cssi/SciSciGPT-SciSciNet huggingface dataset:
809. Suppression of Human Pancreatic Cancer Growth by Lentiviral Vector-Mediated Gene Transfer of Pigment Epithelium Derived Factor (PEDF)

Top of pageAbstract Pancreatic cancer is the fourth leading cause of cancer death. Most patients are diagnosed after metastasis to adjacent organs and blood vessels. Angiogenesis, which is required to for solid tumor growth beyond 1-2 mm3, plays a critical role in pancreatic cancer. Pigment epithelium-derived factor (PEDF) has been identified as the main inhibitor of retinal angiogenesis. Subsequently, PEDF has been shown to critically regulate the vasculature and mass of the pancreas. Here we examined the feasibility of using lentiviral vector-expressed human PEDF gene to treat human pancreatic tumor cell line-derived tumors in a murine model. Mono-cistronic FIV vectors encoding human PEDF or a control protein (eGFP) with each gene linked to neoR via an IRES, were used. PEDF protein produced from transduced cells and direct application of PEDF vector significantly reduced angiogenesis (63% inhibition compared to control) in a capillary formation assay using human umbilical vascular endothelial cells (HUVECs) and in a chick chorioallantoic membrane assay (14% angiogenesis index compared to control index of 64%). Enhanced HUVEC apoptosis was also observed. We examined the therapeutic efficacy of injected PEDF and control vectors on established human pancreatic tumor xenografts in nude mice. Significant anti-tumor effects and prolonged overall survival benefit was observed in PEDF vector-treated mice (> 80% tumor reduction after 1- 2 x 10^7 TU at day 30 post injection). PEDF vector-treated animals survived 52|[plusmn]|2 days compared to 30|[plusmn]|3 days with control vector, n = 16 in each group. Tumors treated with PEDF vector had enhanced apoptosis and vascular endothelial growth factor receptor-1 expression. We also studied tumor formation by stable pancreatic cell lines derived by transduction with PEDF and control vectors and G418 selection. PEDF secreted from these stable tumor cell lines was shown to be biologically active in the in vitro assays and a significant antitumor effect and prolonged overall survival benefit was seen. However, injection of vectors into established tumors had a better therapeutic effect than pre-transducing and selecting cells prior to establishing tumors, and this correlated with up-regulation of VEGFR-1 in the stable tumor cell lines. PEDF is a promising transgene for pancreatic cancer gene therapy.
Hypothalamic and pituitary leukemia inhibitory factor gene expression in vivo: a novel endotoxin-inducible neuro-endocrine interface.

We have recently shown expression of leukemia inhibitory factor (LIF) in human fetal pituitary tissue and its in vitro induction of POMC transcription. We now use qualitative and semiquantitative RT-PCR to demonstrate that LIF and LIF-receptor (LIF-R) are constitutively expressed in the normal mouse hypothalamus and pituitary. Hypothalamic and pituitary LIF and LIF-R are significantly induced (up to 6- and 4-fold, respectively) in vivo in response to lipopolysaccharide endotoxin (LPS) administered to B6D2F1 and C57BL/6 mice. In contrast to the nearly exclusive expression of matrix-associated LIF messenger RNA (mRNA) in control hypothalamus and pituitary, both diffusible and matrix-associated LIF mRNA alternate transcripts are induced by LPS. Furthermore, the time course of peripheral ACTH-response to LPS peaks at 60 min, whereas hypothalamic LIF mRNA increase occurs at 30 min and pituitary LIF induction occurs at 60 min. These results show that mLIF is a novel LPS-inducible proinflammatory neuroendocrine ...
Teaching assistant communication apprehension, willingness to communicate, and state communication anxiety in the classroom

This study investigated the nature of teaching assistant communication apprehension in the university classroom. Teaching assistants were given a survey assessing their general level of communication apprehension and their general willingness to communicate. Additionally, teaching assistant state anxiety specifically associated with teaching in the classroom was assessed. Analyses revealed significant negative correlations between teaching assistant communication apprehension and teaching experience, training in content, and training in teaching. Teaching assistant willingness to communicate was positively correlated with teaching experience and training in content. Teaching assistant state anxiety in the classroom was negatively correlated with training in content and training in teaching.
Behavioral Effects of Pulp Exposure in Mice Lacking Cannabinoid Receptor 2

Abstract Introduction Cannabinoid receptor 2 (CB2) is an intriguing target for the treatment of pain because of its ability to mediate analgesia without psychoactive effects, but little is known about the role of CB2 in pain of endodontic origin. The purpose of this study was to determine the behavioral effects of dental pulp exposure in wild-type (WT) mice and to explore the contribution of CB2 to these behaviors using CB2 knockout (CB2 KO) mice. Methods Pulp exposures were created unilaterally in the maxillary and mandibular first molars of female WT and CB2 KO mice. The open field test was used before pulp exposure or sham surgery, and postoperatively at 1 day, 1 week, 2 weeks, and 3 weeks. Mouse body weight and food consumption were recorded preoperatively and postoperatively at 1 day, 2 days, and 1 week. Results At baseline, CB2 KO mice weighed significantly more and had significantly greater food intake than WT mice. CB2 KO mice exhibited greater anxiety-like behavior in the baseline open field test, having significantly fewer center crossings and less distance traveled than WT mice. Pulp exposure had relatively little effect on the behavior of WT mice. CB2 KO mice with pulp exposures showed a decrease in food intake and body weight after surgery, and pulp exposure resulted in significantly fewer center crossings in the open field test in CB2 KO mice. Conclusions Pulp exposure in CB2 KO mice resulted in behaviors consistent with an increase in pain and/or anxiety.
Niche theory: New insights from an old paradigm

