The Association between Vitamin D Receptor Expression and Prolonged Overall Survival in Breast Cancer.

Summary In this study, we analyzed vitamin D receptor (VDR) expression and survival in a breast cancer patient cohort of 82 breast cancer patients. Immunohistochemical analysis was possible in 91.5% of the patients (75/82). Staining was evaluated using the semi-quantitative assay according to Remmele and Stegner (immunoreactivity score [IRS]). IRS 0–1 was negative/very low, IRS 2–4 was moderate to high, and IRS 6–12 was high. Statistical analysis was performed by Spearman’s correlation test (p<0.05 significant). Overall survival was analyzed using Kaplan-Meier estimations. Only 6 patients had a negative IRS. Moderate IRS values were present in 20 patients. Most of the patients had a high IRS (49). For survival analysis, data were dichotomized (IRS 0–4: negative to moderate and IRS 6–12: high VDR expression). In univariate analysis, VDR expression showed significant differences in progression-free survival (PFS) and overall survival (OS). Patients with high IRS scores showed significantly better PFS and OS than patients with moderate/negative IRS scores for VDR expression. Tumor size was significantly correlated to PFS. When analyzed separately, the three different IRS groups showed significant differences in VDR expression. The present data suggest that VDR expression in breast cancer tissue may be of clinical significance, and the results provide evidence that VDR may be a factor with prognostic relevance. (J Histochem Cytochem 60:121–129, 2012). Keywords: breast cancer, vitamin D receptor, immunohistochemistry, prognosi

Integration of OWL-S into IRS-III

IRS-III is the first WSMO compliant system for supporting the Semantic Web Services technologies and it is based on the IRS-II [3]. This paper presents how we integrated the OWL-S [5] service description ontology to IRS-III. We describe how the underlying model of IRS-III supports OWL-S

NGC 7538 : Multiwavelength Study of Stellar Cluster Regions associated with IRS 1-3 and IRS 9 sources

We present deep and high-resolution (FWHM ~ 0.4 arcsec) near-infrared (NIR) imaging observations of the NGC 7538 IRS 1-3 region (in JHK bands), and IRS 9 region (in HK bands) using the 8.2m Subaru telescope. The NIR analysis is complemented with GMRT low-frequency observations at 325, 610, and 1280 MHz, molecular line observations of H13CO+ (J=1-0), and archival Chandra X-ray observations. Using the 'J-H/H-K' diagram, 144 Class II and 24 Class I young stellar object (YSO) candidates are identified in the IRS 1-3 region. Further analysis using 'K/H-K' diagram yields 145 and 96 red sources in the IRS 1-3 and IRS 9 regions, respectively. A total of 27 sources are found to have X-ray counterparts. The YSO mass function (MF), constructed using a theoretical mass-luminosity relation, shows peaks at substellar (~0.08-0.18 Msolar) and intermediate (~1-1.78 Msolar) mass ranges for the IRS 1-3 region. The MF can be fitted by a power law in the low mass regime with a slope of Gamma ~ 0.54-0.75, which is much shallower than the Salpeter value of 1.35. An upper limit of 10.2 is obtained for the star to brown dwarf ratio in the IRS 1-3 region. GMRT maps show a compact HII region associated with the IRS 1-3 sources, whose spectral index of 0.87+-0.11 suggests optical thickness. This compact region is resolved into three separate peaks in higher resolution 1280 MHz map, and the 'East' sub-peak coincides with the IRS 2 source. H13CO+ (J=1-0) emission reveals peaks in both IRS 1-3 and IRS 9 regions, none of which are coincident with visible nebular emission, suggesting the presence of dense cloud nearby. The virial masses are approximately of the order of 1000 Msolar and 500 Msolar for the clumps in IRS 1-3 and IRS 9 regions, respectively.Comment: 27 pages, 18 figures, 5 tables. Accepted for publication in MNRA

