Small Business Innovation Research Grants Research Articles

An acute respiratory distress syndrome drug development collaboration stimulated by the Virginia Drug Discovery Consortium.

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, Old Dominion University, and a university spinout company, KeViRx, Inc., partnered under a NIH Small Business Innovation Research grant, to produce potential therapeutics for acute respiratory distress syndrome resulting from the ongoing COVID-19 pandemic.

Translational research: from basic research to regional biomedical entrepreneurship.

This paper examines the effect of translational research on knowledge production and biomedical entrepreneurship across U.S. regions. Researchers have earlier investigated the outputs of translational research by focusing on academic publications. Little attention has been paid to linking translational research to biomedical entrepreneurship. We construct an analytical model based on the knowledge spillover theory of entrepreneurship and the entrepreneurial ecosystem approach to examine the relationship between translational research, biomedical patents, clinical trials, and biomedical entrepreneurship. We test the model across 381 U.S. metropolitan statistical areas using 10 years of panel data related to the NIH Clinical and Translational Science Awards (CTSA) program. CTSA appears to increase the number of biomedical patents and biomedical entrepreneurship as proxied by the NIH Small Business Innovation Research (SBIR) grants. However, the magnitudes of the effects are relatively small. Path analysis shows that the effect of translational research on regional biomedical entrepreneurship is not strongly conveyed through biomedical patents or clinical trials.

PD27-01 PREDICTING EXTRA-PROSTATIC EXTENSION (EPE) FOR SURGICAL GUIDANCE IN PROSTATE CANCER: A COMPARISON OF BIOPSY PATHOLOGY, MULTIPARAMETRIC MRI, AND PSMA-PET

You have accessJournal of UrologyCME1 May 2022PD27-01 PREDICTING EXTRA-PROSTATIC EXTENSION (EPE) FOR SURGICAL GUIDANCE IN PROSTATE CANCER: A COMPARISON OF BIOPSY PATHOLOGY, MULTIPARAMETRIC MRI, AND PSMA-PET Clinton Bahler, Mark Green, Mark Tann, Katrina Collins, Jordan Swensson, Eric Brocken, Liang Cheng, Carla Mathias, David Alexoff, Hank Kung, Gary Hutchins, and Michael Koch Clinton BahlerClinton Bahler More articles by this author , Mark GreenMark Green More articles by this author , Mark TannMark Tann More articles by this author , Katrina CollinsKatrina Collins More articles by this author , Jordan SwenssonJordan Swensson More articles by this author , Eric BrockenEric Brocken More articles by this author , Liang ChengLiang Cheng More articles by this author , Carla MathiasCarla Mathias More articles by this author , David AlexoffDavid Alexoff More articles by this author , Hank KungHank Kung More articles by this author , Gary HutchinsGary Hutchins More articles by this author , and Michael KochMichael Koch More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002575.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostatectomy related incontinence and impotency result from injury to nerves and muscle tissue. Preserving nerves and muscle adjacent to the prostate risks positive margins; therefore, preoperative imaging is needed with high sensitivity for extra-prostatic extension. METHODS: Four clinical trials for PSMA-PET targeted imaging prior to prostatectomy were retrospectively evaluated for prediction of extra-prostatic extension as documented on post-surgical whole-mount pathologic analysis. Two different PSMA-PET tracers were included: PSMA-11 and P16-093. A blinded review of PET and MRI scans was performed to predict the risk of extra-prostatic extension (EPE). Stata 13.1 was used. Pearson’s Chi2 and McNemar’s Chi2 were used for accuracy statistics. RESULTS: Pre-operative PSMA-PET imaging was performed in 71 patients with either 68Ga-P16-093 (n=25) or 68Ga-PSMA-11 (n=46). Age (62 vs 61 years), PSA (7.3 vs 7.8), and biopsy pathology (3+3: 0 vs 7%, 3+4: 28 vs 39%, 4+3: 24 vs 20%, ≥4+5: 48 vs 35%) were similar between the groups (p >0.30). There were 24 (34%) with pT3a (EPE) and 16 (23%) with pT3b on final pathology. Overall positive margin rate was 17 (24%). Index lesion SUVmax was similar between P16-093 and PSMA-11 (10.3 vs 11.7). EPE Sensitivity (87 vs 92%), Specificity (77 vs 76%), and ROC area (82 vs 84%) were similar between P16-093 and PSMA-11, respectively (p=0.87). MRI (available in 45) found high specificity (83%) but low sensitivity (60%) and the overall ROC area was lower when compared to pooled PSMA-PET (0.72 vs 0.83, p=0.01). For pooled PSMA-PET imaging, a treatment change from “non-nerve sparing” to “nerve sparing” was recommended in 21/71 (30%) of patients. A total of 14 men had nerve-sparing (treatment change) based on PSMA-PET imaging with one (5%) having a positive margin. Figure 1 shows a case where left-sided EPE as accurately predicted by 68Ga-P16-093 scan. CONCLUSIONS: PSMA-PET imaging can improve surgical guidance in men with ≥4+3 prostate cancer resulting in preservation of nerve-bundles. 68Ga-P16-093 PET and 68Ga-PSMA-11 PET had similar accuracy for predicting extra-prostatic extension. Source of Funding: Al Christy Prostate Cancer Fund, R44 CA233140, NIH Small Business Innovation Research grant (SBIR), CTSI NIH/NCRR Grant Number UL1TR001108, ACS-IRG Grant Mechanism (16-192-31) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e493 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Clinton Bahler More articles by this author Mark Green More articles by this author Mark Tann More articles by this author Katrina Collins More articles by this author Jordan Swensson More articles by this author Eric Brocken More articles by this author Liang Cheng More articles by this author Carla Mathias More articles by this author David Alexoff More articles by this author Hank Kung More articles by this author Gary Hutchins More articles by this author Michael Koch More articles by this author Expand All Advertisement PDF DownloadLoading ...

Engaging Early-Career Physicians in Medical Device Innovation and Entrepreneurship.

Engaging Early-Career Physicians in Medical Device Innovation and Entrepreneurship.

Inappropriateness Penalty, Desirability Premium: What Do More Certifications Actually Signal?

Prevailing theory argues that more certifications increase performance. However, emerging empirical evidence implies that obtaining more certifications may actually decrease performance. How do we reconcile this tension? Practically speaking, why would ventures seek additional certifications in light of these recently identified risks? To address this gap between existing theory and recent empirics, we look more closely at ventures’ activities and performance outcomes after they receive their first certification. We posit that different patterns of certification reflect different forms of experimentation. In particular, ventures may be willing to experiment in ways that incur an inappropriateness penalty for the chance to gain a subsequent desirability premium if their experiments succeed. Inappropriateness means that certifications signal divergence from accepted market norms and standards. Desirability means that certifications signal activities that are in the perceived self-interest of the potential audience. We hypothesize that certifications reflecting broad experimentation incur initial inappropriateness penalties, yet when successful, they are more likely to lead to breakthroughs that generate desirability premia. We find support for this idea through an empirical analysis drawing from a sample of 7,440 U.S. ventures that receive one or more Small Business Innovation Research (SBIR) or Small Business Technology Transfer (STTR) grants to commercialize new technologies. This study advances institutional theory of certification to better account not only for its benefits but also for its costs.

