Miracle-dz/UniFAR-FTUs huggingface dataset:
Metoprolol, but not atenolol, reduces stress induced neuropeptide Y release in pigs

Abstract Objectives. To explore if β-adrenergic receptors in the brain are involved in acute and delayed cardiovascular responses to a brief emotional stress, by comparing the effects of the β1-blockers metoprolol (lipophilic) and atenolol (hydrophilic). Design. Male dominant pigs, singleliving, freely moving, with telemetric recordings of intra-arterial pressure and ECG and assay of plasma levels of the adrenergic cotransmittor neuropeptide Y (NPY), were confronted with four alien pigs for three minutes at weekly intervals. Weeks 1 and 4 were controls, in weeks 2 and 3 randomized crossover treatment with metoprolol or atenolol were given. Results. The confrontation caused instant and transient tachycardia and more prolonged effects in terms of increased plasma NPY levels, increased arterial pressure and reduced cardiac vagal activation. The two β-blockers inhibited the tachycardia equally, but only metoprolol reduced the prolonged effects. Conclusions. Emotionally induced sympathetic activation involves peripheral release of NPY causing a prolonged increase of arterial pressure and a reduction of cardiac vagal activity. These effects are prevented by central nervous β-adrenoceptor blockade.
Insights into Mechanism of Glucokinase Activation

Background: Human glucokinase (GK) is a principal regulator of glucose homeostasis. Results: The structure of the catalytic complex of GK has been determined, and multiple conformations have been directly observed in solution. Conclusion: In solution, glucose dose-dependently converts GK from the apo conformation to an active open conformation. Significance: Understanding the conformational changes of GK during the reaction is crucial for designing better glucokinase activators with safer profiles. Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk.
Report: Treatment of commercial, construction and demolition waste in North Rhine-Westphalia: policy-making and operation options

This paper summarizes a long-term-investigation of the mechanical treatment of commercial, construction and demolition waste materials in North Rhine-Westphalia in the light of applied operation standards and a disposal ban on untreated waste. It is shown how both the allocation of output materials from mechanical treatment plants and the subsequent treatment channels have changed since enforcement of the ban in 2005. Based on the findings of the investigation, two waste management scenarios offering alternative policies have been defined and are discussed. It is suggested that consistent enforcement of the ban affects both the diversion of waste to incineration and the recovery of materials on a regional scale. On the other hand, potential energy recovery may be fully exploited only insofar as operators of mechanical treatment plants concentrate their business on the production of refuse-derived fuel.
Physiological Considerations in Artificial Stimulation of the Inner Ear

It has long been established that electric stimulation of the inner ear can produce auditory sensations in severely deaf humans.lV2 However, repeated attempts to develop prosthetic devices based on electric stimulation of the auditory nerve have yielded disappointing result^. ^-^ To date, no experiment on any deaf human subject has produced hearing that could be considered adequate for conventional speech communication.
Computing Free Energies of Hydroxylated Silica Nanoclusters: Forcefield versus Density Functional Calculations

We assess the feasibility of efficiently calculating accurate thermodynamic properties of (SiO2)n·(H2O)m nanoclusters, using classical interatomic forcefields (FFs). Specifically, we use a recently parameterized FF for hydroxylated bulk silica systems (FFSiOH) to calculate zero-point energies and thermal contributions to vibrational internal energy and entropy, in order to estimate the free energy correction to the internal electronic energy of these nanoclusters. The performance of FFSiOH is then benchmarked against the results of corresponding calculations using density functional theory (DFT) calculations employing the B3LYP functional. Results are reported first for a set of (SiO2)n·(H2O)m clusters with n = 4, 8 and 16, each possessing three different degrees of hydroxylation (R = m/n): 0.0, 0.25 and 0.5. Secondly, we consider five distinct hydroxylated nanocluster isomers with the same (SiO2)16·(H2O)4 composition. Finally, the free energies for the progressive hydroxylation of three nanoclusters with R = 0–0.5 are also calculated. Our results demonstrate that, in all cases, the use of FFSiOH can provide estimates of thermodynamic properties with an accuracy close to that of DFT calculations, and at a fraction of the computational cost.
Genotypes of NK cell KIR Receptors , Their Ligands , and Fc γ Receptors in the Response of Neuroblastoma Patients to Hu 14 . 18-IL 2 Immunotherapy : A Children ’ s Oncology Group Report #

