Synthesis and characterization of tantalum(V) boronate clusters : multifunctional Lewis acid cages for binding guests

Open and shut cases: Tantalum(V) boronate clusters [(Cp*Ta)3(μ2‐η2‐RBO2)3(μ2‐O)2(μ2‐OH)(μ3‐OH)] (Cp*=η5‐C5Me5; 1: R=Ph, 2: R=iBu) with Lewis acidic cavities were prepared. Whereas the cavity of 2 is blocked by the iBu groups, that of 1 is open and can bind Lewis basic guests such as ketones (see picture) by interaction with one boronate and one μ3‐OH ligand

GALEX Ultraviolet Photometry of Globular Clusters in M31

We present ultraviolet photometry for globular clusters (GCs) in M31 from 15 square deg of imaging using the Galaxy Evolution Explorer (GALEX). We detect 200 and 94 GCs with certainty in the near-ultraviolet (NUV; 1750 - 2750 Angstroms) and far-ultraviolet (FUV; 1350 - 1750 Angstroms) bandpasses, respectively. Our rate of detection is about 50% in the NUV and 23% in the FUV, to an approximate limiting V magnitude of 19. Out of six clusters with [Fe/H]>-1 seen in the NUV, none is detected in the FUV bandpass. Furthermore, we find no candidate metal-rich clusters with significant FUV flux, because of the contribution of blue horizontal-branch (HB) stars, such as NGC 6388 and NGC 6441, which are metal-rich Galactic GCs with hot HB stars. We show that our GALEX photometry follows the general color trends established in previous UV studies of GCs in M31 and the Galaxy. Comparing our data with Galactic GCs in the UV and with population synthesis models, we suggest that the age range of M31 and Galactic halo GCs are similar.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 200

Chandra and Spitzer unveil heavily obscured quasars in the SWIRE/Chandra Survey

Using the large multi-wavelength data set in the chandra/SWIRE Survey (0.6 square degrees in the Lockman Hole), we show evidence for the existence of highly obscured (Compton-thick) AGN, estimate a lower limit to their surface density and characterize their multi-wavelength properties. Two independent selection methods based on the X-ray and infrared spectral properties are presented. The two selected samples contain 1) 5 X-ray sources with hard X-ray spectra and column densities > 10^24 cm-2, and 2) 120 infrared sources with red and AGN-dominated infrared spectral energy distributions (SEDs). We estimate a surface density of at least 25 Compton-thick AGN per square degree detected in the infrared in the chandra/SWIRE field of which ~40% show distinct AGN signatures in their optical/near-infrared SEDs, the remainings being dominated by the host-galaxy emission. Only ~33% of all Compton-thick AGN are detected in the X-rays at our depth (F(0.3-8 keV)>10^-15 erg/cm2/s. We report the discovery of two sources in our sample of Compton-thick AGN, SWIRE_J104409.95+585224.8 (z=2.54) and SWIRE_J104406.30+583954.1 (z=2.43), which are the most luminous Compton-thick AGN at high-z currently known. The properties of these two sources are discussed in detail with an analysis of their spectra, SEDs, luminosities and black-hole masses.Comment: ApJ accepted (to appear in May 2006 issue, vol. 642, of ApJ) Figures 2, 3, and 14 have been degraded due to space consideration

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

The Look-back Time Evolution of Far-UV Flux from Elliptical Galaxies: The Fornax Cluster and Abell 2670

In order to investigate the origin of the far-UV (FUV) flux from the early-type galaxies, Galaxy Evolution Explorer (GALEX) is collecting the UV data for the elliptical-rich clusters at moderate redshifts (z < 0.2) where the dominant FUV source is predicted to be hot horizontal-branch (HB) stars and their post-HB progeny. Here we present our first result for the early-type galaxies in Abell 2670 at z = 0.076. Compared to NGC 1399, a nearby giant elliptical galaxy in the Fornax cluster, it appears that the rest-frame FUV - V color of the giant ellipticals gets redder by ~ 0.7 mag at the distance of Abell 2670 (z = 0.076; look-back time ~ 1.0 Gyr). Although a detailed comparison with the models is postponed until more cluster data are accumulated, it is interesting to note that this value is consistent with the variation predicted by the population synthesis models where the mean temperature of HB stars declines rapidly with increasing look-back time.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS

124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of ¹⁸F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized C_H2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaC_H2), radiolabeled with iodine-124 (¹²⁴I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging.</p> <p>Methods</p> <p>HuCC49deltaC_H2 was radiolabeled with ¹²⁴I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of ¹²⁴I-HuCC49deltaC_H2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of ¹⁸F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection.</p> <p>Results</p> <p>At approximately 1 hour after i.v. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, ¹²⁴I-HuCC49deltaC_H2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, ¹⁸F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder.</p> <p>Conclusions</p> <p>On microPET imaging, ¹²⁴I-HuCC49deltaC_H2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while ¹⁸F-FDG failed to demonstrate this. The antigen-directed and cancer-specific ¹²⁴I-radiolabled anti-TAG-72 monoclonal antibody conjugate, ¹²⁴I-HuCC49deltaC_H2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.</p

Recurrent, Robust and Scalable Patterns Underlie Human Approach and Avoidance

BACKGROUND. Approach and avoidance behavior provide a means for assessing the rewarding or aversive value of stimuli, and can be quantified by a keypress procedure whereby subjects work to increase (approach), decrease (avoid), or do nothing about time of exposure to a rewarding/aversive stimulus. To investigate whether approach/avoidance behavior might be governed by quantitative principles that meet engineering criteria for lawfulness and that encode known features of reward/aversion function, we evaluated whether keypress responses toward pictures with potential motivational value produced any regular patterns, such as a trade-off between approach and avoidance, or recurrent lawful patterns as observed with prospect theory. METHODOLOGY/PRINCIPAL FINDINGS. Three sets of experiments employed this task with beautiful face images, a standardized set of affective photographs, and pictures of food during controlled states of hunger and satiety. An iterative modeling approach to data identified multiple law-like patterns, based on variables grounded in the individual. These patterns were consistent across stimulus types, robust to noise, describable by a simple power law, and scalable between individuals and groups. Patterns included: (i) a preference trade-off counterbalancing approach and avoidance, (ii) a value function linking preference intensity to uncertainty about preference, and (iii) a saturation function linking preference intensity to its standard deviation, thereby setting limits to both. CONCLUSIONS/SIGNIFICANCE. These law-like patterns were compatible with critical features of prospect theory, the matching law, and alliesthesia. Furthermore, they appeared consistent with both mean-variance and expected utility approaches to the assessment of risk. Ordering of responses across categories of stimuli demonstrated three properties thought to be relevant for preference-based choice, suggesting these patterns might be grouped together as a relative preference theory. Since variables in these patterns have been associated with reward circuitry structure and function, they may provide a method for quantitative phenotyping of normative and pathological function (e.g., psychiatric illness).National Institute on Drug Abuse (14118, 026002, 026104, DABK39-03-0098, DABK39-03-C-0098); The MGH Phenotype Genotype Project in Addiction and Mood Disorder from the Office of National Drug Control Policy - Counterdrug Technology Assessment Center; MGH Department of Radiology; the National Center for Research Resources (P41RR14075); National Institute of Neurological Disorders and Stroke (34189, 05236