Magnetic Evolution and Temperature Variation in a Coronal Hole

We have explored the magnetic flux evolution and temperature variation in a coronal-hole region, using Big Bear Solar Observatory (BBSO) deep magnetograms and {\it SOHO}/EIT images observed from 2005 October 10 to 14. For comparison, we also investigated a neighboring quiet region of the Sun. The coronal hole evolved from its mature stage to its disappearance during the observing period. We have obtained the following results: (1) When the coronal hole was well developed on October 10, about 60 % of the magnetic flux was positive. The EUV brightness was 420 counts pixel$^{-1}$, and the coronal temperature, estimated from the line ratio of the EIT 195 {\AA} and 171 {\AA} images, was 1.07 MK. (2) On October 14, when the coronal hole had almost disappeared, 51 % of the magnetic flux was positive, the EUV radiance was 530 counts pixel$^{-1}$, and the temperature was 1.10 MK. (3) In the neighboring quiet region, the fraction of positive flux varied between 0.49 and 0.47. The EUV brightness displayed an irregular variation, with a mean value of 870 counts pixel$^{-1}$. The temperature was almost constant at 1.11 MK during the five-day observation. Our results demonstrate that in a coronal hole less imbalance of the magnetic flux in opposite polarities leads to stronger EUV brightness and higher coronal temperatures

High rate, long-distance quantum key distribution over 250km of ultra low loss fibres

We present a fully automated quantum key distribution prototype running at 625 MHz clock rate. Taking advantage of ultra low loss fibres and low-noise superconducting detectors, we can distribute 6,000 secret bits per second over 100 km and 15 bits per second over 250km

Gene identification for the cblD defect of vitamin B12 metabolism

Background Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine. Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementation analysis. One of these defects, the cblD defect, can cause isolated methylmalonic aciduria, isolated homocystinuria, or both. Affected persons present with multisystem clinical abnormalities, including developmental, hematologic, neurologic, and metabolic findings. The gene responsible for the cblD defect has not been identified. Methods We studied seven patients with the cblD defect, and skin fibroblasts from each were investigated in cell culture. Microcell-mediated chromosome transfer and refined genetic mapping were used to localize the responsible gene. This gene was transfected into cblD fibroblasts to test for the rescue of adenosylcobalamin and methylcobalamin synthesis. Results The cblD gene was localized to human chromosome 2q23.2, and a candidate gene, designated MMADHC (methylmalonic aciduria, cblD type, and homocystinuria), was identified in this region. Transfection of wild-type MMADHC rescued the cellular phenotype, and the functional importance of mutant alleles was shown by means of transfection with mutant constructs. The predicted MMADHC protein has sequence homology with a bacterial ATP-binding cassette transporter and contains a putative cobalamin binding motif and a putative mitochondrial targeting sequence. Conclusions Mutations in a gene we designated MMADHC are responsible for the cblD defect in vitamin B12 metabolism. Various mutations are associated with each of the three biochemical phenotypes of the disorder

Epigenetic Silencing of Immune-Checkpoint Receptors in Bone Marrow- Infiltrating T Cells in Acute Myeloid Leukemia.

Background Immune-checkpoint (IC) inhibitors have revolutionized the treatment of multiple solid tumors and defined lymphomas, but they are largely ineffective in acute myeloid leukemia (AML). The reason why especially PD1/PD-L1 blocking agents are not efficacious is not well-understood but it may be due to the contribution of different IC ligand/receptor interactions that determine the function of T cells in AML. Methods To analyze the interactions of IC ligands and receptors in AML, we performed a comprehensive transcriptomic analysis of FACS-purified leukemia stem/progenitor cells and paired bone marrow (BM)-infiltrating CD4+ and CD8+ T cells from 30 patients with AML. The gene expression profiles of activating and inhibiting IC ligands and receptors were correlated with the clinical data. Epigenetic mechanisms were studied by inhibiting the histone deacetylase with valproic acid or by gene silencing of PAC1. Results We observed that IC ligands and receptors were mainly upregulated in leukemia stem cells. The gene expression of activating IC ligands and receptors correlated with improved prognosis and vice versa. In contrast, the majority of IC receptor genes were downregulated in BM-infiltrating CD8+ T cells and partially in CD4+ T cells, due to pathological chromatin remodeling via histone deacetylation. Therefore, treatment with histone deacetylase inhibitor (HDACi) or silencing of PAC1, as a T cell-specific epigenetic modulator, significantly increased the expression of IC receptors and defined effector molecules in CD8+ T cells. Conclusions Our results suggest that CD8+ T cells in AML are dysfunctional mainly due to pathological epigenetic silencing of activating IC receptors rather than due to signaling by immune inhibitory IC receptors, which may explain the limited efficacy of antibodies that block immune-inhibitory ICs in AML

ASAS/WHO ICF Core Sets for ankylosing spondylitis (AS): how to classify the impact of AS on functioning and health

Objective: To report on the results of a standardised consensus process agreeing on concepts typical and/or relevant when classifying functioning and health in patients with ankylosing spondylitis (AS) based on the International Classification of Functioning and Health (ICF).Methods: Experts in AS from different professional and geographical backgrounds attended a consensus conference and were divided into three working groups. Rheumatologists were selected from members of the Assessment of SpondyloArthritis international Society (ASAS). Other health professionals were recommended by ASAS members. The aim was to compose three working groups with five to seven participants to allow everybody's contribution in the discussions. Experts selected ICF categories that were considered typical and/or relevant for AS during a standardised consensus process by integrating evidence from preceding studies in alternating working group and plenary discussions. A Comprehensive ICF Core Set was selected for the comprehensive classification of functioning and a Brief ICF Core Set for application in trials.Results: The conference was attended by 19 experts from 12 countries. Eighty categories were included in the Comprehensive Core Set, which included 23 Body functions, 19 Body structures, 24 Activities and participation and 14 Environmental factors. Nineteen categories were selected for the Brief Core Set, which included 6 Body functions, 4 Body structures, 7 Activities and participation and 2 Environmental factors.Conclusion: The Comprehensive and Brief ICF Core Sets for AS are now available and aim to represent the external reference to define consequences of AS on functioning