Response to immunocytokine (IC) therapy is dependent on natural killer (NK) cells in murine neuroblastoma (NBL) models. Furthermore, killer immunoglobulin-like receptor (KIR) / KIRligand mismatch is associated with improved outcome to autologous stem cell transplant for NBL. Additionally, clinical anti-tumor response to monoclonal antibodies has been associated with specific polymorphic-FcγR alleles. Relapsed/refractory NBL patients received the hu14.18-IL2 IC (humanized anti-GD2 monoclonal antibody linked to human IL2) in a Children’s Oncology Group (COG) Phase II trial. In this report, these patients were genotyped for KIR, HLA and FcR alleles to determine if KIR receptor-ligand mismatch or specific FcγR alleles were associated with antitumor response. Thirty-eight of 39 patients enrolled had DNA available for analysis; 24 were found to have autologous KIR/KIR -ligand mismatch; 14 were matched. Seven of 24 mismatched patients experienced either complete response or improvement of their disease after IC therapy. #This is manuscript # 9982 of the Children’s Oncology Group (COG) *Correspondence to: Paul M. Sondel MD PhD, Depts. of Pediatrics and Human Oncology, University of Wisconsin, 1159 WIMR, 1111 Highland Ave, Madison WI, 53705, 608-263-9069, pmsondel@humonc.wisc. edu. Prior Presentation: This study has not been previously published but was presented at the 2010 American Society of Pediatric Hematology and Oncology (ASPHO) meeting in Montreal QUE, on April 9, 2010. NIH Public Access Author Manuscript Cancer Res. Author manuscript; available in PMC 2011 December 1. Published in final edited form as: Cancer Res. 2010 December 1; 70(23): 9554–9561. doi:10.1158/0008-5472.CAN-10-2211. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript There was no response or comparable improvement of disease in patients who were matched. Thus KIR/KIR-ligand mismatch was associated with response/improvement to IC (p = 0.03). There was a trend towards patients with the FcγR2A 131-H/H genotype showing a higher response rate compared to other FcγR2A genotypes (p = 0.06). These analyses indicate that response or improvement of relapsed/refractory neuroblastoma patients after IC treatment is associated with autologous KIR/KIR-ligand mismatch, consistent with a role for NK cells in this clinical response.
Emerging Technological Approaches for Controlling the Hard Core DUI Offender in the U.S.

Drivers convicted of impaired driving are substantially overrepresented in alcohol-related fatal crashes. Because many such offenders continue to drive with suspended operators' licenses, monitoring their postconviction driving is a significant problem for the criminal justice system. Technology for tracking the location and drinking of such offenders is a rapidly developing field, which promises to provide methods for monitoring offenders on a 24/7 basis. The status of traditional monitoring methods is reviewed and contrasted with the new technologies that are being implemented. Although those technologies offer considerable promise, they have not yet been evaluated in programs for impaired driving offenders. Eight issues related to the probability of rapid implementation of the new technologies are discussed.
A Five-year Multi-practice Clinical Study on Posterior Resin-bonded Bridges

Previous clinical observations have revealed that resin-bonded bridges for posterior tooth replacements are less retentive than anterior resin-bonded bridges. Improved bonding procedures and preparation designs, however, may have a positive effect on the functional durability of these restorations. The present study reports the final analysis of a randomized controlled clinical trial in which different designs of posterior resin-bonded bridges were evaluated for a period of at least 5 years. The operational hypothesis was that the bonding system and the preparation design used in posterior resin-bonded bridges have an influence on the survival and clinical functioning of these restorations. Survival in this study was defined at two levels: (1) 'complete' survival (survival without any debonding), and (2) 'functional' survival (survival including loss of retention on one occasion and successful rebonding of the original RBB without further debonding). With regard to 'complete' survival, no significant differences were found between the bonding systems used for adherence of the restorations to abutment teeth (etching/Clearfil F2, sandblasting/Panavia EX, and silica-coating/Microfill Pontic C). The variable 'preparation form' (conventional preparation form vs. modified preparation form) for complete survival was statistically in favor of the modified preparation form (62% vs. 46%), but did not influence the functional survival. With regard to 'functional' survival, the combination of silica coating and Microfill Pontic C was more retentive than the other bonding systems (90% survival vs. 72% and 75%, p < 0.01). Factor location was found to be highly significant for both survival levels [Cox's PH model, p = 0.0002 (Cox, 1972)]: The five-year 'complete' survival rates were 65% for maxillary restorations and 40% for mandibular restorations, while the five-year 'functional' survival rates were 89% and 68%, respectively. It is concluded that preparation of grooves in abutment teeth for posterior resin-bonded bridges is beneficial to their chance of survival. Resin-bonded bridges placed in the maxilla have a better prognosis than those made in the mandible. The bonding systems used in this study appear to have no influence on the chance of failure. In rebonded posterior resin-bonded bridges, the bonding system silica-coating/Microfill Pontic C was more retentive than the other systems tested.
A low-cost directional log periodic log spiral antenna

The Square Kilometer Array (SKA) derives its name from its total aperture area, predominately achieved by thousands of parabolic dishes, each with an antenna feed situated at its focal point. The type of antenna feed selected for SKA operation in the 1 GHz to 10 GHz frequency range, referred to as a Wide Band Single Pixel Feed (WB+SPF) [1], has drawn increasing attention. This paper introduces a new WB+SPF to meet SKA scientific demands while also providing a cost-effective solution. The wide bandwidth of this new antenna is achieved by employing frequency independent (FI) design principles for the development of a log periodic (LP) antenna [2]. A basic adherence to FI principles can be seen in several of the antennas currently proposed as WB+SPF solutions for the SKA, including the Allen Telescope Array (ATA) feed [3], the Quasi-Self-Complementary (QSC) feed [4], and the Eleven feed [5]. These antennas efficiently illuminate the radio dish with a single main lobe, ruling out entirely planar FI antennas, which generate two radiation lobes orthogonal to the plane of the antenna. High sensitivity requirements prohibit the 3 dB power loss that would result from attenuating one of the lobes with an absorption cavity, as is often done for directional FI antennas. Scaling the LP elements into three-dimensional space, potentially over a ground plane [6], is the present method used for directional LP antennas. We instead propose confining these often complex LP elements into a single plane, while the ground “plane” takes on a three dimensional form. Planar LP patterns permit low-cost implementations, including PCB and water jet cutting technology, without requiring the introduction of a complicated scaffolding to support the LP elements in 3-D. Additionally, various technologies such as metal spinning, can cost-effectively shape the ground “plane” into a 3-D structure. This low-cost WB+SPF solution would scale well in the implementation of the thousands of antenna feeds that the SKA demands. We also introduce a previously unreported LP design: the log periodic log spiral (LPLS) antenna.
Synthesis of Polarization Transformers

We study the possibility of analytically synthesizing different polarization-transforming devices realized as arrays of small particles. The proposed method is based on general relations between the reflection and transmission coefficients and the polarizabilities of arbitrary bi-anisotropic particles. As an example, we reveal all possible types of inclusions which can be used to realize twist polarizers, select one of them and synthesize a novel twist polarizer. The synthesized twist polarizer is then fitted on a standard printed circuit board, optimized numerically, and finally manufactured and measured. The experimental results for the twist polarizer show good correspondence with the simulations and the new method is found to be a useful tool for developing any polarization-transforming devices. As one more example, a novel circular polarization selective surface is synthesized.
The Action of Cyclosporin A on the Endocrine Pancreas in Vitro - Functional and Morphological Studies

We investigated the effect of Cyclosporin A (100 ng/ml - 12000 ng/ml) on functional parameters of the endocrine pancreas in vitro. The insulin secretion of isolated islets in response to a variety of secretory stimulators is characterized by minimal alteration occasionally observed in the presence of very high Cyclosporin A concentrations. Cyclosporin A did not alter the glucose-induced biphasic insulin secretion, nor the arginine-stimulated glucagon secretion of the perfused rat pancreas. Exposure of isolated islets to 2000 ng Cyclosporin A/ml for 3 weeks resulted in a minimal decrease of insulin content and a marked reduction of glucagon content, which were not accompanied by drastic alterations of insulin secretion. Scanning electron micrographs of these Cyclosporin A-treated islets did not differ from cultured control islets. The results let us assume that Cyclosporin A exerts no toxic effects on the endocrine pancreas in vitro, when exposed to concentrations greater than or equal to 2000 ng/ml.
Myeloid lineage switch of Pax5 mutant but not wild‐type B cell progenitors by C/EBPα and GATA factors

The developmental potential of hematopoietic progenitors is restricted early on to either the erythromyeloid or lymphoid lineages. The broad developmental potential of Pax5−/− pro‐B cells is in apparent conflict with such a strict separation, although these progenitors realize the myeloid and erythroid potential with lower efficiency compared to the lymphoid cell fates. Here we demonstrate that ectopic expression of the transcription factors C/EBPα, GATA1, GATA2 and GATA3 strongly promoted in vitro macrophage differentiation and myeloid colony formation of Pax5−/− pro‐B cells. GATA2 and GATA3 expression also resulted in efficient engraftment and myeloid development of Pax5−/− pro‐B cells in vivo. The myeloid transdifferentiation of Pax5−/− pro‐B cells was accompanied by the rapid activation of myeloid genes and concomitant repression of B‐lymphoid genes by C/EBPα and GATA factors. These data identify the Pax5−/− pro‐B cells as lymphoid progenitors with a latent myeloid potential that can be efficiently activated by myeloid transcription factors. The same regulators were unable to induce a myeloid lineage switch in Pax5+/+ pro‐B cells, indicating that Pax5 dominates over myeloid transcription factors in B‐lymphocytes.
Electrophoretic Separation of Urine Proteins of Healthy Dogs and Dogs with Nephropathy and Detection of Some Urine Proteins of Dogs Using Immunoblotting

La presence de proteines dans les urines chiens atteints nephropathie est relativement frequente. La detection et la caracterisation de ces proteinuries peuvent considerablement aider a l'etablissementdu diagnostic et du prognostic des maladies renales. Sur un effectif de 50 chiens dont 25 sont des chiens en bonne sante (groupe sain) et 25 sont atteints de nephropathies (groupe malade), les proteines urinaires et la proteinurie ont ete evaluees par la determination du rapport de la concentration urinaire en proteines sur la concentration urinaire de creatinine (UPr/Cr), par analyse electrophoretique en conditions denaturantes (SDS-PAGE) et par immunoblotting. Le rapport UPr/Cr a ete significativement plus eleve chez les malades que chez les chiens sains ( 0.558 ′ 0.425 and 0.041 ′ 0.026, p < 0.05 respectivement) et 21 chiens malades (soit 84 %) ont presente un rapport UPr/Cr superieur a 0.2, ce qui indique une proteinurie pathologique. Au moins 10 bandes differentes ont ete mises en evidence par SDS-PAGE et elles ont ete reparties en 3 groupes: proteines de faible poids moleculaire (inferieur a 66 kD), proteines de poids moleculaire moyen (entre 66 et 76 kD) et proteines de haut poids moleculaire (superieur a 76 kD). Dans le groupe des malades, 2 types de proteinurie ont ete identifies: une proteinurie a la fois glomerulaire et tubulaire caracterisee par la presence, et de proteines de poids moleculaire eleve ou/et moyen, et de proteines de faible poids moleculaire obtenue dans 67 % des chiens presentant une proteinurie elevee; une proteinurie tubulaire caracterisee par la presence seulement de proteines de faible poids moleculaire obtenue dans 33 % des cas. Chez les chiens sains, de rares bandes ont ete visualisees par SDS-PAGE. Par immunoblotting, transferrine, α 1 -microglobulin, β 2 -microglobuline et RBP ont ete plus frequemment detectees chez les chiens malades que chez les sains (p < 0.05). De plus, RBP a ete retrouvee chez tous les chiens malades presentant une proteinurie significative alors que cette proteine n'a ete detectee que chez 2 chiens sains, et pourrait etre specifique d'une atteinte tubulaire.
Necrotizing pulmonary aspergillosis and ventricular assist device infection: case report and review of literature

