Miracle-dz/UniFAR-FTUs huggingface dataset:
Sympatholytic properties of several AT1-receptor antagonists in the isolated rabbit thoracic aorta

Objective To evaluate the facilitating effect of angiotensin II on sympathetic neurotransmission to quantitatively compare the sympatho-inhibitory potencies of the selective AT1-receptor antagonists losartan, irbesartan and telmisartan in the isolated rabbit thoracic aorta. Design To investigate the influence of pharmacological compounds on pre-junctional sympathetic transmission, the quantification of sympathetic transmitter release is the most straightforward approach. Methods To investigate the sympatholytic properties of AT1-blockers, we studied their effects on the enhancement by angiotensin II of electrical field stimulation (EFS)-evoked (2 Hz) sympathetic transmission in a modified spillover model. Results Angiotensin II (0.01 nmol/l−0.1 μmol/l) caused a concentration-dependent enhancement of EFS-evoked noradrenaline release (control versus concentrations 0.1 nmol/l−0.1 μmol/l, P < 0.05). The maximal augmentation, by almost 100%, was observed at a concentration of 1 nmol/l (FR2/ FR1, 2.03 ± 0.11 versus control, 0.99 ± 0.03). Higher concentrations (up to 0.1 μmol/l) produced less than maximal facilitation. The AT1-receptor antagonists losartan (0.1 nmol/l−0.1 μmol/l), telmisartan (0.01–10 nmol/l) and irbesartan (0.1 nmol/l−0.1 μmol/l) concentration dependently attenuated the angiotensin II-mediated (1 nmol/l) enhancement of EFS-evoked sympathetic outflow. The concentrations that reduced the enhancement by 50% (IC50 values, expressed as −log mol/l ± SEM) were 9.05 ± 0.16 losartan, 10.28 ± 0.20 telmisartan and 9.20 ± 0.23 irbesartan. Accordingly, the order of potency with respect to sympatho-inhibition proved telmisartan > irbesartan = losartan (where > signifies P < 0.05). Conclusions The facilitating effect of angiotensin II on the sequelae of neuronal stimulation appears to be mediated by pre-synaptically located AT1-receptors. Facilitation can be concentration dependently attenuated by AT1-blockade. The order of potency with respect to sympatho-inhibition is telmisartan > irbesartan = losartan. These differences may be explained by differences in affinity for the pre-synaptic AT1-receptor.
Relative effects of grazers and nutrients on seagrasses: a meta-analysis approach

Recent large-scale seagrass declines have prompted experimental investigations of potential mechanisms. Although many studies have implicated eutrophication or reductions of epi- phyte grazers in these declines, few experiments have simultaneously manipulated both factors to assess their relative effects. This study used meta-analyses of 35 published seagrass studies to com- pare the relative strength of 'top-down' grazer effects and 'bottom-up' nutrient effects on epiphyte biomass and seagrass above-ground growth rate, above-ground biomass, below-ground biomass, and shoot density. A surprising result was that seagrass growth and biomass were limited in situ by sediment nutrients; light limitation has been emphasized in the literature to date. Water column enrichments, which were correlated with increased epiphyte biomass, had strong negative effects on seagrass biomass. Grazers overall had a positive effect on shoot density, but negligible effects on sea- grass biomass and growth rate. However, analyzing epiphyte grazers separately from other grazers revealed positive effects of grazing on seagrass response variables and corresponding negative impacts on epiphyte biomass. The positive effects of epiphyte grazers were comparable in magnitude to the negative impacts of water column nutrient enrichment, suggesting that the 2 factors should not be considered in isolation of each other. Until the determinants of epiphyte grazer populations are empirically examined, it will be difficult to address the contribution that overfishing and cascading trophic effects have had on seagrass decline. Because increases in water column nutrients are docu- mented in many regions, efforts to reduce coastal eutrophication are an appropriate and necessary focus for the management and conservation of seagrass ecosystems.
The Impact of Fiscal Policy on Profits

This paper investigates the impact of fiscal policy on profits using panel data for 19 high-income OECD countries during the period 1975-1999. We estimate a profit equation in which profits depend on a set of fiscal variables. Our empirical method is based on a consistent treatment of the government budget constraint, and we try to disentangle the effects of different spending and taxation items. As far as public spending is concerned, our results strongly suggest that capital expenditures are associated with higher profits, while expenditures on wages and salaries deteriorate profits. At the same time our results indicate that transport and communication expenditures increase profits, while the opposite holds for defense expenditures. On the revenue side, both direct and indirect taxation tend to decrease profits. However, a more detailed sub-division of direct taxation indicates that social security contributions have a neutral effect on profits.
The effect of interconnect schemes on the dependability of a modular multi-processor system with shared resources

AlliedSignal's Avionics & Lighting business unit is expanding the performance of its flight safety avionics by means of functional integration (added functionality enabled by exchanging information between traditionally stand-alone subsystems), as well as physical integration (sharing of system resources) and full dual redundancy. Major performance goals of this integrated modular architecture are a significant increase in system dispatchability and reduction of the loss-of-function probability of individual junctions. Success of this architectural migration depends on the scheme that is used to fully interconnect the various processing and input/output modules. Two of the considered interconnect schemes are discussed: a dual LAN and a dual-dual LAN. In both schemes, all modules can receive data from all LANs. In the prior scheme, all system modules have time-multiplexed transmit privileges on both LANs. In the latter scheme (patent pending), the modules are grouped into two identical sets. The modules in a set can only transmit on two of the four LANs. Dependability of the system has been modeled and analyzed with the HIMAP tool for both schemes, and the results are presented.
Treatment with bortezomib in a patient with heavily pretreated refractory T‐cell lymphoblastic lymphoma

Abstract: T‐cell lymphoblastic lymphomas are highly aggressive non‐Hodgkin's lymphoma (NHL) and account for approximately 3% of all adult NHL histologies, with poor prognosis. We describe a 38‐year‐old patient with T‐cell lymphoblastic lymphoma, who responds to bortezomib and doxorubincin combination, following a failure of conventional chemotherapy. Two months after treatment, the patient showed near complete remission of the lymphadenopathy. These data suggest a possible synergistic effect with bortezomib in combination with doxorubincin and dexamethasone. To our knowledge, this is the first case of T‐cell lymphoblastic lymphoma treated with bortezomib.
Sympathetic denervation facilitates L-type Ca2+ channel activation in renal but not in mesenteric resistance arteries

Objectives: Sympathetic denervation enhances agonist-induced vasoconstriction. This effect may involve altered function of signaling mechanisms such as Rho kinase (Rock) and L-type Ca2+ channels downstream from vasoconstrictor receptors. We tested if enhanced Rock and L-type calcium channel activation contribute to exaggerated norepinephrine-induced vasoconstrictions in renal and mesenteric resistance arteries after sympathectomy. Methods: Rats underwent neonatal sympathectomy or sham sympathectomy. Resistance arteries were investigated by small vessel myography. Vascular Rock and L-type Ca2+ channel expression as well as Rock activation were investigated by quantitative real-time PCR and Western blot. Vascular smooth muscle cell (VSMC) membrane potential was recorded with microelectrodes. Results: Sympathetic denervation enhanced norepinephrine sensitivity in renal and mesenteric arteries. Both, Rock inhibition or L-type Ca2+ inhibition shifted the norepinephrine concentration–response curve to the right. This effect was more pronounced in renal than in mesenteric arteries from sympathectomized vs. sham-sympathectomized animals. The L-type Ca2+ channel activator S-(-)-BayK8644 elicited strong vasoconstrictions only in renal arteries from sympathectomized rats. Rock activity and L-type Ca2+ channel &agr;-subunit expression were similar in renal arteries from sympathectomized and sham-sympathectomized animals. VSMC membrane potential was −57.5 ± 2.0 and −64.3 ± 0.3 mV (P < 0.01), respectively, in renal arteries from sympathectomized and from sham-sympathectomized rats. Depolarization enhanced and KATP channel activation abolished S-(-)-BayK8644-induced contractions in renal arteries from sympathectomized rats. Conclusion: Sympathetic denervation enhances L-type Ca2+ channel-dependent signaling in renal but not in mesenteric arteries. This effect may be partly explained by the decreased VSMC membrane potential in denervated renal arteries.
New Fe-Pt media for perpendicular magnetic recording

Ordered Fe-Pt perpendicular magnetic recording media were studied in terms of the effects of magnetic domain sizes on the recording performances. As the domain size decreased, the magnetization reversal changed from the wall motion to the rotational mode, and the medium noise reduced. A high SNR, 39 dB/sub p-p/rms/, was achieved for a track width of 2.7 /spl mu/m at a recording density of 100 kFRPI for a single-layer medium with an 82 nm magnetic domain size. On the other hand, little recording demagnetization was observed in the medium with a steep slope in the M-H loop. A composite medium with a soft-magnetic backlayer exhibited an extremely high signal output. The possibility of high recording resolution was discussed by the MFM spectrum analysis for the recording patterns.
Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical‐trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case–control subset. During a mean follow‐up of 11‐years, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR = 0.65, 95% CI: 0.40–1.04; ptrend = 0.065), but not with lignans. Among flavonoid subclasses, flavanols were inversely associated with HCC risk (HR = 0.62, 95% CI: 0.39–0.99; ptrend = 0.06). Dietary NEAC was inversely associated with HCC (FRAP: HR 0.50, 95% CI: 0.31–0.81; ptrend = 0.001; TRAP: HR 0.49, 95% CI: 0.31–0.79; ptrend = 0.002), but statistical significance was lost after exclusion of the first 2 years of follow‐up. This study suggests that higher intake of dietary flavanols and antioxidants may be associated with a reduced HCC risk.
Cytoplasmic Clusterin Expression Is Associated with Longer Survival in Patients with Resected Non–Small Cell Lung Cancer

Background: Clusterin is a glycoprotein that has been implicated in many processes, including apoptosis, cell cycle regulation, and DNA repair. Previous studies have examined the prognostic value of clusterin expression in various malignancies. In the present study, we examined clusterin staining in tumors resected from patients with non–small cell lung cancer (NSCLC). Materials and Methods: Tumor specimens were obtained for 113 patients with completely resected NSCLC from paraffin-embedded tissue microarrays and stained with an antibody specific for clusterin. Staining patterns were observed and graded based on intensity and then correlated with clinical data. Results: Positive cytoplasmic clusterin staining was observed in 44 patients, and weak/negative staining was observed in 62 patients. Patients who had tumors that stained positive for cytoplasmic clusterin had significantly longer survival in multivariate analysis (hazard ratio 0.487, 95% confidence interval 0.27-0.89). A correlation was also observed for recurrence-free survival, which approached statistical significance (hazard ratio 0.345, 95% confidence interval 0.12-1.02). In univariate analysis, patients with clusterin-positive tumors had a 63% 3-year survival, whereas patients with clusterin-negative tumors had a 42% 3-year survival (P = 0.0108); clusterin-positive tumors also had significantly less recurrence (P = 0.0231). Conclusions: Cytoplasmic clusterin staining is present in a substantial number of NSCLC tumors and may be a biomarker for longer survival in patients with surgically resected NSCLC. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1845–51)
An Examination of Social Comparison and Suicide Ideation Through the Lens of the Integrated Motivational–Volitional Model of Suicidal Behavior

We aimed to investigate whether negative social comparisons are associated with key components of the integrated motivational-volitional (IMV) model of suicidal behavior. Specifically, we investigated the relationship between negative social comparisons, suicide ideation, defeat, entrapment, socially prescribed perfectionism, and resilience. Adult participants (N = 422) completed an online survey comprised of a range of psychological measures. An initial regression analysis indicated that negative social comparisons were associated with suicide ideation. Three mediation models were tested based on the IMV model, all controlling for depressive symptoms. In the first, social comparison partially mediated the relationship between socially prescribed perfectionism and defeat. In the second, defeat mediated the relationship between negative social comparisons and entrapment, and resilience moderated the relationship when defeat was high. In the final model, entrapment mediated the relationship between defeat and suicide ideation, with resilience moderating this relationship when entrapment was high. These findings are novel and lend support to the IMV model. The clinical implications include highlighting the importance of targeting resilience given its potential association with defeat and entrapment.
Alterations of Fc gamma receptor I and Toll‐like receptor 4 mediate the antiinflammatory actions of microglia and astrocytes after adrenaline‐induced blood–brain barrier opening in rats

Blood–brain barrier (BBB) opening occurs under many physiological and pathological conditions. BBB opening will lead to the leakage of large circulating molecules into the brain parenchyma. These invasive molecules will induce immune responses. Microglia and astrocytes are the two major cell types responsible for immune responses in the brain, and Fc gamma receptor I (FcγRI) and Toll‐like receptor 4 (TLR4) are the two important receptors mediating these processes. Data suggest that activation of the FcγRI pathway mediates antiinflammatory processes, whereas activation of TLR4 pathway leads to proinflammatory activities. In the present study, we tested the hypothesis that BBB opening could lead to alterations in FcγRI and TLR4 pathways in microglia and astrocytes, thus limiting excessive inflammation in the brain. The transient BBB opening was induced by adrenaline injection through a caudal vein in Sprague‐Dawley rats. We found that the FcγRI pathway was significantly activated in both microglia and astrocytes, as exhibited by the up‐regulation of FcγRI and its key downstream molecule Syk, as well as the increased production of the effector cytokines, interleukin (IL)‐10 and IL‐4. Interestingly, after transient BBB opening, TLR4 expression was also increased. However, the expression of MyD88, the central adapter of the TLR4 pathway, was significantly inhibited, with decreased production of the effector cytokines IL‐12a and IL‐1β. These results indicate that, after transient BBB opening, FcγRI‐mediated antiinflammatory processes were activated, whereas TLR4‐mediated proinflammatory activities were inhibited in microglia and astrocytes. This may represent an important neuroprotective mechanism of microglia and astrocytes that limits excessive inflammation after BBB opening. © 2008 Wiley‐Liss, Inc.
Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development

Tendon function involves the development of an organized hierarchy of collagen fibrils. Small leucine‐rich proteoglycans have been implicated in the regulation of fibrillogenesis and decorin is the prototypic member of this family. Decorin‐deficient mice demonstrate altered fibril structure and mechanical function in mature skin and tail tendons. However, the developmental role(s) of decorin needs to be elucidated. To define these role(s) during tendon development, tendons (flexor digitorum longus) were analyzed ultrastructurally from postnatal day 10 to 90. Decorin‐deficient tendons developed abnormal, irregularly contoured fibrils. Finite mixture modeling estimated that the mature tendon was a three‐subpopulation mixture of fibrils with characteristic diameter ranges. During development, in each subpopulation the mean diameter was consistently larger in mutant mice. Also, diameter distributions and the percentage of fibrils in each subpopulation were altered. Biomechanical analyses demonstrated that mature decorin‐deficient tendons had significantly reduced strength and stiffness; however, there was no reduction in immature tendons. Expression of decorin and biglycan, a closely related family member, was analyzed during development. Decorin increased with development while biglycan decreased. Spatially, both had a comparable localization throughout the tendon. Biglycan expression increased substantially in decorin‐deficient tendons suggesting a potential functional compensation. The accumulation of structural defects during fibril growth, a period associated with decorin expression and low biglycan expression, may be the cause of compromised mechanical function in the absence of decorin. Our findings indicate that decorin is a key regulatory molecule and that the temporal switch from biglycan to decorin is an important event in the coordinate regulation of fibrillogenesis and tendon development. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.
Teenagers’ Licensing Decisions and Their Views of Licensing Policies: A National Survey

Objective: One objective was to determine teenage licensing rates on a national basis, interest in early licensure, and reasons for delay. A second objective was to learn teenagers’ opinions about licensing policies, important in states considering ways to upgrade their current licensing systems. Methods: One thousand three hundred eighty-three 15- to 18-year-olds completed an online survey in November 2010. They were drawn from a nationally representative panel of US households recruited using probability-based sampling. The panel included cell phone–only households, and Internet access was provided to those without it. Weighting procedures were applied so that the study population represented the national US population of 15- to 18-year-olds. Results: Most teens said that they were interested in getting a license as soon as legally possible, but many had not started the process. At 16, teens were about equally divided among those who had not started, those in the learner stage, and those with a restricted or full license. At 18, 62 percent had full licenses; 22 percent had not started. For those old enough to start, lack of a car, costs, parent availability, ability to get around without a car, and being busy with other activities were leading reasons for delay. The majority of teens were not in favor of higher licensing ages. Forty-six percent thought the minimum learner age should be 16; 30 percent thought the full license age should be 18 or older. The majority approved of night (78%) and passenger (57%) restrictions, and 85 and 93 percent endorsed cell phone and texting bans, respectively. When these policies were packaged together in a single law that included an age 16 start, night, passenger, cell phone and texting bans, and a full license at age 18, 74 percent of teens were in favor. Conclusions: Teenagers are not as supportive of strong licensing policies as parents of teens, but there is evidence that they will support comprehensive policies likely to lead to further reductions in teen crash rates.
Mortality Associated With Seasonal and Pandemic Influenza Among Pregnant and Nonpregnant Women of Childbearing Age in a High-HIV-Prevalence Setting-South Africa, 1999-2009.

BACKGROUND Information on the mortality burden associated with seasonal and pandemic influenza virus infection among pregnant women is scarce in most settings, particularly in sub-Saharan Africa where pregnancy and maternal mortality rates as well as human immunodeficiency virus (HIV) prevalence are elevated. METHODS We used an ecological study design to estimate the seasonal and A(H1N1)pdm09 influenza-associated mortality among pregnant and nonpregnant women of childbearing age (15-49 years) by HIV serostatus during 1999-2009 in South Africa. Mortality rates were expressed per 100 000 person-years. RESULTS During 1999-2009, the estimated mean annual seasonal influenza-associated mortality rates were 12.6 (123 deaths) and 7.3 (914 deaths) among pregnant and nonpregnant women, respectively. Among pregnant women, the estimated mean annual seasonal influenza-associated mortality rates were 74.9 (109 deaths) among HIV-infected and 1.5 (14 deaths) among HIV-uninfected individuals. Among nonpregnant women, the estimated mean annual seasonal influenza-associated mortality rate was 41.2 (824 deaths) among HIV-infected and 0.9 (90 deaths) among HIV-uninfected individuals. Pregnant women experienced an increased risk of seasonal influenza-associated mortality compared with nonpregnant women (relative risk [RR], 2.8; 95% confidence interval [CI], 1.7-3.9). In 2009, the estimated influenza A(H1N1)pdm09-associated mortality rates were 19.3 (181 deaths) and 9.4 (1189 deaths) among pregnant and nonpregnant women, respectively (RR, 3.2; 95% CI, 2.3-4.1). CONCLUSIONS Among women of childbearing age, the majority of estimated seasonal influenza-associated deaths occurred in HIV-infected individuals. Pregnant women experienced an increased risk of death associated with seasonal and A(H1N1)pdm09 influenza infection compared with nonpregnant women.