Miracle-dz/UniFAR-FTUs huggingface dataset:
Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats

Chronic treatment of methamphetamine (MAP) in rats desynchronized the locomotor activity rhythm from the light–dark cycle. When the activity rhythm was completely phase‐reversed with respect to a light dark‐cycle, 24 h profiles were examined for the clock gene (rPer1, rPer2, rBMAL1, rClock) expressions in several brain structures by in situ hybridization, and for the pineal as well as plasma melatonin levels. In the MAP‐treated rats, the rPer1 expression in the suprachiasmatic nucleus (SCN) showed a robust circadian rhythm which was essentially identical to that in the control rats. Circadian rhythms in pineal as well as plasma melatonin were not changed significantly in the MAP‐treated rats. However, robust circadian rhythms in the rPer1, rPer2 and rBMAL1 expressions detected in the caudate‐putamen (CPU) and parietal cortex were completely phase‐reversed in the MAP‐treated rats, compared with those in the control rats, indicating desynchronization from the SCN rhythm. Such desynchronization was not observed in the circadian rhythms of clock gene expression in the nucleus accumbens and cingulate cortex. The circadian rClock expression rhythm in the MAP‐treated rats was not phase‐reversed in the CPU and parietal cortex. These findings indicate that the locomotor activity rhythm in rats is directly driven by the pacemaker outside the SCN, in which rPer1, rPer2 and rBMAL1 in the CPU and parietal cortex are involved.
Japanese guidelines for the management of pemphigus

The Committee for Guidelines for the Management of Pemphigus was organized as one element of the Japanese Dermatological Association (JDA) and the Ministry of Health, Labour, and Welfare (MHLW) Research Project on Measures for Research Committee for Intractable Skin Disease. Pemphigus has been defined as a group of intractable autoimmune blistering diseases caused by anti‐desmoglein 1 and/or anti‐desmoglein 3 IgG autoantibodies by the MHLW. The diagnosis of this condition and the criteria for assessing its severity are based on suggestions from the MHLW Research Group. The clinical practice guidelines presented here are those that are currently recommended in Japan. However, symptoms and complications can vary widely among individual pemphigus patients, so not all therapies will be required to be in complete agreement with these guidelines.
Brca2 (XRCC11) Deficiency Results in Radioresistant DNA Synthesis and a Higher Frequency of Spontaneous Deletions

ABSTRACT We show here that the radiosensitive Chinese hamster cell mutant (V-C8) of group XRCC11 is defective in the breast cancer susceptibility gene Brca2. The very complex phenotype of V-C8 cells is complemented by a single human chromosome 13 providing the BRCA2 gene, as well as by the murine Brca2 gene. The Brca2 deficiency in V-C8 cells causes hypersensitivity to various DNA-damaging agents with an extreme sensitivity toward interstrand DNA cross-linking agents. Furthermore, V-C8 cells show radioresistant DNA synthesis after ionizing radiation, suggesting that Brca2 deficiency affects cell cycle checkpoint regulation. In addition, V-C8 cells display tremendous chromosomal instability and a high frequency of abnormal centrosomes. The mutation spectrum at the hprt locus showed that the majority of spontaneous mutations in V-C8 cells are deletions, in contrast to wild-type V79 cells. A mechanistic explanation for the genome instability phenotype of Brca2-deficient cells is provided by the observation that the nuclear localization of the central DNA repair protein in homologous recombination, Rad51, is reduced in V-C8 cells.
Levels of arsenic in the United States food supply

At the present time, the Food and Drug Administration (FDA) accords the highest priority to mercury, lead, cadmium, arsenic, selenium, and zinc in its program on toxic elements in foods. The only regulatory levels for arsenic in foods in the U. S. are the tolerances which have been established for its residues in specified foods, resulting from the application of arsenical pesticides on food and feed crops and from animal feed additives. FDA has monitored for arsenic in its Total Diet Survey since the inception of this program. The data from this program indicate that the average daily intake for arsenic (as As2O3) has decreased from about 130 μg/day in 1968 to about 20 μg/day in 1974. Most of the arsenic is found in the meat-fish-poultry food class of the total diet. In individual foods, the highest levels were found in fish, with a mean level of about 1.5 ppm (as As2O3) in the edible portion of finfish. Much lower levels were found in all the other food types analyzed; of these, the highest levels found were a mean level of 0.08 ppm in chicken and 0.16 ppm in rice. FDA toxicologists do not believe that the average daily intake of arsenic, or its levels in the different food commodities, pose a hazard to the consumer.
To kill a mockingbird robot

Robots are being introduced in our society but their social status is still unclear. A critical issue is if the robot's exhibition of intelligent life-like behavior leads to the users' perception of animacy. The ultimate test for the life-likeness of a robot is to kill it. We therefore conducted an experiment in which the robot's intelligence and the participants' gender were the independent variables and the users' destructive behavior of the robot the dependent variables. Several practical and methodological problems compromised the acquired data, but we can conclude that the robot's intelligence had a significant influence on the users' destructive behavior. We discuss the encountered problems and the possible application of this animacy measuring method.
Clinical outcomes of fast MRI-based trombolysis in wake-up strokes compared to superacute ischemic strokes within 12 hours

Abstract Background: It is unknown whether thrombolysis is beneficial in patients with Wake-Up Ischemic Strokes (WUIS). This study compares the clinical outcomes of MRI-based intravenous thrombolysis in patients with hyperacute ischemic stroke presenting within 12 hours of symptom onset against WUIS patients receiving the same therapy. Methods: Patients presenting within 12 hours of acute stroke symptom onset and those with WUIS confirmed by CT, and without intracranial hemorrhage, were encouraged to perform an emergent brain MRI scan to confirm the diagnosis of hyperacute ischemic stroke [hyper-intense in diffusion-weighted imaging (DWI) and no hypo-intense change in T2-weighted imaging (T2WI) or FLAIR]. These patients then received intravenous thrombolytic therapy with tissue-type plasminogen activator (rt-PA). All patients were divided into either stroke presenting within 12 hours or WUIS. The clinical outcomes were assessed by the modified Rankin Scale (mRS) and the Barthal Index (BI) at baseline and at 90 days after the thrombolysis therapy. Results: A total of 427 patients presenting with stroke like symptoms were given a MRI scan. Of these, 240 patients had confirmed diagnosis of hyperacute ischemic stroke (WUIS, n = 68, 68/116 = 58·62% versus within 12 hour, n = 172, 172/311 = 55·3%). Altogether, 186 patients (138 in within 12 hours group, and 48 in WUIS group) received intravenous thrombolytic therapy with rt-PA. No significant differences were found in clinical outcomes between the two groups at the baseline and at 90 days after the thrombolysis therapy. Also, no difference was found in the incidence rate of secondary hemorrhage (including both of asymptomatic and symptomatic) and mortality rate between the two groups. Conclusion: Our study suggested that MRI-based intravenous thrombolysis is safe and effective in both of patients’ hyperacute stroke within 12 hours of symptom onset and WUIS.
Latent variable methods for visualization through time

This doctoral thesis presents the results of my work into the visualization of high dimensional time-dependent data. Specifically, two new algorithms are presented: Probabilistic Principal Components Through Time, and GTM Through Time. The former is a linear mapping taking time dependence into account, which is a special case of the linear Kalman Filter. The lat¬ ter is a non-linear mapping technique where a non-linear two-dimensional manifold, discretized as a regular grid of points, is fitted through the data. Each grid point corresponds to a hidden state of a Hidden Markov Model. The model builds on the existing Generative Topographical Mapping (GTM) technique for time-independent data. Both techniques utilize a particular form of probabilistic graphical model, namely a Directed Acyclic Graph, in order to achieve the extension from a time-independent model to the time dependent case. The models are trained by maximizing the log likelihood of the data given the model using the Expectation-Maximization (EM) algo¬ rithm. The behaviour of the techniques is demonstrated using toy data, and results are also presented using a real engineering data set, from a human patient monitoring application.
Motivating Cancer Prevention and Early Detection Behaviors using Psychologically Tailored Messages

ABSTRACT Tailoring health messages to make them salient to recipients is a strategy to motivate cancer prevention and early detection behaviors. Various tactics can be used to tailor health materials; our approach involves tailoring messages to individual differences in the psychological processes by which people understand health information. To summarize our tailoring approach, we review findings from six field experiments (four published, two pending publication) conducted in collaboration with the National Cancer Institute's (NCI's) Cancer Information Service (CIS) examining the utility of psychologically tailored messages. Messages were tailored to individual variability in the following: (a) need for cognition, (b) monitor/blunting coping style, (c) health locus of control, and (d) regulatory focus. Collectively, the findings suggest that, as hypothesized, messages congruent with the recipients’ psychological style of health information processing (i.e., matched messages) are more persuasive in promoting screening mammography and fruit and vegetable consumption than mismatched messages. This line of research provides evidence for the utility of psychological tailoring as a health communication strategy and direction for developing effective health messages in a variety of settings.
Glide2, a second glial promoting factor in Drosophila melanogaster

The fly glial cell deficient/glial cell missing (glide/gcm) gene codes for a transcription factor that induces gliogenesis. Lack of its product eliminates lateral glial cells in the embryonic nervous system. Here we identify a second gene, glide2, that is homologous to glide/gcm in the binding domain and that is also necessary and sufficient to promote glial differentiation. glide2 codes for a transcription factor that displays a weaker and delayed expression compared with glide/gcm. The two genes, which are located 27 kb apart and share cis‐regulatory elements, are able to auto‐ and cross‐regulate, indicating that they form a gene complex. Finally, we show that lack of both products eliminates all lateral glial cells, which means that the two genes contain all the fly lateral glial promoting activity.
Pharmacokinetic characterization of 14C‐vascular endothelial growth factor controlled release microspheres using a rat model

The objectives of this study were to characterize the pharmacokinetics of vascular endothelial growth factor (VEGF) in poly(lactic‐co‐glycolic) acid (PLGA) microspheres using a rat model, and to develop a pharmacokinetic model for this controlled release formulation. 14C‐VEGF was encapsulated using a solid‐in‐oil‐in‐water emulsification method. The microspheres were administered subcutaneously to rats and the pharmacokinetic parameters were compared with those of protein solutions. Intravenous administration of protein solutions resulted in short half‐lives and subcutaneous administration resulted in rapid clearance from the subcutaneous tissue, with high plasma concentrations as expressed by rapid absorption and elimination. The subcutaneous administration of the VEGF microspheres produced low plasma concentrations and high subcutaneous concentrations over a period of 7 weeks. The area under the curve (AUC), the time required to achieve the maximum concentration (tmax), the maximum concentration (Cmax) in blood samples and the elimination rate constant (kel) values at the subcutaneous tissue site were selected to compare the pharmacokinetic characterization of VEGF microspheres with that of protein solutions. The in‐vivo release profiles of the proteins were slower than the in‐vitro release profiles and they followed the same trend as the in‐vitro and in‐vivo PLGA degradation rates. The PLGA microsphere degradation was the determinant step for VEGF release from the microspheres and its absorption at the subcutaneous site. Microspheres appear to be an attractive system for the localized rate‐controlled delivery of VEGF. 14C‐Methylation via reductive alkylation of VEGF did not affect its mitogenic activity, however approximately 25% activity was lost following release from PLGA microspheres. This loss of activity may be due to degradation in an acidic environment as a result of PLGA degradation.
Prediction of dry matter intake based on ruminal degradation from milking cows grazing coast-cross grass

Dry matter intake (DMI) of coastcross bermudagrass grazing by crossbred Holstein-Zebu and Zebu lactating cows was calculated using in vitro dry matter digestibility from extrusa (four esophageal fistulated cows) and fecal output estimate with mordent chromium by the non linear model. Pasture was managed in a rotational system with three days of occupation and 27 days of resting period, adopting a stocking rate of 1.6 and 3.2 cows/ha respectively during the dry and rainy season. Four different equations based on ruminal degradation were used to predict dry matter intake: DMI = -1.19 + 0.035 (a+ b) + 28.5c (1), DMI = -0.822 + 0.0748 (a+ b) + 40.7c (2), DMI = -8.286 + 0.266a + 0.102b +17.696c (3) and DMI = [%FDN na MS]* [FDN intake] / [(1-a-b)/KP +b/(c+ kp)]/24] (4). The coastcross DMI predicted by the equations were different from results obtained with the model (6.3 kg of dry matter/cow/day). The data achieved using the equations 1 and 2 (12.2 and 12.7 kg/cow/day respectively) were similar and superior from results obtained by equation 4 (7.8 kg/ cow/day). Those values overestimated the results obtained using mordent chromium. The data obtained by equation 3 (5.5 kg/cow/day) was lower than those determined by equations and underestimated the DMI calculated with external marker. The prediction of dry matter intake from cows grazing tropical forages using equations based in ruminal degradation parameters constitutes an important potential for those evaluations, but it should be still studied before being employed in practice.
Color image generation and display technologies

The goal of this article is to provide an overview of the transformations and limitations that occur in color imaging input and output devices. We concentrate on two common recording devices and three common output devices. First we provide an overview of digital scanners and cameras, and then we discuss inkjet and laser printers. Finally, liquid crystal display (LCD) devices are presented.
Class EF2 inverters for wireless power transfer applications

Class EF inverters are hybrid inverters that combine the improved switch voltage and current waveforms of Class F and Class F-1 inverters with the efficient switching of Class E inverters. As a result, their switch voltage and current stresses are reduced, and their efficiency, output power and power-output capability can be higher than the Class E inverter. These improved features of Class EF inverters over Class E inverters can be beneficial in a wireless power transfer (WPT) via magnetic induction application. This paper demonstrates the application of a Class EF inverter operating at a 6.78MHz for a 25W WPT system. A sixth-order piecewise-linear state space model is presented to analyse the inverter and to derive values of its components to achieve optimum switching operation. Experimental results are provided to confirm validity of the state-space model and the design of the inverter and a DC-DC efficiency of 87% was achieved.
Treatment of murine macrophages with interferon‐γ inhibits their ability to bind leishmania promastigotes

The binding of leishmania promastigotes to macrophages pretreated with interferon‐γ (IFN‐γ) was compared to binding to untreated (resident) cells. IFN‐ γ‐treated macrophages bound fewer leishmania promastigotes than did untreated cells. The decreased binding was apparent over a wide dose range of parasite inocula when he assays were performed in the absence of exogenous complement. This decrease was specific to leishmania, since treated and untreated macrophages bound comparable amounts of immunoglobulin G‐ and complement‐coated sheep red blood cells. Decreased parasite binding occurred early in the macrophage activation pathway. Pretreatment of macrophages with IFN‐7 for as little as 6 h, a time insufficient to induce other macrophage activation parameters, significantly reduced their ability to bind leishmania promastigotes. To determine the mechanism of this decreased phagocytosis by activated cells, macrophages were pretreated with specific inhibitors before the addition of leishmania. The binding of promastigotes to untreated (resident) macrophages was inhibited by approximately 50% by reagents that blocked either of two macrophage receptors, complement receptor type 3 (Mac‐1) or a leishmania species‐specific lectin‐like receptor. Binding to IFN‐γ ‐treated macrophage populations, in contrast, was substantially inhibited only by antibody to Mac‐1. Saccharides that were 50% inhibitory in the resident cell population, decreased binding by less than 10% in activated cells. The lack of saccharide inhibition by IFN‐γ ‐treated cells was also reflected in an inability of activated macrophages to bind to beads coated with purified leishmania lipophosphoglycan (LPG). These LPG‐coated beads bound well to resident macrophages but poorly to activated cells. Thus, leishmania bind to macrophages by two distinct mechanisms, one that utilizes Mac‐1 and a second mechanism that does not depend on complement and is saccharide inheritable. These two binding mechanisms are distinct and differentially regulated in resident and activated cells.
Migration as a source of changing party strength.

The author examines the impact of international migration on the U.S. political system. He "discusses partisan change and the role migration may play within it and identifies the conditions under which migration is likely to have its greatest effect. This effect is illustrated by an intensive analysis of a Sun Belt county which has witnessed both a wave of migration-based population growth and a dramatic change in the local partisan balance. " (EXCERPT)
Magnetization transfer in MRI: a review

This review describes magnetization transfer (MT) contrast in magnetic resonance imaging. A qualitative description of how MT works is provided along with experimental evidence that leads to a quantitative model for MT in tissues. The implementation of MT saturation in imaging sequences and the interpretation of the MT‐induced signal change in terms of exchange processes and direct effects are presented. Finally, highlights of clinical uses of MT are outlined and future directions for investigation proposed. Copyright © 2001 John Wiley & Sons, Ltd.
The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic Hemostasis and Proton Pump Inhibition are Associated with Improved Outcomes in a Real-Life Setting

OBJECTIVES:From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), we determined clinical outcomes and explored the roles of endoscopic and pharmacologic therapies in a contemporary real-life setting.METHODS:Analysis of randomly selected patients endoscoped for nonvariceal upper gastrointestinal bleeding at 18 community and tertiary care institutions between 1999 and 2002. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression models identified predictors of outcomes.RESULTS:One thousand eight-hundred and sixty-nine patients were included (66 ± 17 yr, 38% female, 2.5 ± 1.6 comorbid conditions, hemoglobin, 96 ± 27 g/L, 54% received a mean of 2.9 ± 1.7 units of blood). Endoscopy was performed within 24 h in 76%, with ulcers (55%) most commonly noted. High-risk endoscopic stigmata and endoscopic therapy were reported in 37%. Rebleeding, surgery, and mortality rates were 14.1%, 6.5%, and 5.4%, respectively. Decreased rebleeding was significantly and independently associated with PPI use (85% of patients, mean daily dose 56 ± 53 mg) in all patients regardless of endoscopic stigmata, (odds ratio (OR):0.53, 95% confidence interval, 95% CI:0.37–0.77) and endoscopic hemostasis in patients with high-risk stigmata (OR:0.39, 95% CI:0.25–0.61). PPI use (OR:0.18, 95% CI:0.04–0.80) and endoscopic therapy (OR:0.31, 95% CI:0.11–0.91) were also each independently associated with decreased mortality in patients with high-risk stigmata.CONCLUSIONS:These results appear to confirm the protective role of endoscopic therapy in patients with high-risk stigmata, and suggest that acute use of PPIs may be associated with a reduction of rebleeding in all patients, and lower mortality in patients with high-risk stigmata. Independent prospective validation of these observational findings is now required.
The ‘real-life’ impact of adding bevacizumab to first-line therapy in metastatic colorectal cancer patients: A large Israeli retrospective cohort study

Abstract Background. After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear. Objective. To evaluate ‘real-life’ outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice. Methods. Using the computerized administrative database of Clalit Health Services’ (CHS), Israel's largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS’ patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates. Results. Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15. 0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77). Conclusion. In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from ‘real-life’ practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.