Necrotizing pulmonary aspergillosis and Aspergillus device infection are rare and have potentially fatal complications after left ventricular assist device (LVAD) implantation. To date, few cases of patients surviving Aspergillus device infection have been published, with survival reported only after device removal. We present a patient implanted with an LVAD in whom necrotizing pulmonary aspergillosis with device involvement was successfully treated by segmentectomy and prolonged antifungal treatment without device exchange or removal. Similar cases in the literature were searched for and are discussed in view of the severity of this complication.
Brome Mosaic Virus RNA Replication Proteins 1a and 2a Colocalize and 1a Independently Localizes on the Yeast Endoplasmic Reticulum

ABSTRACT The universal membrane association of positive-strand RNA virus RNA replication complexes is implicated in their function, but the intracellular membranes used vary among viruses. Brome mosaic virus (BMV) encodes two mutually interacting RNA replication proteins: 1a, which contains RNA capping and helicase-like domains, and the polymerase-like 2a protein. In cells from the natural plant hosts of BMV, 1a and 2a colocalize on the endoplasmic reticulum (ER). 1a and 2a also direct BMV RNA replication and subgenomic mRNA synthesis in the yeast Saccharomyces cerevisiae, but whether the distribution of 1a, 2a, and active replication complexes in yeast duplicates that in plant cells has not been determined. For yeast expressing 1a and 2a and replicating BMV genomic RNA3, we used double-label confocal immunofluorescence to define the localization of 1a, 2a, and viral RNA and to explore the determinants of replication complex targeting. As in plant cells, 1a and 2a colocalized on and were retained on the yeast ER, with no detectable accumulation in the Golgi apparatus. 1a and 2a were distributed over most of the ER surface, with strongest accumulation on the perinuclear ER. In vivo labeling with bromo-UTP showed that the sites of 1a and 2a accumulation were the sites of nascent viral RNA synthesis. In situ hybridization showed that completed viral RNA products accumulated predominantly in the immediate vicinity of replication complexes but that some, possibly more mature cells also accumulated substantial viral RNA in the surrounding cytoplasm distal to replication complexes. Additionally, we find that 1a localizes to the ER when expressed in the absence of other viral factors. These results show that BMV RNA replication in yeast duplicates the normal localization of replication complexes, reveal the intracellular distribution of RNA replication products, and show that 1a is at least partly responsible for the ER localization and retention of the RNA replication complex.
Statin Compounds Reduce Human Immunodeficiency Virus Type 1 Replication by Preventing the Interaction between Virion-Associated Host Intercellular Adhesion Molecule 1 and Its Natural Cell Surface Ligand LFA-1

ABSTRACT A variety of host factors, including membrane proteins acquired by human immunodeficiency virus type 1 (HIV-1), play a dominant role in HIV-1 adsorption onto host cells. Examples include the integrin intercellular adhesion molecule 1 (ICAM-1), which, once acquired by HIV-1, promotes virus infectivity via ligation to LFA-1. We tested the ability of statins to diminish HIV-1 replication, based on the idea that these compounds have been shown to block ICAM-1-LFA-1 interactions. Our data indicate that statins diminish HIV-1 attachment to target cells by suppressing ICAM-1-LFA-1 interactions. The capacity of statins to limit the initial steps in virus replication could represent an interesting approach for the treatment of HIV-1 infection.