Cryogenic Insulation Systems

The results of a comparative study of cryogenic insulation systems performed are presented. The key aspects of thermal insulation relative to cryogenic system design, testing, manufacturing, and maintenance are discussed. An overview of insulation development from an energy conservation perspective is given. Conventional insulation materials for cryogenic applications provide three levels of thermal conductivity. Actual thermal performance of standard multilayer insulation (MLI) is several times less than laboratory performance and often 10 times worse than ideal performance. The cost-effectiveness of the insulation system depends on thermal performance; flexibility and durability; ease of use in handling, installation, and maintenance; and overall cost including operations, maintenance, and life cycle. Results of comprehensive testing of both conventional and novel materials such as aerogel composites using cryostat boil-off methods are given. The development of efficient, robust cryogenic insulation systems that operate at a soft vacuum level is the primary focus of this paper

Mitochondrial precursor proteins are imported through a hydrophilic membrane environment

We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites

Loss of Liver Kinase B1 (LKB1) in Beta Cells Enhances Glucose-stimulated Insulin Secretion Despite Profound Mitochondrial Defects

The tumor suppressor liver kinase B1 (LKB1) is an important regulator of pancreatic β cell biology. LKB1-dependent phosphorylation of distinct AMPK (adenosine monophosphate-activated protein kinase) family members determines proper β cell polarity and restricts β cell size, total β cell mass, and glucose-stimulated insulin secretion (GSIS). However, the full spectrum of LKB1 effects and the mechanisms involved in the secretory phenotype remain incompletely understood. We report here that in the absence of LKB1 in β cells, GSIS is dramatically and persistently improved. The enhancement is seen both in vivo and in vitro and cannot be explained by altered cell polarity, increased β cell number, or increased insulin content. Increased secretion does require membrane depolarization and calcium influx but appears to rely mostly on a distal step in the secretion pathway. Surprisingly, enhanced GSIS is seen despite profound defects in mitochondrial structure and function in LKB1-deficient β cells, expected to greatly diminish insulin secretion via the classic triggering pathway. Thus LKB1 is essential for mitochondrial homeostasis in β cells and in parallel is a powerful negative regulator of insulin secretion. This study shows that β cells can be manipulated to enhance GSIS to supra-normal levels even in the face of defective mitochondria and without deterioration over months

Limited tolerance towards folded elements during secretion of the autotransporter Hbp

Many virulence factors secreted by pathogenic Gram-negative bacteria belong to the autotransporter (AT) family. ATs consist of a passenger domain, which is the actual secreted moiety, and a β-domain that facilitates the transfer of the passenger domain across the outer membrane. Here, we analysed folding and translocation of the AT passenger, using Escherichia coli haemoglobin protease (Hbp) as a model protein. Dual cysteine mutagenesis, instigated by the unique crystal structure of the Hbp passenger, resulted in intramolecular disulphide bond formation dependent on the periplasmic enzyme DsbA. A small loop tied off by a disulphide bond did not interfere with secretion of Hbp. In contrast, a bond between different domains of the Hbp passenger completely blocked secretion resulting in degradation by the periplasmic protease DegP. In the absence of DegP, a translocation intermediate accumulated in the outer membrane. A similar jammed intermediate was formed upon insertion of a calmodulin folding moiety into Hbp. The data suggest that Hbp can fold in the periplasm but must retain a certain degree of flexibility and/or modest width to allow translocation across the outer membrane

Young people, crime and school exclusion: a case of some surprises

During the 1990s the number of young people being permanently excluded from schools in England and Wales increased dramatically from 2,910 (1990/91) to a peak of 12,700 (1996/97). Coinciding with this rise was a resurgence of the debate centring on lawless and delinquent youth. With the publication of Young People and Crime (Graham and Bowling 1995) and Misspent Youth (Audit Commission 1996) the 'common sense assumption' that exclusion from school inexorably promoted crime received wide support, with the school excludee portrayed as another latter day 'folk devil'. This article explores the link between school exclusion and juvenile crime, and offers some key findings from a research study undertaken with 56 young people who had experience of being excluded from school. Self-report interview questions reveal that whilst 40 of the young people had offended, 90% (36) reported that the onset of their offending commenced prior to their first exclusion. Moreover, 50 (89.2% of the total number of young people in the sample), stated that they were no more likely to offend subsequent to being excluded and 31 (55.4%) stated that they were less likely to offend during their exclusion period. Often, this was because on being excluded, they were 'grounded' by their parents

Production of ethanol from refinery waste gases. Phase 3. Engineering development. Annual report, April 1, 1995--May 15, 1996

Refineries discharge large volumes of H2, CO, and CO 2 from cracking, coking, and hydrotreating operations. This R&D program seeks to develop, demonstrate, and commercialize a biological process for converting these waste gases into ethanol for blending with gasoline. A 200,000 BPD refinery could produce up to 38 million gallons ethanol per year. The program is being conducted in 3 phases: II, technology development; III, engineering development; and IV, demonstration. Phase I, exploratory development, has been completed. The research effort has yielded two strains (Isolates O-52 and C-01) which are to be used in the pilot studies to produce ethanol from CO, CO2, and H2 in petroleum waste gas. Results from single continuous stirred tank reactor (CSTR) laboratory tests have shown that 20-25 g/L ethanol can be produced with < 5 g/L acetic acid byproduct. Laboratory studies with two CSTRs in series have yielded ethanol concentrations of 30-35 g/L with 2-4 g/L acetic acid byproduct. Water recycle from distillation back to the fermenter shows that filtration of the water before distillation eliminates the recycle of toxic materials back to the fermenter. Product recovery in the process will use direct distillation to the azeotrope, followed by adsorption to produce neat ethanol. This is less energy intensive than e.g. solvent extraction, azeotropic distillation, or pervaporation. Economic projections are quite attractive; the economics are refinery stream dependent and thus vary depending on refinery location and operation

Starting to Stop: Young Offenders' Desistance from Crime

This paper explores the complexities of the interplay between structural and agentic changes in 21 young offenders' lives as they start to stop offending. The young people's ability to desist from crime was dependent upon their engagement with a 'hook for change', their development of prosocial relationships and 'knifing off' of elements of their offending past, the extent of their identity change, and their confidence about desistance. Desistance was less likely in the absence of a 'hook' and where offenders were running a 'condemnation script'. The study challenges previous research that argues that desistance from crime in adolescence is unlikely

A Natural Genetic Variant of Granzyme B Confers Lethality to a Common Viral Infection

Many immune response genes are highly polymorphic, consistent with the selective pressure imposed by pathogens over evolutionary time, and the need to balance infection control with the risk of auto-immunity. Epidemiological and genomic studies have identified many genetic variants that confer susceptibility or resistance to pathogenic micro-organisms. While extensive polymorphism has been reported for the granzyme B (GzmB) gene, its relevance to pathogen immunity is unexplored. Here, we describe the biochemical and cytotoxic functions of a common allele of GzmB (GzmBW) common in wild mouse. While retaining ‘Asp-ase ’ activity, GzmBW has substrate preferences that differ considerably from GzmBP, which is common to all inbred strains. In vitro, GzmBW preferentially cleaves recombinant Bid, whereas GzmBP activates pro-caspases directly. Recombinant GzmBW and GzmBP induced equivalent apoptosis of uninfected targets cells when delivered with perforin in vitro. Nonetheless, mice homozygous for GzmBW were unable to control murine cytomegalovirus (MCMV) infection, and succumbed as a result of excessive liver damage. Although similar numbers of anti-viral CD8 T cells were generated in both mouse strains, GzmBW-expressing CD8 T cells isolated from infected mice were unable to kill MCMV