Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Membrane Potential in Endothelium-Dependent Relaxation of Isolated Mouse Main Pulmonary Artery

The physiology of smooth muscle and endothelial cells of a particular vascular bed and from different species differs from each other. Acetylcholine causes an endothelium-dependent relaxation of preconstricted pulmonary arteries from the rat. This relaxation is mediated by nitric oxide (NO) plus a yet-unidentified endothelium-derived hyperpolarizing factor, which relaxes the smooth muscles by hyperpolarizing them. Our aim is to test whether these observations could be generalized to the smooth muscle cells from the mouse pulmonary artery. Smooth muscle or endothelial cell membrane potential of strips of murine pulmonary artery were measured simultaneously with the force developed by the strip. Acetylcholine hyperpolarized the endothelial cells. However, acetylcholine did not induce an endothelium-dependent hyperpolarization of the smooth muscle, while it relaxed the strip in an endothelium-dependent manner. This relaxation was abolished by an inhibitor of NO synthesis, nitro-L-arginine. Moreover, nitroglycerin relaxed the strips without changing the membrane potential of the smooth muscle cells. Injection of Lucifer yellow into the endothelial cells and the smooth muscle cells did not show heterocellular dye coupling. Furthermore, electron microscopy did not show gap junction plate at the myoendothelial junctions. We conclude that in the mouse main pulmonary artery, NO alone is responsible for the acetylcholine-induced endothelium-dependent vasodilatation, whereas the phenomenon called endothelium-derived hyperpolizing factor is not present. Therefore, caution should be taken when comparing different animal models to study pulmonary circulation and its reactivity.
Competition in the Manuka Honey Industry in New Zealand

This paper examines the problems of spatial competition in the beekeeping segment of the New Zealand manuka honey industry. Competition between two close apiaries results in negative reciprocal production externalities. A basic geometric model of spatial competition between two apiaries is developed. Various forms of possible management and regulation of the industry are explored, drawing on the experience of management and regulation of production activities with similar externality problems, particularly oil and gas reservoirs, and New Zealand competition policy.
Microfluorometric monitoring of pHi in cultured heart cells: Na+-H+ exchange.

Continuous measurement of intracellular pH (pHi) should enhance the likelihood of defining the mechanisms of pHi regulation in actively contracting preparations of cardiac muscle. A filter microfluorometric technique was adapted for use with growth-oriented embryonic chick heart cells to continuously monitor changes in the fluorescence intensity of the pH-sensitive chromophore 6-carboxyfluorescein, generated in situ. Data pertaining to the direction and the rate of pHi changes assisted in thermodynamically characterizing and ascertaining net kinetic parameters of a Na+-H+ exchange mechanism. Imposing an outward Na+ gradient across the cardiac cell membrane rapidly (t 1/2 = 44 s) induced cytosolic acidification, whereas an inward Na+ gradient produced cytosolic alkalinization (t 1/2 = 40 s). Amiloride (10(-3) M) caused the cytoplasm to acidify (t 1/2 = 46 s) and also reversibly blocked the acidification induced by low extracellular Na+. These results are consistent with the presence of a rapid Na+-H+ exchange mechanism in the cardiac cell membrane. Further investigations are required to characterize the involvement of Na+-H+ exchange in pHi regulation and to differentiate the effects of Na+-H+ exchange from other ion gradient-coupled mechanisms, e.g., Na+-Ca2+ exchange.
Escaping the lianoid habit: evolution of shrub-like growth forms in Aristolochia subgenus Isotrema (Aristolochiaceae).

UNLABELLED PREMISE OF THE STUDY A large range of growth forms is a notable aspect of angiosperm diversity and arguably a key element of their success. However, few studies within a phylogenetic context have explored how anatomical, developmental, and biomechanical traits are linked with growth form evolution. Aristolochia (∼500 species) consists predominantly of climbers, but a handful of shrub-like species are known from Aristolochia subgenus Isotrema (hereafter, shortened to Isotrema). We test hypotheses proposing that the establishment of functional traits linked to lianescence might limit the ability to evolve structurally diverse growth forms, particularly self-supporting forms. • METHODS We focus on the origin of the shrub habit in Isotrema, from which we sampled representatives from climbing to self-supporting forms. Morphological, anatomical, and biomechanical characters are optimized on a chloroplast- and nuclear-derived phylogeny. • KEY RESULTS Character-state reconstructions revealed that the climbing habit is plesiomorphic in Isotrema and shrub-like forms are derived from climbers. However, shrubs do not constitute a monophyletic group. Both shrubs and climbers show large multiseriate rays, but differ in terms of vessel size and proportion of fibers and soft tissues. • CONCLUSION We suggest that while shrub-like species might have partly escaped from the constraints of life as lianas; their height size and stability are not typical of self-supporting shrubs and trees. Shrubs retained lianoid stem characters that are known to promote flexibility such as ray parenchyma. The transitions to a shrub-like form likely involved relatively simple, developmental changes that may be attributed to heterochronic processes.
Does export diversification converge? Evidence from cross-country analysis

This study examines the export diversification convergence across a broad set of countries. In particular, it focuses on whether the 127 Non-OECD countries are converging with 34 OECD countries in terms of export diversification. The study uses the annual data of 161 countries from 1995 to 2016. Techniques such as panel unit root tests, panel data models, and panel club convergence technique are applied for analysis. The results derived from these techniques support the evidence of export diversification convergence. This implies that the lower export diversified (Non-OECD) countries are â€˜catching up' with the higher export diversified (OECD) countries. Further, the findings suggest that Non-OECD countries should diversify their export with a speed of more than 3% to catch the OECD countries in order to achieve high and stable economic growth
Paving the Way for Self-Employment: Does Society Matter?

This paper empirically investigates the extent to which institutional and individual factors predict the level of intention relating to self-employment. Arriving at a better understanding of intentions will assist to provide answers as to why ratios of self-employment are as they are and how public and economic policy may respond to an often perceived requirement to increase the level of self-employment. Using the dataset of 2017 Amway Global Entrepreneurship Research (AGER) for Austria, the United Kingdom, Italy, the United States, and Brazil this study finds that all variables predicting the intention to enter self-employment are significant at varying degree. The research explores the interplay between age, risk, gender, and education, on the one hand, and unemployment (OECD Labour Force Statistics) and political constitution as measured by the EFW index, on the other hand. Distinguishing between “no intention”, an “indifferent intention,” and a “strong intention” towards self-employment, the findings show that all variables can predict a willingness for self-employment in different, but significant, ways to comparable measures (an indifferent intention relative to no intention, and a strong intention to no intention). The paper concludes with an outlook to some more general perspectives of institutional economics and needs for further research.
Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects.

PURPOSE Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA. PATIENTS AND METHODS We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls. RESULTS Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels. CONCLUSION Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.
Designing Paris Gare du Nord for pedestrians or for clients? New retail patterns as flow optimization strategies

ABSTRACT This article explores the links between flow management and retail development in railway stations. Questioning the way in which planners as well as station managers consider the relations between movement and commerciality, it combines theoretical insight and empirical findings at Paris Gare du Nord. In the planning literature, the progress of pedestrian traffic models and the social understanding of passenger behaviour have long been perceived as separate scientific goals. Today, however, the two domains are converging towards a more comprehensive approach, which in recent times has become a crucial aspect of railway competition strategies. In light of this, dynamic mapping conducted over the period 2010–2017 at Paris Gare du Nord shows how railway designers are reorganizing space to foster free movement and consumption. The article concludes with the presentation and discussion of two main principles of station retail planning and design. First, the production of a ‘servicescape’ through the intensification of nudge strategies. Second, the delivery of a ‘stationscape’ based on the use of trademarks as landmarks and a three-dimensional design that accentuates the socio-economic fragmentation of space.
A comparison between antisense P75NTR oligonucleotides and neurotrophic factors in promoting the survival of postnatal sensory neurons in vitro

