Outcome Prediction for Unipolar Depression

Although effective drug and non-drug treatment for unipolar depressive illness exist, different individuals respond differently to different treatments. It is not uncommon for a given patient to lw switched several times from one treatment to another until an effective remedy for that particular patient is found. This process is costly in terms of time, money and suffering. It is thus desirable to determine at the outset the likdy response of a patient to the available treatments, so that the optimal one can be selected. Although prior attempts at outcome prediction with linear regression models have failed, recent work on this problem has indicated that the nonlinear predictive techniques of backpropagation and quadratic regression call account for a significant proportion of the variance in the data. The present research applies the nonlinear predictive technique of kernel regression to this problcrn, and employs cross-validation to test the ability of the resulting model to extract, from extremely noisy dinical data, information with predictive value. The importance of comparison with a suitable null hypothesis is illustrated.Office of Naval Research (N00014-95-1-0409

One-pot synthesis of GABA amides via the nucleophilic addition of amines to 3, 3-disubtituted cyclopropenes

A one-pot synthesis of various GABA amides has been demostrated, employing the nucleophilic addition of primary and secondary amines across the double bond of cyclopropene-3-carboxamides, followed by ring-opening of the resulting donor-acceptor cyclopropanes and subsequent in situ reduction of enamine (imine) intermediates

Assessing the Risk of 100-year Freshwater Floods in the Lamprey River Watershed of New Hampshire Resulting from Changes in Climate and Land Use

What is the coastal resource issue the project sought to address? Both the magnitude and frequency of freshwater flooding is on the rise in seacoast NH and around much of New England. In the Great Bay watershed, this is the result of two primary causes: 1) increases in impervious surface stemming from a three-to-four fold increase in developed land since 1962; and 2) changing rainfall patterns in part exemplified by a doubling in the frequency of extreme weather events that drop more than 4 inches of precipitation in less than 48 hours (Wake et al., 2011) over the same time period. Moreover, the size of the 100-year precipitation event in this region has increased 26% from 6.3 inches to 8.5 inches from the mid 1950’s to 2010 (NRCC and NRCS, 2012). One consequence is the occurrence of three 100-year floods measured on the Lamprey River at Packers Falls since 1987, and a fourth if the three days of flooding in March of 2010 had occurred instead in two days (Figure 1). Flooding events are expected to continue to increase in magnitude and frequency as land in the watershed is further developed and climate continues to change in response to anthropogenic forcing (e.g., Hayhoe et el., 2007; IPCC, 2007; Karl et al., 2009). Land use management strategies, in particular low impact development (LID) zoning requirements, are one strategy that communities can employ for increased resiliency to flooding with the greatest influence in urban environments

A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development.

EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, given that EphBs signal through multiple mechanisms, it has been challenging to define which signaling functions of EphBs regulate particular developmental events. To address these issues, we engineered triple knock-in mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly and specifically blocked. We found that the tyrosine kinase activity of EphBs was required for axon guidance in vivo. In contrast, EphB-mediated synaptogenesis occurred normally when the kinase activity of EphBs was inhibited, suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. Taken together, our data indicate that EphBs control axon guidance and synaptogenesis by distinct mechanisms and provide a new mouse model for dissecting EphB function in development and disease

Expression profiling of human renal carcinomas with functional taxonomic analysis

BACKGROUND: Molecular characterization has contributed to the understanding of the inception, progression, treatment and prognosis of cancer. Nucleic acid array-based technologies extend molecular characterization of tumors to thousands of gene products. To effectively discriminate between tumor sub-types, reliable laboratory techniques and analytic methods are required. RESULTS: We derived mRNA expression profiles from 21 human tissue samples (eight normal kidneys and 13 kidney tumors) and two pooled samples using the Affymetrix GeneChip platform. A panel of ten clustering algorithms combined with four data pre-processing methods identified a consensus cluster dendrogram in 18 of 40 analyses and of these 16 used a logarithmic transformation. Within the consensus dendrogram the expression profiles of the samples grouped according to tissue type; clear cell and chromophobe carcinomas displayed distinctly different gene expression patterns. By using a rigorous statistical selection based method we identified 355 genes that showed significant (p < 0.001) gene expression changes in clear cell renal carcinomas compared to normal kidney. These genes were classified with a tool to conceptualize expression patterns called "Functional Taxonomy". Each tumor type had a distinct "signature," with a high number of genes in the categories of Metabolism, Signal Transduction, and Cellular and Matrix Organization and Adhesion. CONCLUSIONS: Affymetrix GeneChip profiling differentiated clear cell and chromophobe carcinomas from one another and from normal kidney cortex. Clustering methods that used logarithmic transformation of data sets produced dendrograms consistent with the sample biology. Functional taxonomy provided a practical approach to the interpretation of gene expression data

Endogenous Group Formation Via Unproductive Costs

Sacrifice is widely believed to enhance cooperation in churches, communes, gangs, clans, military units, and many other groups. We find that sacrifice can also work in the lab, apart from special ideologies, identities, or interactions. Our subjects play a modified VCM game—one in which they can voluntarily join groups that provide reduced rates of return on private investment. This leads to both endogenous sorting (because free-riders tend to reject the reduced-rate option) and substitution (because reduced private productivity favours increased club involvement). Seemingly unproductive costs thus serve to screen out free-riders, attract conditional cooperators, boost club production, and increase member welfare. The sacrifice mechanism is simple and particularly useful where monitoring difficulties impede punishment, exclusion, fees, and other more standard solutions