Identification of the Amino Acids 300–600 of IRS-2 as 14-3-3 Binding Region with the Importance of IGF-1/Insulin-Regulated Phosphorylation of Ser-573

Phosphorylation of insulin receptor substrate (IRS)-2 on tyrosine residues is a key event in IGF-1/insulin signaling and leads to activation of the PI 3-kinase and the Ras/MAPK pathway. Furthermore, phosphorylated serine/threonine residues on IRS-2 can induce 14-3-3 binding. In this study we searched IRS-2 for novel phosphorylation sites and investigated the interaction between IRS-2 and 14-3-3. Mass spectrometry identified a total of 24 serine/threonine residues on IRS-2 with 12 sites unique for IRS-2 while the other residues are conserved in IRS-1 and IRS-2. IGF-1 stimulation led to increased binding of 14-3-3 to IRS-2 in transfected HEK293 cells and this binding was prevented by inhibition of the PI 3-kinase pathway and an Akt/PKB inhibitor. Insulin-stimulated interaction between endogenous IRS-2 and 14-3-3 was observed in rat hepatoma cells and in mice liver after an acute insulin stimulus and refeeding. Using different IRS-2 fragments enabled localization of the IGF-1-dependent 14-3-3 binding region spanning amino acids 300–600. The 24 identified residues on IRS-2 included several 14-3-3 binding candidates in the region 300–600. Single alanine mutants of these candidates led to the identification of serine 573 as 14-3-3 binding site. A phospho-site specific antibody was generated to further characterize serine 573. IGF-1-dependent phosphorylation of serine 573 was reduced by inhibition of PI 3-kinase and Akt/PKB. A negative role of this phosphorylation site was implicated by the alanine mutant of serine 573 which led to enhanced phosphorylation of Akt/PKB in an IGF-1 time course experiment. To conclude, our data suggest a physiologically relevant role for IGF-1/insulin-dependent 14-3-3 binding to IRS-2 involving serine 573

IRS III: a platform and infrastructure for creating WSMO based semantic web services

The IRS project has the overall aim of supporting the automated or semi-automated construction of semantically enhanced systems over the inter-net. IRS-I supported the creation of knowledge intensive systems structured acording to the UPML framework and IRS-II integrated the UPML framework with web service technologies. In this paper we describe IRS-III. Within IRS-III we have now incorporated and extended the WSMO ontology. Our extensions to WSMO include the addition of input and output roles to goals and web services and a new type of mediator. As well as summarizing our additions to WSMO we outline the architecture of IRS-III and the associated interfaces

Multiple Sources toward the High-mass Young Star S140 IRS1

S140 IRS1 is a remarkable source where the radio source at the center of the main bipolar molecular outflow in the region is elongated perpendicular to the axis of the outflow, an orientation opposite to that expected if the radio source is a thermal jet exciting the outflow. We present results of 1.3 cm continuum and H2O maser emission observations made with the VLA in its A configuration toward this region. In addition, we also present results of continuum observations at 7 mm and re-analyse observations at 2, 3.5 and 6 cm (previously published). IRS 1A is detected at all wavelengths, showing an elongated structure. Three water maser spots are detected along the major axis of the radio source IRS 1A. We have also detected a new continuum source at 3.5 cm (IRS 1C) located ~0.6'' northeast of IRS 1A. The presence of these two YSOs (IRS 1A and 1C) could explain the existence of the two bipolar molecular outflows observed in the region. In addition, we have also detected three continuum clumps (IRS 1B, 1D and 1E) located along the major axis of IRS 1A. We discuss two possible models to explain the nature of IRS 1A: a thermal jet and an equatorial wind.Comment: 17 pages, 4 figures, to be published in A

Mathematical Evaluation of Community Level Impact of Combining Bed Nets and Indoor Residual Spraying upon Malaria Transmission in Areas where the main Vectors are Anopheles Arabiensis Mosquitoes.

Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset, PermaNet 2.0, Icon Life nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset or PermaNet 2.0 nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus