fundamental mechanisms behind emission processes. The polarization of emissions from a bright celestial X-ray source, the Crab, is reported here for the first time in the hard X-ray band (~20-160 keV). The Crab is a complex system consisting of a central pulsar, a diffuse pulsar wind nebula, as well as structures in the inner nebula including a jet and torus. Measurements are made by a purpose-built and calibrated polarimeter, PoGO+. The polarization vector is found to be aligned with the spin axis of the pulsar for a polarization fraction, PF = (20.9 ± 5.0)%. This is higher than that of the optical diffuse nebula, implying a more compact emission site, though not as compact as, e.g., the synchrotron knot. Contrary to measurements at higher energies, no significant temporal evolution of phase-integrated polarisation parameters is observed. The polarization parameters for the pulsar itself are measured for the first time in the X-ray energy band and are consistent with observations at optical wavelengths.

pMINERVA: A donor-acceptor system for the in vivo recombineering of scFv into IgG molecules.

Phage display is the most widely used method for selecting binding molecules from recombinant antibody libraries. However, validation of the phage antibodies often requires early production of the cognate full-length immunoglobulin G (IgG). The conversion of phage library outputs to a full immunoglobulin via standard subcloning is time-consuming and limits the number of clones that can be evaluated. We have developed a novel system to convert scFvs from a phage display vector directly into IgGs without any in vitro subcloning steps. This new vector system, named pMINERVA, makes clever use of site-specific bacteriophage integrases that are expressed in Escherichia coli and intron splicing that occurs within mammalian cells. Using this system, a phage display vector contains both bacterial and mammalian regulatory regions that support antibody expression in E. coli and mammalian cells. A single-chain variable fragment (scFv) antibody is expressed on the surface of bacteriophage M13 as a genetic fusion to the gpIII coat protein. The scFv is converted to an IgG that can be expressed in mammalian cells by transducing a second E. coli strain. In that strain, the phiC31 recombinase fuses the heavy chain constant domain from an acceptor plasmid to the heavy chain variable domain and introduces controlling elements upstream of the light chain variable domain. Splicing in mammalian cells removes a synthetic intron containing the M13 gpIII gene to produce the fusion of the light chain variable domain to the constant domain. We show that phage displaying a scFv and recombinant IgGs generated using this system are expressed at wild-type levels and retain normal function. Use of the pMINERVA completely eliminates the labor-intensive subcloning and DNA sequence confirmation steps currently needed to convert a scFv into a functional IgG Ab.

Association between anaerobic components of the maximal accumulated oxygen deficit and 30-second Wingate test

The purpose of this study was to analyze the relationship between the anaerobic components of the maximal accumulated oxygen deficit (MAOD) and of the 30-second Wingate anaerobic test (30-WAnT). Nine male physical education students performed: a) a maximal incremental exercise test; b) a supramaximal constant workload test to determine the anaerobic components of the MAOD; and c) a 30-WAnT to measure the peak power (PP) and mean power (MP). The fast component of the excess post-exercise oxygen consumption and blood lactate accumulation were measured after the supramaximal constant workload test in order to determine the contributions made by alactic (ALMET) and lactic (LAMET) metabolism. Significant correlations were found between PP and ALMET (r=0.71; P=0.033) and between MP and LAMET (r=0.72; P=0.030). The study results suggested that the anaerobic components of the MAOD and of the 30-WAnT are similarly applicable in the assessment of ALMET and LAMET during high-intensity exercise.

Association between anaerobic components of the maximal accumulated oxygen deficit and 30-second Wingate test.

The purpose of this study was to analyze the relationship between the anaerobic components of the maximal accumulated oxygen deficit (MAOD) and of the 30-second Wingate anaerobic test (30-WAnT). Nine male physical education students performed: a) a maximal incremental exercise test; b) a supramaximal constant workload test to determine the anaerobic components of the MAOD; and c) a 30-WAnT to measure the peak power (PP) and mean power (MP). The fast component of the excess post-exercise oxygen consumption and blood lactate accumulation were measured after the supramaximal constant workload test in order to determine the contributions made by alactic (ALMET) and lactic (LAMET) metabolism. Significant correlations were found between PP and ALMET (r=0.71; P=0.033) and between MP and LAMET (r=0.72; P=0.030). The study results suggested that the anaerobic components of the MAOD and of the 30-WAnT are similarly applicable in the assessment of ALMET and LAMET during high-intensity exercise.

Measurement of higher order chromatic dispersion in a photonic bandgap fiber: comparative study of spectral interferometric methods.

Chromatic dispersion of a 37 cm long, solid-core photonic bandgap (PBG) fiber was studied in the wavelength range of 740-840 nm with spectral interferometry employing a Mach-Zehnder interferometer and a high resolution spectrometer. The interferometer was illuminated by a Ti:sapphire laser providing 20 fs pulses. A comparative study has been carried out to find the most accurate spectral phase retrieval method that is suitable for measuring higher order chromatic dispersion. The stationary phase point, the minima-maxima, the cosine function fit, the Fourier transform, and the windowed Fourier transform methods were tested. It was shown that out of these five techniques, the Fourier-transform method provided the dispersion coefficients with the highest accuracy, and it could also detect rapid phase changes in the vicinity of leaking mode frequencies within the transmission band of the PBG fiber.

Reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes and normal CD14 soluble levels in juvenile systemic lupus erythematosus.

In order to evaluate Fas and Bcl-2 expressions in CD14+ monocytes, to measure soluble CD14 serum levels and to analyze the relationships with lupus nephritis and disease activity, we enrolled 41 patients with juvenile systemic lupus erythematosus (JSLE) and 27 healthy volunteers. Disease activity was determined by SLEDAI score. Peripheral monocytes were stained for CD14, Fas and Bcl-2 molecules, and cellular expressions were determined by flow cytometry. Soluble CD14 levels were measured by a quantitative ELISA kit. JSLE patients, those with active disease and those with nephritis, presented significantly reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes compared with healthy controls. Significant inverse correlations between percentages of CD14+Fas+ cells, SLEDAI score and anti-dsDNA antibodies were observed. JSLE patients had soluble CD14 levels similar to controls, although sCD14 levels positively correlated with ESR, but not with SLEDAI score. JSLE patients with nephritis also presented sCD14 levels similar to controls. In conclusion, the reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes from JSLE patients depict that monocyte apoptotic mechanisms may be important in lupus pathogenesis.

Magnetoelectric confinement and stabilization of Z pinch in a soft-x-ray Ar(+8) laser.

Magnetoelectric confinement and stabilization of the plasma column in a soft-x-ray Ar(+8) laser, which is excited by a capillary Z pinch, via the combined magnetic and electric fields of the gliding surface discharge is experimentally demonstrated. Unlike soft-x-ray lasers excited by the conventional capillary Z pinches, the magnetoelectric confinement and stabilization of plasma do provide the laser operation without using any external preionization circuit.

Aerobic profile of climbers during maximal arm test.

This study compared measurements of upper body aerobic fitness in elite (EC; n=7) and intermediate rock climbers (IC; n=7), and a control group (C; n=7). Subjects underwent an upper limb incremental test on hand cycle ergometer, with increments of 23 W · min(-1), until exhaustion. Ventilation (VE) data were smoothed to 10 s averages and plotted against time for the visual determination of the first (VT1) and second (VT2) ventilatory thresholds. Peak power output was not different among groups [EC=130.9 (±11.8) W; IC=122.1 (±28.4) W; C=115.4 (±15.1) W], but time to exhaustion was significantly higher in EC than IC and C. VO(2 PEAK) was significantly higher in EC [36.8 (±5.7) mL.kg(-1).min(-1)] and IC [35.5 (±5.2) mL.kg(-1).min(-1)] than C [28.8 (±5.0) mL.kg(-1).min(-1)], but there was no difference between EC and IC. VT1 was significantly higher in EC than C [EC=69.0 (±9.4) W; IC=62.4 (±13.0) W; C=52.1 (±11.8) W], but no significant difference was observed in VT2 [EC=103.5 (±18.8) W; IC=92.0 (±22.0) W; C=85.6 (±19.7) W]. These results show that elite indoor rock climbers elicit higher aerobic fitness profile than control subjects when measured with an upper body test.

Predicting MAOD using only a supramaximal exhaustive test.

The objective of this study was to propose an alternative method (MAOD(ALT)) to estimate the maximal accumulated oxygen deficit (MAOD) using only one supramaximal exhaustive test. Nine participants performed the following tests: (a) a maximal incremental exercise test, (b) six submaximal constant workload tests, and (c) a supramaximal constant workload test. Traditional MAOD was determined by calculating the difference between predicted O(2) demand and accumulated O(2) uptake during the supramaximal test. MAOD(ALT) was established by summing the fast component of excess post-exercise oxygen consumption and the O(2) equivalent for energy provided by blood lactate accumulation, both of which were measured during the supramaximal test. There was no significant difference between MAOD (2.82+/-0.45 L) and MAOD(ALT) (2.77+/-0.37 L) (P=0.60). The correlation between MAOD and MAOD(ALT) was also high (r=0.78; P=0.014). These data indicate that the MAOD(ALT) can be used to estimate the MAOD.

MHC class I and II expression in juvenile dermatomyositis skeletal muscle.

