Synthesis, stabilization and formulation of [177Lu]Lu-AMBA, a systemic radiotherapeutic agent for Gastrin Releasing Peptide receptor positive tumors.

A robust formulation was developed for [(177)Lu]Lu-AMBA ((177)Lu-DO3A-CH(2)CO-G-[4-aminobenzoyl]-QWAVGHLM-NH(2)), a Bombesin-like agonist with high affinity for Gastrin Releasing Peptide (GRP) receptors. During optimization of labeling, the effect of several radiostabilizers was evaluated; a combination of selenomethionine and ascorbic acid showed superiority over other tested radiostabilizers. The resulting two-vial formulation maintains a radiochemical purity (RCP) of >90% for at least 2 days at room temperature.

The mechanism of action of beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine involves a second metabolic pathway leading to beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine 5'-triphosphate, a potent inhibitor of the hepatitis C virus RNA-dependent RNA polymerase.

beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) is a potent inhibitor of hepatitis C virus (HCV) RNA replication in an HCV replicon assay. The 5'-triphosphate of PSI-6130 is a competitive inhibitor of the HCV RNA-dependent RNA polymerase (RdRp) and acts as a nonobligate chain terminator. Recently, it has been shown that the metabolism of PSI-6130 also results in the formation of the 5'-triphosphate of the uridine congener, beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine (PSI-6206; RO2433).

Standardized platform for coregistration of nonconcurrent diffuse optical and magnetic resonance breast images obtained in different geometries.

We present a novel methodology for combining breast image data obtained at different times, in different geometries, and by different techniques. We combine data based on diffuse optical tomography (DOT) and magnetic resonance imaging (MRI). The software platform integrates advanced multimodal registration and segmentation algorithms, requires minimal user experience, and employs computationally efficient techniques.

Improving the drug selection and development process for combination devices.

Combination devices are at the interface of both pharmaceutical and medical device research. While there have been several notable successes in bringing combination devices to market there are drug selection criteria that both the pharmaceutical and medical device companies need to consider. A successful combination device creates a product that has efficacy greater than the sum of the parts.

Improved model-based, platform-independent feature extraction for mass spectrometry.

Motivation: Mass spectrometry (MS) is increasingly being used for biomedical research. The typical analysis of MS data consists of several steps. Feature extraction is a crucial step since subsequent analyses are performed only on the detected features.

Shape regression machine.

We present a machine learning approach called shape regression machine (SRM) to segmenting in real time an anatomic structure that manifests a deformable shape in a medical image. Traditional shape segmentation methods rely on various assumptions. For instance, the deformable model assumes that edge defines the shape; the Mumford-Shah variational method assumes that the regions inside/outside the (closed) contour are homogenous in intensity; and the active appearance model assumes that shape/appearance variations are linear.

Mechanism of activation of beta-D-2'-deoxy-2'-fluoro-2'-c-methylcytidine and inhibition of hepatitis C virus NS5B RNA polymerase.

Beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) is a potent specific inhibitor of hepatitis C virus (HCV) RNA synthesis in Huh-7 replicon cells. To inhibit the HCV NS5B RNA polymerase, PSI-6130 must be phosphorylated to the 5'-triphosphate form. The phosphorylation of PSI-6130 and inhibition of HCV NS5B were investigated.

BoCaTFBS: a boosted cascade learner to refine the binding sites suggested by ChIP-chip experiments.

Comprehensive mapping of transcription factor binding sites is essential in postgenomic biology. For this, we propose a mining approach combining noisy data from ChIP (chromatin immunoprecipitation)-chip experiments with known binding site patterns. Our method (BoCaTFBS) uses boosted cascades of classifiers for optimum efficiency, in which components are alternating decision trees; it exploits interpositional correlations; and it explicitly integrates massive negative information from ChIP-chip experiments.

The effects of stimulus rotation and familiarity in visual search.

Rauschenberger and Yantis (2006) observed that an intersecting circle-line combination enjoyed significantly greater search efficiency when it was oriented to resemble a "Q" than when it was oriented so that the intersecting line was vertical (cf. Treisman and Souther, 1985). Although a control experiment made it unlikely that the obliqueness of the line was responsible for the observed benefit, there was no direct evidence that this benefit was attributable to the "Q-ness" of the stimulus.

A flexible method for preparation of peptide homo- and heterodimers functionalized with affinity probes, chelating ligands, and latent conjugating groups.

Dimerization of peptides can provide high binding entities to serve as targeted diagnostics or therapeutics. We developed methods for the preparation of homo- and heterodimer peptides bearing functional molecules (affinity probes, chelating ligands, or latent conjugating moieties). Monomer peptides, optionally bearing spacer groups, are tethered using a bifunctional linker, (di-succinimidyl glutarate, DSG) to provide the dimers.

From sample similarity to ensemble similarity: probabilistic distance measures in reproducing kernel Hilbert space.

This paper addresses the problem of characterizing ensemble similarity from sample similarity in a principled manner. Using reproducing kernel as a characterization of sample similarity, we suggest a probabilistic distance measure in the reproducing kernel Hilbert space (RKHS) as the ensemble similarity. Assuming normality in the RKHS, we derive analytic expressions for probabilistic distance measures that are commonly used in many applications, such as Chernoff distance (or the Bhattacharyya distance as its special case), Kullback-Leibler divergence, etc.

Tracking and analysis of cine-delayed enhancement MR.

