Miracle-dz/UniFAR-FTUs huggingface dataset:
CENTRAL CARDIOVASCULAR EFFECTS OF DIHYDROPYRIDINES IN SPONTANEOUSLY HYPERTENSIVE RATS

Summary— Intracerebroventricular (i.c.v.) injections of dihydropyridine derivatives calcium channel agonist (BAY K8644) and antagonists (nifedipine, nicardipine, PN 200–110) induced opposite long‐lasting changes in blood pressure (BP) in pentobarbital anesthetized spontaneously hypertensive rats (SMR). I.c. v. nifedipine (NIF), nicardipine (NIC), and PN 200–110 decreased mean blood pressure dose‐dependently and stereoselec‐tively, (+) NIC and (+) PN being 8 and 3 times more potent than their (‐) isomers, respectively. The decrease in BP was due to a withdrawal of the sympathetic tone, since NIF‐ and NIC‐induced falls in BP were suppressed after either hexamethonium (HXM), 6 OHDA or bilateral adrenalectomy. I.c. v. BAY K8644 increased BP dose‐dependently. The i.c. v. BAY K8644‐induced hypertensive effect was inhibited: a), by NIF and (+) PN but not by (‐) PN, therefore probably occurring at central DHP sites; b), by HXM and reserpine, thus probably mediated by an increase in sympathetic tone; c), by i.c. v. methylatropine (MA) while i.v. MA and i.c. v. HXM had no inhibitory effect, thus probably involving central muscarinic sites. In SHR, NIC did not after the K+‐evoked ACh release but suppressed the BAY K8644‐induced increase in ACh release. In anesthetized normotensive control rats (WKY), neither i.c. v. NIF, NIC or BAY K8644 changed BP, nor did the latter after ACh release. Moreover, in conscious WKY, i.c. v. nicardipine increased BP and HR while, in conscious SHR it decreased BP without any change in HR. These data suggest that central DHP sites may be involved in the cholinergic transmission and may participate in genetic hypertension via sympathetic tone.
KinDER : A Biocuration Tool for Extracting Kinase Knowledge from Biomedical Literature

Kinases are enzymes that mediate phosphate transfer. Extracting information on kinases from biomedical literature is an important task which has direct implications for applications such as drug design. In this work, we develop KinDER, Kinase Document Extractor and Ranker, a biomedical natural language processing tool for extracting functional and disease related information on kinases. This tool combines information retrieval and machine learning techniques to automatically extract information about protein kinases. First, it uses several bio-ontologies to retrieve documents related to kinases and then uses a supervised classification model to rank them according to their relevance. This was developed to participate in the Text-mining services for Human Kinome Curation Track of the BioCreative VI challenge. According to the official BioCreative evaluation results, KinDER provides stateof-the-art performance for extracting functional information on kinases from abstracts. Keywords—kinase; proteins; machine learning; biomedical natural language processing; BioCreative; text classification; supervised learning
The Artificial Pancreas: How Sweet Engineering Will Solve Bitter Problems

An artificial pancreas is a closed-loop system containing only synthetic materials which substitutes for an endocrine pancreas. No artificial pancreas system is currently approved; however, devices that could become components of such a system are now becoming commercially available. An artificial pancreas will consist of functionally integrated components that will continuously sense glucose levels, determine appropriate insulin dosages, and deliver the insulin. Any proposed closed loop system will be closely scrutinized for its safety, efficacy, and economic impact. Closed loop control utilizes models of glucose homeostasis which account for the influences of feeding, stress, insulin, exercise, and other factors on blood glucose levels. Models are necessary for understanding the relationship between blood glucose levels and insulin dosing; developing algorithms to control insulin dosing; and customizing each user's system based on individual responses to factors that influence glycemia. Components of an artificial pancreas are now being developed, including continuous glucose sensors; insulin pumps for parenteral delivery; and control software, all linked through wireless communication systems. Although a closed-loop system providing glucagon has not been reported in 40 years, the use of glucagon to prevent hypoglycemia is physiologically attractive and future devices might utilize this hormone. No demonstration of long-term closed loop control of glucose in a free-living human with diabetes has been reported to date, but many centers around the world are working on closed loop control systems. It is expected that many types of artificial pancreas systems will eventually be available, and they will greatly benefit patients with diabetes.
Chromosome Rearrangement and Diversification of Francisella tularensis Revealed by the Type B (OSU18) Genome Sequence

