bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRV120027, a Novel β-Arrestin Biased Ligand at the Angiotensin II Type I Receptor, Unloads the Heart and Maintains Renal Function When Added to Furosemide in Experimental Heart Failure
Authors: Boerrigter Guido , Soergel David G. , Violin Jonathan D. , Lark Michael W. , Burnett John C. 
Published: August 2012

Background—
TRV120027 is a novel β-arrestin biased ligand of the angiotensin II type 1 receptor; it antagonizes canonical G-protein–mediated coupling while, in contrast to classical angiotensin II type 1 receptor antagonists, it engages β-arrestin–mediated signaling. Consequently, TRV120027 inhibits angiotensin II–mediated vasoconstriction while, via β-arrestin coupling, it increases cardiomyocyte contractility. We hypothesized that TRV120027 would elicit beneficial cardiorenal actions when added to furosemide in experimental heart failure.

Methods and Results—

Two groups of anesthetized dogs (n=6 each) with tachypacing-induced heart failure were studied. After a baseline clearance, 1 group (F+V) received furosemide (1 mg/kg per hour) plus saline for 90 minutes, whereas the other (F+T) received the same dose of furosemide plus TRV120027 (0.3 and 1.5 µg/kg per minute for 45 minutes each); 2 clearances were done during drug infusion. After a washout, a postinfusion clearance was done; *
P
<0.05 between groups. F+V and F+T increased diuresis and natriuresis to a similar extent during drug administration, but urine flow* and urinary sodium excretion* were higher in the postinfusion clearance with F+T. Glomerular filtration rate was preserved in both groups. Renal blood flow increased with F+T but this was not significant versus F+V. Compared with F+V, F+T decreased mean arterial pressure*, systemic* and pulmonary* vascular resistances, and atrial natriuretic peptide*. Pulmonary capillary wedge pressure* decreased to a larger extent with F+T than with F+V.

Conclusions—
When added to furosemide, TRV120027, a novel β-arrestin biased angiotensin II type 1 receptor ligand, preserved furosemide-mediated natriuresis and diuresis, while reducing cardiac preload and afterload. These results provide support for TRV120027 as a promising novel therapeutic for the treatment of heart failure.
Subclinical Left Ventricular Dysfunction in Preeclamptic Women With Preserved Left Ventricular Ejection Fraction
Authors: Shahul Sajid , Rhee Julie , Hacker Michele R. , Gulati Gaurav , Mitchell John D. , Hess Phil , Mahmood Feroze , Arany Zolt , Rana Sarosh , Talmor Daniel 
Published: August 2012

Background—
Patients with preeclampsia are at risk for cardiovascular disease. Changes in cardiac function are subtle in preeclampsia and are difficult to quantify with conventional imaging. Strain measurements using speckle-tracking echocardiography have been used to sensitively quantify abnormalities in other disease settings.

Methods and Results—

We evaluated the feasibility and sensitivity of strain imaging using speckle-tracking echocardiography in women with preeclampsia. Forty-seven women were enrolled in this pilot study and 39 were analyzed: 11 with preeclampsia, 17 without a hypertensive disorder, and 11 with nonproteinuric hypertension. Echocardiographic ejection fraction and global peak longitudinal, radial, and circumferential strain were measured. Longitudinal strain was significantly worsened in women with preeclampsia compared with women without a hypertensive disorder (
P
=0.0001). Similar results were observed for radial strain (
P
=0.006) and circumferential strain (
P
=0.03). Women with preeclampsia also had significantly worsened longitudinal (
P
=0.04), radial (
P
=0.01), and circumferential (
P
=0.002) strain compared with women with nonproteinuric hypertension. Women with preeclampsia did not have a significantly different ejection fraction compared with women without a hypertensive disorder (
P
=0.16) and women with nonproteinuric hypertension (
P
=0.44).

Conclusions—
Myocardial strain imaging using speckle tracking is more sensitive than left ventricular ejection fraction to detect differences in left ventricular systolic function in women with and without preeclampsia.
Automated Violin Fingering Transcription Through Analysis of an Audio Recording
Authors: Maezawa Akira , Itoyama Katsutoshi , Komatani Kazunori , Ogata Tetsuya , Okuno Hiroshi G. 
Published: August 2012

We present a method to recuperate fingerings for a given piece of violin music in order to recreate the timbre of a given audio recording of the piece. This is achieved by first analyzing an audio signal to determine the most likely sequence of two-dimensional fingerboard locations (string number and location along the string), which recovers elements of violin fingering relevant to timbre. This sequence is then used as a constraint for finding an ergonomic sequence of finger placements that satisfies both the sequence of notated pitch and the given fingerboard-location sequence.Fingerboard-location-sequence estimation is based on estimation of a hidden Markov model, each state of which represents a particular fingerboard location and emits a Gaussian mixture model of the relative strengths of harmonics. The relative strengths of harmonics are estimated from a polyphonic mixture using score-informed source segregation, and compensates for discrepancies between observed data and training data through mean normalization.Fingering estimation is based on the modeling of a cost function for a sequence of finger placements. We tailor our model to incorporate the playing practices of the violin.We evaluate the performance of the fingerboard-location estimator with a polyphonic mixture, and with recordings of a violin whose timbral characteristics differ significantly from that of the training data. We subjectively evaluate the fingering estimator and validate the effectiveness of tailoring the fingering model towards the violin.
Long-range inhibitory mechanisms in the visual system are impaired in migraine sufferers
Authors: Wagner Doreen , Manahilov Velitchko , Gordon Gael E , Storch Peter 
Published: August 2012

Background: After viewing dynamic noise surrounding a homogeneous grey patch (artificial scotoma), observers perceive a prolonged twinkling-noise after-image within the unstimulated area. It has been suggested that noise-stimulated neurons induce a long-range inhibition in neurons within the artificial scotoma, which generates a rebound signal perceived as twinkling noise following noise termination. We used this paradigm to test whether migraineurs have enhanced excitability or weakened inhibition. Methods: Twinkling-noise duration was measured in 13 headache-free volunteers, 13 migraineurs with aura and 13 migraineurs without aura. Results: The durations of the after-image were significantly shorter for both migraine groups compared to controls. Discussion: Enhanced excitation of noise-activated neurons in migraineurs would produce stronger rebound activity and longer after-image durations, while weakened inhibitory mechanisms would diminish the rebound activity and shorten the after-image durations compared to control subjects. The results suggest that cortical inhibitory mechanisms might be impaired in migraineurs with and without aura.
Multiparametric MRI correlates of sensorimotor function in the spinal cord in multiple sclerosis
Authors: Oh Jiwon , Zackowski Kathleen , Chen Min , Newsome Scott , Saidha Shiv , Smith Seth A , Diener-West Marie , Prince Jerry , Jones Craig K , Van Zijl Peter CM , Calabresi Peter A , Reich Daniel S 
Published: August 2012

Background: Spinal cord (SC) pathology is a major contributor to clinical disability in multiple sclerosis (MS). Conventional magnetic resonance imaging (MRI), specifically SC-MRI lesion load measures that include lesion count and volume, demonstrate only a modest relationship with the clinical status of MS patients. Although SC cross-sectional area (CSA) correlates better with clinical dysfunction than MRI lesion count, SC atrophy likely signifies irreversible tissue loss. Using quantitative MRI indices sensitive to early and late microstructural changes in the spinal cord, we searched for the presence of better correlations between MRI measures and clinical status in MS. Objectives: We investigated whether diffusion-tensor imaging indices and the magnetization-transfer ratio (MTR) were better associated with the clinical status of MS patients than conventional SC-MRI measures. Methods: A total of 129 MS patients underwent 3-tesla cervical SC-MRI and quantitative sensorimotor function testing, using the Vibratron-II and dynamometer. Regions-of-interest circumscribed the SC on axial slices between C3-C4. We calculated SC-CSA, fractional anisotropy (FA), mean diffusivity (MD), perpendicular diffusivity (λ⊥), parallel diffusivity (λ||) and MTR. We used multivariable linear regression to determine if there were any associations between MRI indices and clinical measures of dysfunction. Results: All MRI indices were significantly different in subjects with MS versus healthy controls, and between the progressive versus relapsing MS subtypes, with the exception of λ||. In multivariable regression models that were adjusted for age, sex, brain parenchymal fraction, and SC-CSA, the MRI indices independently explained variability in hip flexion strength ( p-values: MD, λ⊥, λ|| < 0.001; FA = 0.07), vibration sensation threshold ( p-values: FA = 0.04; MTR = 0.05; λ⊥ = 0.06), and Expanded Disability Status Scale scores ( p-values: FA = 0.003; MD = 0.03; λ⊥ = 0.005; MTR = 0.02). Conclusions: In a large, heterogeneous MS sample, quantitative SC-MRI indices demonstrated independent associations with system-specific and global clinical dysfunction. Our findings suggest that the indices studied may provide important information about microstructural SC changes and the substrates of limb disability in MS. The identified structure-function relationships underpin the potential utility of these measures in assessments of therapeutic efficacy.
Micronutrient modulation of NF-κB in oral keratinocytes exposed to periodontal bacteria
Authors: Milward Michael R , Chapple Iain LC , Carter Kevin , Matthews John B , Cooper Paul R 
Published: August 2012

Chronic periodontal diseases are characterised by a dysregulated and exaggerated inflammatory/immune response to plaque bacteria. We have demonstrated previously that oral keratinocytes up-regulate key molecular markers of inflammation, including NF-κB and cytokine signalling, when exposed to the periodontal bacteria Porphyromonas gingivalis and Fusobacterium nucleatum in vitro. The purpose of the current study was to investigate whether α-lipoic acid was able to abrogate bacterially-induced pro-inflammatory changes in the H400 oral epithelial cell line. Initial studies indicated that α-lipoic acid supplementation (1–4 mM) significantly reduced cell attachment; lower concentrations (<0.5 mM) enabled >85% cell adhesion at 24 h. While a pro-inflammatory response, demonstrable by NF-κB translocation, gene expression and protein production was evident in H400 cells following exposure to P. gingivalis and F. nucleatum, pre-incubation of cells with 0.5 mM α-lipoic acid modulated this response. α-Lipoic acid pre-treatment significantly decreased levels of bacterially-induced NF-κB activation and IL-8 protein production, and differentially modulated transcript levels for IL-8, IL-1β, TNF-α and GM-CSF, TLR2, 4, 9, S100A8, S100A9, lysyl oxidase, NF-κB1, HMOX, and SOD2. Overall, the data indicate that α-lipoic acid exerts an anti-inflammatory effect on oral epithelial cells exposed to periodontal bacteria and thus may provide a novel adjunctive treatment for periodontal diseases.
EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress
Authors: Peslak Scott A. , Wenger Jesse , Bemis Jeffrey C. , Kingsley Paul D. , Koniski Anne D. , McGrath Kathleen E. , Palis James 
Published: August 2012

AbstractErythropoiesis is a robust process of cellular expansion and maturation occurring in murine bone marrow and spleen. We previously determined that sublethal irradiation, unlike bleeding or hemolysis, depletes almost all marrow and splenic erythroblasts but leaves peripheral erythrocytes intact. To better understand the erythroid stress response, we analyzed progenitor, precursor, and peripheral blood compartments of mice post–4 Gy total body irradiation. Erythroid recovery initiates with rapid expansion of late-stage erythroid progenitors–day 3 burst-forming units and colony-forming units, associated with markedly increased plasma erythropoietin (EPO). Although initial expansion of late-stage erythroid progenitors is dependent on EPO, this cellular compartment becomes sharply down-regulated despite elevated EPO levels. Loss of EPO-responsive progenitors is associated temporally with a wave of maturing erythroid precursors in marrow and with emergence of circulating erythroid progenitors and subsequent reestablishment of splenic erythropoiesis. These circulating progenitors selectively engraft and mature in irradiated spleen after short-term transplantation, supporting the concept that bone marrow erythroid progenitors migrate to spleen. We conclude that sublethal radiation is a unique model of endogenous stress erythropoiesis, with specific injury to the extravascular erythron, expansion and maturation of EPO-responsive late-stage progenitors exclusively in marrow, and subsequent reseeding of extramedullary sites.
SDAR: a practical tool for graphical analysis of two-dimensional data
Authors: Weeratunga Saroja , Hu Nien-Jen , Simon Anne , Hofmann Andreas 
Published: August 2012

Abstract

Background
Two-dimensional data needs to be processed and analysed in almost any experimental laboratory. Some tasks in this context may be performed with generic software such as spreadsheet programs which are available ubiquitously, others may require more specialised software that requires paid licences. Additionally, more complex software packages typically require more time by the individual user to understand and operate. Practical and convenient graphical data analysis software in Java with a user-friendly interface are rare.

Results
We have developed SDAR, a Java application to analyse two-dimensional data with an intuitive graphical user interface. A smart ASCII parser allows import of data into SDAR without particular format requirements. The centre piece of SDAR is the Java class GraphPanel which provides methods for generic tasks of data visualisation. Data can be manipulated and analysed with respect to the most common operations experienced in an experimental biochemical laboratory. Images of the data plots can be generated in SVG-, TIFF- or PNG-format. Data exported by SDAR is annotated with commands compatible with the Grace software.

Conclusion
Since SDAR is implemented in Java, it is truly cross-platform compatible. The software is easy to install, and very convenient to use judging by experience in our own laboratories. It is freely available to academic users athttp://www.structuralchemistry.org/pcsb/. To download SDAR, users will be asked for their name, institution and email address. A manual, as well as the source code of the GraphPanel class can also be downloaded from this site.
Runs of homozygosity and population history in cattle
Authors: Purfield Deirdre C , Berry Donagh P , McParland Sinead , Bradley Daniel G 
Published: August 2012

Abstract

Background
Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes that are present in an individual due to parents transmitting identical haplotypes to their offspring. The extent and frequency of ROHs may inform on the ancestry of an individual and its population. Here we use high density (n = 777,962) bi-allelic SNPs in a range of cattle breed samples to correlate ROH with the pedigree-based inbreeding coefficients and to validate subsequent analyses using 54,001 SNP genotypes. This study provides a first testing of the inference drawn from ROH through comparison with estimates of inbreeding from calculations based on the detailed pedigree data available for several breeds.

