Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute and subacute effects of diazepam on psychomotor skills: interaction with alcohol.

Effects of diazepam and alcohol on psychomotor skills were measured in two trials. In the first one, 200 healthy students volunteered for a double-blind single-dose study. Three doses of diazepam (5, 10 and 20 mg) and alcohol (0.5, 0.8 and 1.2 g/kg) were used alone and combined to construct dose-response graphs. All doses of alcohol impaired divided attention while co-ordinative skills were impaired by the 1.2 g/kg dose. Diazepam alone did not impair reactive or co-ordinative skills whereas the combinations of diazepam and alcohol did so. To further elucidate the subactue effects, a double-blind randomized study was conducted administering 2 and 10 mg of diazepam t.i. d. for two weeks to 18 healthy volunteers. The psychomotor tests were performed on the 7th and 14th days of drug administration, and 0.5 g/kg of alcohol was given on either day. Diazepam 2 mg, alone or with alcohol, did not differ from placebo. 10 mg of diazepam slightly increased reaction times but not reaction mistakes, and impaired both co-ordination and attention. Alcohol did not enhance diazepam effects. We suggest that a development of tolerance to diazepam may compensate the deleterious interaction of the agents found in acute studies.
Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole.

BACKGROUND The efficacy of permanent cardiac pacing in patients with neurocardiogenic (or vasovagal) syncope associated with bradycardia or asystole is not clear. We compared the efficacy of cardiac pacing with that of oral drug therapy in the prevention of hypotension and syncope during head-up tilt testing. METHODS Among 70 patients with a history of syncope in whom hypotension and syncope could be provoked during head-up tilt testing, 22 had bradycardia (a heart rate < 60 beats per minute, with a decline in the rate by at least 20 beats per minute) or asystole along with hypotension during testing. There were 9 men and 13 women, with a mean (+/- SD) age of 41 +/- 17 years. Head-up tilt testing was repeated during atrioventricular sequential pacing (in 20 patients with sinus rhythm) or ventricular pacing (in 2 patients with atrial fibrillation). Regardless of the results obtained during artificial pacing, all the patients subsequently had upright-tilt testing repeated during therapy with oral metoprolol, theophylline, or disopyramide. RESULTS During the initial tilt test, 6 patients had asystole and 16 had bradycardia along with hypotension. Despite artificial pacing, the mean arterial pressure during head-up tilt testing still fell significantly, from 97 +/- 19 to 57 +/- 19 mm Hg (P < 0.001); 5 patients had syncope, and 15 had presyncope. By contrast, 19 patients who later received only medical therapy (metoprolol in 10, theophylline in 3, and disopyramide in 6), 2 patients who received both metoprolol and atrioventricular sequential pacing, and 1 patient who received only atrioventricular sequential pacing had negative head-up tilt tests. After a median follow-up of 16 months, 18 of the 19 patients who were treated with drugs alone (94 percent) remained free of recurrent syncope or presyncope, whereas the patient treated only with permanent dual-chamber pacemaker had recurrent syncope. CONCLUSIONS In patients with neurocardiogenic syncope associated with bradycardia or asystole, drug therapy is often effective in preventing syncope, whereas artificial pacing is not.
Dendritic Cells Expressing Plasmacytoid Marker PDCA-1 Are Trojan Horses during Toxoplasma gondii Infection1

Plasmacytoid dendritic cells (pDCs) play a key role in the innate immune response to viral infection, due largely to their ability to produce large quantities of type I IFNs. These cells are also notable for their ability to differentiate into conventional dendritic cells after appropriate stimulation. Here, we show that a splenic population of murine CD11c+ cells expressing pDC markers Gr-1, B220, and PDCA-1 is preferentially parasitized after infection with the virulent RH strain of Toxoplasma gondii. Although these markers are closely associated with pDCs, the population we identified was unusual because the cells express CD11b and higher than expected levels of CD11c. By adoptive transfer of CD45.1-positive cells into CD45.2 congenic mice, we show that CD11c+Gr-1+ cells migrate from the peritoneal cavity to the spleen. During infection, these cells accumulate in the marginal zone region. Recruitment of infected CD11c+Gr-1+ cells to the spleen is partially dependent upon signaling through chemokine receptor CCR2. Intracellular cytokine staining demonstrates that infected, but not noninfected, splenic CD11c+Gr-1+ dendritic cells are suppressed in their ability to respond to ex vivo TLR stimulation. We hypothesize that Toxoplasma exploits pDCs as Trojan horses, targeting them for early infection, suppressing their cytokine effector function, and using them for dissemination within the host.
Are valuations of place-based amenities driven by scale?