Abstract We apply a quantification of contemporary niche theory to several related topics of current interest: competition for alternative resources, the effect of consumers on those resources, and contemporary and evolutionary patterns at the community level attributable to the sequential colonization of resources and their consumers. Although the first topic is the traditional purview of niche theory, we believe that our model brings several issues into sharper focus than heretofore: The breadths of species' niches, overlap between them and the resulting interspecific effects all depend on the strategies by which competitors exploit heterogeneous environments. For our second application, we allow the alternative resources to be animate, and discover a positive relationship between predation and prey species diversity. Because we expect such a relationship for reasons that differ from those motivating the disturbance hypothesis, these ideas are easily distinguished. Finally, we consider the development of communities whose constituent populations behave according to the tenets of niche theory. Because successive trophic levels are colonized sequentially, patterns resulting from resource competition are replaced by those resulting from predation on consumers. For instance, consumer species-abundance distributions, which are uneven initially, become increasingly even during succession. Similar processes occur in evolutionary time, but the results have been reported as individual taxon cycles of invasion, accommodation and extinction or reinvasion. Niche theory suggests strategies and efficiencies of resource use that would facilitate invasion and prevent extinction. Though these last three are novel applications, the potential of this theory far exceeds them all. Moreover, the resulting insights augment the theory itself, increasing its general applicability. As a consequence of such feedback, niche theory may yet become a unifying concept in population biology.
Trend reversion in real output and unemployment

Abstract Quarterly data on aggregate real output and unemployment in the United States, Canada, United Kingdom, France, West Germany and Japan are decomposed into independent stationary and non-stationary components using the Kalman filter and maximum likelihood. In four of the six countries, a large, persistent stationary component is apparent, indicating a substantial amount of reversion to a smooth growth trend. In each case, this estimated stationary component is closely related to the estimated stationary component of the unemployment rate. For the United States, an expanded bivariate model indicates that independence of the two output components is a reasonable assumption.
Transcriptome analysis of human adipocytes implicates the NOD-like receptor pathway in obesity-induced adipose inflammation.

Adipose tissue inflammation increases with obesity, but adipocyte vs. immune cell contributions are unclear. In the present study, transcriptome analyses were performed on highly-purified subcutaneous adipocytes from lean and obese women, and differentially expressed genes/pathways were determined in both adipocyte and stromal vascular fraction (SVF) samples. Adipocyte but not SVF expression of NOD-like receptor pathway genes, including NLRP3 and PYCARD, which regulate caspase-1-mediated IL-1β secretion, correlated with adiposity phenotypes and adipocyte class II major histocompatibility complex (MHCII) gene expression, but only MHCII remained after adjusting for age and body mass index. IFNγ stimulated adipocyte MHCII, NLRP3 and caspase-1 expression, while adipocyte MHCII-mediated CD4+ T cell activation, an important factor in adipose inflammation, induced IFNγ-dependent adipocyte IL-1β secretion. These results uncover a dialogue regulated by interactions among T cell IFNγ and adipocyte MHCII and NLRP3 inflammasome activity that appears to initiate and escalate adipose tissue inflammation during obesity.
The viscosity of oxygen and of some of its mixtures with other gases

Abstract The paper reports new measurements of the viscosity of oxygen and air, and of the binary mixtures O2-Ar, O2-Kr and N2-O2, together with check values for the pure gases which appear in them. The measurements were performed in an oscillating-disk viscometer at atmospheric pressure and extrapolated to zero density. The nominal temperature range is 25–600°C, and the precision deteriorates from ±0.1% at 25°C to ±0.3% at 600°C. The experimental results are interpreted in terms of the Chapman-Enskog theory and the law of corresponding states due to Kestin, Ro and Wakeham. All tests show that the synthesis thus provided “predicts” the measured values with an uncertainty which does not exceed ±0.5% in most cases. The data yield new values of the binary diffusion coefficients of the mixtures, but do not permit us to calculate the thermal conductivity. Nevertheless, the analysis makes it plausible that Keyes's correlation for the thermal conductivity of oxygen might be acceptable.
Late quaternary alluvial stratigraphy of a low-order tributary in central Texas, USA and its response to climate and sediment supply

