Miracle-dz/UniFAR-FTUs huggingface dataset:
Reserpine Increases Chromaffin Cell Enkephalin Stores Without a Concomitant Decrease in Other Proenkephalin‐Derived Peptides

Abstract: Reserpine increases the levels of enkephalins in adrenal medullary chromaffin cells; however, the origin of the newly apparent pentapeptides has been the subject of debate, because no increase in the levels of proenkephalin mRNA has been observed. The present study was performed for determining if the reserpine‐induced increase in content of enkephalins was derived from processing of preexisting fragments of proenkephalin. Bovine chromaffin cell enkephalins and larger enkephalin‐containing peptides were separated by reversed‐phase HPLC and identified by approximate molecular weight, elution with peptide standards, and enkephalin sequences contained. Treatment of the cells with reserpine increased the levels of enkephalins and of enkephalin‐containing peptides of up to ∼3 kilo‐daltons without reducing the levels of larger enkephalin‐containing peptides. Similar results were obtained with another catecholamine‐depleting drug, tetrabenazine. In contrast, treatment of chromaffin cells with theophylline or forskolin increased the levels of both enkephalins and enkephalin‐containing peptides of all sizes. The results suggest that new synthesis of proenkephalin is required for the effects of reserpine, although proenkephalin processing is also altered by this drug.
Lsm1-7-Pat1 complex: A link between 3’ and 5’-ends in mRNA decay?

Messenger RNA decay occurs via two major pathways (3’ to 5’ and 5’ to 3’ pathways) that are conserved in all eukaryotes. A key feature of these pathways is that mRNAs are targeted for degradation only after they have undergone deadenylation so that polyadenylated mRNAs are not attacked. Thus, in the 5’ to 3’ pathway, oligoadenylated mRNAs (but not polyadenylated mRNAs) are selectively decapped and then degraded in a 5’ to 3’ exonucleolytic manner. Here, normal rates of decapping require the decapping activator, the Lsm1-7-Pat1 complex. This complex has a strong intrinsic binding preference for oligoadenylated mRNAs over polyadenylated mRNAs and such preferential binding ability is crucial for its mRNA decay function. This suggests that this complex contributes to the deadenylation dependence of decapping in the 5’ to 3’ pathway by selectively targeting oligoadenylated messages for decapping. The Lsm1-7-Pat1 complex is also capable of recognizing the presence of U-tracts at the 3’-end of RNA and such recognition appears to be important in facilitating the decapping and 5’ to 3’ decay of histone mRNAs in response to oligouridylation. Thus, this complex influences decapping event at the 5’-end by recognizing simple sequence features at the 3’-end of the mRNA. Additional studies implicate this complex in the inhibition of exosome mediated 3’ to 5’ decay of mRNAs raising the possibility that in vivo, the major mode of decay of an mRNA could be determined by the efficiency of binding of the Lsm1-7-Pat1 complex to that mRNA.
Design of a K-band wideband controlled variable attenuator for microwave Built-In-Self-Test applications

This paper presents a new microwave wideband controlled variable attenuator designed in a BiCMOS process. This variable attenuator is implanted as part of a microwave Built-In-Self-Test (BIST) circuit. The proposed BIST cell is dedicated for direct low cost measurement of the gain and the input 1dB compression point (CP1) of a K-band satellite reception chain (18.2 GHz-22 GHz). The simulation of the controlled variable attenuator with RLCk parasitic extraction shows that it can operate up to 100 GHz with a consumption of 4 mA, an area less than 0.009 mm2 excluding pads and a gain range of 36 dB when the attenuator is alone and 17 dB when it is concatenated to the other blocks. This result was confirmed with the performed measurement on the BIST device. This BIST circuit gives new perspectives in term of test strategy, cost reduction and measurement accuracy for mm-wave integrated circuits.
Enhanced endothelin receptor type B‐mediated vasodilation and underlying [Ca2+]i in mesenteric microvessels of pregnant rats

Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin‐1 (ET‐1) causes vasoconstriction via endothelin receptor type A (ETAR), but could activate ETBR in the endothelium and release vasodilator substances. However, the roles of ETBR in the regulation of vascular function during pregnancy and the vascular mediators involved are unclear.
Triage of low-risk prostate cancer patients with PSA levels 10 ng/ml or less: comparison of apparent diffusion coefficient value and transrectal ultrasound-guided target biopsy.