Chardonnay Grape Marc Powder Supplementation May Increase Insulin Sensitivity in Obese and Overweight Men and Women

Abstract Objectives Chardonnay grape marc (CM) is the remaining skins and seeds from winemaking that offers a rich source of phytonutrients. The objective was to evaluate glucose metabolism following the addition of CM to the diet. Methods Overweight or obese men and women with mild hyperlipidemia between 35–65 y were recruited for this double-blinded 16-week crossover study. Subjects consumed 1500mg of 1) microcrystalline cellulose (MCC), 2) high chardonnay seed extract/WellVine™ marc blend (HE) or 3) high WellVine™ chardonnay marc/seed extract blend (HM) in a randomized order. Each intervention arm lasted 3 weeks and included two 3-week washout periods. Following each intervention, fasting blood was drawn and assayed for glucose and insulin. Indexes of insulin resistance (HOMA-IR, McAuley) and insulin sensitivity (QUICKI) were calculated. Data were transformed before conducting analyses, when appropriate. Analyses were conducted with 24 completed subjects and intention to treat (ITT) with 3 subjects who withdrew using linear mixed model ANOVA. Results In the ITT analysis, fasting glucose and insulin showed a significant main effect of intervention (P = 0.04 and P = 0.03, respectively). For both glucose and insulin, pairwise comparisons showed a significant difference between HM and MCC (P = 0.03 and P = 0.03, respectively). The indexes, HOMA-IR and QUICKI showed a significant main effect of intervention (P = 0.04 and P = 0.03, respectively), whereas there was no effect with the McAuley index. For HOMA-IR and QUICKI, pairwise comparisons showed a significant difference between HM and MCC (P = 0.04 and P = 0.03, respectively). Conclusions There was an increase in QUICKI, indicating an increase in insulin sensitivity following the HM arm compared to MCC. This has important implications if it is followed up in a larger cohort. Following the HM arm there was also a decrease in fasting insulin and decrease in HOMA-IR compared to the MCC arm; in this case, the magnitude of these changes are not sufficient to suggest improvement in insulin resistance by clinical definitions. This was a proof of concept study, thus future studies should further explore these findings. Funding Sources NIFA Phase II Small Business Innovation Research Grant awarded to Sonomaceuticals, LLC, USDA CRIS 2032–51,530-025–00D.

A role for embedded instrumentation in real-time hardware assurance and online monitoring against cybersecurity threats

Our 2019 AUTOTESTCON paper [1] introduced the concept of hardware assurance for security and trust that focused on Trojan payloads and triggers and the use of embedded instruments and data collection from those instruments as one of the detection strategies. A Phase I Small Business Innovation Research grant funded the proof of concept of using a COTS board as a sandboxed emulation environment to safely study the attack scenarios associated with various Trojan attacks, and that effort is described in this article.

Evaluating Postprandial Lipid Response Following Chardonnay Grape Marc Powder Supplementation

Abstract Objectives Chardonnay grape marc is the remaining skins and seeds after pressing and is a byproduct of winemaking that offers a rich source of phytonutrients. The objective was to evaluate postprandial lipid response following adding Chardonnay grape marc powder to the diet. Methods Overweight or obese men and women with hyperlipidemia between 35–65 y were recruited for this randomized, double-blinded 16-week crossover study. Subjects consumed 1500 mg of 1) placebo, 2) high Chardonnay seed extract, low Chardonnay marc blend (HE) or 3) high chardonnay marc, low chardonnay seed extract blend (HM) in a randomized order. Each intervention arm lasted 3 weeks and included two 3-week washout periods. Following each intervention, fasting blood was drawn, then subjects consumed a high fat challenge meal. Postprandial blood was subsequently drawn at 1, 2 and 3 hours. Incremental area under the curve (iAUC) was also calculated. Data were not normally distributed thus were log transformed before conducting analyses. Analyses were conducted with 24 completed subjects and intention to treat for 3 subjects who withdrew using linear mixed model ANOVA. Results Incremental area under the triglyceride curve response to a meal showed a significant effect of intervention (P = 0.05). Pairwise comparisons showed a significant difference between HE and HM (P = 0.04). Conclusions Following HM intervention, there was a significantly lower triglyceride iAUC compared to the HE intervention, but no difference compared to placebo. HM intervention resulted in better triglyceride clearance compared to the HE intervention. Funding Sources NIFA Phase II Small Business Innovation Research Grant awarded to Sonomaceuticals, LLC.

