Data mining for ontology development.

A multi-laboratory ontology construction effort during the summer and fall of 2009 prototyped an ontology for counterfeit semiconductor manufacturing. This effort included an ontology development team and an ontology validation methods team. Here the third team of the Ontology Project, the Data Analysis (DA) team reports on their approaches, the tools they used, and results for mining literature for terminology pertinent to counterfeit semiconductor manufacturing. A discussion of the value of ontology-based analysis is presented, with insights drawn from other ontology-based methods regularly used in the analysis of genomic experiments. Finally, suggestions for future work are offered

Iron dynamics during injection of dissolved organic carbon into a sandy aquifer

The dynamics of dissolved, colloidal, and solid-phase iron were examined during a forced-gradient field experiment in Georgetown, South Carolina, in the summer of 1990. The experiment involved injection of 80,000 L of oxygenated water containing high levels of dissolved organic carbon (66 mg/L DOC) into a sandy aquifer. Iron dynamics were followed for 2 weeks in three saturated horizons at sampling wells located 1.5 (A wells) and 3 m (B wells) from the injection well. The initial oxidation/reduction potential of the aquifer favored Fe(II) in the iron-rich groundwater. As oxygen-rich water was introduced into the groundwater, the redox potential was expected to increase. The impacts of the changing redox potential on iron dynamics were hypothesized to be as follows: (1) Fe(II) may decrease and Fe(III) may increase due to oxidation, but otherwise Fe(II) may be mobile and conservative. (2) Fe(III) is mostly in the ferric oxide/hydroxide colloidal fraction, that is, the ferric fraction may be found predominantly in sizes >{sup {approximately}}1 nm(or >3000 mol wt), and the transport of colloidal iron oxide may be limited. (3) Ferric oxide/hydroxide colloids may have positive or near-zero surface charge in the pH range of the groundwater (6.0-7.2). (4) The turbidity of groundwater may increase as a result of the formation of iron colloids. During the course of injection, dissolved oxygen (DO), pH, iron concentration, DOC concentration, and turbidity were measured. Samples were also collected for microelectrophoretic mobility measurement (Coulter model: Delsa 440), particle-size analysis (Coulter model: N4MD, based on photon correlation spectrometry (PCS)) and scanning electron microscopic examination (ISI-40). The results from the two sampling wells are summarized briefly. 4 refs., 3 figs., 1 tab

Making sense of the evolving nature of depression narratives and their inherent conflicts

Originally a psychiatric diagnosis fashioned by Western psychiatry in the 20th Century, depression evolved to encompass varying lineages of discourse and care. This article elucidates some of the current challenges – as well as emerging discourses – influencing the category of depression. Depression-like experiences are shaped by (at times conflicting) subjectivities, claims to knowledge, material realities, social contexts and access to resources. With no unified understanding of the category of ‘depression’ available, lay people, social and neuro scientists, GPs, psychiatrists, talking therapists and pharmaceutical companies all attempt to shape narratives of depression. The current paper focuses on patient narratives about depression – in the context of these wider debates – to better elucidate the ways in which depression discourses are publically developing along varying lines. In conclusion, the paper suggests that we could better conceptualise the resulting ‘depression(s)’ with concepts such as ‘society of mind’ and notions of subjectivity unbounded by individuals

CD4+ T Cell Effects on CD8+ T Cell Location Defined Using Bioluminescence

T lymphocytes of the CD8+ class are critical in delivering cytotoxic function and in controlling viral and intracellular infections. These cells are “helped” by T lymphocytes of the CD4+ class, which facilitate their activation, clonal expansion, full differentiation and the persistence of memory. In this study we investigated the impact of CD4+ T cells on the location of CD8+ T cells, using antibody-mediated CD4+ T cell depletion and imaging the antigen-driven redistribution of bioluminescent CD8+ T cells in living mice. We documented that CD4+ T cells influence the biodistribution of CD8+ T cells, favoring their localization to abdominal lymph nodes. Flow cytometric analysis revealed that this was associated with an increase in the expression of specific integrins. The presence of CD4+ T cells at the time of initial CD8+ T cell activation also influences their biodistribution in the memory phase. Based on these results, we propose the model that one of the functions of CD4+ T cell “help” is to program the homing potential of CD8+ T cells

Risk management activities at the DOE Class A reactor facilities

The probabilistic risk assessment (PRA) and risk management group of the Association for Excellence in Reactor Operation (AERO) develops risk management initiatives and standards to improve operation and increase safety of the DOE Class A reactor facilities. Principal risk management applications that have been implemented at each facility are reviewed. The status of a program to develop guidelines for risk management programs at reactor facilities is presented

Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism

BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50)

Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism

BACKGROUND: The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. METHODS: We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. RESULTS: In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. CONCLUSIONS: These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. ABBREVIATIONS: Armstrong 53b (Arm53b); baculovirus Autographa californica GP64 (GP64); charge-coupled device (CCD); dystroglycan (DG); feline immunodeficiency virus (FIV); glycoprotein precursor (GP-C); firefly luciferase (Luc); lymphocytic choriomeningitis virus (LCMV); nuclear targeted β-galactosidase (ntLacZ); optical density (OD); PBS/0.1% (w/v) Tween-20 (PBST); relative light units (RLU); Rous sarcoma virus (RSV); transducing units per milliliter (TU/ml); vesicular stomatitis virus (VSV-G); wheat germ agglutinin (WGA); 50% reduction in binding (C50)

The role of the ubiquitination–proteasome pathway in breast cancer: Ubiquitin mediated degradation of growth factor receptors in the pathogenesis and treatment of cancer

Aberrant activity of growth factor receptors has been implicated in the pathogenesis of a wide variety of malignancies. The negative regulation of signaling by growth factor receptors is mediated in large part by the ubiquitination, internalization, and degradation of the activated receptor. Over the past few years, considerable insight into the mechanisms that control receptor downregulation has been gained. There are also data suggesting that mutations that lead to inhibition of downregulation of growth factor receptors could play a role in the pathogenesis of cancer. Therapies directed at enhancing the degradation of growth factor receptors offer a promising approach to the treatment of malignancies