This paper presents the first comprehensive late Quaternary alluvial stratigraphic study of a low-order tributary in central Texas, using Cowhouse Creek as a case study. The late Pleistocene Jackson (JA) alluvium forms the elevated T2 terrace. The entrenched Holocene valley is filled with the buried Georgetown (GT) alluvium (approximately 11,000 to 8000 14C yr B.P.) and associated Royalty paleosol, and the surficially exposed Fort Hood (FH) alluvium (approximately 7000 to 5000 14C yr B.P.) and West Range (WR) alluvium (approximately 4200 to 600 14C yr B.P.) forming the broad T1 terrace. The Ford (FO) alluvium (<600 14C yr B.P.) forms the modern T0 floodplain entrenched into T1. Conditioned by cooler and wetter climates, Cowhouse Creek was characterized by relatively high base flow and low sediment supply during deposition of the JA and GT alluvium. Appreciable upland soil erosion ensued during the middle Holocene in response to warmer climate conditions, resulting in widespread valley filling by the FH alluvium. Deposition of the late Holocene WR and F0 alluvium was characterized by diminished sediment storage during relatively stable climate conditions. The temporal alluvial stratigraphic framework of the bedrock-confined Cowhouse Creek valley is out of phase with the alluvial sequence in the larger Brazos River valley.
Stray-light reduction in a WFOV star tracker lens

Lawrence Livermore National Laboratory (LLNL) has recently developed a wide-field-of- view (28 degree(s) X 44 degree(s)) camera for use as a star tracker navigational sensor. As for all sensors, stray light rejection performance is critical. Due to the baffle dimensions dictated by the large field angles, the 2-part sunshade/baffle configuration commonly seen on space- born telescopes is impractical. Meeting the required stray light rejection performance (of 10-7 Point Source Transmittance, (PST)) with a 1-part baffle required iterative APART modeling (APART is an industry standard stray light evaluation program), hardware testing, and mechanical design correction. This paper presents a chronology of lens and baffle improvements that resulted in the meeting of the stray light rejection goal outside the solar exclusion angle of the baffle stage. Comparisons with APART analyses are given, and future improvements in mechanical design are discussed. Stray light testing methods and associated experimental difficulties are presented.
Thermographic NDT Of Graphite Epoxy Filament-Wound Structures

A large graphite epoxy filament-wound tank was inspected by thermographic methods. Suspected areas of delamination were verified and mapped. The tank was then cut into pieces and the pieces were inspected ultrasonically; these results were compared to the results of the thermographic tests.
The immunohistochemical reactivity of a human monoclonal antibody with tissue sections of human mammary tumors

Human monoclonal antibodies have been generated following the fusion of human lymphocytes (obtained from axillary lymph nodes of mastectomy patients) with a murine nonimmunoglobulin secreting myeloma cell line. We report a detailed analysis of the reactivity of a human IgM monoclonal antibody secreted by one of these double cloned hybridoma cell lines. Tissue sections of both malignant and benign human mammary tumors, as well as apparently normal tissues, were tested using the immunoperoxidase technique and the human monoclonal antibody. Eighty-one per cent (54/67) of primary malignant mammary tumors, 100% (20/20) of metastatic breast lesions, and 14% (3/22) of benign breast lesions reacted positively with a moderate for strong intensity. The per cent of mammary carcinoma cells that stained and the pattern of staining varied among different tumor samples. While reactivity was observed with selected carcinomas of nonbreast origin, little or no reactivity was observed with apparently normal human tissues including normal mammary epithelium. The antibody reactivity observed was shown to be clearly distinct from those of both anti-T and anticarcinoembryonic antigen sera.
Planning and performance assessment of industrial trade shows: An exploratory study

Abstract Trade shows are an important element of the promotion mix for industrial products. However, the assessment of a firm's performance at a trade show has been a difficult problem because data on key variables is usually not available. In this paper, the authors propose lead generation efficiency as an important index of trade show performance and examine the impact of several show related variables on lead generation. The results from an empirical application conducted on a pilot scale using data from 27 shows suggest that the quality of a firm's booth personnel, the total expenditure on the show relative to attendance and the show's narrowness of focus are critical variables that affect lead efficiency. Based on their model the authors discuss implications for trade show selection and assessment of a firm's current spending policy.
Electric fields and plasma convection in the plasmasphere

A review is given of present theoretical and experimental information on quasistatic electric fields in and near the plasmasphere with the aim of discussing plasma flow within the plasmasphere, dynamo electric fields, and the penetration of electric fields of magnetospheric origin to low latitudes. Data are presented that suggest that the mean temporal variation of electric fields at all latitudes is diurnal, that dynamo electric fields are more important near L = 3 and are less important near and beyond L = 4 than are fields of magnetospheric origin, and that magnetospheric fields with periods that are a reasonable fraction of one day efficiently penetrate the plasmapause.
Time-ordered classification

SUMMARY Classification for the special situation where observations after a certain time no longer come from the initial population is considered. The discussion focuses on inference about that time, often called the change-point. Some useful approximations are derived for the distributions of change-point statistics, and large-sample results are established for nuisance-parameter situations.
Selection of therapeutic agents for intraocular proliferative disease 3. Effects of fluoropyrimidines on cell-mediated contraction of human fibroblasts.

We evaluated the efficacy of 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUR) as anticontractile agents in an in vitro model that measures the ability of human and rabbit fibroblasts to contract a collagen gel. Human fibroblasts were more contractile than rabbit fibroblasts, required higher concentrations of 5-FUR for inhibition of contraction, and were able to tolerate higher doses of the drug. 5-FU failed to inhibit contraction of human fibroblasts at concentrations up to 1·5 m m (200 μ g ml −1 ), but significantly inhibited rabbit fibroblast contraction, although to a lesser degree than 5-FUR under similar conditions. 5-Fluorouridine (100 μ m , 26 μ g ml −1 ) inhibited contraction of human fibroblasts by more than 80%, whereas only 10 μ m (2·6 μ g ml −1 ) 5-FUR was required for 90% inhibition of rabbit fibroblast contraction. 5-FUR was cytotoxic to rabbit fibroblasts at concentrations of 200 μ m (52 μ g ml −1 ) or greater, but 800 μ m was non-toxic to human fibroblasts after 96 hr exposure. At concentrations of 1·5 m m , 5-FU had no significant effects on the viability of either human or rabbit fibroblasts. These results suggest that 5-FUR may prove useful for the treatment of human ocular proliferative disorders in which contraction of fibrocellular elements is thought to play a part. They also suggest that fluoropyrimidine dosages found to be effective in a rabbit model of proliferative vitreoretinopathy may be less effective in humans and that 5-FUR levels shown to be toxic to rabbit-derived cells may be tolerated by humans cells.
Rating comic book violence: Contributions of gender and trait hostility

In this study the influence of gender and trait hostility on perceptions of extremely violent and mildly violent comic books was assessed. Participants rated comic books on a variety of factors, including levels of violence and humor. Gender, but not trait hostility, was significantly related to the comic book ratings. The methodological and psychological implications of these findings are discussed.
Polymerization of pyromellitic dianhydride with 3,3′-diaminobenzidine in aprotic solvents I. Reaction variables†

The solution polymerization of pyromellitic dianhydride with 3,3′-diaminobenzidine to form poly(amide acid amine) was investigated under a variety of reaction conditions. Polymer viscosity and gel formation were highly affected by changes in the order of monomer addition, the type of process (powder or solution), monomer concentration, monomer stoichiometry, and type of solvent. Minor effects were noted with changes in polymerization temperature and the presence of small amounts of water. A limiting intrinsic viscosity of 1.2–1.5 dl/g was observed, regardless of polymerization conditions. The polymerization had a strong tendency to gel at high concentrations and when monomer molar ratios approached 1:1. The conditions which retarded or promoted the formation of macrogel were well-defined, and macrogel but not microgel could be prevented. The polymerization was conducted successfully only in aprotic solvents. No imidazopyrrol-one units were detected in polymer made in polyphosphoric acid at elevated temperatures.
Effects of Progressive Intratracheal Administration of Perflubron During Conventional Gas Ventilation in Anesthetized Dogs with Oleic Acid Lung Injury

The respiratory distress syndrome of prematurity (RDS) is due to immaturity of alveolar type II cells which fail to produce adequate surfactant. The resultant increase in alveolar surface tension leads to both alveolar flooding and alveolar collapse, decreased compliance, and increased shunt with hypoxemia. Exogenous replacement of surfactant has reduced morbidity and mortality from RDS, though the most premature infants often fail to respond. Another possible therapy for RDS is liquid breathing (LB). Introduced by Kylstra et al. (1962), LB refers to a ventilatory mode in which the lungs are filled with a liquid perfluorocarbon (PFC) or hyperbarically oxygenated saline to functional residual capacity (FRC) followed by tidal ventilation with additional liquid. Using PFC’s with surface tensions of ≈ 15 dynes/cm, Shaffer et al. (1983a, 1983b) showed markedly improved arterial oxygenation during LB compared to gas ventilation in surfactant-deficient, very premature lambs. Interestingly, even after drainage of PFC from the lungs of these lambs, persistent improvements in FRC, compliance, and gas exchange were seen, suggesting that residual PFC coating the alveoli improved alveolar surface tension.
Mitochondrial dynamic abnormalities in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord. Currently, there is no cure or effective treatment for ALS and the cause of disease is unknown in the majority of ALS cases. Neuronal mitochondria dysfunction is one of the earliest features of ALS. Mitochondria are highly dynamic organelles that undergo continuous fission, fusion, trafficking and turnover, all of which contribute to the maintenance of mitochondrial function. Abnormal mitochondrial dynamics have been repeatedly reported in ALS and increasing evidence suggests altered mitochondrial dynamics as possible pathomechanisms underlying mitochondrial dysfunction in ALS. Here, we provide an overview of mitochondrial dysfunction and dynamic abnormalities observed in ALS, and discuss the possibility of targeting mitochondrial dynamics as a novel therapeutic approach for ALS.
Defining sustainability: a conceptual orientation

Despite the ubiquity of the concept of sustainability, defining the term and construing meaning for different contexts is difficult. This paper presents several archetypes of sustainability that are useful for classifying and understanding existing definitions. Definitions that emphasize one part or another of the core concept of sustainability will be necessary at varying scales and in different contexts. This paper presents a conceptual guide that contrasts a dominant paradigm of economic growth and development with ‘thick’ and ‘thin’ versions of sustainability. Definitions of sustainability are explored in terms of their orientation to the ontology of nature, substitutability of resources, economic growth, population growth, role of technology, and social equity. Copyright © 2007 Society of Chemical Industry
Property Taxation and the Demand for Homeownership

The purpose of this article is to analyze the impact of an increase in the effective Abstract rate of property taxation on the probability of homeownership by individuals at different income levels residing within central city and suburban housing markets. A theoretical model is provided that indicates that an increase in the tax rate produces two opposing effects on the demand for homeownership: (1) due to the property tax deduction, the price of ownership declines relative to renting, and (2) the overall price of housing rises relative to the cost of non housing goods. The strengths of these effects are investigated by conducting a logit analysis of the probability of homeownership with data from the Panel Study of Income Dynamics. Results show that a tax rate increase reduces the probability of homeownership, especially for middle-income households.
Combustion Model for Pyrophoric Metal Foils

A model for the combustion of pyrophoric metal foils has been developed. The diffusive mass transport, heat transport, and chemical reactions of porous iron foils have been described. The temperature and radiated energy of these materials has been predicted as a function of the physical characteristics of the material (porosity, pore size, specific surface area) for different atmospheric conditions (temperatures and oxygen concentrations varied with altitude and wind velocity).
When oral corticosteroids are essential for persistent severe asthma

When oral corticosteroids are indicated for patients with asthma, the response to treatment should be anticipated and weighed against potential risks or side effects. This discussion is focused on the immune effects of systemic corticosteroids. In some patients with persistent severe asthma, it might be impossible to achieve effective control of asthma without oral corticosteroids. As outpatients, patients can begin to respond within 1 to 2 hours of initiation of prednisone as part of an action plan, whereas other patients might require 6 to more than 48 hours or longer to begin to improve. The half-life of prednisone is between 1 and 3 hours, and anti-inflammatory effects from oral or intravenous corticosteroids occur promptly. CD4 T-lymphocyte and peripheral blood eosinophil numbers decrease in the first few hours. Peripheral blood eosinophil numbers can decrease from 10% on admission to less than 2% in 8 to 24 hours after oral or intravenous corticosteroids in patients admitted for acute severe asthma (status asthmaticus) who have not received oral corticosteroids as an outpatient. Sputum eosinophilia decreases substantially in the first 48 hours. It can be expected that patients have tissue eosinophilia without peripheral blood eosinophilia. There are many clinically useful and anti-inflammatory effects of corticosteroids in the treatment of asthma, examples of which are presented in Table I. Alternatively, when a patient with severe, corticosteroiddependent asthma is admitted for acute severe asthma despite receiving 40 to 60 mg of prednisone daily for 5 to 7 days as part of an action plan and peripheral blood eosinophils of 8% to 10% are recorded, the disappearance of eosinophils within 8 to 24 hours of receiving intravenous or supervised oral steroids suggests nonadherence with prednisone and not severe corticosteroid-dependent asthma.
Cytomegalovirus antiviral drug resistance: future prospects for prevention, detection and management

Human cytomegalovirus (CMV) is one of the most important viral pathogens affecting hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients, because infection is frequent and it exerts short- and long-term effects on host immunity. The direct effects of active CMV infection include fever, bone marrow suppression and invasive end organ disease. Indirectly, CMV increases risk for other infections and is associated with increased rejection, graft loss, mortality and transplant costs [1]. Given the impact of CMV on transplant outcomes, prevention of active infection and aggressive treatment of invasive disease are essential. Prevention strategies include universal antiviral prophylaxis or pre-emptive therapy that is based on sequential viral load monitoring in blood. Both approaches prevent CMV disease in at-risk patients, but they are limited by the toxicities of available anti-CMV drugs (i.e., cytopenias from valganiclovir, ganciclovir and cidofovir, and nephrotoxicity from foscarnet and cidofovir) and the potential for the virus to develop antiviral drug resistance (AVR). Furthermore, optimal viral load thresholds for the initiation of pre-emptive therapy have not been defined and it is likely that these cut-offs will vary based on host factors as well as the quantitative PCR assay used for testing. Due to these complexities, an ideal preventative approach has yet to be identified. Only prophylaxis would be expected to prevent CMV indirect effects, but early treatment of viremia (i.e., pre-emptive therapy) may allow some reconstitution of protective immunity. Current approaches HSCT programs generally apply preemptive therapy to avoid the marrow suppressive effects of valganciclovir (VGCV) or ganciclovir (GCV). Some centers also utilize prophylaxis for unrelated, HLAmismatched or cord blood transplants. SOT programs also typically use prophylaxis for the highest risk patients (CMV seropositive donor [D+]/CMV seronegative recipient [R-]), and may consider pre-emptive approaches for moderate-risk R+ liver or kidney recipients. The routine use of prolonged CMV prophylaxis (i.e., ≥6 months of VGCV) has raised concern about AVR,
Effects of the anticonvulsant retigabine on cultured cortical neurons: Changes in electroresponsive properties and synaptic transmission