Cine-DEMR is a new cardiac imaging technique which combines aspects of Cine and Delayed Enhancement MR. Like Cine, it displays the heart beating over time allowing for the detection of motion abnormalities. Like DEMR, non-viable (dead) tissues appear with increased signal intensity (it has been shown that the extent of non-viable tissue in the left ventricle (LV) of the heart is a direct indicator of patient survival rate).

A novel phantom-less spatial and temporal ultrasound calibration method.

This paper introduces a novel method for ultrasound calibration for both spatial and temporal parameters. The main advantage of this method is that it does not require a phantom, which is usually expensive to fabricate. Furthermore, the method does not require extensive image processing.

Stereo matching with linear superposition of layers.

In this paper, we address stereo matching in the presence of a class of non-Lambertian effects, where image formation can be modeled as the additive superposition of layers at different depths. The presence of such effects makes it impossible for traditional stereo vision algorithms to recover depths using direct color matching-based methods. We develop several techniques to estimate both depths and colors of the component layers.

Covariation analysis of local amino acid sequences in recurrent protein local structures.

Local structural information is supposed to be frequently encoded in local amino acid sequences. Previous research only indicated that some local structure positions have specific residue preferences in some particular local structures. However, correlated pairwise replacements for interacting residues in recurrent local structural motifs from unrelated proteins have not been studied systematically.

Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of vascular endothelial growth factor.

Tuftsin, Thr-Lys-Pro-Arg (TKPR), is an immunostimulatory peptide with reported nervous system effects as well. We unexpectedly found that tuftsin and a higher affinity antagonist, TKPPR, bind selectively to neuropilin-1 and block vascular endothelial growth factor (VEGF) binding to that receptor. Dimeric and tetrameric forms of TKPPR had greatly increased affinity for neuropilin-1 based on competition binding experiments.

Automatic registration of portal images and volumetric CT for patient positioning in radiation therapy.

The efficacy of radiation therapy treatment depends on the patient setup accuracy at each daily fraction. A significant problem is reproducing the patient position during treatment planning for every fraction of the treatment process. We propose and evaluate an intensity based automatic registration method using multiple portal images and the pre-treatment CT volume.

Design, synthesis, and antiviral activity of 2'-deoxy-2'-fluoro-2'-C-methylcytidine, a potent inhibitor of hepatitis C virus replication.

The pyrimidine nucleoside beta-d-2'-deoxy-2'-fluoro-2'-C-methylcytidine (1) was designed as a hepatitis C virus RNA-dependent RNA polymerase (HCV RdRp) inhibitor. The title compound was obtained by a DAST fluorination of N(4)-benzoyl-1-(2-methyl-3,5-di-O-benzoyl-beta-d-arabinofuranosyl]cytosine to provide N(4)-benzoyl-1-[2-fluoro-2-methyl-3,5-di-O-benzoyl-beta-d-ribofuranosyl]cytosine. The protected 2'-C-methylcytidine was obtained as a byproduct from the DAST fluorination and allowed for the preparation of two biologically active compounds from a common precursor.

Progress in xenotransplantation.

Organ transplantation is considered the most effective treatment for end-stage organ failure; currently it is limited by a severe worldwide shortage of human donor organs. This has led to investigation of the potential use of animals as organ donors. For a number of reasons, the pig represents the most likely organ donor candidate.

Racial and ethnic disparities and perceptions of health care: does health plan type matter?

Objective: To examine whether racial and ethnic differences in the distribution of individuals across types of health plans explain differences in satisfaction and trust with their physicians.

Data Sources: Data were derived from the 1998-1999 Community Tracking Household and Followback Studies and consisted of a nationwide sample of adults (18 years and older).

Data Collection: The data were collected by telephone survey.

Robust anisotropic Gaussian fitting for volumetric characterization of pulmonary nodules in multislice CT.

This paper proposes a robust statistical estimation and verification framework for characterizing the ellipsoidal (anisotropic) geometrical structure of pulmonary nodules in the Multislice X-ray computed tomography (CT) images. Given a marker indicating a rough location of a target, the proposed solution estimates the target's center location, ellipsoidal boundary approximation, volume, maximum/average diameters, and isotropy by robustly and efficiently fitting an anisotropic Gaussian intensity model. We propose a novel multiscale joint segmentation and model fitting solution which extends the robust mean shift-based analysis to the linear scale-space theory.

An information fusion framework for robust shape tracking.

Abstract-Existing methods for incorporating subspace model constraints in shape tracking use only partial information from the measurements and model distribution. We propose a unified framework for robust shape tracking, optimally fusing heteroscedastic uncertainties or noise from measurement, system dynamics, and a subspace model. The resulting nonorthogonal subspace projection and fusion are natural extensions of the traditional model constraint using orthogonal projection.

Gradient vector flow fast geometric active contours.

In this paper, we propose an edge-driven bidirectional geometric flow for boundary extraction. To this end, we combine the geodesic active contour flow and the gradient vector flow external force for snakes. The resulting motion equation is considered within a level set formulation, can deal with topological changes and important shape deformations.

A vision for health in our new century.

Our vision of good health is changing. Extraordinary progress was made over the course of the 20th century--life expectancy at birth increased by nearly 30 years and scientific insights revealed that our health fates are determined by interacting factors within each of the five major health domains. As life expectancies extend far beyond customary notions of old age, attention shifts from survival and toward improving the quality of life.

Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots.

Recent studies of human populations suggest that the genome consists of chromosome segments that are ancestrally conserved ('haplotype blocks'; refs. 1-3) and have discrete boundaries defined by recombination hot spots. Using publicly available genetic markers, we have constructed a first-generation haplotype map of chromosome 19.