Meropenem Prevents Levofloxacin-Induced Resistance in Penicillin-Resistant Pneumococci and Acts Synergistically with Levofloxacin in Experimental Meningitis

The aim of the present study was to investigate the potential synergy between meropenem and levofloxacin in vitro and in experimental meningitis and to determine the effect of meropenem on levofloxacin-induced resistance in vitro. Meropenem increased the efficacy of levofloxacin against the penicillin-resistant pneumococcal strain KR4 in time-killing assays in vitro and acted synergistically against a second penicillin-resistant strain WB4. In the checkerboard, only an additive effect (FIC indices: 1.0) was observed for both strains. In cycling experiments in vitro, levofloxacin alone led to a 64-fold increase in the MIC for both strains after 12 cycles. Addition of meropenem in sub-MIC concentrations (0.25×MIC) completely inhibited the selection of levofloxacin-resistant mutants in WB4 after 12 cycles. In KR4, the addition of meropenem led to just a twofold increase in the MIC for levofloxacin after 12 cycles. Mutations detected in the genes encoding for topoisomerase IV (parC) and gyrase (gyrA) confirmed the levofloxacin-induced resistance in both strains. Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4. In experimental meningitis, meropenem, given in two doses (2×125mg/kg), produced a good bactericidal activity (−0.45 Δlog10 cfu/ml·h) comparable to one dose (1×10mg/kg) of levofloxacin (−0.44 Δlog10 cfu/ml·h) against the penicillin-resistant strain WB4. Meropenem combined with levofloxacin acted synergistically (−0.93 Δlog10 cfu/ml·h), sterilizing the CSF of all rabbit

Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci

Ceftriaxone acted synergistically with levofloxacin in time-killing assays in vitro over 8 h against two penicillin-resistant pneumococcal strains (WB4 and KR4; MIC of penicillin: 4 mg/L). Synergy was confirmed with the chequerboard method, showing FIC indices of 0.25. In the experimental rabbit meningitis model, ceftriaxone (1× 125 mg/kg) was slightly less bactericidal (-0.30 Δlog10 cfu/mL.h) compared with levofloxacin (-0.45 Δlog10 cfu/mL.h) against the penicillin-resistant strain WB4. The combination therapy (levofloxacin and ceftriaxone) was significantly superior (-0.64 Δlog10 cfu/mL.h) to either monotherapy. In cycling experiments in vitro, the addition of ceftriaxone at a sub-MIC concentration (1/16 MIC) reduced levofloxacin-induced resistance in the two strains KR4 and WB4. After 12 cycles with levofloxacin monotherapy, the MIC increased 64-fold in both strains versus a 16-fold increase with the combination (levofloxacin + ceftriaxone 1/16 MIC). In both strains, levofloxacin-induced resistance was confirmed by mutations detected in the genes parC and gyrA, encoding for subunits of topoisomerase IV and gyrase, respectively. The addition of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in both strain

Problems Encountered With Control Networks in Highly-Restructurable Digital Systems

This paper discusses problems encountered with control networks in highly restructurable digital systems. In particular the treatment of implementation errors is covered with emphasis on concurrent processing. The implementation of concurrent processing networks may result in errors which will be quite complex to detect and systematic methods are warranted. Four meta control elements are employed in obtaining convenient concurrent structures. We analyze several error detecting schemes and conclude that the arc-node method with node partitioning appears to be the most realistic approach at this time

Left ventricular function at 24 hours, 14 days and 6 months after acute myocardial infarction

To determine the natural history of left ventricular function at rest and during exercise and to assess the impact of this variable on subsequent mortality, 165 patients were studied with radionuclide angiography within 24 hours of acute myocardial infarction. The ejection fraction of the 19 patients who died during the 6 month follow-up was lower than that of the 146 survivals: 41±16% vs 50±13% (P<0.001). Before hospital discharge (14±4 days), 83 patients had a rest and submaximal exercise radionuclide study. The ejection fraction of the 42 patients with anterior infarction was 44±12% and remained unchanged during exercise, while the 41 patients with posterior infarction had a resting value of 54±9% which increased to 57±10% (P<0.001) during exercise. The ejection fraction during exercise increased slightly but significantly in 37/61 patients with single vessel disease, while it did not change in the 24/61 patients with multivessel disease. At a mean of 4±1 months following infarction, 58 patients underwent a symptom-limited exercise radionuclide study. Mean value of resting ejection fraction for the group or anterior-posterior infarction subgroups did not change from initial or predischarge values. The 27 patients with anterior infarction showed no change in ejection fraction during exercise, while the 31 patients with posterior infarction increased their ejection fraction from 53±11% to 57±12% (P<0.001). Thus, ejection fraction measured by radionuclide angiography 24 hours following acute myocardial infarction provides useful prognostic information. Moreover, data collected 14 days and 4 months after infarction indicate that no significant change in ejection fraction occurred at rest or during exercise compared with values at rest for the group as a whole. However, ejection fraction values of patients with posterior infarction or of patients with single vessel disease increased with exercise, indicating that after myocardial infarction the capacity for improvement in myocardial function does exist in those patients who manifest the least extensive ischaemic or necrotic damag