ABSTRACT The γ-proteobacterium Francisella tularensis is one of the most infectious human pathogens, and the highly virulent organism F. tularensis subsp. tularensis (type A) and less virulent organism F. tularensis subsp. holarctica (type B) are most commonly associated with significant disease in humans and animals. Here we report the complete genome sequence and annotation for a low-passage type B strain (OSU18) isolated from a dead beaver found near Red Rock, Okla. , in 1978. A comparison of the F. tularensis subsp. holarctica sequence with that of F. tularensis subsp. tularensis strain Schu4 (P. Larsson et al., Nat. Genet. 37:153-159, 2005) highlighted genetic differences that may underlie different pathogenicity phenotypes and the evolutionary relationship between type A and type B strains. Despite extensive DNA sequence identity, the most significant difference between type A and type B isolates is the striking amount of genomic rearrangement that exists between the strains. All but two rearrangements can be attributed to homologous recombination occurring between two prominent insertion elements, ISFtu1 and ISFtu2. Numerous pseudogenes have been found in the genomes and are likely contributors to the difference in virulence between the strains. In contrast, no rearrangements have been observed between the OSU18 genome and the genome of the type B live vaccine strain (LVS), and only 448 polymorphisms have been found within non-transposase-coding sequences whose homologs are intact in OSU18. Nonconservative differences between the two strains likely include the LVS attenuating mutation(s).
Immediate loading of dental implants in the edentulous maxilla.

OBJECTIVE Immediate loading of dental implants in the edentulous mandible has proven to be an effective, reliable, and predictable procedure. There is little long-term data available on similar treatments in the edentulous maxilla. The aim of the present study was to clinically evaluate edentulous maxilla rehabilitation with removable prostheses supported by the Ankylos SynCone (Dentsply-Friadent) system. METHOD AND MATERIALS The treatment method was based on immediate loading of four implants in the completely edentulous maxilla. A total of 180 implants were inserted in 45 patients. Dentures were placed on and retained by prefabricated conical crowns that were inserted into the existing denture base by direct intraoral polymerization immediately after surgery and supported by corresponding conical primary implant abutments. RESULTS During the observation period, two implants (1.11%) were removed due to the lack of osseointegration. One implant was removed due to peri-implantitis, and one other (0.55%) implant was removed because of a fracture after 6 months of function. The overall implant survival rate was 97.77%, while the prosthesis survival rate was 100%. Swelling or suppuration was not observed. After a total observation period of 26.7 months (range 12 to 54 months), all implants had healthy peri-implant soft tissue that showed low values of clinical parameters. Only seven implants (3.97%) presented a sulcus bleeding index of 3. CONCLUSION This method facilitates edentulous maxilla rehabilitation with removable prostheses. The conical crown concept presented resulted in stable complete-denture retention, reduced denture base, and improved oral hygiene.
Co-Administration of Melatonin Effectively Enhances the Therapeutic Effects of Pioglitazone on Mesenchymal Stem Cells Undergoing Indoxyl Sulfate-Induced Senescence through Modulation of Cellular Prion Protein Expression

Background: Mesenchymal stem cells (MSCs) are a promising source for regenerative medicine. However, their therapeutic potential in patients with chronic kidney disease (CKD) is restricted by the presence of uremic toxins. To address this limitation, we explored the protective effect of melatonin and pioglitazone on MSCs undergoing senescence induced by the uremic toxin, indoxyl sulfate (IS). Methods: MSC senescence was induced by IS, and the therapeutic effects of melatonin and pioglitazone were identified. The expression of cellular prion protein (PrPC) was suppressed by transfection of MSCs with prion protein gene (PRNP) siRNA. Subsequently, these cells were used to study the protective effects of melatonin and pioglitazone against IS-induced senescence; Results: The IS-induced senescence of MSCs was significantly reduced by co-treatment with melatonin and pioglitazone compared to treatment with melatonin or pioglitazone alone. In the presence of IS, the reduced MSC proliferation was rescued by co-treatment with melatonin and pioglitazone. Melatonin and pioglitazone enhanced the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) in MSCs, which resulted in the augmentation of PrPC level. The inhibitory effect of the co-treatment with melatonin and pioglitazone on IS-induced senescence in MSCs was blocked by the knockdown of PRNP. In addition, the restorative effect of the co-treatment on the reduced MSC proliferation induced by IS was also blocked by the knockdown of PRNP. These findings indicate that co-treatment with melatonin and pioglitazone protected MSCs from uremic toxin-induced senescence through the regulation of the PPAR-γ-PrPC axis. Conclusions: Our study suggests that co-treatment of MSCs with melatonin and pioglitazone may represent a novel strategy for the development of MSC-based therapies for patients with CKD.
Potential explanations for the educational gradient in coronary heart disease: a population-based case-control study of Swedish women.

