An economics perspective of patenting behavior in small entrepreneurial firms

This dissertation explores the use of patents as an Intellectual Property Protection Mechanism (IPPM) among small entrepreneurial firms both from a theoretical and an empirical perspective. I borrow from the patenting and firm signaling literature to frame my theoretical models and to ask empirical questions with an eye on broadening the scope of the existing literature. I start with a review of the patenting literature which motivated the need to document cross-country differences in patent laws. Theoretically, I model the use of patents among small firms as a signal of technological ability. I propose two patent signaling games where in both, a higher and a lower ability firm try to use the number of patents that they hold to signal their ability. However, in one model, patents are productive and generate higher profits whereas in the other they are not (in appendix B, I develop an augmented signaling model where start-ups are given the choice to either accept or decline an offer). Conditions for the existence of both pooling and separating equilibria are identified. In the pooling equilibria, types cannot be distinguished making patents an ambiguous signal. However, in the separating equilibria, patents are informative. Empirically, I first study relevant covariates that are associated with the use of patents as an IPPM among small firms using a probit model. Next, I make causal inferences about the theoretical models using a two-stage least squares estimator, a control function approach and a “full switching regression approach” to account for heterogenous treatment effects. I use Lewbel’s method of generated instruments combined with other external instruments as a robustness check. The results show that R&D intensity, firm size, market structure, the sector in which the firm operates, human capital and demographic characteristics of founders, firm location (in some instances) are all relevant covariates that are associated with the use of patents as an IPPM among small entrepreneurial firms. The empirical analyses also provided evidence in support of the model in which patents are a signal that do not impact a firm’s productivity measured as sales growth. The data used in the empirical sections come from the Advancing Knowledge-Intensive Innovation for Growth and Social Well-being in Europe (AEGIS) dataset which relate to small entrepreneurial firms in 10 European-Union countries

Characterization of a new pathway that activates lumisterol <i>in vivo</i> to biologically active hydroxylumisterols

Abstract Using LC/qTOF-MS we detected lumisterol, 20-hydroxylumisterol, 22-hydroxylumisterol, 24-hydroxylumisterol, 20,22-dihydroxylumisterol, pregnalumisterol, 17-hydroxypregnalumisterol and 17,20-dihydroxypregnalumisterol in human serum and epidermis, and the porcine adrenal gland. The hydroxylumisterols inhibited proliferation of human skin cells in a cell type-dependent fashion with predominant effects on epidermal keratinocytes. They also inhibited melanoma proliferation in both monolayer and soft agar. 20-Hydroxylumisterol stimulated the expression of several genes, including those associated with keratinocyte differentiation and antioxidative responses, while inhibiting the expression of others including RORA and RORC. Molecular modeling and studies on VDRE-transcriptional activity excludes action through the genomic site of the VDR. However, their favorable interactions with the A-pocket in conjunction with VDR translocation studies suggest they may act on this non-genomic VDR site. Inhibition of RORα and RORγ transactivation activities in a Tet-on CHO cell reporter system, RORα co-activator assays and inhibition of (RORE)-LUC reporter activity in skin cells, in conjunction with molecular modeling, identified RORα and RORγ as excellent receptor candidates for the hydroxylumisterols. Thus, we have discovered a new biologically relevant, lumisterogenic pathway, the metabolites of which display biological activity. This opens a new area of endocrine research on the effects of the hydroxylumisterols on different pathways in different cells and the mechanisms involved

Contribution of Matrix Metalloproteinase-9 to Cerebral Edema and Functional Outcome following Experimental Subarachnoid Hemorrhage

Background: Cerebral edema is an important risk factor for death and poor outcome following subarachnoid hemorrhage (SAH). However, underlying mechanisms are still poorly understood. Matrix metalloproteinase (MMP)-9 is held responsible for the degradation of microvascular basal lamina proteins leading to blood-brain barrier dysfunction and, thus, formation of vasogenic cerebral edema. The current study was conducted to clarify the role of MMP-9 for the development of cerebral edema and for functional outcome after SAH. Methods: SAH was induced in FVB/N wild-type (WT) or MMP-9 knockout (MMP-9(-/-)) mice by endovascular puncture. Intracranial pressure (ICP), regional cerebral blood flow (rCBF), and mean arterial blood pressure (MABP) were continuously monitored up to 30 min after SAH. Mortality was quantified for 7 days after SAH. In an additional series neurological function and body weight were assessed for 3 days after SAH. Subsequently, ICP and brain water content were quantified. Results: Acute ICP, rCBF, and MABP did not differ between WT and MMP-9(-/-) mice, while 7 days' mortality was lower in MMP-9(-/-) mice (p = 0.03; 20 vs. 60%). MMP-9(-/-) mice also exhibited better neurological recovery, less brain edema formation, and lower chronic ICP. Conclusions: The results of the current study suggest that MMP-9 contributes to the development of early brain damage after SAH by promoting cerebral edema formation. Hence, MMP-9 may represent a novel molecular target for the treatment of SAH. Copyright (C) 2011 S. Karger AG, Base

