A monte-carlo floating-point unit for self-validating arithmetic

Monte-Carlo arithmetic is a form of self-validating arith-metic that accounts for the effect of rounding errors. We have implemented a floating point unit that can perform ei-ther IEEE 754 or Monte-Carlo floating point computation, allowing hardware accelerated validation of results during execution. Experiments show that our approach has a mod-est hardware overhead and allows the propagation of round-ing error to be accurately estimated

Altered glycosylation of glycodelin in endometrial carcinoma

Glycodelin is a major glycoprotein expressed in reproductive tissues, like secretory and decidualized endometrium. It has several reproduction related functions that are dependent on specific glycosylation, but it has also been found to drive differentiation of endometrial carcinoma cells toward a less malignant phenotype. Here we aimed to elucidate whether the glycosylation and function of glycodelin is altered in endometrial carcinoma as compared with a normal endometrium. We carried out glycan structure analysis of glycodelin expressed in HEC-1B human endometrial carcinoma cells (HEC-1B Gd) by mass spectrometry glycomics strategies. Glycans of HEC-1B Gd were found to comprise a typical mixture of high-mannose, hybrid, and complex-type N-glycans, often containing undecorated LacNAc (Gal beta 1-4GlcNAc) antennae. However, several differences, as compared with previously reported glycan structures of normal human decidualized endometrium-derived glycodelin isoform, glycodelin-A (GdA), were also found. These included a lower level of sialylation and more abundant poly-LacNAc antennae, some of which are fucosylated. This allowed us to select lectins that showed different binding to these classes of glycodelin. Despite the differences in glycosylation between HEC-1B Gd and GdA, both showed similar inhibitory activity on trophoblast cell invasion and peripheral blood mononuclear cell proliferation. For the detection of cancer associated glycodelin, we established a novel in situ proximity-ligation based histochemical staining method using a specific glycodelin antibody and UEAI lectin. We found that the UEAI reactive glycodelin was abundant in endometrial carcinoma, but virtually absent in normal endometrial tissue even when glycodelin was strongly expressed. In conclusion, we established a histochemical staining method for the detection of endometrial carcinoma-associated glycodelin and showed that this specific glycodelin is exclusively expressed in cancer, not in normal endometrium. Similar methods can be used for studies of other glycoproteins. Glycodelin is a major endometrial glycoprotein. The authors analyzed glycan structures of endometrial carcinoma associated glycodelin and established a novel glycodelin-glycoform specific histochemical staining method. With this, they showed that glycodelin is differentially glycosylated in endometrial carcinoma tissue, as compared to normal endometrium, representing a neoantigen with potential clinical applications.Peer reviewe

Competing risk bias in prognostic models predicting hepatocellular carcinoma occurrence: impact on clinical decision making

Existing models predicting hepatocellular carcinoma (HCC) occurrence do not account for competing risk events and, thus, may overestimate the probability of HCC. Our goal was to quantify this bias for patients with cirrhosis and cured hepatitis C. We analyzed a nationwide cohort of patients with cirrhosis and cured hepatitis C infection from Scotland. Two HCC prognostic models were developed: (1) a Cox regression model ignoring competing risk events and (2) a Fine-Gray regression model accounting for non-HCC mortality as a competing risk. Both models included the same set of prognostic factors used by previously developed HCC prognostic models. Two predictions were calculated for each patient: first, the 3-year probability of HCC predicted by model 1 and second, the 3-year probability of HCC predicted by model 2. The study population comprised 1629 patients with cirrhosis and cured HCV, followed for 3.8 years on average. A total of 82 incident HCC events and 159 competing risk events (ie, non-HCC deaths) were observed. The mean predicted 3-year probability of HCC was 3.37% for model 1 (Cox) and 3.24% for model 2 (Fine-Gray). For most patients (76%), the difference in the 3-year probability of HCC predicted by model 1 and model 2 was minimal (ie, within 0 to ±0.3%). A total of 2.6% of patients had a large discrepancy exceeding 2%; however, these were all patients with a 3-year probability exceeding >5% in both models. Prognostic models that ignore competing risks do overestimate the future probability of developing HCC. However, the degree of overestimation—and the way it is patterned—means that the impact on HCC screening decisions is likely to be modest

Decidual glycodelin-A polarizes human monocytes into a decidual macrophage-like phenotype through Siglec-7

Decidual macrophages constitute 20-30% of the total leukocytes in the uterus of pregnant women, regulating the maternal immune tolerance and placenta development. Abnormal number or activities of decidual macrophages (dMs) are associated with fetal loss and pregnancy complications, such as preeclampsia. Monocytes differentiate into dMs in a decidua-specific microenvironment. Despite their important roles in pregnancy, the exact factors that regulate the differentiation into dMs remain unclear. Glycodelin-A (PAEP, hereafter referred to as GdA) is a glycoprotein that is abundantly present in the decidua, and plays an important role in fetomaternal defense and placental development. It modulates the differentiation and activity of several immune cell types residing in the decidua. In this study, we demonstrated that GdA induces the differentiation of human monocytes into dM-like phenotypes in terms of transcriptome, cell surface marker expression, secretome, and regulation of trophoblast and endothelial cell functions. We found that Sialic acid-binding Ig-like lectin 7 (Siglec-7) mediates the binding and biological actions of GdA in a sialic acid-dependent manner. We, therefore, suggest that GdA, induces the polarization of monocytes into dMs to regulate fetomatemal tolerance and placental development.Peer reviewe