OBJECTIVES This study examined the association between educational attainment and coronary heart disease (CHD) and the factors that may explain this association. METHODS This population-based case-control study included 292 women with CHD who were 65 years or younger and 292 age-matched controls. RESULTS Compared with the adjusted odds ratio for CHD associated with college education, the age-adjusted odds ratio associated with mandatory education (< or = 9 years) was 1.87 (95% confidence interval [CI] = 1.23, 2.84) and the odds ratio for high school education was 1.35 (95% CI = 0.81, 2.25) (P for trend < .01). The odds ratio for mandatory education was reduced by 82%, to 1.16 (95% CI = 0.69, 2.09), after adjustment for psychosocial stress, unhealthy lifestyle patterns, hemostatic factors, hypertension, and lipids. CONCLUSIONS Much of the increased risk of CHD in women with low education appears to be linked to psychosocial stress and lifestyle factors. Hemostatic factors, lipids, and hypertension also contribute to a lesser extent. These factors may be considered in strategies geared to reducing socioeconomic inequalities in cardiovascular health.
Oversecretion of IL‐18 in haemophagocytic lymphohistiocytosis: a novel marker of disease activity

We investigated the significance of interleukin (IL)‐18 levels in the pathophysiology of haemophagocytic lymphohistiocytosis (HLH). IL‐18 levels were significantly elevated in all nine patients with active HLH compared with those of healthy controls. Serial determination of IL‐18 levels in three cases, showed a gradual decrease compared with those of IL‐12, interferon (IFN)‐γ or soluble Fas ligand (sFasL) in the course of clinical improvement, and seemed to be elevated until complete disappearance of disease activity. IL‐18 and IFN‐γ (CC 0.711, P = 0.018), and IFN‐γ and sFasL (CC 0.849, P = 0.0049) levels were significantly correlated. On the other hand, correlation between IL‐12 and IFN‐γ, IL‐18 and sFasL, or IL‐18 and IL‐12 was not observed. IL‐18, IFN‐γ and sFasL levels significantly correlated with disease activity such as fever and alanine transaminase (ALT) levels. IL‐18 mRNA expression was enhanced in spleen, but not in peripheral blood mononuclear cells (MNC), bone marrow MNC, liver from patients of active HLH, or the tumour from a patient with lymphoma‐associated haemophagocytic syndrome (LAHS). These results suggest that IL‐18 may play important roles in the pathogenesis of HLH, particularly through induction of Th1 cells. IL‐18 measurement may be useful for the diagnosis and for the detection of smouldering disease activity.
Acute lung injury in pediatric intensive care in Australia and New Zealand—A prospective, multicenter, observational study*

