Finding Business "Idols": A New Model to Accelerate Start-Ups

Explores a novel approach to finding high-tech entrepreneurial enterprises that is transforming how high-tech entrepreneurs are identified, their businesses launched, and the growth of their operations accelerated

Migration creation, diversion, and retention: new deal grants and migration ; 1935 - 1940

During the 1930s the federal government embarked upon an ambitious series of grant programs designed to counteract the Great Depression. Public works and relief programs combated unemployment by hiring workers and building social overhead capital while the Agricultural Adjustment Administration (AAA) sought to raise farm incomes by paying farmers not to produce. The amounts distributed varied widely across the country and potentially contributed to population shifts. We examine the extent to which New Deal spending affected domestic migration patterns in the second half of the 1930s. We estimate an aggregate discrete choice model, in which household heads choose among 466 economic subregions. The structural model allows us to decompose the effects of program spending on migration into three categories: the effect of spending on keeping households in their origin (retention), the effect of pulling non-migrants out of their origin (creation), and the effect of causing migrants to substitute away from an alternative destination (diversion). An additional dollar of public works and relief spending increased net migration into an area primarily by retaining the existing population and creating new migration into the county. Only a small share of the increase in net migration rate was caused by diversion of people who had already chosen to migrate. AAA spending contributed to net out migration, primarily by creating new out migrants and repelling potential in migrants. A counterfactual analysis that examines what would have happened had there been no New Deal spending during the 1930s suggests that the uneven distribution of New Deal public works and relief spending explains about twelve percent of the internal migration flows in the United States between 1935 and 1940. The uneven distribution of AAA spending accounted for about one percent

New methodologies for in vitro analysis of binding and functional activity of sigma receptor ligands

Sigma receptors represent a promising drug development target for a number of therapeutic indications including cancer, depression, psychostimulant abuse and stroke. To date, two subtypes of sigma receptors have been identified; sigma1 and sigma2. Their respective roles in normal physiology and in disease processes are a subject of ongoing studies. Consequently, the discovery and development of subtype specific agonist and antagonist ligands remains a key research goal. To date, no in vitro functional assay suitable for routine screening of putative sigma ligands has been reported. As a result, radioligand binding assays are used as a primary screen. Therefore, to support the critical role of receptor binding assays, a new sigma1 selective radioligand, [3H]-SN56, was characterized, and efforts were undertaken to develop medium throughput methods for binding affinity determinations for both sigma receptor subtypes. To fill the unmet need for an in vitro functional assay for sigma1 ligands, preliminary studies were performed to develop an immunological assay based on the ligand sensitive interaction of sigma1 and binding immunoglobulin protein (BiP). The results of the studies with [3H]SN56 show that it possesses high affinity and selectivity for sigma1 receptors and offers considerable advantages over the currently used radioligand, [3H](+)- pentazocine. Competition binding studies with established sigma ligands assayed in rat brain homogenates labeled with [3H]SN56 or [ 3H](+)-pentazocine yielded comparable Ki values, indicating that the two radioligands bind the same site. Saturation studies revealed similar Bmax values for [3H]SN56 and [3H](+)-pentazocine, further supporting the notion that both ligands bind specifically to the site identified as the sigma1 receptor. Conventional radioligand binding studies for sigma receptors utilize a cell harvester. Newer medium and high throughput technologies exist that have been applied to the analysis of numerous classical receptors. 96-well filtration and scintillation proximity assay (SPA) were evaluated for the analysis of sigma receptor ligand binding. Adaptation of the conventional binding assay to the higher throughput methods required the use of rat liver membranes because sigma receptor densities were too low in rat brain membranes to support reliable filtration in the 96-well format or use with SPA. Analysis of a series of reference compounds by 96-well filtration yielded binding affinities that correlated with values measured using the conventional method, for both sigma receptor subtypes. Following validation with the reference compounds, the 96-well filtration procedure was successfully used to determine Ki values for sigma receptors for a novel series of 2(3)-benzothiazolones. Studies with SPA demonstrated that this technique also yields results that are equivalent to the conventional method, but the cost of beads is prohibitively high with currently available radioligands used in conjunction with tissue derived membranes; this cost could potentially be significantly reduced if higher specific activity radioligands were available or if membranes from cells overexpressing sigma receptors were utilized. Preliminary studies were performed to assess the feasibility of developing a high throughput in vitro functional assay for the sigma1 receptor using Alphascreen as a read-out of agonist induced disruption of the sigma1/BiP complex. These efforts, which included a basic assessment of the Alphascreen platform, and attempts to determine if endogenous or recombinant proteins could serve as suitable substrates, were largely unsuccessful. However, these experiments did yield information that should prove useful for future development of an in vitro functional assay based on this protein-protein interaction

Predominant sarcomatoid carcinoma of the lung concurrent with jejunal metastasis and leukocytosis

Sarcomatoid carcinoma is an extremely rare biphasic tumor characterized by a combination of malignant epithelial and mesenchymal cells. Limited data on sarcomatoid carcinoma showed that most cases occurred with advanced local disease and metastasis, and paraneoplastic syndromes were rare. We present the case of a 63-year-old man with lung sarcomatoid carcinoma associated with jejunum metastasis and leukocytosis, and its clinical, macroscopic, and histopathological features. This case emphasizes the importance of recognizing paraneoplastic syndromes and metastasis of sarcomatoid carcinoma at diagnosis