The whole-cell patch-clamp technique was used to examine the effects of retigabine, a novel anticonvulsant drug, on the electroresponsive properties of individual neurons as well as on neurotransmission between monosynaptically connected pairs of cultured mouse cortical neurons. Consistent with its known action on potassium channels, retigabine significantly hyperpolarized the resting membrane potentials of the neurons, decreased input resistance, and decreased the number of action potentials generated by direct current injection. In addition, retigabine potentiated inhibitory postsynaptic currents (IPSCs) mediated by activation of gamma-aminobutyric acid(A) (GABA(A)) receptors. IPSC peak amplitude, 90-to-10% decay time, weighted decay time constant, slow decay time constant, and, consequently, the total charge transfer were all significantly enhanced by retigabine in a dose-dependent manner. This effect was limited to IPSCs; retigabine had no significant effect on excitatory postsynaptic currents (EPSCs) mediated by activation of non-N-methyl-D-aspartate ionotropic glutamate receptors. A form of short-term presynaptic plasticity, paired-pulse depression, was not altered by retigabine, suggesting that its effect on IPSCs is primarily postsynaptic. Consistent with the hypothesis that retigabine increases inhibitory neurotransmission via a direct action on the GABA(A) receptor, the peak amplitudes, 90-to-10% decay times, and total charge transfer of spontaneous miniature IPSCs were also significantly increased. Therefore, retigabine potently reduces excitability in neural circuits via a synergistic combination of mechanisms.
Lung cancer and regular use of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs.

Purpose Lung cancer is the leading cause of cancer death in the US. There is evidence of a reduced risk of some cancer sites associated with use of aspirin (ASA) and nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs). Our objective was to examine the association of regular use of ASA and NANSAIDs with lung cancer. Methods A hospital-based case–control study of 1884 incident cases of lung cancer and 6251 controls with noncancer diagnoses. Use of ASA and NANSAIDs was considered ‘regular’ if it occurred on ≥4 days/week and lasted for ≥3 months. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals. Results The OR for regular use of ASA was 1.1 (0.9–1.4), and the corresponding estimate for regular NANSAID use was 1.0 (0.7–1.3). There was no evidence of decreased risk within strata of age, sex, years of education, or interview year. Examining the association within strata of duration of use, recency of use, cigarette smoking status, pack-years of cigarette smoking, or histologic type of cancer produced no ORs significantly different from 1.0. Conclusions The hypothesis that regular use of ASA or NANSAIDs reduces the risk of lung cancer is not supported by the present data. Copyright © 2007 John Wiley & Sons, Ltd.
The Hiddenness of God

Neither the existence of God nor the nature of God is apparent or obvious. If God exists, why is it not entirely clear to everyone that this is so? How can theists explain God's hiddenness, and how plausible are their explanations? God, if God exists, is an omnipotent, morally good, omnipresent being, than whom none greater can be conceived. Surely it is well within the abilities of God to let God's existence and nature be known to us. Why isn't the existence and nature of our Heavenly Father as apparent as, say, the existence of our various earthly fathers?
Radical Retropubic Prostatectomy and Blood Transfusion

Objective To determine whether there is a reduction in blood loss and blood transfusions associated with radical retropubic prostatectomy (RRP) by measuring the amount of blood loss and incidence of red blood cell (RBC) transfusions over time along with factors that may influence transfusions. Patients and Methods This is a retrospective study of patients who underwent RRP with and without the nerve-sparing dorsal venous complex (DVC) technique from 1985 to 1993 and in 1999. Transfusion rate, mean RBC loss, and preoperative and postoperative hemoglobin values were assessed. Univariate and multivariate regression analyses were performed. Results A total of 438 RRPs (276 DVC technique, 162 non-DVC technique) were reviewed and included in the study. The percentage of patients receiving allogeneic RBC transfusion decreased from 69% during 1985 to 1986 to 7.1% during 1999, and there was a decline in discharge hemoglobin values from 12.0 to 10.9 g/dL during this period. There was a significant reduction in mean hemoglobin concentration lost over time in the DVC technique group from 4.9 to 4.0 g/dL ( P =.04) during the 1985 to 1990 study period, which persisted in 1999. Conclusion Improvement in surgical technique and reduction in transfusion triggers resulted in large decreases of allogeneic RBC transfusions in patients undergoing RRP.
Analysis of nerve conduction block induced by direct current