Reflections on 7 Years of Strategy Instruction

Most investigations of literacy programs are relatively short-term endeavors. Here, we reflect on what we have learned in 7 years of studying a program to teach word-learning strategies. The program was developed with a 3-year Institute of Education Sciences (IES) Small Business Innovation Research (SBIR) grant and is currently being studied in a 4-year IES Efficacy grant. Here, we describe our choice of a topic; describe the curriculum, instruction, and teacher preparation in the program; and reflect on positive aspects of the program and aspects of it that could be improved. We believe that much of what we discuss is relevant to various types of instruction.

High‐precision and Scalable Fabrication of Biomimetic Culture Environments for Replicating the Extracellular Matrix In Vitro

In vivo, cell and tissue organization is driven by a complex interplay of cells and their environment, including the extracellular matrix (ECM). The ECM can provide varied cues such as structure, protein content, mechanical stiffness, stretch, and electrical stimulation to influence cell and tissue development and function. Traditional in vitro cell culture environments—typically composed of non‐dynamic hard and unstructured glass or plastic—fail to fulfill the roles of the ECM in development. Consequently, many in vitro cell models fall short in correctly reproducing critical in vivo phenotypes as evidenced when cultured cells lose type‐specific characteristics or express phenotypes indicative of an immature developmental stage. Considerable effort is directed at fabricating biomimetic culture environments that maintain or promote mature phenotypes. However, making biomimetic substrates typically involves costly or hard‐to‐reproduce techniques that are often incompatible with many standard assays. These challenges are further compounded when using high‐throughput assays. In this study, our objective is to develop a host of techniques for recapitulating certain aspects of the ECM in vitro. To replicate the shape and stiffness of the extracellular niche, we first developed novel nanopatterning techniques based on high‐precision photolithography methods that are highly reproducible, scalable, and amenable to integration with most industry‐standard endpoint assays, including high‐NA microscopy. Our data demonstrate that a variety of cell types‐‐including cardiac, skeletal, endothelial, neuronal, and cancer‐‐can cue off of patterns that mimic the fibrous structure of the native ECM. We then extended this biomimetic patterning technique to deformable elastomeres which permitted the addition of mechanical strain to recapitulate mechanical signals present in the ECM of specific tissues. Our data show that mechanical strain can orient skeletal muscle cells and tissues along the axis of stretch, resulting in a polarized orientation that is similar to what is seen in vivo but is not recapitulated in traditional culture environments. Last, we demonstrate that a combination of ECM patterning, mechanical stretch, and electrical pacing can reproduce the extracellular environment of the intact myocardium to facilitate studies of induced pluripotent stem cell‐derived cardiomyocytes. We conclude that our approach is a viable method for recreating specific aspects of the ECM that are critical for driving the development and maturation of cells in culture in a cell, instrument, and assay‐agnostic manner.Support or Funding InformationNational Institutes of Health Small Business Innovation Research Grant.

Enhancing Stem Cell‐based Toxicity Assays by Engineering the Culture Niche in a High‐throughput, Assay‐agnostic Manner