Radio Astronomy

Contains reports on eleven research projects.National Science Foundation (Grant AST79-25075)National Science Foundation (Grant AST79-20984)National Science Foundation (Grant AST79-19553)U.S. Navy - Office of Naval Research (Contract N00014-80-C-0348)National Aeronautics and Space Administration (Grant NAG2-50)MIT Sloan Fund for Basic ResearchJoint Services Electronics Program(Contract DAAG80-C-0104)Lockheed Aircraft Corporation (Contract LS90B4860F)National Aeronautics and Space Administration (Grant NAG5-10)National Aeronautics and Space Administration (Contract NAS5-22929)U.S. Department of Commerce, National Oceanic and Atmospheric Administration (Grant 04-8-MO1-1)California Institute of Technology Jet Propulsion Laboratory (Contract LZ-727891)California Institute of Technology Jet Propulsion Laboratory Subcontract 956059California Institute of Technology Jet Propulsion Laboratory Task Order RD-15

Clinical utility of and correlation between Sniffin' Sticks and TIB smell identification test (TIBSIT) among Hong Kong Chinese with or without chronic rhinosinusitis

IntroductionOlfactory dysfunction (OD) is common among patients with chronic rhinosinusitis (CRS). Validated and culturally specific tests, such as the “Sniffin’ Sticks” test (SST) and the TIB Smell Identification Test (TIBSIT), are crucial for the diagnosis and monitoring of OD. However, they have not been utilised in Hong Kong Chinese and their correlations are unknown.MethodsTwelve CRS patients and twenty healthy volunteers were prospectively recruited from a joint allergy-otorhinolaryngology clinic in Hong Kong and performed both SST and TIBSIT. Demographics, baseline characteristics and all test results were compared and analysed.ResultsPatients with CRS demonstrated significantly lower test scores than healthy controls (all p < 0.001). Significant and strong correlations were observed between all composite and subtest scores, particularly between the composite SST and TIBSIT scores (ρ = 0.789, p < 0.001). Multivariate analysis demonstrated that the presence of CRS and increasing age were significantly associated with OD.ConclusionBoth SST and TIBSIT are useful olfactory tests and are strongly correlated among Hong Kong Chinese. We advocate that either test can be used for measuring OD among CRS patients

Radio Astronomy

Contains reports on sixteen research projects.National Science Foundation (Grant AST81-21416)National Science Foundation (Grant AST80-22864)National Aeronautics and Space Administration (Contract S-10665-C)National Aeronautics and Space Administration (Contract NAGW373)National Science Foundation (Grant AST79-19553)National Oceanic and Atmospheric Administration (Grant 04-8-M01-1)National Aeronautics and Space Administration (Grant NAG5-10)National Aeronautics and Space Administration (Contract NAS5-22929)Defense Advanced Research Projects Agency (Contract MDA 903-82-K-0521)Intelsat (Contract Intel-188)Joint Services Electronics Program (Contract DAAG29-80-C-0104)Lockheed Missiles and Space Company (Contract LS90B4860F

Identifying Currents in the Gene Pool for Bacterial Populations Using an Integrative Approach

The evolution of bacterial populations has recently become considerably better understood due to large-scale sequencing of population samples. It has become clear that DNA sequences from a multitude of genes, as well as a broad sample coverage of a target population, are needed to obtain a relatively unbiased view of its genetic structure and the patterns of ancestry connected to the strains. However, the traditional statistical methods for evolutionary inference, such as phylogenetic analysis, are associated with several difficulties under such an extensive sampling scenario, in particular when a considerable amount of recombination is anticipated to have taken place. To meet the needs of large-scale analyses of population structure for bacteria, we introduce here several statistical tools for the detection and representation of recombination between populations. Also, we introduce a model-based description of the shape of a population in sequence space, in terms of its molecular variability and affinity towards other populations. Extensive real data from the genus Neisseria are utilized to demonstrate the potential of an approach where these population genetic tools are combined with an phylogenetic analysis. The statistical tools introduced here are freely available in BAPS 5.2 software, which can be downloaded from http://web.abo.fi/fak/mnf/mate/jc/software/baps.html

Progress report no. 4

Statement of responsibility on title-page reads: editors: M.J. Driscoll, D.D. Lanning, I. Kaplan, A.T. Supple ; contributors: A. Alvim, G.J. Brown, J.K. Chan, T.P. Choong, M.J. Driscoll, G. A. Ducat, I.A. Forbes, M.V. Gregory, S.Y. Ho, C.M. Hove, O. K. Kadiroglu, R.J. Kennerley, D.D. Lanning, J.L. Lazewatsky, L. Lederman, A.S. Leveckis, V.A. Miethe, P. A. Scheinert, A.M. Thompson, N.E. Todreas, C.P. Tzanos, and P.J. WoodIncludes bibliographical referencesProgress report; June 30, 1973U.S. Atomic Energy Commission contract: AT(11-1)225