Private specificities can dominate the humoral response to self-antigens in patients with cryptogenic fibrosing alveolitis

BACKGROUND: The pathogenetic mechanisms that underlie the interstitial lung disease cryptogenic fibrosing alveolitis (CFA) may involve an immunological reaction to unidentified antigens in the lung, resulting in tissue damage. METHOD: In order to identify the range of target autoantigens, we used expression cloning, employing serum from an index patient as the probe against an expressed cDNA library that was derived from a tumour cell line. We screened over 5 × 10(5) recombinants and obtained sequence information on three antigens that had provoked strong responses with immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition. RESULTS: All of the antigens were identifiable by comparison with sequence data from the US National Center for Biotechnology Information. Alanyl tRNA synthetase (ATS) was picked on six occasions; five of these incidences reflected independent recombination events, indicating that the library was not biased. Antibodies to ATS (anti-PL-12) represent the most common reactivity that defines the antisynthetase syndrome, which is typically expressed as polymyositis, dermatomyositis and interstitial lung disease (ILD). The index patient never showed symptoms other than those associated with alveolitis, even though sera obtained from him over a period of 2 years contained antibodies with the same specificity. Autoantibodies to ATS were never detected in serial bleeds from 11 other patients with CFA, and neither did we detect antibodies to the other two antigens identified from the serum of the index patient. CONCLUSION: The humoral response in patients with CFA can be dominated by autoantibodies with private specificities. This suggests that the antibodies are epiphenomenal and are a secondary feature of tissue damage induced by some other mechanism

HLW Melter Control Strategy Without Visual Feedback VSL-12R2500-1 Rev 0

Plans for the treatment of high level waste (HL W) at the Hanford Tank Waste Treatment and Immobilization Plant (WTP) are based upon the inventory of the tank wastes, the anticipated performance of the pretreatment processes, and current understanding of the capability of the borosilicate glass waste form [I]. The WTP HLW melter design, unlike earlier DOE melter designs, incorporates an active glass bubbler system. The bubblers create active glass pool convection and thereby improve heat and mass transfer and increase glass melting rates. The WTP HLW melter has a glass surface area of 3.75 m{sup 2} and depth of ~ 1.1 m. The two melters in the HLW facility together are designed to produce up to 7.5 MT of glass per day at 100% availability. Further increases in HL W waste processing rates can potentially be achieved by increasing the melter operating temperature above 1150�C and by increasing the waste loading in the glass product. Increasing the waste loading also has the added benefit of decreasing the number of canisters for storage

TECHNETIUM RETENTION IN WTP LAW GLASS WITH RECYCLE FLOW-SHEET DM10 MELTER TESTING VSL-12R2640-1 REV 0

Melter tests were conducted to determine the retention of technetium and other volatiles in glass while processing simulated Low Activity Waste (LAW) streams through a DM10 melter equipped with a prototypical off-gas system that concentrates and recycles fluid effiuents back to the melter feed. To support these tests, an existing DM10 system installed at Vitreous State Laboratory (VSL) was modified to add the required recycle loop. Based on the Hanford Tank Waste Treatment and Immobilization Plant (WTP) LAW off-gas system design, suitably scaled versions of the Submerged Bed Scrubber (SBS), Wet Electrostatic Precipitator (WESP), and TLP vacuum evaporator were designed, built, and installed into the DM10 system. Process modeling was used to support this design effort and to ensure that issues associated with the short half life of the {sup 99m}Tc radioisotope that was used in this work were properly addressed and that the system would be capable of meeting the test objectives. In particular, this required that the overall time constant for the system was sufficiently short that a reasonable approach to steady state could be achieved before the {sup 99m}Tc activity dropped below the analytical limits of detection. The conceptual design, detailed design, flow sheet development, process model development, Piping and Instrumentation Diagram (P&ID) development, control system design, software design and development, system fabrication, installation, procedure development, operator training, and Test Plan development for the new system were all conducted during this project. The new system was commissioned and subjected to a series of shake-down tests before embarking on the planned test program. Various system performance issues that arose during testing were addressed through a series of modifications in order to improve the performance and reliability of the system. The resulting system provided a robust and reliable platform to address the test objectives

FINAL REPORT INTEGRATED DM1200 MELTER TESTING OF BUBBLER CONFIGURATIONS USING HLW AZ-101 SIMULANTS VSL-04R4800-4 REV 0 10/5/04