Human induced pluripotent stem cell (hiPSC)‐based assays hold great promise for ameliorating human disease and improving the translation of new therapies, but they have shortcomings that hamper their ability to accurately model human physiology. For example, hiPSC‐Cardiomyocytes (CMs) mis‐classify several compounds of known cardiotoxicity. One likely source of this is the maturity of the cells; most culture techniques result in hiPSC‐CMs that express fetal phenotypes, leading to inaccurate or difficult‐to‐translate results. While engineering the extracellular matrix (ECM) has demonstrated improvements to both structural and functional phenotypes, it is often hampered by challenges with integration into industry‐standard assays or instrumentation. Further, the ability to engineer increasingly intricate and multi‐faceted artificial culture environments often drives decisions that trade off biological complexity with experimental throughput. Here, we developed bioengineering techniques to create biomimetic patterns that mimic the shape and structure of the ECM on a transparent polymer‐coated glass layer. The resultant structure directs focal adhesion assembly mechanisms in individual cells to drive higher‐ordered structuring of 2D tissues. This forms 2D anisotropic syncytia from iPSC‐CMs in industry‐standard microplate formats that are compatible with transmitted light microscopy. The method is extended to micro‐electrode arrays (MEA) in a manner that maintains both the quality of MEA recordings and baseline electrophysiological properties. iPSC‐CMs grown this way exhibit several structural and biochemical phenotypes including adult protein isoform expression, myofibril alignment, and sarcomere spacing, length, and width. We show that biomimetic cues enhance the electrophysiological response of cardiomyocytes to various drugs of known effect. Since ECM structuring recapitulates the polarized nature of cells and their concomitant gap junctions, we used the gap junction blocker carbenoxolone for validation studies. Polarized tissues enable differential conduction block measurements between longitudinal and transverse directions. Our MEA data show that patterned tissues exhibit increased sensitivity to carbenoxolone over unpatterned constructs (IC50’s of 14.71 nM versus 398.1 nM, respectively) comparing favorably to clinically relevant unbound concentrations reported in the low nM range. Our biomimetic engineering approach is instrument‐ and assay agnostic, effective on a variety of cell types and lines (including neuronal cells; examples to be presented), and compatible with high‐throughput approaches.Support or Funding InformationNational Institutes of Health Small Business Innovation Research Grant.(A) decellularized ex‐vivo cardiac tissue slices demonstrate a polarized meshwork of extracellular matrix (ECM) fibers; (B) our biomimetic patterning technique recapitulates the nanoscale structure and orientation of the ECM; (C) the technique can be expanded to the surface of high‐throughput MEAs without degradation to electrical signal detection while maintaining the nanoscale pattern (inset); (D) FCDI iCell2 Cardiomyocytes cultured on traditional plastic surfaces show unstructured morphology; (E) iCell2 Cardiomyocytes cultured on our biomimetic surfaces recapitulate the anisotropic structure of adult heart tissue.Figure 1(A) sarcomere lengths (B) and widths of cells on biomimetic nanosurfaces (green) compared to conventional surfaces (gray) are increased; (C) adult isoforms of structural proteins are enhanced with biomimetic nanopatterning; (D) patterned cells exhibit higher oxygen consumption rate; (E) patch clamp data demonstrate increased action potential duration on patterned tissues; (F) asymmetric conduction on patterned tissues enhances the sensitivity of MEA assays to conduction blockers;Figure 2

WM380 (675–700 GHz) Bandpass Filters in Milled, Split-Block Construction

Filters play an invaluable role in RF analysis and communications hardware, blocking unwanted signals, limiting bandwidth, attenuating harmonic components, etc. In waveguide construction for mm-wave frequencies, where the powers are generally low, the iris-coupled-resonator bandpass filter has proven to be very practical and amenable to easy machining. At Virginia Diodes, much of our technology has been constructed using standard “split-block” techniques, in which high-precision computer numerical control milling machines are used to mill out the features from solid blocks of metal. Typical machining tolerances are on the order of +/−5–10 μ m. Construction of such filters to ∼200 GHz has been routine but pushing the operation into the Terahertz regime requires special considerations. Described here is a WM380 (WR1.5) filter for the 500–750 GHz waveguide band having a passband of 675–700 GHz. The filter is proof of concept for a 640 GHz heterodyne polarimeter, designed as a part of a Small Business Innovative Research (SBIR) Grant to develop technology for NASA's planned Aerosol, Cloud, and Ecosystems mission. From the very beginning, filter design and optimizations were carried out assuming the structure would be milled, hence necessitating that all internal features accommodate the finite radii of available machine tools. Construction of this filter required careful attention to machining tolerances to be able to push the milling machines to their absolute limits of +/−2.5 μ m or better. Measured results of a batch of filters are shown and compared to simulations to illustrate just how well these filters can be made. Furthermore, the filters can be tuned by simple mechanical means and data are presented to illustrate how easily the filters can be adjusted. Additional modifications to the filter topology to simplify machining, and allow other construction techniques to be utilized are also demonstrated. Ultimately it should be possible to push the split block technology to manufacture iris coupled resonator filters for use at frequencies of well over 1 THz.