SummaryThe 75-kDa low-affinity neurotrophin receptor (p75NTR) has been shown in previous reports to mediate neuronal cell death in vitro and in vivo under certain circumstances. Antisense oligonucleotides directed against p75NTR promote the survival of nerve growth factor-deprived dorsal root ganglia sensory neurons in vitro (Barrett, G.; Bartlett, P., Proc. Natl. Acad. Sci. USA 91:6501–6505; 1994) and axotomized dorsal root ganglia sensory neurons in vivo (Cheema, S. S.; Barrett, G. L.; Bartlett, P. F., J. Neurosci. Res. 46:239–245; 1996). In this study we compared the neuroprotective effects of antisense p75NTR oligonucleotides with two neurotrophic factors, namely nerve growth factor (NGF) and leukemia inhibitory factor, on cultured sensory neurons derived from postnatal day 7 and 14 rat dorsal root ganglia. After 3 d in culture, treatment with the neurotrophic factors had significant survival effects on sensory neuron cultures compared to treatment with basal medium (control). However, after 6 and 9 d in culture these rescue effects were not apparent. In contrast, antisense p75NTR oligonucleotides rescued significantly higher numbers of dorsal root ganglia sensory neurons after 6 and 9 d in culture than treatment with neurotrophic factors, sense oligonucleotides, and basal medium. Furthermore, antisense p75NTR oligonucleotides rescued trkA-, B-, and C-expressing neurons, while NGF and leukemia inhibitory factor targeted primarily the trkA-positive neurons. These findings suggest that antisense-based strategies that inhibit gene expression of cytotoxic molecules are more efficient at preventing postnatal sensory neuronal death in vitro than treatment with individual neurotrophic factors.
Interaction between demand-control and social support in the occurrence of common mental disorders

ABSTRACT OBJECTIVE To analyze the interaction between the psychosocial aspects of work and the occurrence of common mental disorders among health workers. METHODS This is a cross-sectional study conducted with a representative sample of workers of the primary health care of five municipalities of the State of Bahia, Brazil, in 2012. The variable of outcome were the common mental disorders evaluated by the SRQ-20, and the variables of exposure were high demand (high psychological demand and low control over the work) and low social support in the workplace. Interaction was checked by the deviation of the additivity of the effects for the factors studied from the calculation of excess risk from interaction, proportion of cases attributed to interaction, and the synergy index. RESULTS The global prevalence of common mental disorders was 21%. The group of combined exposure has shown higher magnitude (high demand and low social support), reaching 28% when compared to the 17% in the situation of no exposure (low demand and high social support). CONCLUSIONS The results strengthen the hypothesis of interaction between the factors investigated, directing to the synergy of the effects.
A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation

Summary. After surgery in haemophilia, haemostasis is difficult to maintain in the presence of an antifactor VIII antibody. This study assessed the pharmacokinetics of recombinant activated factor VII (rFVIIa) and its efficacy in securing post‐operative haemostasis in haemophiliacs with inhibitors. Continuous infusion of rFVIIa was evaluated for elective major orthopaedic surgery in nine patients with neutralizing antibodies to FVIII and at high risk of bleeding. After an initial preoperative bolus of 90 µg/kg, rFVIIa was infused at a fixed rate of 50 µg/kg/h for a median of 20 d (range 7–20 d). The median plasma FVII coagulant activity (FVII:C) at 24 h, 72 h and 20 d after surgery was 38 IU/ml (range 22–169 IU/ml), 45 IU/ml (range 17–88 IU/ml) and 31 IU/ml (range 27–46 IU/ml) respectively. The median plasma FVIIa:C at the same time points was 51 (range 24–211), 63 (range 22–99) and 44 (range 28–76) IU/ml respectively. Median total rFVIIa clearance remained stable during the rFVIIa continuous infusion period and was 40 (range 9–70), 34 (range 17–86) and 48 (range 32–55)ml/kg/h at the end of 24 h, 72 h and 20 d infusion respectively. Post‐operatively, there were bleeds in six patients, which settled readily after a single bolus of rFVIIa (60 µg/kg). There was a good clinical outcome for all patients. These data indicate that rFVIIa infusion at50 µg/kg/h achieves continuous plasma FVII procoagulant activity in excess of 30 IU/ml (12–15 nmol/l) and provides adequate haemostatic control for inhibitor patients during major orthopaedic surgery.
Live Candida albicans Suppresses Production of Reactive Oxygen Species in Phagocytes