The mechanisms of nerve conduction block induced by direct current (DC) were investigated using a lumped circuit model of the myelinated axon based on Frankenhaeuser-Huxley (FH) model. Four types of nerve conduction block were observed including anodal DC block, cathodal DC block, virtual anodal DC block, and virtual cathodal DC block. The concept of activating function was used to explain the blocking locations and relation between these different types of nerve block. Anodal/cathodal DC blocks occurred at the axonal nodes under the block electrode, while virtual anodal/cathodal DC blocks occurred at the nodes several millimeters away from the block electrode. Anodal or virtual anodal DC block was caused by hyperpolarization of the axon membrane resulting in the failure of activating sodium channels by the arriving action potential. Cathodal or virtual cathodal DC block was caused by depolarization of the axon membrane resulting in inactivation of the sodium channel. The threshold of cathodal DC block was lower than anodal DC block in most conditions. The threshold of virtual anodal/cathodal blocks was about three to five times higher than the threshold of anodal/cathodal blocks. The blocking threshold was decreased with an increase of axonal diameter, a decrease of electrode distance to axon, or an increase of temperature. This simulation study, which revealed four possible mechanisms of nerve conduction block in myelinated axons induced by DC current, can guide future animal experiments as well as optimize the design of electrodes to block nerve conduction in neuroprosthetic applications.
Bounding Prefix Transposition Distance for Strings and Permutations

A transposition is an operation that exchanges two adjacent substrings. When it is restricted so that one of the substrings is a prefix, it is called a prefix transposition. The prefix transposition distance between a pair of strings (permutations) is the shortest sequence of prefix transpositions required to transform a given string (permutation) into another given string (permutation). This problem is a variation of the transposition distance problem, related to genome rearrangements. An upper bound of n-1 and a lower bound of n/2 are known. We improve the bounds to n-log8 n and 2n/3 respectively. We also give upper and lower bounds for the prefix transposition distance on strings. For example, n/2 prefix transpositions are always sufficient for binary strings. We also prove that the exact prefix transposition distance problem on strings is NP complete.
Virtual machine effects on network traffic dynamics

Although virtual machine performance has been widely studied in the context of CPU utilization, the effects of virtual machines on network traffic dynamics has received far less attention. In this study, using VMware's GSX server on a Linux host, we evaluate the impact of VM overhead on TCP performance in both a LAN and emulated WAN environment. It is shown that when multiple VM hosted TCP senders compete on a LAN, sustained aggregate throughput decreases significantly and that ack arrival distributions are strongly affected. In the emulated WAN environment, TCP is shown to exhibit increasingly bursty behavior with associated increases in loss rate as the number of virtual Web servers increases.
Seasonal Pattern of Acute Myocardial Infarction in the National Registry of Myocardial Infarction

Objectives The purpose of this study was to determine whether the rate of hospital admission for acute myocardial infarction (AMI) varies seasonally in a large, prospective U.S. registry. Background Identification of specific patterns in the timing of the onset of AMI is of importance because it implies that there are triggers external to the atherosclerotic plaque. Using death certificate data, most investigators have noted a seasonal pattern to the death rate from AMI. However, it is unclear whether this observation is due to variation in the prevalence of AMI or to other factors that may alter the likelihood of a fatal outcome. Methods We examined the seasonal mean number of cases of AMI (adjusted for the length of days in each season) that were submitted to the National Registry of Myocardial Infarction (NRMI) by 138 high volume core hospitals over a 3-year period (December 21,1990 through December 20,1993) during which the number of hospitals participating in the Registry was stable. Data were analyzed using general linear modeling and analysis of variance. Results High volume core hospitals reported 83,541 cases of AMI to the Registry during the study period. Approximately 10% more such cases were entered into the Registry in winter or spring than in summer (p Conclusions We conclude that there is a seasonal pattern to the reporting rate of cases of AMI in the NRMI. This observation further supports the hypothesis that acute cardiovascular events may be triggered by events that are external to the atherosclerotic plaque.
Potential availability of urban wood biomass in Michigan: Implications for energy production, carbon sequestration and sustainable forest management in the U.S.A.

Abstract Tree and wood biomass from urban areas is a potentially large, underutilized resource viewed in the broader social context of biomass production and utilization. Here, data and analysis from a regional study in a 13-county area of Michigan, U.S.A. are combined with data and analysis from several other studies to examine this potential. The results suggest that urban trees and wood waste offer a modest amount of biomass that could contribute significantly more to regional and national bio-economies than it does at present. Better utilization of biomass from urban trees and wood waste could offer new sources of locally generated wood products and bio-based fuels for power and heat generation, reduce fossil fuel consumption, reduce waste disposal costs and reduce pressure on forests. Although wood biomass generally constitutes a “carbon-neutral” fuel, burning rather than burying urban wood waste may not have a net positive effect on reducing atmospheric CO 2 levels, because it may reduce a significant long term carbon storage pool. Using urban wood residues for wood products may provide the best balance of economic and environmental values for utilization.
Seeing and Windows of Integration