OBJECTIVE: To assess MHC I and II expressions in muscle fibres of juvenile dermatomyositis (JDM) and compare with the expression in polymyositis (PM), dermatomyositis (DM) and dystrophy. PATIENTS AND METHODS: Forty-eight JDM patients and 17 controls (8 PM, 5 DM and 4 dystrophy) were studied. The mean age at disease onset was 7.1+/-3.0 years and the mean duration of weakness before biopsy was 9.4+/-12.9 months. Routinehistochemistry and immunohistochemistry (StreptABComplex/HRP) for MHC I and II (Dakopatts) were performed on serial frozen muscle sections in all patients. Mann-Whitney, Kruskal Wallis, chi-square and Fisher's exact statistical methods were used. RESULTS: MHC I expression was positive in 47 (97.9%) JDM cases. This expression was observed independent of time of disease, corticotherapy previous to muscle biopsy and to the grading of inflammation observed in clinical, laboratorial and histological parameters. The expression of MHC I was similar on JDM, PM and DM, and lower in dystrophy. On the other hand, MHC II expression was positive in just 28.2% of JDM cases and was correlated to histological features as inflammatory infiltrate, increased connective tissue and VAS for global degree of abnormality (p<0.05). MHC II expression was similar in DM/PM and lower in JDM and dystrophy, and it was based on the frequency of positive staining rather than to the degree of the MCH II expression. CONCLUSIONS: MHC I expression in muscle fibres is a premature and late marker of JDM patient independent to corticotherapy, and MHC II expression was lower in JDM than in PM and DM.

Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive tumour for which an increasing incidence has been reported. A new human polyomavirus, Merkel cell polyomavirus (MCV), was recently isolated from these tumours by applying digital transcriptome subtraction methodology. OBJECTIVES: To detect the presence or absence of MCV in MCCs and other, randomly selected neoplasms. METHODS: Nine primary or recurrent MCCs from seven patients were examined; 29 other tumours (squamous cell, basal cell and basosquamous carcinomas and malignant melanomas) were examined for comparative purposes. Viral large T protein (LT1 and LT3), and viral capsid protein (VP1) were detected by primer-directed amplification, using a polymerase chain reaction (PCR)-based method, and the amplified PCR products were analysed by agarose gel electrophoresis and subsequent sequence analysis. RESULTS: The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in seven of the eight MCC lesions. None of the comparative samples contained MCV DNA. CONCLUSIONS: Our findings strongly support the hypothesis that MCV infection may well be specific for MCC, and MCV may play a role in the pathogenesis of MCC.

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations.

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

Antinucleosome antibodies in patients with juvenile systemic lupus erythematosus.

Our objective was to evaluate the frequency of antinucleosome antibodies (anti-Ncs) in juvenile systemic lupus erythematosus (JSLE) comparing it to that observed for anti-DNA and to correlate the presence of these antibodies with clinical manifestations and disease activity. Anti-Ncs and anti-DNA were detected by ELISA in 74 patients with JSLE and 64 normal controls. Clinical records were reviewed. Disease activity was assessed by SLEDAI score. Anti-Ncs and anti-DNA showed sensitivity of 52.7% and 54% and specificity of 98.4% and 95.3%, respectively. Disagreement between the two assays was found in 25.7% of the cases: isolated positive Anti-Ncs in nine cases (12.2%) and isolated positive anti-DNA in 10 cases (13.5%). Agreement was found in 74.3%: both positive antibodies in 30 cases and both negative in 25. The presence of anti-Ncs was significantly associated with malar erythema, hemolytic anemia, anti-DNA and low complement levels, but not with renal manifestations. The presence of anti-Ncs was associated with a higher SLEDAI median (P < 0.001) and its titers correlated with the SLEDAI score (r = 0.504; P < 0.001). The frequency, sensitivity and specificity values were similar between anti-Ncs and anti-DNA antibodies in patients with JSLE. Nevertheless, the discordance of 25.7% between the two assays suggests that both antibodies may have a complementary diagnostic role. The association and correlation between anti-Ncs and several disease activity parameters demonstrated its usufulness in the follow-up of these patients.

Rituximab in refractory autoimmune diseases: Brazilian experience with 29 patients (2002-2004).

OBJECTIVE: Rituximab, a monoclonal antibody against B-lymphocytes that express CD 20, is already available for the treatment of non-Hodgkin's lymphoma. Due to the increased relevance of B-cell regulation in the pathogenesis of autoimmune diseases, rituximab is being used in the treatment of patients whose condition is refractory to conventional therapy. METHODS: We retrospectively evaluated the short-term efficacy and tolerance of rituximab in patients with various autoimmune diseases who were treated at the Hospital Israelita Albert Einstein in the city of Sao Paulo. RESULTS: During the period 2002-2004, 29 patients with various autoimmune diseases were treated with rituximab 375 mg/m2 for 4 consecutive weeks, or two doses of 1 g 2 weeks apart. We observed remarkable short-term results in all cases, except for one patient with thrombocytopenic purpura. Of note, we describe the results in two patients with diseases not previously treated with rituximab (hypergammaglobulinemic purpura of Waldenstrom and eosinophilic fasciitis with hypergammaglobulinemia). Treatment was well tolerated, with no unexpected adverse events. We also observed a marked reduction in steroid dosage. CONCLUSION: Rituximab seems to be safe and effective in the treatment of patients with a variety of autoimmune diseases that are refractory to other modalities of treatment.