Objective: Acute lung injury (ALI) is poorly defined in children. The objective of this prospective study was to clarify the incidence, demographics, management strategies, outcome, and mortality predictors of ALI in children in Australia and New Zealand. Design: Multicenter prospective study during a 12-month period. Setting: Intensive care unit. Patients: All children admitted to intensive care and requiring mechanical ventilation were screened daily for development of ALI based on American-European Consensus Conference guidelines. Identified patients were followed for 28 days or until death or discharge. Interventions: None. Measurements and Main Results: There were 117 cases of ALI during the study period, giving a population incidence of 2.95/100,000 <16 yrs. ALI accounted for 2.2% of pediatric intensive care unit admissions. Mortality was 35% for ALI, and this accounted for 30% of all pediatric intensive care unit deaths during the study period. Significant preadmission risk factors for mortality were chronic disease, older age, and immunosuppression. Predictors of mortality during admission were ventilatory requirements (peak inspiratory pressures, mean airway pressure, positive end-expiratory pressure) and indexes of respiratory severity on day 1 (Pao2/Fio2 ratio and oxygenation index). Higher maximum and median tidal volumes were associated with reduced mortality, even when corrected for severity of lung disease. Development of single and multiple organ failure was significantly associated with mortality. Conclusions: ALI in children is uncommon but has a high mortality rate. Risk factors for mortality are easily identified. Ventilatory variables and indexes of lung severity were significantly associated with mortality.
Structural basis for the higher Ca(2+)-activation of the regulated actin-activated myosin ATPase observed with Dictyostelium/Tetrahymena actin chimeras.

Replacement of residues 228-230 or 228-232 of subdomain 4 in Dictyostelium actin with the corresponding Tetrahymena sequence (QTA to KAY replacement: half chimera-1; QTAAS to KAYKE replacement: full chimera) leads to a higher Ca(2+)-activation of the regulated acto-myosin subfragment-1 ATPase activity. The ratio of ATPase activation in the presence of tropomyosin-troponin and Ca(2+) to that without tropomyosin-troponin becomes about four times as large as the ratio for the wild-type actin. To understand the structural basis of this higher Ca(2+)-activation, we have determined the crystal structures of the 1:1 complex of Dictyostelium mutant actins (half chimera-1 and full chimera) with gelsolin segment-1 to 2.0 A and 2.4 A resolution, respectively, together with the structure of wild-type actin as a control. Although there were local changes on the surface of the subdomain 4 and the phenolic side-chain of Tyr230 displaced the side-chain of Leu236 from a non-polar pocket to a more solvent-accessible position, the structures of the actin chimeras showed that the mutations in the 228-232 region did not introduce large changes in the overall actin structure. This suggests that residues near position 230 formed part of the tropomyosin binding site on actin in actively contracting muscle. The higher Ca(2+)-activation observed with A230Y-containing mutants can be understood in terms of a three-state model for thin filament regulation in which, in the presence of both Ca(2+) and myosin heads, the local changes of actin generated by the mutation (especially its phenolic side-chain) facilitate the transition of thin filaments from a "closed" state to an "open" state. Between 394 and 469 water molecules were identified in the different structures and it was found that actin recognizes hydrated forms of the adenine base and the Ca ion in the nucleotide binding site.
Noise in advanced bipolar transistors at mm-wave frequencies

Small-signal and noise characteristics of advanced InP/InGaAs, InGaP/GaAs and Si/SiGe heteroj unction bipolar transistors (HBTs) were measured and modeled over a broad frequency and collector current density range. HICUM was employed for modeling the HBTs and for analyzing them in terms of decomposed internal noise sources. Compared to Si/SiGe HBTs, higher noise is observed in InP/InGaAs HBTs, at lower frequencies due to the contribution of the higher base current and its related shot noise. The correlation between the collector current shot noise and the dynamic base current related shot noise in InP/InGaAs and Si/SiGe HBTs was found to be negligible in the 1-50 GHz frequency band in contrast to InGaP/GaAs HBTs. Although nonequilibrium electron transport was observed in InP and GaAs HBTs, the spectral density of intervalley scattering related current fluctuations has negligible impact on NFmin itself.
Accurate d‐spacings from zero‐order laue zone patterns

Experimental d‐spacing values are criteria towards the identification of crystallites by electron diffraction. Conclusive identifications often rely on accurate d‐spacings. It is shown here that accurate orthogonal components (in mm) for the primitive unit vectors of a zero‐level diffraction pattern can be obtained through least‐squares processing of (x,y) coordinates for all spots on the film. Valid vectors hom the origin spot to any spot in the plane of the film are integer linear combinations of the two selected unit vectors. Accurate lengths and standard deviations for such vectors therefore can be calculated from the least‐squares results. Corresponding d‐spacings can then be calculated from the vector lengths on the film and the camera constant. In order to obtain d‐spacing values that are not only precise, but also accurate, an accurate value of the camera constant should be used. This requires calibration of the experimental setup with reference materials in the same experimental conditions, with careful control of the sample height. For the same quality of measurements, the improvement in the accuracy of the d‐spacings obtained with the proposed method is approximately proportional to the square root of the number of measurements taken. Practically, typical improvement in accuracy is about threefold, and accuracies of a fraction of a percent in d‐spacings are achievable in this way. The above approach has been programmed as an option in the NRCBED program. © 1992 Wiley‐Liss, Inc.
Differential mechanisms of inorganic pyrophosphate production by plasma cell membrane glycoprotein-1 and B10 in chondrocytes.