RAMMS - A High-Throughput Membrane Measurement System for Fuel Cell Manufacturing

The objective of this work was to develop a robust, high-throughput polymer electrolyte membrane (PEM) resistance measurement system for fuel cell manufacturing quality control (QC). The principal outcome was the Rapid Membrane Measurement System (RAMMS), a fully-automated, off-line device that can be used by membrane manufacturers during production for QC and by membrane users for lot acceptance of a critical component of PEM fuel cell systems. The prototype RAMMS, shown in Figure 1(a), was designed and developed with the following functions and features in mind: (1) rapid and simple sample loading and unloading of bare membrane, (2) safe, long-term, unattended operation, (3) stable control of the cell environment (temperature, RH), and (4) reproducible electrode clamping pressure, (5) user-selectable operating parameters (electrode pressure, temperature, RH, conditioning time, etc.) to facilitate evaluation of membranes of various properties (thickness, conditioning kinetics) and/or with different resistance specification conditions. After developing a detailed specification for the RAMMS in collaboration with an industrial stakeholder, we designed, fabricated and tested a prototype unit. The system includes a novel humidification and environmental control system; integrated sample chamber, electrode and actuator system; impedance measurement for through-thickness membrane resistance; and application software. Studies with the prototype revealed that electrode durability, in particular adhesion of platinum deposit on a porous metallic substrate, was the most significant technical challenge and performance limitation of the device. It was concluded that acceptable durability could not be obtained with any of the deposition methods and post-deposition treatments designed to improve coating adhesion. Custom-fabricated porous platinum electrodes exhibited acceptable durability. In addition to conditioning time, the electrode squeeze pressure was identified as a primary test variable. Quantification of the effect of electrode squeeze pressure on the area-normalized HFR is shown in Figure 1(b). As hypothesized, lower HFR is strongly correlated with greater squeeze pressure. This is rationalized as being primarily driven by decreasing interfacial resistance with increasing electrode contact pressure, and secondarily, some compression and thinning of the membrane. In addition to the decrease in mean HFR, the range and standard deviation also decrease with increasing squeeze pressure. At the highest pressure investigated (2.36 MPa), the relative standard deviation (= standard deviation / mean) was 2.6% (n = 9). The dependence of the HFR on the electrode contact pressure demonstrated by the data in Figure 1(b) is not inconsistent with the statements that variation in the pressure is not the primary source of variability in HFR. We observed that the effect of contact pressure on the HFR was -0.044 mΩ/kPa (-0.3 mΩ/PSI). That is, the resistance decreased approximately 0.044 mΩ per kPa (0.3 mΩ per PSI) increase in squeeze pressure. Other results indicated that the test-to-test variation in squeeze pressure was < 6.9 kPa (< 1 PSI). Therefore, < 0.3 mΩ of variation could be attributed to test-to-test variability in the electrode contact pressure, which is smaller than the observed variability. Thus, the bulk of the test-to-test variation in observed resistance was not due to variation in the electrode squeeze pressure. Acknowledgement: This work was supported by a U.S. Department of Energy Small Business Innovation Research grant (DE-FG02-06ER84574). The support of Will Johnson (W.L. Gore & Associates) and the Gore Fuel Cell Group for helpful discussions and technical assistance is gratefully acknowledged. Figure 1