This report documents melter and off-gas performance results obtained on the DM1200 HLW Pilot Melter during processing of AZ-101 HLW simulants. The tests reported herein are a subset of six tests from a larger series of tests described in the Test Plan for the work; results from the other tests have been reported separately. The solids contents of the melter feeds were based on the WTP baseline value for the solids content of the feeds from pretreatment which changed during these tests from 20% to 15% undissolved solids resulting in tests conducted at two feed solids contents. Based on the results of earlier tests with single outlet 'J' bubblers, initial tests were performed with a total bubbling rate of 651 pm. The first set of tests (Tests 1A-1E) addressed the effects of skewing this total air flow rate back and forth between the two installed bubblers in comparison to a fixed equal division of flow between them. The second set of tests (2A-2D) addressed the effects of bubbler depth. Subsequently, as the location, type and number of bubbling outlets were varied, the optimum bubbling rate for each was determined. A third (3A-3C) and fourth (8A-8C) set of tests evaluated the effects of alternative bubbler designs with two gas outlets per bubbler instead of one by placing four bubblers in positions simulating multiple-outlet bubblers. Data from the simulated multiple outlet bubblers were used to design bubblers with two outlets for an additional set of tests (9A-9C). Test 9 was also used to determine the effect of small sugar additions to the feed on ruthenium volatility. Another set of tests (10A-10D) evaluated the effects on production rate of spiking the feed with chloride and sulfate. Variables held constant to the extent possible included melt temperature, plenum temperature, cold cap coverage, the waste simulant composition, and the target glass composition. The feed rate was increased to the point that a constant, essentially complete, cold cap was achieved, which was used as an indicator of a maximized feed rate for each test. The first day of each test was used to build the cold cap and decrease the plenum temperature. The remainder of each test was split into two- to six-day segments, each with a different bubbling rate, bubbler orientation, or feed concentration of chloride and sulfur

A comprehensive functional analysis of tissue specificity of human gene expression

<p>Abstract</p> <p>Background</p> <p>In recent years, the maturation of microarray technology has allowed the genome-wide analysis of gene expression patterns to identify tissue-specific and ubiquitously expressed ('housekeeping') genes. We have performed a functional and topological analysis of housekeeping and tissue-specific networks to identify universally necessary biological processes, and those unique to or characteristic of particular tissues.</p> <p>Results</p> <p>We measured whole genome expression in 31 human tissues, identifying 2374 housekeeping genes expressed in all tissues, and genes uniquely expressed in each tissue. Comprehensive functional analysis showed that the housekeeping set is substantially larger than previously thought, and is enriched with vital processes such as oxidative phosphorylation, ubiquitin-dependent proteolysis, translation and energy metabolism. Network topology of the housekeeping network was characterized by higher connectivity and shorter paths between the proteins than the global network. Ontology enrichment scoring and network topology of tissue-specific genes were consistent with each tissue's function and expression patterns clustered together in accordance with tissue origin. Tissue-specific genes were twice as likely as housekeeping genes to be drug targets, allowing the identification of tissue 'signature networks' that will facilitate the discovery of new therapeutic targets and biomarkers of tissue-targeted diseases.</p> <p>Conclusion</p> <p>A comprehensive functional analysis of housekeeping and tissue-specific genes showed that the biological function of housekeeping and tissue-specific genes was consistent with tissue origin. Network analysis revealed that tissue-specific networks have distinct network properties related to each tissue's function. Tissue 'signature networks' promise to be a rich source of targets and biomarkers for disease treatment and diagnosis.</p

Martin Brasier's contribution to the palaeobiology of the Ediacaran–Cambrian transition

Martin Brasier's work spanned almost the entire geological column, but the origin of animals and the nature of the Cambrian explosion were areas of particular interest to him. Martin adopted a holistic approach to the study of these topics that considered the interplay between multiple geological and biological phenomena and he sought to interpret the fossil record within the broad context of geological, biogeochemical and ecological changes in the Earth system. Here we summarize Martin's main contributions to this area of research and assess the impact of his findings on the development of this field