The role of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma among endemic population: a meta-analysis of the phase iii randomized trials

<p>Abstract</p> <p>Background</p> <p>The main objective of this meta-analysis was to determine the clinical benefit of concurrent chemoradiotherapy (CCRT) compared with radiation alone (RT) in the treatment of nasopharyngeal carcinoma (NPC) patients in endemic geographic areas.</p> <p>Methods</p> <p>Using a prospective meta-analysis protocol, two independent investigators reviewed the publications and extracted the data. Published randomized controlled trials (RCTs) in which patients with NPC in endemic areas were randomly assigned to receive CCRT or RT alone were included.</p> <p>Results</p> <p>Seven trials (totally 1608 patients) were eligible. Risk ratios (RRs) of 0.63 (95% CI, 0.50 to 0.80), 0.76 (95% CI, 0.61 to 0.93) and 0.74 (95% CI, 0.62 to 0.89) were observed for 2, 3 and 5 years OS respectively in favor of the CCRT group. The RRs were larger than that detected in the previously reported meta-analyses (including both endemic and non-endemic), indicating that the relative benefit of survival was smaller than what considered before.</p> <p>Conclusions</p> <p>This is the first meta-analysis of CCRT vs. RT alone in NPC treatment which included studies only done in endemic area. The results confirmed that CCRT was more beneficial compared with RT alone. However, the relative benefit of CCRT in endemic population might be less than that from previous meta-analyses.</p

Prevalence of systemic inflammatory response syndrome (SIRS) in hospitalized children: a point prevalence study

<p>Abstract</p> <p>Background</p> <p>In accordance with the 1st International pediatric sepsis consensus conference, where sepsis was defined as SIRS associated with suspected or proven infection, we have identified the need to assess the prevalence of SIRS and sepsis in children with abnormal temperatures hospitalized in The Children's Clinical University Hospital in Latvia.</p> <p>Methods</p> <p>A descriptive prospective point prevalence study (using two time periods, each 24 h, randomly chosen) was conducted on all children (n = 943) treated in the hospital. All children with abnormal temperatures – fever or hypothermia (n = 92) – were included in the study. Questionnaires evaluating age-specific SIRS criteria were completed. The prevalence of SIRS was detected with 95% CI.</p> <p>Results</p> <p>Out of a total of 943 patients treated in the hospital, 10% (n = 92) had abnormal temperatures. In all these cases the abnormal temperature was a fever; hypothermia was not established in any patient. Of the children with fever, 72% (n = 66) had SIRS. Of the SIRS patients, 8% (n = 5) developed sepsis, 5% (n = 3) severe sepsis and 2% (n = 1) septic shock. Seventy-six percent (n = 50) of the SIRS patients had fever in combination with respiratory rate >2 SD above normal for age; 50% (n = 33) had fever with abnormal leukocyte count; 15% (n = 10) had fever with tachycardia >2 SD above normal for age. Most of the SIRS patients (39%, n = 25) were aged 2–5 years. Twenty-one percent (n = 14) of the children with SIRS and 50% (n = 2) of those with severe sepsis and septic shock had an underlying disease. In no case was SIRS and sepsis recognized by doctors and the diagnoses were not recorded on the patients' cards.</p> <p>Conclusion</p> <p>Our results would indicate a high risk for sepsis development in children with SIRS. Early SIRS diagnosis and awareness of risk of developing sepsis could change the medical approach to the patient in everyday clinical practice, eventually leading to early, goal-directed therapy for sepsis.</p

Shifting suitability for malaria vectors across Africa with warming climates

<p>Abstract</p> <p>Background</p> <p>Climates are changing rapidly, producing warm climate conditions globally not previously observed in modern history. Malaria is of great concern as a cause of human mortality and morbidity, particularly across Africa, thanks in large part to the presence there of a particularly competent suite of mosquito vector species.</p> <p>Methods</p> <p>I derive spatially explicit estimates of human populations living in regions newly suitable climatically for populations of two key <it>Anopheles gambiae </it>vector complex species in Africa over the coming 50 years, based on ecological niche model projections over two global climate models, two scenarios of climate change, and detailed spatial summaries of human population distributions.</p> <p>Results</p> <p>For both species, under all scenarios, given the changing spatial distribution of appropriate conditions and the current population distribution, the models predict a reduction of 11.3–30.2% in the percentage of the overall population living in areas climatically suitable for these vector species in coming decades, but reductions and increases are focused in different regions: malaria vector suitability is likely to decrease in West Africa, but increase in eastern and southern Africa.</p> <p>Conclusion</p> <p>Climate change effects on African malaria vectors shift their distributional potential from west to east and south, which has implications for overall numbers of people exposed to these vector species. Although the total is reduced, malaria is likely to pose novel public health problems in areas where it has not previously been common.</p

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes