Miracle-dz/UniFAR-FTUs huggingface dataset:
The Emergence of Regional Cultures and Practices: A Comparative Study of Canadian Software Entrepreneurship

Despite the ‘cultural turn’ in economic geography, the discipline has yet to conclusively describe the processes through which culture influences actors’ daily economic and social practices. Without a better understanding of the role of culture, it is difficult to explain the emergence and influence of the heterogeneous landscapes of regional business culture we readily observe. This problem is particularly acute in the study of entrepreneurial environments, where regional culture is theorized to play an important role in the local entrepreneurship process. This dissertation proposes an alternative approach to culture which draws on the work of Pierre Bourdieu to reveal the underlying social processes connecting culture with entrepreneurial action. Through qualitative case studies of software entrepreneurs in three Canadian cities — KitchenerWaterloo, Ontario; Ottawa, Ontario and Calgary, Alberta — this dissertation examines the emergence and evolution of regional cultures and how they have helped to create distinct contexts which encourage unique forms of entrepreneurial practices, outlooks and strategies. This new perspective allows for a more detailed and dynamic analysis of regional cultures and provides new tools for researchers and policy makers to understand the role of cultures within regional economic development.
Relaxin increases sympathetic nerve activity and activates spinally-projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

Pregnancy is characterized by increased blood volume and baseline sympathetic nerve activity (SNA), vasodilation, and tachycardia. Relaxin (RLX), an ovarian hormone elevated in pregnancy, activates forebrain sites involved in control of blood volume and SNA through ANG II-dependent mechanisms and contributes to adaptations during pregnancy. In anesthetized, arterial baroreceptor-denervated nonpregnant (NP) rats, RLX microinjected into the subfornical organ (SFO; 0.77 pmol in 50 nl) produced sustained increases in lumbar SNA (8 ± 3%) and mean arterial pressure (MAP; 26 ± 4 mmHg). Low-dose intracarotid artery infusion of RLX (155 pmol·ml(-1)·h(-1); 1.5 h) had minor transient effects on AP and activated neurons [increased Fos-immunoreactivity (IR)] in the SFO and in spinally projecting (19 ± 2%) and arginine-vasopressin (AVP)-IR (21 ± 5%) cells in the paraventricular nucleus of the hypothalamus of NP, but not pregnant (P), rats. However, mRNA for RLX and ANG II type 1a receptors in the SFO was preserved in pregnancy. RLX receptor-IR is present in the region of the SFO in NP and P rats and is localized in astrocytes, the major source of angiotensinogen in the SFO. These data provide an anatomical substrate for a role of RLX in the resetting of AVP secretion and increased baseline SNA in pregnancy. Since RLX and ANG II receptor expression was preserved in the SFO of P rats, we speculate that the lack of response to exogenous RLX may be due to maximal activation by elevated endogenous levels of RLX in near-term pregnancy.
Structure-Based Mutational Analysis of Several Sites in the E Protein: Implications for Understanding the Entry Mechanism of Japanese Encephalitis Virus

ABSTRACT Japanese encephalitis virus (JEV), which causes viral encephalitis in humans, is a serious risk to global public health. The JEV envelope protein mediates the viral entry pathway, including receptor-binding and low-pH-triggered membrane fusion. Utilizing mutagenesis of a JEV infectious cDNA clone, mutations were introduced into the potential receptor-binding motif or into residues critical for membrane fusion in the envelope protein to systematically investigate the JEV entry mechanism. We conducted experiments evaluating infectious particle, recombinant viral particle, and virus-like particle production and found that most mutations impaired virus production. Subcellular fractionation confirmed that five mutations—in I0, ij, BC, and FG and the R9A substitution—impaired virus assembly, and the assembled virus particles of another five mutations—in kl and the E373A, F407A, L221S, and W217A substitutions—were not released into the secretory pathway. Next, we examined the entry activity of six mutations yielding infectious virus. The results showed N154 and the DE loop are not the only or major receptor-binding motifs for JEV entry into BHK-21 cells; four residues, H144, H319, T410, and Q258, participating in the domain I (DI)-DIII interaction or zippering reaction are important to maintain the efficiency of viral membrane fusion. By continuous passaging of mutants, adaptive mutations from negatively charged amino acids to positively charged or neutral amino acids, such as E138K and D389G, were selected and could restore the viral entry activity. IMPORTANCE Recently, there has been much interest in the entry mechanism of flaviviruses into host cells, including the viral entry pathway and membrane fusion mechanism. Our study provides strong evidence for the critical role of several residues in the envelope protein in the assembly, release, and entry of JEV, which also contributes to our understanding of the flaviviral entry mechanism. Furthermore, we demonstrate that the H144A, H319A, T410A, and Q258A mutants exhibit attenuated fusion competence, which may be used to develop novel vaccine candidates for flaviviruses.
Porcine endothelium supports transendothelial migration of human leukocyte subpopulations: anti-porcine vascular cell adhesion molecule antibodies as species-specific blockers of transendothelial monocyte and natural killer cell migration.

BACKGROUND In cases where hyperacute rejection has been prevented, pig to primate organ transplantation results in a delayed rejection mediated by graft-infiltrating leukocytes. The migration of human leukocytes across porcine endothelium is poorly characterized, but may offer targets for species-specific antirejection therapy. METHODS Transwell tissue culture inserts with endothelial cells growing on polycarbonate filters were used to characterize the migration of peripheral blood monocuclear cells and purified leukocyte subpopulations across pig and human endothelial cells and cell lines. Endothelial cell morphology was evaluated by scanning and transmission electron microscopy, and the contribution of different adhesion receptor pairs to transendothelial migration was evaluated by antibody blocking experiments. RESULTS There were no evident quantitative or qualitative differences in the capacity of human and porcine endothelium to support transendothelial migration of human leukocytes [T, B, and natural killer (NK) cells, monocytes, and neutrophils]. Monocytes and large granular CD3+ lymphocytes migrated most efficiently across the endothelium. Antiporcine vascular cell adhesion molecule-1 antibodies blocked transendothelial migration of human monocytes and NK cells across tumor necrosis factor-alpha stimulated pig endothelium by at least 60%. Anti-CD18 antibodies had no effect on the migration of human NK cells across pig endothelium, whereas they partly blocked migration of NK cells across human endothelium and migration of monocytes across porcine endothelium. Interleukin-2 stimulated, but not unstimulated, T and NK cells were cytotoxic to porcine endothelium. CONCLUSIONS Porcine endothelium supports transendothelial migration of human leukocyte subpopulations as efficiently as human endothelium. Incompatibilities in some adhesion receptor pairs may be compensated for by other adhesion receptor pairs, as exemplified by human NK cells whose migration across human, but not pig, endothelium was blocked by anti-CD18 antibodies. Antiporcine vascular cell adhesion molecule-1 antibodies may be used as species-specific blockers of transendothelial NK cell and monocyte migration, and as such may prove to be useful inhibitors of cellular organ xenograft rejection.
Water and tissue equivalence of a new PRESAGE(®) formulation for 3D proton beam dosimetry: a Monte Carlo study.

PURPOSE To evaluate the water and tissue equivalence of a new PRESAGE(®) 3D dosimeter for proton therapy. METHODS The GEANT4 software toolkit was used to calculate and compare total dose delivered by a proton beam with mean energy 62 MeV in a PRESAGE(®) dosimeter, water, and soft tissue. The dose delivered by primary protons and secondary particles was calculated. Depth-dose profiles and isodose contours of deposited energy were compared for the materials of interest. RESULTS The proton beam range was found to be ≈27 mm for PRESAGE(®), 29.9 mm for soft tissue, and 30.5 mm for water. This can be attributed to the lower collisional stopping power of water compared to soft tissue and PRESAGE(®). The difference between total dose delivered in PRESAGE(®) and total dose delivered in water or tissue is less than 2% across the entire water∕tissue equivalent range of the proton beam. The largest difference between total dose in PRESAGE(®) and total dose in water is 1.4%, while for soft tissue it is 1.8%. In both cases, this occurs at the distal end of the beam. Nevertheless, the authors find that PRESAGE(®) dosimeter is overall more tissue-equivalent than water-equivalent before the Bragg peak. After the Bragg peak, the differences in the depth doses are found to be due to differences in primary proton energy deposition; PRESAGE(®) and soft tissue stop protons more rapidly than water. The dose delivered by secondary electrons in the PRESAGE(®) differs by less than 1% from that in soft tissue and water. The contribution of secondary particles to the total dose is less than 4% for electrons and ≈1% for protons in all the materials of interest. CONCLUSIONS These results demonstrate that the new PRESAGE(®) formula may be considered both a tissue- and water-equivalent 3D dosimeter for a 62 MeV proton beam. The results further suggest that tissue-equivalent thickness may provide better dosimetric and geometric accuracy than water-equivalent thickness for 3D dosimetry of this proton beam.
Yeast glycolytic mRNAs are differentially regulated

The regulation of glycolytic genes in response to carbon source in the yeast Saccharomyces cerevisiae has been studied. When the relative levels of each glycolytic mRNA were compared during exponential growth on glucose or lactate, the various glycolytic mRNAs were found to be induced to differing extents by glucose. No significant differences in the stabilities of the PFK2, PGK1, PYK1, or PDC1 mRNAs during growth on glucose or lactate were observed. PYK::lacZ and PGK::lacZ fusions were integrated independently into the yeast genome at the ura3 locus. The manner in which these fusions were differentially regulated in response to carbon source was similar to that of their respective wild-type loci. Therefore, the regulation of glycolytic mRNA levels is mediated at the transcriptional level. When the mRNAs are ordered with respect to the glycolytic pathway, two peaks of maximal induction are observed at phosphofructokinase and pyruvate kinase. These enzymes (i) catalyze the two essentially irreversible steps on the pathway, (ii) are the two glycolytic enzymes that are circumvented during gluconeogenesis and hence are specific to glycolysis, and (iii) are encoded by mRNAs that we have shown previously to be coregulated at the translational level in S. cerevisiae (P. A. Moore, A. J. Bettany, and A. J. P. Brown, NATO ASI Ser. Ser. H Cell Biol. 49:421-432, 1990). This differential regulation of glycolytic mRNA levels might therefore have a significant influence upon glycolytic flux in S. cerevisiae.
Perceived Effort Step-up Procedure for Self-Regulating Stationary Cycle Exercise Intensity by Patients with Cardiovascular Disease

This study examined the strategy utilized by patients with cardiovascular disease to regulate exercise intensity using the Rating of Perceived Exertion (RPE) and tested if a step-up procedure would reduce overshoot of target heart rate (HR). Also the study investigated if Prescription Congruence and Intensity Discrimination, components of the Intensity Self-regulation Model, could be validated for these patients. An estimation and production paradigm was used. HR was measured at 2-min. intervals during 6-min. stationary cycle ergometer exercise trials. Data for four experimental trials were compared: (1) a work intensity set by experimenter to achieve a target RPE of 11 (Estimation 11), (2) an intensity set by experimenter to achieve a target RPE of 13 (Estimation 13), (3) an intensity varied by participant every 2 min. to produce a target RPE of 13 (Production 13), and (4) a Step-up Procedure with the intensity varied by participant, first producing a target RPE of 11 during the first 2 min., followed by producing a target RPE of 13 from min. 2 to 6 of exercise (Production 11 + 13). A very small effect size was found for HR between Production 13 and Estimation 13, and a moderate effect size was noted for the increased HR when patients produced a target RPE of 13 as compared to 11. The participants could be divided into 2 groups: 10 patients comprised a Higher group whose HR at 2 min. during Production 13 was greater than HR at 2 min. during Estimation 13, and 6 patients in a Lower group with HR at 2 min. during Production 13 less than or equal to HR during Estimation 13. A large effect size was found at 6 min. for the reductions of the Higher group's HR overshoot and for the Lower group's HR undershoot during Production 13. All participants in the Higher group (n = 10) had a clinically significant 1ER overshoot of 5 beats · min.−1 at 2 min. during Production 13. Using a Step-up Procedure (Production 11 + 13), a large effect size was found for the reduced number of patients (n = 3) with an overshoot of 5 beats · min.−1 at 2 min. This supports the ability of participants in cardiac rehabilitation programs to meet the Prescription Congruence and Intensity Discrimination components of the Intensity Self-regulation Model in the RPE 11–13 zone. Evidence was found for overshoot/undershoot of target HR at 2 min., supporting a proposed third component, Production Strategy, of the Intensity Self-regulation Model. The 2-min. Step-up Procedure reduced some patients' tendency to “overshoot” target intensity.
Statin therapy in Alzheimer's disease

Previous studies have suggested that statin therapy may be of benefit in treating Alzheimer's disease (AD). We initiated a double‐blind, placebo‐controlled, randomized (1:1) trial with a 1‐year exposure to once‐daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo among individuals with mild‐to‐moderate AD [Mini‐Mental State Examination (MMSE) score of 12–28]. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of most other medications in the treatment of co‐morbidities. We demonstrated that atorvastatin treatment produced significantly (P = 0.003) improved performance on cognition and memory after 6 months of treatment (ADAS‐cog) among patients with mild‐to‐moderate AD. This superior effect persisted at 1 year (P = 0.055). This positive effect on the ADAS‐cog performance after 6 months of treatment was more prominent among individuals entering the trial with higher MMSE scores (P = 0.054). Benefit on other clinical measures was identified in the atorvastatin‐treated population compared with placebo. Accordingly, atorvastatin therapy may be of benefit in the treatment of mild‐to‐moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment. Evidence also suggests that atorvastatin may slow the progression of mild‐to‐moderate AD, thereby prolonging the quality of an afflicted individual's life.
Smackdown: Adventures in simulation standards and interoperability

The paucity of existing employer-driven simulation education and the need for workers broadly trained in Modeling & Simulation (M&S) poses a critical need that the simulation community as a whole must address. This paper will describe how this need became an impetus for a new inter-university activity that allows students to learn about simulation by doing it. The event, called Smackdown, was demonstrated for the first time in April at the Spring Simulation Multi-conference. Smackdown is an adventure in international cooperation. Students and faculty took part from the US and Europe supported by IEEE/SISO standards, industry software and National Aeronautics and Space Administration (NASA) content of a re-supply mission to the Moon. The developers see Smackdown providing all participants with a memorable, interactive, problem-solving experience, which can contribute, importantly to the workforce of the future. This is part of the larger need to increase undergraduate education in simulation and could be a prime candidate for senior design projects.
CYP 3 A 4 IS MAINLY RESPONSIBILE FOR THE METABOLISM OF A NEW VINCA ALKALOID , VINORELBINE , IN HUMAN LIVER MICROSOMES

The metabolism of vinorelbine, a new anticancer agent belonging to the vinca alkaloid family, was investigated in human liver microsomes. Vinorelbine biotransformation consisted of one saturable and one nonsaturable process, and the Km and Vmax values for the saturable process were 1.90 mM and 25.3 pmol/min/mg of protein, respectively. Several studies, including metabolism by cytochrome P450 (CYP) enzymes in a cDNA expression system and inhibition by specific antibodies and chemical inhibitors, showed that the main CYP enzyme involved in vinorelbine metabolism was CYP3A4. Also, the effects of vinorelbine on each of the CYP activities in human liver microsomes were investigated. High concentrations (100 mM) of vinorelbine inhibited CYP3A4 activity (testosterone 6b-hydroxylation activity) by 45.2%. However, the inhibitory effects of vinorelbine on the other CYP activities were minimal. The 50% inhibitory concentration (IC50) of vinorelbine for testosterone 6b-hydroxylase was estimated to be 155 mM. The plasma concentration in patients is expected to be much lower than this value. These results indicate that vinorelbine metabolism is expected to be modulated by the drugs that are able to inhibit or induce CYP3A
Intravertebral clefts opacified during vertebroplasty: pathogenesis, technical implications, and prognostic significance.

BACKGROUND AND PURPOSE Intravertebral clefts have long been considered as pathognomonic for avascular necrosis and as a rare cause of compression fracture. We have observed unsuspected clefts opacifying frequently during vertebroplasty. Our purpose in this study was to determine the incidence of these clefts in symptomatic osteoporotic compression fractures, assess the sensitivity of MR imaging and conventional radiography in the detection of these clefts, and determine whether there is any prognostic significance of these clefts in patients treated with vertebroplasty. METHODS Retrospective chart reviews were conducted of 135 vertebroplasty procedures performed during a 2-year period. MR images and conventional radiographs were reviewed for the presence of clefts defined as fluid-filled cavities on MR images or gas-filled cavities on conventional radiographs. Digital radiographs obtained at the time of the procedure were inspected for the presence of opacified clefts. Imaging findings were correlated with subjective pain scores documented before the procedure and at 1 week, 1 month, 6 months, and 12 months after vertebroplasty. RESULTS Two hundred thirty-six osteoporotic compression fractures were treated with polymethylmethacrylate in 125 patients. Thirty-one and eight-tenths percent of the fractures were noted to contain clefts at the time of vertebroplasty. Fluid-filled clefts were detected on preoperative MR images in only 52.8% of the fractures with opacified clefts at vertebroplasty. Gas-filled clefts were evident on preoperative conventional radiographs in only 11.4% of the fractures with opacified clefts at vertebroplasty. No significant difference was noted in numerical pain scores between the two populations at baseline or 1 week or 1 month after the procedure. Pain scores at 6 and 12 months after vertebroplasty showed a trend toward greater pain relief in patients with clefts, although the difference was not statistically significant. A sustained, statistically significant decrease in pain scores after treatment (P <.01) was noted in both groups. CONCLUSION Intravertebral clefts are much more common than previously described and probably represent fracture nonunions. Imaging is not sensitive in detecting these clefts before vertebroplasty. We advocate complete filling of the cleft with cement during vertebroplasty to maximize stabilization of the fracture fragments. There is a trend toward greater pain relief being achieved 6 and 12 months after the procedure in patients with clefts that are opacified at the time of vertebroplasty.
Antioxidant function of a novel selenoprotein in Drosophila melanogaster

Background: Insects appear to have diverged from both higher and lower organisms in their defense mechanisms against oxidative damage. They do not encode glutathione peroxidases or glutathione reductases, and their thioredoxin reductases exhibit distinct properties from those of higher and lower species. Nonetheless, appropriate balance of anti‐oxidants and pro‐oxidants, and protection from damaging reactive oxygen species are clearly crucial in insects for viability, normal functioning of signalling pathways and morphogenesis, and have been implicated in studies on longevity in flies and other organisms.
Post‐tetanic potentiation in the rat calyx of Held synapse

We studied synaptic plasticity in the calyx of Held synapse, an axosomatic synapse in the auditory brainstem, by making whole‐cell patch clamp recordings of the principal cells innervated by the calyces in a slice preparation of 7‐ to 10‐day‐old rats. A 5 min 20 Hz stimulus train increased the amplitude of excitatory postsynaptic currents (EPSCs) on average more than twofold. The amplitude of the synaptic currents took several minutes to return to control values. The post‐tetanic potentiation (PTP) was accompanied by a clear increase in the frequency, but not the amplitude, of spontaneous EPSCs, which returned to baseline more rapidly than the potentiation of evoked release. The size of the readily releasable pool of vesicles was increased by about 30%. In experiments in which presynaptic measurements of the intracellular calcium concentration were combined with postsynaptic voltage clamp recordings, PTP was accompanied by an increase in the presynaptic calcium concentration to about 210 nm. The decay of the PTP matched the decay of this increase. When the decay of the calcium transient was shortened by dialysing the terminal with EGTA, the PTP decay sped up in parallel. Our experiments suggest that PTP at the calyx of Held synapse is due to a long‐lasting increase in the presynaptic calcium concentration following a tetanus, which results in an increase in the release probability of the vesicles of the readily releasable pool. Although part of the PTP can be explained by a direct activation of the calcium sensor for phasic release, other mechanisms are likely to contribute as well.
The fate of macroaggregated albumin used in lung scanning.

Macroaggregated albumin labeled with radioactive tracers was selected for diagnostic purposes because of the rapid metabolism of the material once it had been introduced into the vascular system. A number of reports are now available which evaluate the clinical usefulness of this procedure [1-9]. Several investiga tions of the toxicity, distribution, physiological response and metabolism of the aggregated albumin have been published [1-3, 5-8, 10]. Further studies of the fate of the injected particle are reported in this paper.