An analysis of the NIH-supported sickle cell disease research portfolio

Sickle cell disease (SCD), an inherited blood disorder is due to a single amino acid substitution on the beta chain of hemoglobin, and is characterized by anemia, severe infections, acute and chronic pain, and multi-organ damage. The National Institutes of Health (NIH) is dedicated to support basic, translational and clinical science research to improve care and ultimately, to find a cure for SCD that causes such suffering. This report provides a detailed analysis of grants funded by the NIH for SCD research in Fiscal Years 2007 through 2013. During this period, the NIH supported 247 de novo grants totaling $272,210,367 that address various aspects of SCD. 83% of these funds supported research project grants investigating the following 5 scientific themes: Pathology of Sickle Red Blood Cells; Globin Gene Expression; Adhesion and Vascular Dysfunction; Neurological Complications and Organ-specific Dysfunction; and Pain Management and Intervention. The remaining 17% of total funds supported career development and training grants; Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants; large Center grants; and Conference grants. Further analysis showed that the National Heart, Lung, and Blood Institute (NHLBI) is the largest funder of SCD research within NIH with 67% of total grants, contributing 77% of total funds; followed by the National Institute for Digestive Diseases and Kidney (NIDDK) that is funding 19% of grants, contributing 13% of total funds. The remaining 14% of grants totaling 10% of the funds were supported by all other NIH Institutes/Centers (ICs) combined. In summary, the NIH is using multiple funding mechanisms to support a sickle cell disease research agenda that is intended to advance the detection, treatment, and cure of this debilitating genetic disease.

What Types of Start-ups Receive Funding from the Small Business Innovation Research (SBIR) Program?: Evidence from the Kauffman Firm Survey

This paper integrates the Kauffman Firm Survey with the Small Business Innovation Research (SBIR) recipient dataset to examine in more depth the characteristics of small business start-ups that received R&D subsidy from SBIR. Our selection analysis first shows that SBIR program funds are distributed disproportionately to start-ups whose owner has a post-graduate education. The odds of being granted SBIR R&D subsidies are also higher for those who had prior R&D experience and owned patents at the start of their business operations. Start-ups that are operating in the high-technology sector are also more likely to receive SBIR funds than start-ups in traditional sectors. Surprisingly, start-ups that did not sell goods and services are more likely to receive SBIR grants. Interestingly, location matters but at a different direction: start-ups located in states that are not known for their R&D performance are more likely to receive SBIR funding.

Avoiding the Valley of Death: A Cross-Case Analysis of SBIR Innovation Processes

Small Business Innovation Research grant recipients experience a challenging and complex environment from innovation and product commercialization. This study examined the dynamics of small and medium-size SBIR-awardee firms through 20 cross-case analyses in the context of effectuation, new product development, and institutional theory, among other concepts, to develop process models based upon the firm size differences. We find medium-sized firms indicated significant tendencies to connect with the grantor through themes of co- creation, though all firms consistently indicated that full commercialization was elusive at best. Several smaller firms, possibly through a regional advantage, showed success at bringing products to development. We suggest that adaptation in the context of significant organizational contradictions allows for the optional-ization of assets. Keywords: innovation, complexity, co-creation.

The geographic extent of venture capital externalities on innovation

A stream of literature has demonstrated that venture capital generates externalities that enhance the knowledge base of a given region and accordingly assist firms in high-technology industries to improve their innovative performance. What has gone largely unexamined in this literature is the geographic extent of such externality impact. In this research we address the issue at hand. We do so by analyzing the association between the patenting rate of all life sciences firms (LSFs) that have won Small Business Innovation Research grants from 1983 to 2006 and the venture capital investments that have occurred at increasingly distant spatial units from those firms. Controlling for firm-specific and environmental factors as well as for endogeneity concerns, we document that LSFs tend to produce more patents whenever they are situated in very close proximity to where venture capital investments occur. Further, we find that improvements of the patenting rate of focal firms largely emanate from investments that reflect the expertise of venture capitalists on advancing existing prototypes closer to commercialization. We conclude the paper with a discussion on research and policy implications of our findings.