ABSTRACT Production of reactive oxygen species (ROS) is an important aspect of phagocyte-mediated host responses. Since phagocytes play a crucial role in the host response to Candida albicans, we examined the ability of Candida to modulate phagocyte ROS production. ROS production was measured in the murine macrophage cell line J774 and in primary phagocytes using luminol-enhanced chemiluminescence. J774 cells, murine polymorphonuclear leukocytes (PMN), human monocytes, and human PMN treated with live C. albicans produced significantly less ROS than phagocytes treated with heat-killed C. albicans. Live C. albicans also suppressed ROS production in murine bone marrow-derived macrophages from C57BL/6 mice, but not from BALB/c mice. Live C. albicans also suppressed ROS in response to external stimuli. C. albicans and Candida glabrata suppressed ROS production by phagocytes, whereas Saccharomyces cerevisiae stimulated ROS production. The cell wall is the initial point of contact between Candida and phagocytes, but isolated cell walls from both heat-killed and live C. albicans stimulated ROS production. Heat-killed C. albicans has increased surface exposure of 1,3-β-glucan, a cell wall component that can stimulate phagocytes. To determine whether surface 1,3-β-glucan exposure accounted for the difference in ROS production, live C. albicans cells were treated with a sublethal dose of caspofungin to increase surface 1,3-β-glucan exposure. Caspofungin-treated C. albicans was fully able to suppress ROS production, indicating that suppression of ROS overrides stimulatory signals from 1,3-β-glucan. These studies indicate that live C. albicans actively suppresses ROS production in phagocytes in vitro, which may represent an important immune evasion mechanism.
Screening for Mental Illness in Primary Care Clinics

Objectives: To assess the prevalence of mental disorders in inner city outpatient clinics and to improve the diagnosis of mental illness in primary care. Methods: The Problem Oriented Patient Report (POPR), a patient self-report checklist, was administered to 362 outpatients at two inner-city Buffalo primary care clinics. Patients' completed POPR checklists were evaluated to identify those with potential mental illness diagnoses and were available for the physicians' review during the patients' visits. After the visit, clinical charts were reviewed to determine the frequency of new mental illness diagnoses among continuing and new patients. Results: The screening checklist (POPR) revealed potential mental illnesses in 148/362 outpatients, of which 98% had not been identified by the physicians who had reviewed the patients' completed POPR forms. Only five new diagnoses of mental illnesses were independently made by clinics' physicians—all in follow-up (continuing) patients. Conclusions: The physicians in the two clinics did not diagnose mental illnesses in their patients, even when written checklists of self-reports were available to them. Differences in staff attitudes may influence the data collection process, and patients' as well as physicians' responses. A weakness of this study is that the POPR might generate false positive results. Even if this were the case, the rate of previous diagnoses was still extremely low.
The importance of Foxp3 antibody and fixation/permeabilization buffer combinations in identifying CD4+CD25+Foxp3+ regulatory T cells