Abstract Amenities play an important role in explaining regional attractiveness as they increase the competition between places and the demand for housing. This paper contributes to the literature on valuations of place-based amenities by estimating hedonic prices for a differentiated set of amenities, and by examining the link between urban density and amenity valuations. The empirical analysis is based on a sample of 8319 single-family home sales observed during the period 2001–2011. Results show that amenities are valued differently depending on their size, the relationship between size and distance and neighbourhood characteristics. Differentiating among a set of nature- and culture based amenities shows that it is profoundly the value of proximity to open space that vary with neighbourhood density. Results are robust when testing for non-constant implicit prices over different time periods and novel to the literature on valuation of open spaces using the hedonic price model.
Translating the semi-structured assessment for drug dependence and alcoholism in the Western Pacific: rationale, study design and reliability of alcohol dependence.

AIMS The aims of this study were to develop a bilingual version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) in English and Samoan and determine the reliability of assessments of alcohol dependence in American Samoa. METHODS The study consisted of development and reliability-testing phases. In the development phase, the SSADDA alcohol module was translated and the translation was evaluated through cognitive interviews. In the reliability-testing phase, the bilingual SSADDA was administered to 40 ethnic Samoans, including a sub-sample of 26 individuals who were retested. RESULTS Cognitive interviews indicated the initial translation was culturally and linguistically appropriate except items pertaining to alcohol tolerance, which were modified to reflect Samoan concepts. SSADDA reliability testing indicated diagnoses of DSM-III-R and DSM-IV alcohol dependence were reliable. Reliability varied by language of administration. CONCLUSION The English/Samoan version of the SSADDA is appropriate for the diagnosis of DSM-III-R alcohol dependence, which may be useful in advancing research and public health efforts to address alcohol problems in American Samoa and the Western Pacific. The translation methods may inform researchers translating diagnostic and assessment tools into different languages and cultures.
Counter regulation of the high affinity IgE receptor, FcεRI, on human airway dendritic cells by IL‐4 and IL‐10

Background: Immunoglobulin E is a signalling molecule within the environment of the respiratory tract, the high affinity receptor for which, FcεRI, is expressed by dendritic cells (DC). Little is known, however, of the expression and function of FcεRI on DC in the human respiratory tract.
Hypoxia induces adaptive and reversible gross morphological changes in crucian carp gills

SUMMARY We show that crucian carp (Carassius carassius) living in normoxic (aerated) water have gills that lack protruding lamellae, the primary site of O2 uptake in fish. Such an unusual trait leads to a very small respiratory surface area. Histological examination showed that the lamellae (secondary lamellae) of these fish were embedded in a cell mass (denoted embedded lamellae). When the fish were kept in hypoxic water, a large reduction in this cell mass occurred, making the lamellae protrude and increasing the respiratory surface area by ∼7.5-fold. This morphological change was found to be reversible and was caused by increased apoptosis combined with reduced cell proliferation. Carp with protruding lamellae had a higher capacity for oxygen uptake at low oxygen levels than fish with embedded lamellae, but water and ion fluxes appeared to be increased, which indicates increased osmoregulatory costs. This is, to our knowledge, the first demonstration of an adaptive and reversible gross morphological change in the respiratory organ of an adult vertebrate in response to changes in the availability of oxygen.
Kinetic analysis of human T-cell leukemia virus type I Tax-mediated activation of NF-kappa B

