Erratum: Is it possible to infer the equation of state of a mixture of hard discs from that of the one-component system?

The numerical values in the sixth and seventh columns of table 1 of the paper Molec. Phys., 1999, 96, 1185-1188 are not correct. Consequently, some of the comments made in the paper are wrong. The corrected version of table 1 is reprinted here and the results are briefly discussed.Comment: 2 pages; Erratum to Molec. Phys., 1999, 96, 1185-1188; to be published in Molec. Phy

WebFR3D—a server for finding, aligning and analyzing recurrent RNA 3D motifs

WebFR3D is the on-line version of ‘Find RNA 3D’ (FR3D), a program for annotating atomic-resolution RNA 3D structure files and searching them efficiently to locate and compare RNA 3D structural motifs. WebFR3D provides on-line access to the central features of FR3D, including geometric and symbolic search modes, without need for installing programs or downloading and maintaining 3D structure data locally. In geometric search mode, WebFR3D finds all motifs similar to a user-specified query structure. In symbolic search mode, WebFR3D finds all sets of nucleotides making user-specified interactions. In both modes, users can specify sequence, sequence–continuity, base pairing, base-stacking and other constraints on nucleotides and their interactions. WebFR3D can be used to locate hairpin, internal or junction loops, list all base pairs or other interactions, or find instances of recurrent RNA 3D motifs (such as sarcin–ricin and kink-turn internal loops or T- and GNRA hairpin loops) in any PDB file or across a whole set of 3D structure files. The output page provides facilities for comparing the instances returned by the search by superposition of the 3D structures and the alignment of their sequences annotated with pairwise interactions. WebFR3D is available at http://rna.bgsu.edu/webfr3d

Plasma contactor technology for Space Station Freedom

Hollow cathode plasma contactors were baselined for Space Station Freedom (SSF) to control the electrical potentials of surfaces to eliminate/mitigate damaging interactions with the space environment. The system represents a dual-use technology which is a direct outgrowth of the NASA electric propulsion program and in particular the technology development effort on ion thruster systems. Specific efforts include optimizing the design and configuration of the contactor, validating its required lifetime, and characterizing the contactor plume and electromagnetic interference. The plasma contact or subsystems include the plasma contact or unit, a power electronics unit, and an expellant management unit. Under this program these will all be brought to breadboard and engineering model development status. New test facilities were developed, and existing facilities were augmented, to support characterizations and life testing of contactor components and systems. The magnitude, scope, and status of the plasma contactor hardware development program now underway and preliminary test results on system components are discussed

Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer

Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer

Arcjet exploratory tests of ARC optical window design for the AFE vehicle

Tests were made in the 20 MW arc jet facility at the NASA ARC to determine the suitability of sapphire and fused silica as window materials for the Aeroassist Flight Experiment (AFE) entry vehicle. Twenty nine tests were made; 25 at a heating rate about 80 percent of that expected during the AFE entry and 4 at approximately the full, 100 percent AFE heating rate profile, that produces a temperature of about 2900 F on the surface of the tiles that protect the vehicle. These tests show that a conductively cooled window design using mechanical thermal contacts and sapphire is probably not practical. Cooling the window using mechanical thermal contacts produces thermal stresses in the sapphire that cause the window to crack. An insulated design using sapphire, that cools the window as little as possible, appears promising although some spectral data in the vacuum-ultra-violet (VUV) will be lost due to the high temperature reached by the sapphire. The surface of the insulated sapphire windows, tested at the 100 percent AFE heating rate, showed some slight ablation, and cracks appeared in two of three test windows. One small group of cracks were obviously caused by mechanical binding of the window in the assembly, which can be eliminated with improved design. Other cracks were long, straight, thin crystallographic cracks that have very little effect on the optical transmission of the window. Also, the windows did not fall apart along these crystallographic cracks when the windows were removed from their assemblies. Theoretical results from the thermal analysis computer program SINDA indicate that increasing the window thickness from 4 to 8 mm may enable surface ablation to be avoided. An insulated design using a fused silica window tested at the nominal AFE heating rate experienced severe ablation, thus fused silica is not considered to be an acceptable window material

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

RNA CoSSMos: Characterization of Secondary Structure Motifs—a searchable database of secondary structure motifs in RNA three-dimensional structures

RNA secondary structure is important for designing therapeutics, understanding protein–RNA binding and predicting tertiary structure of RNA. Several databases and downloadable programs exist that specialize in the three-dimensional (3D) structure of RNA, but none focus specifically on secondary structural motifs such as internal, bulge and hairpin loops. The RNA Characterization of Secondary Structure Motifs (RNA CoSSMos) database is a freely accessible and searchable online database and website of 3D characteristics of secondary structure motifs. To create the RNA CoSSMos database, 2156 Protein Data Bank (PDB) files were searched for internal, bulge and hairpin loops, and each loop's structural information, including sugar pucker, glycosidic linkage, hydrogen bonding patterns and stacking interactions, was included in the database. False positives were defined, identified and reclassified or omitted from the database to ensure the most accurate results possible. Users can search via general PDB information, experimental parameters, sequence and specific motif and by specific structural parameters in the subquery page after the initial search. Returned results for each search can be viewed individually or a complete set can be downloaded into a spreadsheet to allow for easy comparison. The RNA CoSSMos database is automatically updated weekly and is available at http://cossmos.slu.edu

miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer

Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change)