Rewards and risks for physicist entrepreneurs

Butler and Anderson reply: We appreciate Peter Foukal’s comments and the examples that he provides. However, based on interviews over the past four years with physicist founders of 91 companies, we believe that physics startups are high-risk ventures in today’s economy, and those that succeed today must focus on more than research. Foukal’s two examples were founded in 1958 and 1985 during a different economy, when even corporate giants like AT&T and GE funded blue-sky, pure research. We described the move away from that economy in our previous article “Industrial R&D in transition” (Physics Today, July 2009, page 36). Our data on more recent startups indicate that in today’s economy, companies committing substantial funds to pure research are essentially betting on the lottery. Are there winners? Yes, but they are sufficiently rare that they don’t provide an effective business model for physicists starting their own companies. Recent changes in Small Business Innovation Research and government grant policies further discourage funding a company based on pure research that has little or no focus on commercialization.The companies that we investigated probably provide a better example of current practices. Our database suggests that for better or worse, most companies operating as Foukal advocates have already gone the way of Bell Labs. Nor would we expect PerkinElmer to continue Cambridge Research and Instrumentation’s blue-sky research practices. They have, after all, fiduciary obligations to their investors. Nor do we think that the physicist founders of the companies we studied would agree that their business models have “limited the appeal of entrepreneurship as an alternative career path.” Many physicist entrepreneurs we interviewed told us they would prefer to transform their research into commercial products affecting the lives of millions than to publish papers read by only a few.© 2013 American Institute of Physics.

Gender differences in hepatic lipogenic and inflammatory genes after 72 hours of high fat diet

High fat diets (HFD) promote obesity and fatty liver disease in part due to upregulation of hepatic lipogenesis; females however are protected from this at long exposures to HFD. The purpose of this study was to investigate gender differences in Long‐Evans rats fed a 72 hour HFD. Body composition and qPCR was measured for hepatic lipogenic and inflammatory genes. Both genders fed HFD equally increased caloric consumption compared to low fat (LF) controls (p&lt;0.05). HFD‐fed males had an increase in adiposity in the visceral and subcutaneous mass compared to LF controls (48.40 g vs 68.46 g; 43.60 g vs 57.86 g; p&lt;0.05); however females were protected from such increases. Lipogenic and inflammatory gene expression was significantly downregulated after 72 hours with no gender difference observed. Females fed HFD had reduced inflammatory gene expression compared to LF‐fed females (p&lt;0.05). HFD‐fed females also had reduced total XBP1 expression compared to both male groups (p&lt;0.05). These results indicate that both genders respond appropriately to nutrient excess. Malfunctions in hepatic lipogenesis observed during the development of obesity occur at longer exposures to HFDs. This research was supported in part by USDA ARS NC06871, UNCG Office of Research and Economic Development, Small Business Innovation Research Grants Program (USDA) and the Georgia Research Alliance Eminent Scholar endowment.

Geographic scope of proximity effects among small life sciences firms

A large number of studies have demonstrated that proximity effects from knowledge spillovers, network externalities and other forms of knowledge transfers among like firms are geographically bounded. However, only a few studies have measured the strength and geographic scope of such externalities and even fewer have done so for firms in very close proximity. In this study, we examine the size and geographic scope of proximity effects among all life science firms that have received Small Business Innovation Research (SBIR) grants in the US over a 23-year period while controlling for relevant regional and firm characteristics. From our empirical analysis, we conclude that proximity effects among nearby small life science firms are strong within one-tenth of a mile distance and are exhausted within a radius of 1.5 miles. By examining the location of all firms in the sample, we offer possible explanations for the narrow geographic scope of the measured proximity effects. We also explain the significance of such findings for academic research that seeks to understand the nature of spatial externalities and for public policy.