HLW Melter Control Strategy Without Visual Feedback VSL-12R2500-1 Rev 0

Plans for the treatment of high level waste (HL W) at the Hanford Tank Waste Treatment and Immobilization Plant (WTP) are based upon the inventory of the tank wastes, the anticipated performance of the pretreatment processes, and current understanding of the capability of the borosilicate glass waste form [I]. The WTP HLW melter design, unlike earlier DOE melter designs, incorporates an active glass bubbler system. The bubblers create active glass pool convection and thereby improve heat and mass transfer and increase glass melting rates. The WTP HLW melter has a glass surface area of 3.75 m{sup 2} and depth of ~ 1.1 m. The two melters in the HLW facility together are designed to produce up to 7.5 MT of glass per day at 100% availability. Further increases in HL W waste processing rates can potentially be achieved by increasing the melter operating temperature above 1150�C and by increasing the waste loading in the glass product. Increasing the waste loading also has the added benefit of decreasing the number of canisters for storage

Genesis and character of thin-bedded turbidites associated with submarine channels

Acknowledgements We acknowledge the support of the PRACSS Joint Industry Project at University of Aberdeen, funded by BG Group, BP, DONG, RWE Dea, Petrochina, Statoil and Tullow Oil. We also acknowledge the entire crew of the Urania Research vessel which was used to acquire the CHIRP lines, bathymetric data and gravity cores from the Tyrrhenian Sea, Italy. Our colleagues Michal Janocko and Mike Mayall are thanked for the discussions and comments. Our colleagues Pan Li, Amanda Santa Catharina, Guilherme Bozetti and Matheus Silveira Sobiesiak are thanked for their assistance during field work where some of the ideas in this paper were synthesized. Finally we thank one anonymous reviewer and Brian Romans for their invaluable feedback which made some of the ideas introduced in this review much more succinct.Peer reviewedPostprin

TECHNETIUM RETENTION IN WTP LAW GLASS WITH RECYCLE FLOW-SHEET DM10 MELTER TESTING VSL-12R2640-1 REV 0

Melter tests were conducted to determine the retention of technetium and other volatiles in glass while processing simulated Low Activity Waste (LAW) streams through a DM10 melter equipped with a prototypical off-gas system that concentrates and recycles fluid effiuents back to the melter feed. To support these tests, an existing DM10 system installed at Vitreous State Laboratory (VSL) was modified to add the required recycle loop. Based on the Hanford Tank Waste Treatment and Immobilization Plant (WTP) LAW off-gas system design, suitably scaled versions of the Submerged Bed Scrubber (SBS), Wet Electrostatic Precipitator (WESP), and TLP vacuum evaporator were designed, built, and installed into the DM10 system. Process modeling was used to support this design effort and to ensure that issues associated with the short half life of the {sup 99m}Tc radioisotope that was used in this work were properly addressed and that the system would be capable of meeting the test objectives. In particular, this required that the overall time constant for the system was sufficiently short that a reasonable approach to steady state could be achieved before the {sup 99m}Tc activity dropped below the analytical limits of detection. The conceptual design, detailed design, flow sheet development, process model development, Piping and Instrumentation Diagram (P&amp;ID) development, control system design, software design and development, system fabrication, installation, procedure development, operator training, and Test Plan development for the new system were all conducted during this project. The new system was commissioned and subjected to a series of shake-down tests before embarking on the planned test program. Various system performance issues that arose during testing were addressed through a series of modifications in order to improve the performance and reliability of the system. The resulting system provided a robust and reliable platform to address the test objectives

Technical issues associated with in situ vitrification of the INEL Subsurface Disposal Area. Volume 2, Application of technical issues to the Acid Pit

In situ vitrification (ISV) has been identified as an alternative technology for remediation of the Acid Pit and Transuranic Pits and Trenches (TRU-PTs) that are present at the Idaho National Engineering Laboratory (INEL) Subsurface Disposal Area (SDA). However, a number of technical issues exist that must be resolved before ISV can be considered applicable to these waste sites. To assist in the ISV technology evaluation, an ISV Steering Committee was formed to identify, prioritize, and develop closure roadmaps for technical issues associated with ISV application at the INEL SDA. The activities of the ISV Steering Committee are summarized in three volumes of this report. Volume 1 identifies the systematic approach used to identify and prioritize the ISV technical issues, and briefly discusses the methodology that will be employed to resolve these issues. This document Volume 2 and Volume 3 discusses each technical issue in greater detail and suggest specific closure roadmaps to be used in resolving technical issues associated with ISV at the SDA Acid Pit and TRU-PTs, respectively