Foxp3 is a key marker for CD4+ regulatory T cells (Tregs) and was used in developing a multiparameter flow cytometric panel to identify Tregs. Achieving reproducible staining and analysis first required optimization of Foxp3 staining. We present a comparative study of PCH101, 236A/E7, 3G3, 206D, 150D, and 259D/C7 clones of anti‐human‐Foxp3 antibodies used in combination with five different fixation/permeabilization buffers. Staining for CD25, CD152, and CD127 was also compared between fixation/permeabilization treatments. Promising antibody/buffer combinations were tested in a panel of peripheral blood mononuclear cells from 10 individuals, and then on fresh versus frozen cells from four individuals. Finally, different fluorochromes coupled to two representative antibodies were compared to optimize separation of Foxp3+ from Foxp3− events. Foxp3 gates were set using two gating strategies based on CD127+CD25− “non‐Tregs” or based on isotype controls. For Foxp3 staining, the best conditions for fixation/permeabilization were obtained using the eBioscience Foxp3, Imgenex, BioLegend, and BD Foxp3 buffers. Comparing results from 10 subjects, 259D/C7, PCH101, 236A/E7, and 206D antibodies yielded statistically higher levels of Foxp3 cells than those by 150D and 3G3 antibodies (mean = 6.9, 5.1, 4.7, and 3.7% compared with 1.7, and 0.3% of CD25+Foxp3+ events within CD4+ cells, respectively). Importantly, the “nonspecificity” of some antibodies observed with a Foxp3 gate based on isotype controls could be eliminated by setting the Foxp3 gate on “non‐Tregs”. Better separation of Foxp3+ and Foxp3− populations was observed using the PCH101 clone coupled to Alexa647 compared with FITC or the 259D/C7 clone coupled to PE compared with Alexa488 fluorochrome. Foxp3 staining can be highly variable and depends on the choice of antibody/buffer pair and the fluorochrome used. Selecting the correct population for setting the Foxp3 gate is critical to avoid including non‐Tregs in the Foxp3+ gate. The experiments presented here will aid in optimization of flow cytometry staining panels to quantify Treg frequencies in humans. © 2009 International Society for Advancement of Cytometry
The Female Player Does Not Exist: Gender Identity Relates to Differences in Player Motivations and Play Styles

This study addresses the female player of massively multiplayer online (role-playing) games and investigates how gender identity (GI), indicating a person's identification with characteristics that are traditionally defined as masculine or feminine, can be used to explain playing patterns within the female gender group. Results from an online survey (n=466) show that females' player motivations and play styles vary as a function of their GI, indicating that it is a relevant and additional predictor of play behavior and confirming that female play behavior cannot be generalized based on stereotypical male/female conceptions.
Sphingosine 1-Phosphate Induces Platelet Activation through an Extracellular Action and Shares a Platelet Surface Receptor with Lysophosphatidic Acid*

Sphingosine 1-phosphate (Sph-1-P) has been implicated as an intracellular second messenger in many studies. We investigated the metabolism of Sph-1-P and the mechanism by which Sph-1-P induces activation in enucleated and highly differentiated platelets. Platelets lack Sph-1-P lyase activity, possess persistently active sphingosine (Sph) kinase, and abundantly store Sph-1-P. Although exogenous Sph-1-P activated platelets, intracellular Sph-1-P, formed from exogenously added Sph by cytosolic Sph kinase, failed to do so. To support the notion that exogenous Sph-1-P stimulates platelets from outside, contact of platelet surfaces with immobilized Sph-1-P covalently linked to glass particles resulted in platelet activation. Furthermore, we detected the specific binding sites for radiolabeled Sph-1-P on the platelet surface, suggesting extracellular effects of Sph-1-P on plasma membrane receptors. This specific Sph-1-P binding was inhibited not by other sphingolipids but by lysophosphatidic acid (LPA), and platelet aggregation response to LPA was specifically desensitized by prior addition of Sph-1-P. Finally, internally stored Sph-1-P is released extracellularly upon stimulation, and the release correlated well with protein kinase C activation in intact platelets. These results suggest that Sph-1-P acts not intracellularly but intercellularly, following discharge from activated platelets, and shares a platelet surface receptor with LPA.