OBJECTIVE The purpose of our study was to identify low-risk prostate cancer on the basis of the D'Amico clinical risk score in patients with prostate-specific antigen (PSA) levels 10 ng/mL or less who had undergone radical prostatectomy by comparing apparent diffusion coefficient (ADC) with transrectal ultrasound (TRUS)-guided target biopsy. MATERIALS AND METHODS In the preliminary study, we used receiver operating characteristic (ROC) analysis and determined the cutoff ADC to identify prostate cancer with a Gleason score of 6 or less for 117 patients. In the primary study, we assessed the combination of routine MRI (T2-weighted and diffusion-weighted imaging) plus the cutoff ADC value ("method A") to identify low-risk prostate cancer for another 89 patients. Their diagnostic value was compared with that of routine MRI combined with the Gleason score obtained from TRUS-guided target biopsies ("method B"). RESULTS The preliminary study showed that a mean ADC of 1.04 × 10(-3) mm(2)/s was the best cutoff. In the primary study, accuracy was statistically higher with method A for each reader (p = 0.041). CONCLUSION In patients with PSA levels 10 ng/mL or less, the combination of MRI findings plus the cutoff ADC is significantly more accurate for the identification of low-risk prostate cancer than is the combination of MRI followed by TRUS-guided target biopsy.
Efficacy of low-level laser therapy in the treatment of temporomandibular disorder.

AIMS To evaluate the effectiveness of low-level laser therapy (LLLT) in patients presenting with temporomandibular disorder (TMD) in a random and placebo-controlled research design. METHODS The sample consisted of 40 patients, divided into an experimental group (G1) and a placebo group (G2). The treatment was done with an infrared laser (830nm, 500mW, 20s, 4J/point) at the painful points, once a week for four consecutive weeks. The patients were evaluated before and after the treatment through a Visual Analogue Scale (VAS) and the Craniomandibular Index (CMI). RESULTS The baseline and posttherapy values of VAS and CMI were compared by the paired T-test, separately for the placebo and laser groups. A significant difference was observed between initial and final values (p < 0.05) in both groups. Baseline and post-therapy values of pain and CMI were compared in the therapy groups by the two-sample T-test, yet no significant differences were observed regarding VAS and CMI (p > 0.05). CONCLUSION After either placebo or laser therapy, pain and temporomandibular symptoms were significantly lower, although there was no significant difference between groups. The low-level laser therapy was not effective in the treatment of TMD, when compared to the placebo.
Insurance Choice Under Third Degree Stochastic Dominance

In this paper, we investigate the insurance choice of a risk-averse and prudent insured by assuming that the insurance premium is calculated by a general mean–variance principle. This general class of premium principles encompasses many widely used premium principles such as expected value, variance related, modified variance and mean value principles. We show that any admissible insurance contract, in which the marginal indemnity above a deductible minimum is decreasing in the loss and has a value greater than zero and less than one, is suboptimal to a dual change-loss insurance policy or a change-loss insurance policy, depending upon the coefficient of variation of the ceded loss. Especially for variance related premium principles, it is shown that the change-loss insurance is optimal. In addition to change-loss insurance, a numerical example illustrates that the dual change-loss insurance may also be an optimal choice when the insurance premium is calculated by mean value principle.
The Male Minor Transplantation Antigen Preferentially Activates Recipient CD4+ T Cells through the Indirect Presentation Pathway In Vivo 1

To evaluate the priming and trafficking of male Ag-reactive CD4+ T cells in vivo, we developed an adoptive transfer model, using Marilyn (Mar) TCR transgenic T cells that are specific for the H-Y minor transplantation Ag plus I-Ab. By manipulating donor and recipient strain combinations, we permitted the Mar CD4+ T cells to respond to the H-Y Ag after processing and presentation by recipient APCs (indirect pathway), or to the male Ag as expressed on donor APCs (direct pathway). Mar CD4+ T cells responding through the indirect pathway specifically proliferated and expressed activation markers between days 2 and 4 posttransplant, migrated to the graft 2–3 days before cessation of graft heartbeat, and were detected in close proximity to transplant-infiltrating recipient APCs. Intriguingly, adoptively transferred Mar T cells did not respond to male heart or skin grafts placed onto syngeneic MHC class II-deficient female recipients, demonstrating that activation of Mar T cell preferentially occurs through cognate interactions with processed male Ag expressed on recipient APCs. The data highlight the potency of indirect processing and presentation pathways in vivo and underscore the importance of indirectly primed CD4+ T cells as relevant participants in both the priming and effector phases of acute graft rejection.
Implications of a large global root biomass for carbon sink estimates and for soil carbon dynamics

Recent evidence suggests that significantly more plant carbon (C) is stored belowground than existing estimates indicate. This study explores the implications for biome C pool sizes and global C fluxes. It predicts a root C pool of at least 268 Pg, 68% larger than previously thought. Although still a low-precision estimate (owing to the uncertainties of biome-scale measurements), a global root C pool this large implies stronger land C sinks, particularly in tropical and temperate forests, shrubland and savanna. The land sink predicted from revised C inventories is 2.7 Pg yr−1. This is 0.1 Pg yr−1 larger than current estimates, within the uncertainties associated with global C fluxes, but conflicting with a smaller sink (2.4 Pg yr−1) estimated from C balance. Sink estimates derived from C inventories and C balance match, however, if global soil C is assumed to be declining by 0.4–0.7% yr−1, rates that agree with long-term regional rates of soil C loss. Either possibility, a stronger land C sink or widespread soil C loss, argues that these features of the global C cycle should be reassessed to improve the accuracy and precision of C flux and pool estimates at both global and biome scales.
Analysis of the energization test of 2600-km long AC-Link composed of similar transmissions lines

This paper presents the analysis of the use of similar transmission lines to represent a trunk of a little more than a half wavelength (HWL+) in order to conduct an on-site energization test. The validation of the AC-Link Test is performed through the analysis of two-port elements constants in the frequency domain. Time domain simulations are also presented to the studied trunk. Results of the response of the AC-Link are analyzed and also it is established the limits of different transmission lines that can still represent a HWL+ trunk in order to enable similar tests within different power systems.
Brief report: condom use consistency associated with beliefs regarding HIV disease transmission among women receiving HIV antiretroviral therapy.

OBJECTIVE To ascertain whether condom use consistency is associated with beliefs regarding a decreased likelihood of HIV transmission as a function of taking antiretroviral therapy. DESIGN Cross-sectional analysis of HIV-positive women from Brooklyn (NY) enrolled in the Women's Interagency HIV Study (WIHS) who were taking any form of antiretroviral therapy at the time of data collection. METHODS Between February and October, 1999, 145 HIV-positive eligible women participated in a structured, face-to-face interview. Interviews assessed attitudes and behaviors related to antiretroviral therapy and sexual risk behavior in the 6 months since a previous study visit. RESULTS Over three fourths of the study sample (77%) disagreed with a statement that being on antiretroviral therapy decreases the chances of transmitting HIV to others. After controlling for number of sexual partners and HIV serostatus of partners, women reporting no association between HIV therapy and disease infectiousness were over three times more likely to report consistent condom use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.2-8.3; p <.05). CONCLUSIONS Antiretroviral therapy may be associated with increased risk behavior when it is believed that regimens may decrease the risk of disease transmission. Education regarding potential deleterious consequences of inconsistent condom use should be part of ongoing HIV care.
Using Leadership Development Programs to Improve Quality and Efficiency in Healthcare

With heightened emphasis on the imperatives to improve the quality and efficiency of healthcare delivered in U.S. hospitals and health systems, healthcare managers are challenged to consider innovative approaches to address these issues. Leadership development programs are increasingly common offerings within healthcare organizations, but linking such initiatives to quality and efficiency improvement programs remains rare. This article uses data from three qualitative studies of leadership development in healthcare to answer the question, "What opportunities might exist to use leadership development programs to improve quality and efficiency? " Interviews from 200 individuals were conducted between September 2003 and December 2007 with hospital and health system managers and executives, academic experts, consultants, individuals representing associations and vendors of leadership development programs, and program participants. Analyses of these data showed that leadership development programs provide four important opportunities to improve quality and efficiency in healthcare: (1) by increasing the caliber of the workforce, (2) by enhancing efficiency in the organization's education and development activities, (3) by reducing turnover and related expenses, and (4) by focusing organizational attention on specific strategic priorities. Several concrete examples of how to leverage leadership development in these ways are provided to help managers consider how to apply these research findings. Healthcare managers can use the results reported from these studies to extend the reach of current leadership development programs or to inform the design of new initiatives that focus specifically on quality and efficiency improvement. Although quantitative metrics are required to measure definitive improvements in quality and efficiency in healthcare, these qualitative data highlight opportunities through which leadership development initiatives can contribute to improvement efforts.
Preclinical Evaluation of Antiangiogenic Thrombospondin-1 Peptide Mimetics, ABT-526 and ABT-510, in Companion Dogs with Naturally Occurring Cancers

Purpose: The angiogenic phenotype of malignant cancers has been established as a target for cancer therapy. ABT-526 and ABT-510, two peptide mimetics of thrombospondin-1 (TSP-1), block angiogenesis in vitro and in vivo and slow tumor growth in mice. To guide the clinical development of these drugs, translational studies in dogs with naturally occurring cancers were initiated. Experimental Design: A prospective open-label trial using ABT-510 or ABT-526 in pet dogs with measurable malignant spontaneously arising tumors. Endpoints included safety, pharmacokinetics, antitumor activity, and preliminary assessment of changes in circulating endothelial cell populations. Results: Two-hundred and forty-two dogs were sequentially entered to this open-label trial. The elimination half-life for ABT-510 and ABT-526 was 0.7 and 0.8 h, respectively (range, 0.5-1 h). No dose-limiting toxicities were seen in any dogs (N = 242). Forty-two dogs receiving peptide had objective responses (>50% reduction in tumor size; n = 6) or significant disease stabilization. Most objective responses were seen after 60 days of exposure to the TSP-1 peptide. Antitumor activity was similar for both peptides and was seen in several histologies, including mammary carcinoma, head and neck carcinoma, soft tissue sarcoma, cutaneous T-cell lymphoma, and non–Hodgkin's lymphoma. Assessment of circulating endothelial cell populations in a small subset of dogs suggested that effective exposure to TSP-1 peptides may be associated with reductions in circulating endothelial cells. Conclusions: These results support the safety and activity of ABT-526 and ABT-510 in dogs with naturally occurring malignant cancers. Data from this preclinical trial support the development of TSP-1 mimetic peptides as anticancer agents.
Identification of the paraproteins and clinical significance of more than one paraprotein in serum of 56 patients

SUMMARY Sera from 56 patients with more than one paraprotein were investigated for immuno-globin class and light chain type of each paraprotein. The patients were divided into two groups according to the diagnosis, that is, myeloma and macroglobulinaemia or others. The frequency of combinations of paraproteins was considered in the whole series and in the two groups. The laboratory and clinical findings were analysed to investigate the diagnostic and prognostic significance of more than one paraprotein in a serum. It is concluded that a lower percentage of patients with more than one paraprotein can definitely be shown to have myeloma than might be expected from studies on monoclonal paraproteinaemia, that patients having IgA paraproteins in the serum had the poorest prognosis, and that paraproteins with lambda light chains were more likely to be associated with myeloma or macroglobulinaemia.
Exposure of Allan Hills 84001 and other achondrites on the Antarctic ice

Abstract— The enrichment of F on Antarctic meteorites is the result of their exposure to the atmosphere, and its measurement allows a subdivision of the terrestrial age into a duration of exposure on the ice and the time a meteorite was enclosed by the ice. In many cases, the periods of surface exposure are only small fractions of the terrestrial ages of meteorites collected in Antarctica. The enrichment of F on the surfaces of Antarctic achondrites was investigated by means of nuclear reaction analysis (NRA): scanning proton beams with an energy of 2.7 and 3.4 MeV were used to induce the reactions 19F(p,αγ)16O and 19F(p, p'γ)19F, respectively. Gamma signals proportional to the F content were measured. The following Antarctic achondrites were investigated: Martian meteorite ALH 84001; diogenite ALHA77256; the eucrites ALHA81011 and ALHA78132; and in addition, the H5 chondrite ALHA79025. For ALH 84001, our data indicate a period of exposure on the ice of <500 years. Thus, this specimen was enclosed in the ice >95% of its terrestrial age of 13 000 years.
Effects of Back School Education and Exercise in Back Injured Municipal Workers

Low back injury is the leading cause of compensable injury. A National Health Objective for the year 2000 is to increase to at least 50% the number of worksites offering back injury protection programs. The 6 week Back School intervention included exercise and education. A portion of the sample of 74 back injured municipal employees also was assigned randomly to a counseling intervention. Pre-intervention and post-intervention testing revealed significant posttest increases in back strength and flexibility. Significant improvements also were noted in psychological well being, depression, anxiety, and perceptions of pain. No significant differences were found, on any of the measures, between employees who did and who did not receive the counseling intervention. Methodological concerns relate to the possibility of sampling bias and instrumentation. Future research with control groups is needed, as well as the testing of interventions that may be both effective and require less work release time.
Phosphorylation sites required for regulation of cardiac calcium channels in the fight-or-flight response

Significance This work defines the in vivo role of phosphorylation of Ser1700 and Thr1704 in CaV1.2 channels in the fight-or-flight response. Mutation of both residues to Ala in STAA mice reduced basal L-type Ca2+ currents and markedly decreased β-adrenergic stimulation of Ca2+ currents and cell contraction. STAA ventricular myocytes exhibited arrhythmic contractions and often failed to sustain contractions when stimulated at 1 Hz. STAA mice have reduced exercise capacity, and cardiac hypertrophy is evident at 3 mo. Our results define the molecular mechanism for Ca2+ channel regulation in the fight-or-flight response and give insight into mechanisms that underlie cardiac homeostasis and hypertrophy. L-type Ca2+ currents conducted by CaV1.2 channels initiate excitation–contraction coupling in the heart. Their activity is increased by β-adrenergic/cAMP signaling via phosphorylation by PKA in the fight-or-flight response, but the sites of regulation are unknown. We describe the functional role of phosphorylation of Ser1700 and Thr1704—sites of phosphorylation by PKA and casein kinase II at the interface between the proximal and distal C-terminal regulatory domains. Mutation of both residues to Ala in STAA mice reduced basal L-type Ca2+ currents, due to a small decrease in expression and a substantial decrease in functional activity. The increase in L-type Ca2+ current caused by isoproterenol was markedly reduced at physiological levels of stimulation (3–10 nM). Maximal increases in calcium current at nearly saturating concentrations of isoproterenol (100 nM) were also significantly reduced, but the mutation effects were smaller, suggesting that alternative regulatory mechanisms are engaged at maximal levels of stimulation. The β-adrenergic increase in cell contraction was also diminished. STAA ventricular myocytes exhibited arrhythmic contractions in response to isoproterenol, and up to 20% of STAA cells failed to sustain contractions when stimulated at 1 Hz. STAA mice have reduced exercise capacity, and cardiac hypertrophy is evident at 3 mo. We conclude that phosphorylation of Ser1700 and Thr1704 is essential for regulation of basal activity of CaV1.2 channels and for up-regulation by β-adrenergic signaling at physiological levels of stimulation. Disruption of phosphorylation at those sites leads to impaired cardiac function in vivo, as indicated by reduced exercise capacity and cardiac hypertrophy.