OBJECTIVE Increased nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in chondrocytes is associated with cartilage matrix inorganic pyrophosphate (PPi) supersaturation in chondrocalcinosis. This study compared the roles of the transforming growth factor beta (TGFbeta)-inducible plasma cell membrane glycoprotein-1 (PC-1) and the closely related B10 NTPPPH activities in chondrocyte PPi metabolism. METHODS NTPPPH expression was studied using reverse transcriptase-polymerase chain reaction and Western blotting. Transmembrane PC-1 (tmPC-1), water-soluble secretory PC-1 (secPC-1), and transmembrane B10 were expressed by adenoviral gene transfer or plasmid transfection, and expression of PPi was assessed in cultured articular chondrocytes and immortalized NTPPPH-deficient costal chondrocytes (TC28 cells). RESULTS PC-1 and B10 messenger RNA were demonstrated in articular cartilages in situ, in untreated cultured normal articular chondrocytes, and in TC28 cells. Expression of tmPC-1 and secPC-1, but not B10, rendered the NTPPPH-deficient TC28 cells able to increase expression of extracellular PPi, with or without addition of TGFbeta (10 ng/ml) to the media. More plasma membrane NTPPPH activity was detected in cells transfected with tmPC-1 than in cells transfected with B10. Furthermore, confocal microscopy with immunofluorescent staining of articular chondrocytes confirmed preferential plasma membrane localization of PC-1, relative to B10. Finally, both PC-1 and B10 increased the levels of intracellular PPi, but PC-1 and B10 appeared to act principally in different intracellular compartments (Golgi and post-Golgi versus pre-Golgi, respectively). CONCLUSION PC-1 and B10 NTPPPH activities were not redundant in chondrocytes. Although increased PC-1 and B10 expression caused elevations in intracellular PPi, the major effects of PC-1 and B10 were exerted in distinct subcellular compartments. Moreover, PC-1 (transmembrane and secreted), but not B10, increased the levels of extracellular PPi. Differential expression of PC-1 and B10 could modulate cartilage mineralization in degenerative joint diseases.
Frequency of greatest temporary hearing threshold shift in harbor porpoises (Phocoena phocoena) depends on the noise level.

Harbor porpoises may suffer hearing loss when they are exposed to high level sounds. After exposure for 60 min to a 6.5 kHz continuous tone at average received sound pressure levels (SPLav.re.) ranging from 118 to 154 dB re 1μPa, the temporary hearing threshold shifts (TTSs) of a harbor porpoise were quantified at the center frequency (6.5 kHz), at 0.5, 1.0, and 1.3 octaves above the center frequency (9.2, 13.0, and 16.0 kHz), and at a frequency assumed to be ecologically important for harbor porpoises (125 kHz, the center frequency of their echolocation signals) by means of a psychoacoustic technique. The hearing frequency at which the maximum TTS occurred depended on the SPLav.re. The higher the SPLav.re. , the higher the TTS induced at frequencies higher than the exposure frequency; below 148 dB re 1 μPa, the maximum TTS was at 6.5 kHz, whereas above 148 dB re 1 μPa, the maximum TTS was at 9.2 kHz. The hearing threshold of the harbor porpoise for the center frequency of its echolocation signals (125 kHz) was not affected at the highest SPLav.re. to which the animal was exposed.
Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection

Hepatic steatosis is one of the histopathologic features of chronic hepatitis C. It was reported recently that the expression of hepatitis C virus (HCV) core protein in transgenic mice induced hepatocellular carcinoma (HCC) in association with steatosis. The objective of this study was to determine the relation between hepatic steatosis and hepatocarcinogenesis in patients with chronic HCV infection.