The human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of cellular genes, at least in part, by activating the endogenous NF-kappa B transcription factors. Induced expression of cellular genes is thought to be important for transformation of T cells to continued growth, a prelude to the establishment of adult T-cell leukemia. However, neither underlying mechanisms nor kinetics of the Tax-mediated activation of NF-kappa B are understood. We have analyzed a permanently transfected Jurkat T-cell line in which the expression of Tax is entirely dependent on addition of heavy metals. The initial NF-kappa B binding activity seen after induction of Tax is due almost exclusively to p50/p65 heterodimers. At later times, NF-kappa B complexes containing c-Rel and/or p52 accumulate. The early activation of p50/p65 complexes is a posttranslational event, since neither mRNA nor protein levels of NF-kappa B subunits had increased at that time. We demonstrate for the first time a Tax-induced proteolytic degradation of the NF-kappa B inhibitor, I kappa B-alpha, which may trigger the initial nuclear translocation of NF-kappa B. As nuclear NF-kappa B rapidly and potently stimulates resynthesis of I kappa B-alpha, the steady-state level of I kappa B-alpha does not significantly change. Thus, the dramatic Tax-induced increase in the I kappa B-alpha turnover may continually weaken inhibition and activate NF-kappa B. Additional, distinct actions of Tax may contribute further to the high levels of NF-kappa B activity seen.
MyMiner: a web application for computer-assisted biocuration and text annotation

MOTIVATION The exponential growth of scientific literature has resulted in a massive amount of unstructured natural language data that cannot be directly handled by means of bioinformatics tools. Such tools generally require structured data, often generated through a cumbersome process of manual literature curation. Herein, we present MyMiner, a free and user-friendly text annotation tool aimed to assist in carrying out the main biocuration tasks and to provide labelled data for the development of text mining systems. MyMiner allows easy classification and labelling of textual data according to user-specified classes as well as predefined biological entities. The usefulness and efficiency of this application have been tested for a range of real-life annotation scenarios of various research topics. AVAILABILITY http://myminer.armi. monash.edu. au.
Cardiovascular and metabolic changes in spontaneously hypertensive rats following streptozotocin administration.

OBJECTIVES To investigate whether the high mortality rate that occurs in streptozotocin (STZ)-diabetic spontaneously hypertensive rats (SHR) is related to abnormalities in glycemic control, in hemodynamics and cardiac function, or in susceptibility to the occurrence of ventricular arrhythmias. METHODS Diabetes was induced in SHR and Wistar-Kyoto (WKY) rats by the intravenous injection of STZ 55 mg/kg. Intraperitoneal glucose tolerance tests were performed after six and 11 weeks. Blood pressure was measured in conscious rats at weeks 0 and 11 with a tail-cuff method and in anesthetized animals at week 12 through a cannulated artery. Response of myocardial function to rapid intravenous infusion of saline 10 mL/kg/min and the times of onset of ventricular arrhythmias during intravenous infusion of aconitine 20 micrograms/kg/min were determined in anesthetized rats at week 12. Plasma samples from the rats were assayed for glucose, insulin, triglycerides and carnitine. RESULTS STZ injection caused hyperglycemia, hypoinsulinemia and glucose intolerance equally in SHR and WKY. Diabetic SHR exhibited significant hypertriglyceridemia, depletion in plasma carnitine, impaired responses of blood pressure and myocardial function to rapid intravenous infusion of saline and a 37.5% mortality rate, whereas diabetic WKY did not exhibit these changes. SHR and WKY, diabetic or nondiabetic, were equally sensitive to the induction of ventricular arrhythmias by aconitine infusion. CONCLUSION Mortality of the STZ-diabetic SHR is not due to an exaggeration of the impaired glycemic control, but may be attributed to the occurrence of cardiac dysfunction. The development of life-threatening cardiac arrhythmias, while unlikely, cannot be completely excluded.
Monitoring Changes in the Oligomeric State of a Candidate Endoplasmic Reticulum (ER) Ceramide Sensor by Single-molecule Photobleaching*

Single-molecule photobleaching has emerged as a powerful non-invasive approach to extract the stoichiometry of multimeric membrane proteins in their native cellular environment. However, this method has mainly been used to determine the subunit composition of ion channels and receptors at the plasma membrane. Here, we applied single-molecule photobleaching to analyze the oligomeric state of an endoplasmic reticulum (ER) resident candidate ceramide sensor protein, SMSr/SAMD8. Co-immunoprecipitation and chemical cross-linking studies previously revealed that the N-terminal sterile alpha motif (or SAM) domain of SMSr drives self-assembly of the protein into oligomers and that SMSr oligomerization is promoted by curcumin, a drug known to perturb ER ceramide and calcium homeostasis. Application of cell spreading surface-active coating materials in combination with total internal reflection fluorescence (TIRF) microscopy allowed us to image GFP-tagged SMSr proteins as single fluorescent spots in the ER of HeLa cells in which expression of endogenous SMSr was abolished. In line with our biochemical analysis, we find that the number of bleaching steps in SMSr-GFP-positive spots displays a substantial drop after removal of the SAM domain. In contrast, treatment of cells with curcumin increased the number of bleaching steps. Our results document the first successful application of single-molecule photobleaching to resolve drug-induced and domain-dependent changes in the oligomeric state of an ER-resident membrane protein, hence establishing a complementary method to unravel the mechanism by which SMSr controls ceramide levels in the ER.
Stable knockdown of CFTR establishes a role for the channel in P2Y receptor‐stimulated anion secretion

P2Y receptor regulation of anion secretion was investigated in porcine endometrial gland (PEG) epithelial cells. P2Y2, P2Y4, and P2Y6 receptors were detected in monolayers of PEG cells and immunocytochemistry indicated that P2Y4 receptors were located in the apical membrane. Apical membrane current measurements showed that Ca2+‐dependent and PKC‐dependent Cl− channels were activated following treatment with uridine triphosphate (UTP) (5 µM). Current‐voltage relationships comparing calcium‐dependent and PKC‐dependent UTP responses under biionic conditions showed significant differences in selectivity between Cl− and I− for the PKC‐dependent conductance (PI/PCl = 0.76), but not for Ca2+‐dependent conductance (PI/PCl = 1.02). The I−/Cl− permeability ratio for the PKC‐dependent conductance was identical to that measured for 8‐cpt cAMP. Furthermore, PKC stimulation using phorbol 12‐myristate 13‐acetate (PMA) activated an apical membrane Cl− conductance that was blocked by the CFTR selective inhibitor, CFTRinh‐172. CFTR silencing, accomplished by stable expression of small hairpin RNAs (shRNA), blocked the PKC‐activated conductance associated with UTP stimulation and provided definitive evidence of a role for CFTR in anion secretion. CFTR activation increased the initial magnitude of Cl− secretion, and provided a more sustained secretory response compared to conditions where only Ca2+‐activated Cl− channels were activated by UTP. Measurements of [cAMP]i following UTP and PMA stimulation were not significantly different than untreated controls. Thus, these results demonstrate that UTP and PMA activation of CFTR occurs independently of increases in intracellular cAMP and extend the findings of earlier studies of CFTR regulation by PKC in Xenopus oocytes to a mammalian anion secreting epithelium. J.Cell. Physiol. © 2005 Wiley‐Liss, Inc.
Potential pitfalls concerning colorectal cancer classification in the seventh edition of the AJCC Cancer Staging Manual.

To the Editor—The seventh edition of the AJCC Cancer Staging Manual has introduced the new site-specific factor tumor deposits (TDs) in colorectal cancer staging, recognizing its prognostic value. TDs are “discrete foci of tumor found in the pericolic or perirectal fat or in adjacent mesentery (mesocolic fat) away from the leading edge of the tumor and showing no evidence of residual lymph node tissue but within the lymph drainage area of the primary carcinoma. ” They “may represent discontinuous spread, venous invasion with extravascular spread (V1/ V2), or a totally replaced lymph node (N1/N2). ” “Their number should be recorded in the site-specific Prognostic Markers on the staging form as Tumor Deposit (TD). ” It is recommended that “the nodule is recorded in the TD category and as a N1c positive node”; N1c is defined as “tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis. ” Finally, after a reminder that “a satellite peritumoral nodule in the pericolorectal adipose tissue of a primary carcinoma without histological evidence of residual lymph node in the nodule may represent discontinuous spread, venous invasion with extravascular spread (V1/V2), or a totally replaced lymph node (N1/N2),” a note recommends that “replaced nodes should be counted separately in the N category, whereas discontinuous spread or venous invasion should be classified and counted in the Site-Specific Factor category Tumor Deposits (TD). ” N1c forces into the N category the “non N type” of TDs, but this can be accepted for practical purposes. However, some incongruities remain. First, the N state of a case with TDs only would be N1c, whereas a case with TDs and 1 to 3 positive “true” lymph node(s) would paradoxically “regress” to N1a/b. Second, why are totally replaced lymph nodes first recognized as one of the variants of TDs, and then requested to be considered separately in the N category? The identification of replaced lymph nodes depends on arbitrary criteria, formerly the size (TNM fifth edition), and later the shape (TNM sixth and seventh editions). In keeping with the general rule postulated in the chapter concerning “Purposes and Principles of Cancer Staging” (“tumor nodule with smooth contour in regional node area classified as positive node”), totally replaced lymph nodes identified by their smooth contour should be unequivocally excluded from TD variants (recalling the definition of “totally replaced lymph node” in the chapter concerning colorectal cancer); alternatively, they should be considered and counted together with the other TDs. Thus, the seventh edition of the AJCC Cancer Staging Manual uses some confounding terms concerning colorectal cancer; the resulting incongruities urge a clarification.
Financial Information Processing Models: An Empirical Study

Given the objective of describing quantitatively how people use financial data to generate financial judgments, second-year graduate business school students were provided with data for each of 60 companies in an experimental setting, and an estimate of the change in security price over a one-year period was obtained from each subject for each security. Properties of the cognitive models people used to generate the price changes were inferred within the context of the Brunswik Lens Model. Topics con- sidered included judgmental accuracy and consistency, types of models used including consideration of linear vs. nonlinear information processing and interjudge agreement. Reported results include empirical evidence on subjective security price change dis- tributions, an encouraging degree of accuracy, a tendency to overestimate the prices of "low-priced" securities, evidence consistent with linear processing of financial data, depiction of distinct clusters of cognitive models and limited interjudge agreement. Sug- gestions for future research also are indicated.
Malignant melanoma in the elderly.

Advancing age is associated with poorer prognosis in malignant melanoma. We studied 3,872 cases of malignant melanoma to evaluate whether the effect of age could be analyzed relative to sex, tumor depth, primary site, and other clinical and pathologic variables. The sex distribution by age shows a slight female predominance in the early and late decades but male predominance in the middle years. The percentage of patients with metastatic disease at initial diagnosis did not vary with age, despite greater diameter and depth of lesions in the older patients. In fact, in the older age groups, initial nodal metastasis occurred slightly less frequently. Trunk primaries decreased in frequency with increasing age, while extremity lesions remained relatively constant, and face, nose, and ear lesions increased. This was in part related to the histopathologic type, as lentigo maligna lesions increased in frequency with age, superficial spreading lesions were somewhat less frequent in the older age group and nodular types were fairly constant. On the basis of both Clark's level and Breslow thickness, there was an increasing proportion of deeper penetrating lesions in the older age group. The mean diameter of these lesions on the skin surface was also greater for the older patients. This would suggest that lesions in the older individual remain confined to the local site longer, penetrate and spread, but do not necessarily metastasize more rapidly. Cox model regression analysis of survival time within stage showed that age was highly significant as a poor prognostic factor. Though the adverse relation of advancing age with survival was partially explained by predominance of other unfavorable factors, such as primary site, depth of lesion, or histologic type, age remained an independent poor prognostic factor (chi 2 = 5.3; P = .02) for death due to melanoma.