Adiabatic normal zone development in MgB2 superconductors

A-priori knowledge of the normal zone development in MgB/sub 2/ conductors is essential for quench protection of applications. Therefore the normal zone propagation in a monofilament MgB/sub 2//Fe conductor under near-adiabatic conditions at 4.2 K has been measured and simulated. The results show normal zone propagation velocities up to several meters per second. In addition, by including the voltage-current relation into the computational model, the influence of the n-value on the normal zone propagation is determined. The simulations show that lower n-values suppress the normal zone propagation velocity due to lower heat generation in the MgB/sub 2/ filaments

Cored Rutherford cables for the GSI fast ramping synchrotron

The new heavy ion synchrotron facility proposed by GSI will have two superconducting magnet rings in the same tunnel, with rigidities of 200 T/spl middot/m and 100 T/spl middot/m. Fast ramp times are needed, which can cause significant problems for the magnets, particularly in the areas of ac loss and field distortion. This paper discusses the 200 T/spl middot/m ring, which will use Cos/spl theta/ magnets based on the RHIC dipole design. We discuss the reasons for choosing Rutherford cable with a resistive core and report loss measurements carried out on cable samples. These measurements are compared with theoretical calculations using measured values of inter-strand resistance. Reasonably good agreement is found, but there are indications of nonuniformity in the adjacent resistance R/sub a/. Using these measured parameters, losses and temperature rise are calculated for a RHIC dipole in the operating cycle of the accelerator. A novel insulation scheme designed to promote efficient cooling is described

Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression

Cancers may escape elimination by the host immune system by rewiring the tumour microenvironment towards an immune suppressive state. Transforming growth factor-β (TGF-β) is a secreted multifunctional cytokine that strongly regulates the activity of immune cells while, in parallel, can promote malignant features such as cancer cell invasion and migration, angiogenesis, and the emergence of cancer-associated fibroblasts. TGF-β is abundantly expressed in cancers and, most often, its abundance associated with poor clinical outcomes. Immunotherapeutic strategies, particularly T cell checkpoint blockade therapies, so far, only produce clinical benefit in a minority of cancer patients. The inhibition of TGF-β activity is a promising approach to increase the efficacy of T cell checkpoint blockade therapies. In this review, we briefly outline the immunoregulatory functions of TGF-β in physiological and malignant contexts. We then deliberate on how the therapeutic targeting of TGF-β may lead to a broadened applicability and success of state-of-the-art immunotherapies.Cancer Signaling networks and Molecular Therapeutic

The Relationship between Nociceptive Detection Thresholds and Pressure-and Electrical Pain Thresholds:An Explorative Study in Rheumatoid Arthritis Patients

Recently, methods have been developed enabling the characterization of the nociceptive function at the detection threshold level by measuring nociceptive detection thresholds (NDTs), rather than at the level of the pain threshold via pain threshold (PT) measurements. Both NDT and PT measurements aim to characterize (parts of) the nociceptive system. To date it is unclear if, and if so to what extent, the two outcomes relate to one another. In this study, the primary aim is to explore the relationship between the two measures in patients with rheumatoid arthritis (RA). As secondary aim, we explore differences in NDT between these RA patients with age-and sex-matched healthy controls (HC) from a readily existing dataset. In total 46 RA patients have been recruited, whereby the pressure-(PPT; bilaterally at two locations) and electrical (EPT) pain threshold were evaluated, as well as the NDTs. Significant, positive correlations were found between the EPT and PPT (R=0.54-0.60), but not with the NDTs (R≤0.25). As compared to HC, higher NDTs were found in the RA group. As the presence of a statistically significant weak relationship can only be evaluated using a larger sample size, our results indicate that there is no moderate or stronger relation between PT and NDT outcomes. This implicates that the two outcomes are not strongly driven by the same (nociceptive) mechanism(s). Future research into NDTs and what factors and/or mechanisms affect the outcome, could yield relevant insights into how to use and interpret the results of this relatively new method.Clinical Relevance-The evaluation of nociceptive detection thresholds, in isolation or together with conventionally evaluated pain thresholds, might provide valuable and complementary insights into nociceptive (dis)function in man.</p

The effects of treatment with chemotherapy on energy metabolism and inflammatory mediators in small-cell lung carcinoma.

A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced resting energy expenditure (REE) and a decreased energy intake contribute to weight loss. Enhanced systemic levels of inflammatory mediators were found to be related to the enhanced REE in lung cancer. The aim of the present study was to investigate energy metabolism and systemic levels of inflammatory mediators in small-cell lung carcinoma (SCLC) patients before and after treatment with chemotherapy. Hypermetabolism and an enhanced inflammatory response have already been demonstrated in SCLC by our group before. Twelve newly diagnosed SCLC patients were consecutively included in the study. REE was measured by indirect calorimetry and body composition was determined by bioelectrical impedance (BIA) before and 1 month after treatment. To assess the inflammatory state the acute-phase proteins, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), both soluble tumour necrosis factor (TNF) receptors, (sTNF-R)-55 and sTNF-R75, and soluble intercellular adhesion molecule (sICAM)-1 were measured in plasma before and 1 month after treatment. CRP was assessed by turbidemetry, whereas the other inflammatory parameters were measured by enzyme-linked immunosorbent assay (ELISA). A significant reduction in REE was found irrespective of therapeutic outcome, whereas body weight and body composition remained stable. The acute-phase proteins CRP and LBP were reduced significantly after treatment with chemotherapy, whereas both sTNF receptors and sICAM-1 remained enhanced. No correlation, however, existed between the decrease in REE and the decrease in the acute-phase proteins. In conclusion, chemotherapeutic treatment attenuates the tumour-related metabolic derangements and acute-phase response

Genomic characterization of the human DNA excision repair gene ERCC-1.

In this report the genomic characterization of the human excision repair gene ERCC-1 is presented. The gene consists of 10 exons spread over approximately 15 kb. By means of a transfection assay the ERCC-1 promoter was confined to a region of + 170 bp upstream of the transcriptional start site. Classical promoter elements like CAAT, TATA and GC-boxes are absent from this region. Furthermore, ERCC-1 transcription is not UV-inducible. A possible explanation is provided for the previously reported alternative splicing of exon VIII. Analysis of ERCC-1 cDNA clones revealed the occurrence of differential polyadenylation which gives ERCC-1 transcripts of 3.4 and 3.8 kb in addition to the major 1.1 kb mRNA. Apparent evolutionary conservation of differential polyadenylation of ERCC-1 transcripts suggests a possible role for this mode of RNA processing in the ERCC-1 repair function

Euro-Collins Solution Versus Uw-Solution for Long-Term Liver Preservation in the Isolated Rat-Liver Perfusion Model

To compare UW-solution (UW) and Euro-Collins (EC) for long-term liver preservation we investigated the morphology and metabolic capacity of rat liver after 18 and 42-hours cold-storage in either UW or EC