Extracellular matrix-modulated expression of human cell surface glycoproteins A42 and J143. Intrinsic and extrinsic signals determine antigenic phenotype.

Extracellular matrix (ECM)' plays an important regulatory role in cellular growth, migration, and differentiation (1-4). Pathologic processes such as tumor cell invasion and metastasis are also determined by cellular interactions with ECM (5, 6). Biochemical studies have identified collagens, fibronectin, laminin, proteoglycans, and several other proteins as major ECM components (1-3), and have shown that ECM composition varies between different normal and tumor tissues. The complexity and heterogeneity of ECM composition have hampered the molecular analysis of ECM-cell interactions . However, a range of phenotypic changes has been described for cultured cells after transfer from plastic surfaces to substrates coated with native ECM (7, 8) or with purified ECM components; ECM-induced phenotypic changes include enhanced substrate adhesiveness, cell spreading and migration, changes in cell morphology and proliferative activity, and expression of differentiated cellular functions (I-4). Some of these effects, e.g., increased substrate adhesion, may result directly from the binding of specialized cell surface structures to ECM molecules. Others are likely mediated by an active cellular response triggered by the interaction of ECM with cell surface receptors. Thus, ECM-derived signals (9) may activate a cascade of molecular changes within the cell and on the cell surface that account for the pleiotropic effects observed with ECM

Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry

We have conducted proteome-wide analysis of fresh surgery specimens derived from breast cancer patients, using an approach that integrates size-based intact protein fractionation, nanoscale liquid separation of peptides, electrospray ion trap mass spectrometry, and bioinformatics. Through this approach, we have acquired a large amount of peptide fragmentation spectra from size-resolved fractions of the proteomes of several breast tumors, tissue peripheral to the tumor, and samples from patients undergoing noncancer surgery. Label-free quantitation was used to generate protein abundance maps for each proteome and perform comparative analyses. The mass spectrometry data revealed distinct qualitative and quantitative patterns distinguishing the tumors from healthy tissue as well as differences between metastatic and non-metastatic human breast cancers including many established and potential novel candidate protein biomarkers. Selected proteins were evaluated by Western blotting using tumors grouped according to histological grade, size, and receptor expression but differing in nodal status. Immunohistochemical analysis of a wide panel of breast tumors was conducted to assess expression in different types of breast cancers and the cellular distribution of the candidate proteins. These experiments provided further insights and an independent validation of the data obtained by mass spectrometry and revealed the potential of this approach for establishing multimodal markers for early metastasis, therapy outcomes, prognosis, and diagnosis in the future. © 2008 American Chemical Society

Refractive Index of Humid Air in the Infrared: Model Fits

The theory of summation of electromagnetic line transitions is used to tabulate the Taylor expansion of the refractive index of humid air over the basic independent parameters (temperature, pressure, humidity, wavelength) in five separate infrared regions from the H to the Q band at a fixed percentage of Carbon Dioxide. These are least-squares fits to raw, highly resolved spectra for a set of temperatures from 10 to 25 C, a set of pressures from 500 to 1023 hPa, and a set of relative humidities from 5 to 60%. These choices reflect the prospective application to characterize ambient air at mountain altitudes of astronomical telescopes.Comment: Corrected exponents of c0ref, c1ref and c1p in Table

CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens

The potency of the immune response has still to be harnessed effectively to combat human cancers. However, the discovery of T-cell targets in melanomas and other tumors has raised the possibility that cancer vaccines can be used to induce a therapeutically effective immune response against cancer. The targets, cancer-testis (CT) antigens, are immunogenic proteins preferentially expressed in normal gametogenic tissues and different histological types of tumors. Therapeutic cancer vaccines directed against CT antigens are currently in late-stage clinical trials testing whether they can delay or prevent recurrence of lung cancer and melanoma following surgical removal of primary tumors. CT antigens constitute a large, but ill-defined, family of proteins that exhibit a remarkably restricted expression. Currently, there is a considerable amount of information about these proteins, but the data are scattered through the literature and in several bioinformatic databases. The database presented here, CTdatabase (http://www.cta.lncc.br), unifies this knowledge to facilitate both the mining of the existing deluge of data, and the identification of proteins alleged to be CT antigens, but that do not have their characteristic restricted expression pattern. CTdatabase is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally. Starting from a compilation of known CT antigens, CTdatabase provides basic information including gene names and aliases, RefSeq accession numbers, genomic location, known splicing variants, gene duplications and additional family members. Gene expression at the mRNA level in normal and tumor tissues has been collated from publicly available data obtained by several different technologies. Manually curated data related to mRNA and protein expression, and antigen-specific immune responses in cancer patients are also available, together with links to PubMed for relevant CT antigen articles

Satellite data for the offshore renewable energy sector: Synergies and innovation opportunities

Can satellite data be used to address challenges currently faced by the Offshore Renewable Energy (ORE) sector? What benefit can satellite observations bring to resource assessment and maintenance of ORE farms? Can satellite observations be used to assess the environmental impact of offshore renewables leading towards a more sustainable ORE sector? This review paper faces these questions presenting a holistic view of the current interactions between satellite and ORE sectors, and future needs to make this partnership grow. The aim of the work is to start the conversation between these sectors by establishing a common ground. We present offshore needs and satellite technology limitations, as well as potential opportunities and areas of growth. To better understand this, the reader is guided through the history, current developments, challenges and future of offshore wind, tidal and wave energy technologies. Then, an overview on satellite observations for ocean applications is given, covering types of instruments and how they are used to provide different metocean variables, satellite performance, and data processing and integration. Past, present and future satellite missions are also discussed. Finally, the paper focuses on innovation opportunities and the potential of synergies between the ORE and satellite sectors. Specifically, we pay attention to improvements that satellite observations could bring to standard measurement techniques: assessing uncertainty, wind, tidal and wave conditions forecast, as well as environmental monitoring from space. Satellite–enabled measurement of ocean physical processes and applications for fisheries, mammals and birds, and habitat change, are also discussed in depth

What is the role of imaging in acute low back pain?

In patients with non specific acute low back pain, without the red flags, a conservative approach is preferable, with assessment in 4–6 weeks. The natural history of low back pain is favorable with improvement over time, thus reassurance to such patients is very important. However, a plain radiograph or more advanced imaging techniques like MRI/CT may be ordered in back pain associated with radiculopathy or spinal stenosis and back pain associated with progressive neurologic deficits. There is limited role of imaging in non specific acute low back pain without the red flags, as the findings correlate poorly with symptoms

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Epidemic space

The aim of this article is to highlight the importance of 'spatiality' in understanding the materialization of risk society and cultivation of risk sensibilities. More specifically it provides a cultural analysis of pathogen virulence (as a social phenomenon) by means of tracing and mapping the spatial flows that operate in the uncharted zones between the microphysics of infection and the macrophysics of epidemics. It will be argued that epidemic space consists of three types of forces: the vector, the index and the vortex. It will draw on Latour's Actor Network Theory to argue that epidemic space is geared towards instability when the vortex (of expanding associations and concerns) displaces the index (of finding a single cause)