I am grateful to Bradley Richards and J. H. Taylor for their thoughtful critiques and for the chance to clarify and re-think the main line of argument in ‘‘The Grain of Vision and the Grain of Attention’’ (Block 2013). My article concerned peripheral vision. Much of normal vision is peripheral. The fovea is the central area of the retina that is needed for fine discrimination, for example in reading. It subtends only 2◦ of visual angle, a bit more than the width of the thumbnail at arm’s length, so if you are looking at something the size of a hand at arm’s length, on any one fixation most of it is seen nonfoveally. All perception degrades in acuity in the periphery because cone cells in the retina decrease with eccentricity. But object-perception in the periphery suffers from more than a degradation in acuity; it suffers from crowding. Crowding is a phenomenon of peripheral vision in which ‘‘things . . . lose the quality of form . . . without losing crispness . . .’’ (Lettvin 1976). It is widely agreed that the explanation of crowding is that vision involves assigning features to objects; but there are minimal ‘‘windows of integration’’ within which the visual system cannot determine which features are to be bound to which objects. (Binding is the process by which the visual registration of a blue square and a red circle involves blueness being attributed to the square instead of the circle.) The windows of integration grow larger farther from the fixation point—that is, where the eyes are pointing. See Figure 1 for an indication of the size and shape of these windows. In the periphery, the windows can be large enough so that normally two or more objects are in the same window. I argued that there is conscious object-seeing without object-attention in a phenomenon that I called identity-crowding. Identity-crowding is the special case of crowding in which the crowded items are all the same so that there is no issue of determining which features are bound to which objects. See Figure 2 for an example. As Taylor and Richards note, my argument was that in identity-crowding, the subject consciously detects the crowded object (in the sense of distinguishing consciously between presence and absence), consciously differentiates the object from the background, consciously discriminates the crowded object from other objects and consciously identifies the crowded object, so it is difficult to see a rationale for denying that
Toward robust and quantifiable automated IFC quality validation

We identify quantifiable rules for testing a good quality IFC file.We define classifications of the validation rules including syntax and semantics.We outline initial list of validation rules covering all aspects of IFC testing.The validation rules include well defined rules for geometry and spatial related tests.We propose rules for automated IFC import testing. The use of IFC as a standard format in exchange processes has been increasing as the industry begins to address the need of interoperability. A current problem with the use of IFC is in the quality of product models. Much effort has addressed this issue in the form of certifications to ensure a minimum quality of exchange requirements for an IFC file. However, even with the recent increasing awareness and effort to improve the quality of IFC files, the process is still too tedious, time consuming and requires manual efforts by experts. Even if those resources are available, there is currently no clear and quantifiable definitions of what exactly is a good quality IFC file. Without such measures, the adoption of IFC as standard exchange format will be hindered and the industry will be left with only restricted alternatives that are mostly vendor dependent. This paper sets out to address this issue in two aspects: first by defining what a good quality IFC model is, and second by proposing rules that can be automated to measure with confidence the completeness and correctness of the IFC model. These two aspects will serve as a starting point toward a more comprehensive and quantifiable measures of the quality of an IFC file. This proposed goal is represented by using well defined and well documented rules collected from various projects the authors had experienced over the years. The rules include all known aspects of IFC, including geometry, which currently requires mostly manual validation. The paper also proposes a method to address import validation that is under-developed compared to the export validation.
Unintended consequences of a strategically ambiguous organizational policy selectively restricting mobile device use at work

Mobile devices have permeated organizations creating diverse communication opportunities and new organizational challenges. This case study examines one of those challenges: creating a strategically ambiguous mobile device use policy to combat misuse in an organization. We use focus group data collection and a subsequent constant comparative analysis to examine a U.S. company with an organizational policy selectively restricting mobile device access for nonmanagerial workers. The findings and resulting theoretical model reflect the tension employees face when interpreting a restrictive mobile device use policy within the context of mobile use as “taken for granted.” This tension is manifest through four unintended consequences of the strategically ambiguous policy: (a) declining productivity, (b) supervisors burdened by overwhelming tasks, (c) decreased professional mobility, and (d) fleeting organizational identification. This research offers an organizational contribution to the current work on mobiles ...
Thermal drawdown-induced flow channeling in a single fracture in EGS

Abstract The evolution of flow pattern along a single fracture and its effects on heat production is a fundamental problem in the assessments of engineered geothermal systems (EGS). The channelized flow pattern associated with ubiquitous heterogeneity in fracture aperture distribution causes non-uniform temperature decrease in the rock body, which makes the flow increasingly concentrated into some preferential paths through the action of thermal stress. This mechanism may cause rapid heat production deterioration of EGS reservoirs. In this study, we investigated the effects of aperture heterogeneity on flow pattern evolution in a single fracture in a low-permeability crystalline formation. We developed a numerical model on the platform of GEOS to simulate the coupled thermo-hydro-mechanical processes in a penny-shaped fracture accessed via an injection well and a production well. We find that aperture heterogeneity generally exacerbates flow channeling and reservoir performance generally decreases with longer correlation length of aperture field. The expected production life is highly variable (5 years to beyond 30 years) when the aperture correlation length is longer than 1/5 of the well distance, whereas a heterogeneous fracture behaves similar to a homogeneous one when the correlation length is much shorter than the well distance. Besides, the mean production life decreases with greater aperture standard deviation only when the correlation length is relatively long. Although flow channeling is inevitable, initial aperture fields and well locations that enable tortuous preferential paths tend to deliver long heat production lives.