Liquid Hydrogen Recirculation System for Forced Flow Cooling Test of Superconducting Conductors

Advances in Cryogenic Engineering: Proceedings of the Cryogenic Engineering Conference (CEC) 2017 (previous edition: CEC-2015). 9–13 July 2017, Madison, Wisconsin, USA.The knowledge of forced flow heat transfer characteristics of liquid hydrogen (LH₂) is important and necessary for design and cooling analysis of high critical temperature superconducting devices. However, there are few test facilities available for LH₂forced flow cooling for superconductors. A test system to provide a LH₂forced flow (∼10 m/s) of a short period (less than 100 s) has been developed. The test system was composed of two LH₂tanks connected by a transfer line with a controllable valve, in which the forced flow rate and its period were limited by the storage capacity of tanks. In this paper, a liquid hydrogen recirculation system, which was designed and fabricated in order to study characteristics of superconducting cables in a stable forced flow of liquid hydrogen for longer period, was described. This LH₂loop system consists of a centrifugal pump with dynamic gas bearings, a heat exchanger which is immersed in a liquid hydrogen tank, and a buffer tank where a test section (superconducting wires or cables) is set. The buffer tank has LHe cooled superconducting magnet which can produce an external magnetic field (up to 7T) at the test section. A performance test was conducted. The maximum flow rate was 43.7 g/s. The lowest temperature was 22.5 K. It was confirmed that the liquid hydrogen can stably circulate for 7 hours

Src tyrosine kinase augments taxotere-induced apoptosis through enhanced expression and phosphorylation of Bcl-2

Activation of Src, which has an intrinsic protein tyrosine kinase activity, has been demonstrated in many human tumours, such as colorectal and breast cancers, and is closely associated with the pathogenesis and metastatic potential of these cancers. In this study, we have examined the effect of activated Src on the sensitivity to taxotere, an anticancer drug targeting microtubules, using v-src-transfected HAG-1 human gall bladder epithelial cells. As compared with parental HAG-1 cell line, v-src-transfected HAG/src3-1 cells became 5.9 and 7.0-fold sensitive to taxotere for 2 and 24-h exposure, respectively. By contrast, HAG-1 cells transfected with activated Ras, which acts downstream of Src, acquired approximately 2.5∼4.8-fold taxotere resistance. The taxotere sensitivity in HAG/src3-1 cells was reversed, if not completely, by herbimycin A, a specific inhibitor of Src family protein tyrosine kinase, indicating that Src protein tyrosine kinase augments sensitivity to taxotere. Treatment of HAG/src3-1 cells with taxotere resulted in phosphorylation of Bcl-2 and subsequent induction of apoptotic cell death, whereas neither Bcl-2 phosphorylation nor apoptosis occurred in parental or c-H-ras-transfected HAG-1 cells. Interestingly, the Bcl-2 protein is overexpressed in v-src-transfected cell line, compared to those in parental or Ras-transfected cell line. Treatment of HAG/src3-1 cells with herbimycin A significantly reduced the expression and phosphorylation of Bcl-2, and abrogated taxotere-induced apoptosis, suggesting a potential role for Src protein tyrosine kinase in the taxotere-induced apoptotic events. H-7, a protein kinase C inhibitor and wortmannin, a phosphatidylinositol-3 kinase (PI-3 kinase) inhibitor, neither altered taxotere sensitivity nor inhibited taxotere-induced apoptosis in these cells. These data indicate that the ability of activated Src to increase taxotere sensitivity would be mediated by apoptotic events occurring through Src to downstream signal transduction pathways toward Bcl-2 phosphorylation, but not by activated Ras, PI-3 kinase or protein kinase C

APCcdh1 Mediates Degradation of the Oncogenic Rho-GEF Ect2 after Mitosis

Background: Besides regulation of actin cytoskeleton-dependent functions, Rho GTPase pathways are essential to cell cycle progression and cell division. Rho, Rac and Cdc42 regulate G1 to S phase progression and are involved in cytokinesis. RhoA GDP/GTP cycling is required for normal cytokinesis and recent reports have shown that the exchange factor Ect2 and the GTPase activating protein MgcRacGAP regulate RhoA activity during mitosis. We previously showed that the transcription factors E2F1 and CUX1 regulate expression of MgcRacGAP and Ect2 as cells enter S-phase. Methodology/Principal Findings: We now report that Ect2 is subject to proteasomal degradation after mitosis, following ubiquitination by the APC/C complex and its co-activator Cdh1. A proper nuclear localization of Ect2 is necessary for its degradation. APC-Cdh1 assembles K11-linked poly-ubiquitin chains on Ect2, depending upon a stretch of,25 amino acid residues that contain a bi-partite NLS, a conventional D-box and two TEK-like boxes. Site-directed mutagenesis of target sequences generated stabilized Ect2 proteins. Furthermore, such degradation-resistant mutants of Ect2 were found to activate RhoA and subsequent signalling pathways and are able to transform NIH3T3 cells. Conclusions/Significance: Our results identify Ect2 as a bona fide cell cycle-regulated protein and suggest that its ubiquitination-dependent degradation may play an important role in RhoA regulation at the time of mitosis. Our findings raise the possibility that the overexpression of Ect2 that has been reported in some human tumors might result not only from deregulated transcription, but also from impaired degradation

An Anillin-Ect2 Complex Stabilizes Central Spindle Microtubules at the Cortex during Cytokinesis

Cytokinesis occurs due to the RhoA-dependent ingression of an actomyosin ring. During anaphase, the Rho GEF (guanine nucleotide exchange factor) Ect2 is recruited to the central spindle via its interaction with MgcRacGAP/Cyk-4, and activates RhoA in the central plane of the cell. Ect2 also localizes to the cortex, where it has access to RhoA. The N-terminus of Ect2 binds to Cyk-4, and the C-terminus contains conserved DH (Dbl homologous) and PH (Pleckstrin Homology) domains with GEF activity. The PH domain is required for Ect2's cortical localization, but its molecular function is not known. In cultured human cells, we found that the PH domain interacts with anillin, a contractile ring protein that scaffolds actin and myosin and interacts with RhoA. The anillin-Ect2 interaction may require Ect2's association with lipids, since a novel mutation in the PH domain, which disrupts phospholipid association, weakens their interaction. An anillin-RacGAP50C (homologue of Cyk-4) complex was previously described in Drosophila, which may crosslink the central spindle to the cortex to stabilize the position of the contractile ring. Our data supports an analogous function for the anillin-Ect2 complex in human cells and one hypothesis is that this complex has functionally replaced the Drosophila anillin-RacGAP50C complex. Complexes between central spindle proteins and cortical proteins could regulate the position of the contractile ring by stabilizing microtubule-cortical interactions at the division plane to ensure the generation of active RhoA in a discrete zone

Mantle Pb paradoxes : the sulfide solution

Author Posting. © Springer, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 152 (2006): 295-308, doi:10.1007/s00410-006-0108-1.There is growing evidence that the budget of Pb in mantle peridotites is largely contained in sulfide, and that Pb partitions strongly into sulfide relative to silicate melt. In addition, there is evidence to suggest that diffusion rates of Pb in sulfide (solid or melt) are very fast. Given the possibility that sulfide melt ‘wets’ sub-solidus mantle silicates, and has very low viscosity, the implications for Pb behavior during mantle melting are profound. There is only sparse experimental data relating to Pb partitioning between sulfide and silicate, and no data on Pb diffusion rates in sulfides. A full understanding of Pb behavior in sulfide may hold the key to several long-standing and important Pb paradoxes and enigmas. The classical Pb isotope paradox arises from the fact that all known mantle reservoirs lie to the right of the Geochron, with no consensus as to the identity of the “balancing” reservoir. We propose that long-term segregation of sulfide (containing Pb) to the core may resolve this paradox. Another Pb paradox arises from the fact that the Ce/Pb ratio of both OIB and MORB is greater than bulk earth, and constant at a value of 25. The constancy of this “canonical ratio” implies similar partition coefficients for Ce and Pb during magmatic processes (Hofmann et al. 1986), whereas most experimental studies show that Pb is more incompatible in silicates than Ce. Retention of Pb in residual mantle sulfide during melting has the potential to bring the bulk partitioning of Ce into equality with Pb if the sulfide melt/silicate melt partition coefficient for Pb has a value of ~ 14. Modeling shows that the Ce/Pb (or Nd/Pb) of such melts will still accurately reflect that of the source, thus enforcing the paradox that OIB and MORB mantles have markedly higher Ce/Pb (and Nd/Pb) than the bulk silicate earth. This implies large deficiencies of Pb in the mantle sources for these basalts. Sulfide may play other important roles during magmagenesis: 1). advective/diffusive sulfide networks may form potent metasomatic agents (in both introducing and obliterating Pb isotopic heterogeneities in the mantle); 2). silicate melt networks may easily exchange Pb with ambient mantle sulfides (by diffusion or assimilation), thus ‘sampling’ Pb in isotopically heterogeneous mantle domains differently from the silicate-controlled isotope tracer systems (Sr, Nd, Hf), with an apparent ‘de-coupling’ of these systems.Our intemperance should not be blamed on the support we gratefully acknowledge from NSF: EAR- 0125917 to SRH and OCE-0118198 to GAG

Lead content and isotopic composition in submound and recent soils of the Volga upland

Literature data on the historical reconstructions of the atmospheric lead deposition in Europe and the isotopic composition of the ores that are potential sources of the anthropogenic lead in the atmospheric deposition in the lower Volga steppes during different time periods have been compiled. The effect of the increasing anthropogenic lead deposition recorded since the Bronze Age on the level of soil contamination has been investigated. For the first time paleosol buried under a burial mound of the Bronze Age has been used as a reference point to assess of the current contamination level. The contents and isotopic compositions of the mobile and total lead have been determined in submound paleosols of different ages and their recent remote and roadside analogues. An increase in the content and fraction of the mobile lead and a shift of its isotopic composition toward less radiogenic values (typical for lead from the recent anthropogenic sources) has been revealed when going from a Bronze-Age paleosol to a recent soil. In the Bronze-Age soil, the isotopic composition of the mobile lead is inherited from the parent rock to a greater extent than in the modern soils, where the lead is enriched with the less radiogenic component. The effect of the anthropogenic component is traced in the analysis of the mobile lead, but it is barely visible for the total lead. An exception is provided by the recent roadside soils characterized by increased contents and the significantly less radiogenic isotopic composition of the mobile and total lead

Polo-Like Kinase Controls Vertebrate Spindle Elongation and Cytokinesis

During cell division, chromosome segregation must be coordinated with cell cleavage so that cytokinesis occurs after chromosomes have been safely distributed to each spindle pole. Polo-like kinase 1 (Plk1) is an essential kinase that regulates spindle assembly, mitotic entry and chromosome segregation, but because of its many mitotic roles it has been difficult to specifically study its post-anaphase functions. Here we use small molecule inhibitors to block Plk1 activity at anaphase onset, and demonstrate that Plk1 controls both spindle elongation and cytokinesis. Plk1 inhibition did not affect anaphase A chromosome to pole movement, but blocked anaphase B spindle elongation. Plk1-inhibited cells failed to assemble a contractile ring and contract the cleavage furrow due to a defect in Rho and Rho-GEF localization to the division site. Our results demonstrate that Plk1 coordinates chromosome segregation with cytokinesis through its dual control of anaphase B and contractile ring assembly

Comparative Genomic Analysis of Clinical Strains of Campylobacter jejuni from South Africa

BACKGROUND: Campylobacter jejuni is a common cause of acute gastroenteritis and is also associated with the post-infectious neuropathies, Guillain-Barré and Miller Fisher syndromes. In the Cape Town area of South Africa, C. jejuni strains with Penner heat-stable (HS) serotype HS:41 have been observed to be overrepresented among cases of Guillain-Barré syndrome. The present study examined the genetic content of a collection of 32 South African C. jejuni strains with different serotypes, including 13 HS:41 strains, that were recovered from patients with enteritis, Guillain-Barré or Miller Fisher syndromes. The sequence-based typing methods, multilocus sequence typing and DNA microarrays, were employed to potentially identify distinguishing features within the genomes of these C. jejuni strains with various disease outcomes. METHODOLOGY/PRINCIPAL FINDINGS: Comparative genomic analyses demonstrated that the HS:41 South African strains were clearly distinct from the other South African strains. Further DNA microarray analysis demonstrated that the HS:41 strains from South African patients with the Guillain-Barré syndrome or enteritis were highly similar in gene content. Interestingly, the South African HS:41 strains were distinct in gene content when compared to HS:41 strains from other geographical locations due to the presence of genomic islands, referred to as Campylobacter jejuni integrated elements (CJIEs). Only the integrated element CJIE1, a Campylobacter Mu-like prophage, was present in the South African HS:41 strains whereas this element was absent in two closely-related HS:41 strains from Mexico. A more distantly-related HS:41 strain from Canada possessed both integrated elements CJIE1 and CJIE2. CONCLUSION/SIGNIFICANCE: These findings demonstrate that CJIEs may contribute to the differentiation of closely-related C. jejuni strains. In addition, the presence of bacteriophage-related genes in CJIE1 may contribute to the genomic diversity of C. jejuni strains. This comparative genomic analysis of C. jejuni provides fundamental information that potentially could lead to improved methods for analyzing the epidemiology of disease outbreaks