Results
All animals genotyped on the HD panel displayed at least one ROH that was between 1–5 Mb in length with certain regions of the genome more likely to be involved in a ROH than others. Strong correlations (r = 0.75, p < 0.0001) existed between the pedigree-based inbreeding coefficient and a statistic based on sum of ROH of length > 0.5 KB and suggests that in the absence of an animal’s pedigree data, the extent of a genome under ROH may be used to infer aspects of recent population history even from relatively few samples.

Conclusions
Our findings suggest that ROH are frequent across all breeds but differing patterns of ROH length and burden illustrate variations in breed origins and recent management.
Computational prediction and validation of C/D, H/ACA and Eh_U3 snoRNAs of Entamoeba histolytica
Authors: Kaur Devinder , Gupta Abhishek Kumar , Kumari Vandana , Sharma Rahul , Bhattacharya Alok , Bhattacharya Sudha 
Published: August 2012

AbstractBackgroundSmall nucleolar RNAs are a highly conserved group of small RNAs found in eukaryotic cells. Genes encoding these RNAs are diversely located throughout the genome. They are functionally conserved, performing post transcriptional modification (methylation and pseudouridylation) of rRNA and other nuclear RNAs. They belong to two major categories: the C/D box and H/ACA box containing snoRNAs. U3 snoRNA is an exceptional member of C/D box snoRNAs and is involved in early processing of pre-rRNA. An antisense sequence is present in each snoRNA which guides the modification or processing of target RNA. However, some snoRNAs lack this sequence and often they are called orphan snoRNAs.ResultsWe have searched snoRNAs ofEntamoeba histolyticafrom the genome sequence using computational programmes (snoscan and snoSeeker) and we obtained 99 snoRNAs (C/D and H/ACA box snoRNAs) along with 5 copies of Eh_U3 snoRNAs. These are located diversely in the genome, mostly in intergenic regions, while some are found in ORFs of protein coding genes, intron and UTRs. The computationally predicted snoRNAs were validated by RT-PCR and northern blotting. The expected sizes were in agreement with the observed sizes for all C/D box snoRNAs tested, while for some of the H/ACA box there was indication of processing to generate shorter products.ConclusionOur results showed the presence of snoRNAs inE. histolytica, an early branching eukaryote, and the structural features ofE. histolyticasnoRNAs were well conserved when compared with yeast and human snoRNAs. This study will help in understanding the evolution of these conserved RNAs in diverse phylogenetic groups.
The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes
Authors: Li Jin , Mao Nai-Ying , Zhang Chen , Yang Meng-Jie , Wang Miao , Xu Wen-Bo , Ma Xue-Jun 
Published: August 2012

Abstract

Background
Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA) are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens.

Methods
A GeXP-based multiplex RT-PCR assay (GeXP assay) was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay.

Results
The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51%) of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours.

Conclusions
In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.
Local decision makers’ awareness of the social determinants of health in Turkey: a cross-sectional study
Authors: Didem Evci Emine , Filiz Ergin , Orhan Okur , Gulnur Saruhan , Erdal Beser 
Published: August 2012

Abstract

Background
Social determinants have been described as having a greater influence than other determinants of health status. The major social determinants of health and the necessary policy objectives have been defined; it is now necessary to evaluate the effectiveness of these policies. Previous studies have shown that descriptions of the awareness level of citizens and local decision makers, practice-based research and evidence, and intersectoral studies are the best options for investigating the social determinants of health at the community level. The objective of the present study was to define local decision makers’ awareness of the social determinants of health in the Aydin province of Turkey.

Methods
A total of 53 mayors serve the Aydin city center, districts and towns. Aydin city center has 22 neighborhoods and 22 headmen responsible for them. The present study targeted all mayors and headmen in Aydin - a total of 75 possible participants. A questionnaire was used to collect the data. The questionnaire was faxed to the mayors and administered face-to-face with the headmen.

Results
Headmen identified the three most important determinants of public health as environmental issues, addictions (smoking, alcohol) and malnutrition. According to the mayors, the major determinant of public health is stress, followed by malnutrition, environmental issues, an inactive lifestyle, and the social and economic conditions of the country. Both groups expressed that the Turkish Ministry of Health, municipalities and universities are the institutions responsible for developing health policy. Headmen were found to be unaware and mayors were aware of the social determinants of health as classified by the World Health Organisation. Both groups were classified as unaware with regard to their awareness of the Marmot Review policy objectives.

Conclusions
Studies such as the present study provide important additional information on the social determinants of health, and help to increase the awareness levels of both local decision-makers and the community. Such studies must be considered a vital first step in future public health research on health determinants and their impact on national and international policies.