Miracle-dz/UniFAR-FTUs huggingface dataset:
Post-Mortem Stability of RNA in Skeletal Muscle and Adipose Tissue and the Tissue-Specific Expression of Myostatin, Perilipin and Associated Factors in the Horse

Obesity, a major concern for equine welfare, is highly prevalent in the leisure horse population. Skeletal-muscle and adipose tissues are important determinants of maintenance energy requirements. The myostatin and perilipin pathways play key roles in the regulation of muscle mass and lipolysis respectively and have both been associated with obesity predisposition in other mammalian species. High quality samples, suitable for molecular biology, are an essential prerequisite for detailed investigations of gene and protein expression. Hence, this study has evaluated a) the post-mortem stability of RNA extracted from skeletal-muscle and adipose-tissues collected under commercial conditions and b) the tissue-specific presence of myostatin, the moystatin receptor (activin receptor IIB, ActRIIB), follistatin and perilipin, genes and proteins across a range of equine tissues. Objectives were addressed using tissues from 7 Thoroughbred horses presented for slaughter at a commercial abattoir; a) samples were collected at 7 time-points from Masseter muscle and perirenal adipose from 5 minutes to 6 hours post-mortem. Extracted RN was appraised by Optical Density analysis and agarose-gel electrophoresis. b) Quantitative real time PCR and Western Blotting were used to evaluate gene and protein expression in anatomically-defined samples collected from 17 tissues (6 organs, 4 skeletal muscles and 7 discrete adipose depots). The results indicate that, under the present collection conditions, intact, good quality RNA could be extracted from skeletal-muscle for up to 2 hours post-mortem. However, RNA from adipose tissue may be more susceptible to degradation/contamination and samples should be collected no later than 30 minutes post-mortem. The data also show that myostatin and ActRIIB genes and proteins were almost exclusively expressed in skeletal muscle. The follistatin gene showed a more diverse gene expression profile, with expression evident in several organs, adipose tissue depots and skeletal muscles. Perilipin gene and protein were almost exclusively expressed by adipose tissue.
Spectroscopic and theoretical approaches for studying radical reactions in class I ribonucleotide reductase

Abstract Ribonucleotide reductases (RNRs) catalyze the production of deoxyribonucleotides, which are essential for DNA synthesis and repair in all organisms. The three currently known classes of RNRs are postulated to utilize a similar mechanism for ribonucleotide reduction via a transient thiyl radical, but they differ in the way this radical is generated. Class I RNR, found in all eukaryotic organisms and in some eubacteria and viruses, employs a diferric iron center and a stable tyrosyl radical in a second protein subunit, R2, to drive thiyl radical generation near the substrate binding site in subunit R1. From extensive experimental and theoretical research during the last decades, a general mechanistic model for class I RNR has emerged, showing three major mechanistic steps: generation of the tyrosyl radical by the diiron center in subunit R2, radical transfer to generate the proposed thiyl radical near the substrate bound in subunit R1, and finally catalytic reduction of the bound ribonucleotide. Amino acid- or substrate-derived radicals are involved in all three major reactions. This article summarizes the present mechanistic picture of class I RNR and highlights experimental and theoretical approaches that have contributed to our current understanding of this important class of radical enzymes.
Psychomotor Retardation in Elderly Untreated Depressed Patients

Background: Psychomotor retardation (PR) is one of the core features in depression according to DSM V (1), but also aging in itself causes cognitive and psychomotor slowing. This is the first study investigating PR in relation to cognitive functioning and to the concomitant effect of depression and aging in a geriatric population ruling out contending effects of psychotropic medication. Methods: A group of 28 non-demented depressed elderly is compared to a matched control group of 20 healthy elderly. All participants underwent a test battery containing clinical depression measures, cognitive measures of processing speed, executive function and memory, clinical ratings of PR, and objective computerized fine motor skill-tests. Statistical analysis consisted of a General Linear Method multivariate analysis of variance to compare the clinical, cognitive, and psychomotor outcomes of the two groups. Results: Patients performed worse on all clinical, cognitive, and PR measures. Both groups showed an effect of cognitive load on fine motor function but the influence was significantly larger for patients than for healthy elderly except for the initiation time. Limitations: Due to the restrictive inclusion criteria, only a relatively limited sample size could be obtained. Conclusion: With a medication free sample, an additive effect of depression and aging on cognition and PR in geriatric patients was found. As this effect was independent of demand of effort (by varying the cognitive load), it was apparently not a motivational slowing effect of depression.
Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress

A short-term exposure to moderately intense physical exercise affords a novel measure of protection against autoimmune-mediated peripheral nerve injury. Here, we investigated the mechanism by which forced exercise attenuates the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain–Barré syndrome. Adult male Lewis rats remained sedentary (control) or were preconditioned with forced exercise (1.2 km/day × 3 weeks) prior to P2-antigen induction of EAN. Sedentary rats developed a monophasic course of EAN beginning on postimmunization day 12.3 ± 0.2 and reaching peak severity on day 17.0 ± 0.3 (N = 12). By comparison, forced-exercise preconditioned rats exhibited a similar monophasic course but with significant (p < .05) reduction of disease severity. Analysis of popliteal lymph nodes revealed a protective effect of exercise preconditioning on leukocyte composition and egress. Compared with sedentary controls, forced exercise preconditioning promoted a sustained twofold retention of P2-antigen responsive leukocytes. The percentage distribution of pro-inflammatory (Th1) lymphocytes retained in the nodes from sedentary EAN rats (5.1 ± 0.9%) was significantly greater than that present in nodes from forced-exercise preconditioned EAN rats (2.9 ± 0.6%) or from adjuvant controls (2.0 ± 0.3%). In contrast, the percentage of anti-inflammatory (Th2) lymphocytes (7–10%) and that of cytotoxic T lymphocytes (∼20%) remained unaltered by forced exercise preconditioning. These data do not support an exercise-inducible shift in Th1:Th2 cell bias. Rather, preconditioning with forced exercise elicits a sustained attenuation of EAN severity, in part, by altering the composition and egress of autoreactive proinflammatory (Th1) lymphocytes from draining lymph nodes.
Complete Fermi surface mapping of Bi2Sr2CaCu2O8+x(001): Coexistence of short range antiferromagnetic correlations and metallicity in the same phase.

The Fermi surface of ${\mathrm{Bi}}_{2}$${\mathrm{Sr}}_{2}$${\mathrm{CaCu}}_{2}$${\mathrm{O}}_{8+\mathit{x}}$(001) has been mapped at nearly 6000 points in k space using angle-resolved photoemission at 300 K. We observe both features that are in good agreement with the local density calculation of Massidda, Yu, and Freeman [Physica (Amsterdam) 158C, 251 (1988)] and others that are missing in the calculation. Among those missing, most importantly, we find a c(2\ifmmode\times\else\texttimes\fi{}2) superstructure on the Fermi surface strongly suggesting short range antiferromagnetic correlations. It is remarkable that this is evident in the metallic state and in the Fermi surface itself.
Ownership types for object encapsulation

Ownership types provide a statically enforceable way of specifying object encapsulation and enable local reasoning about program correctness in object-oriented languages. However, a type system that enforces strict object encapsulation is too constraining: it does not allow efficient implementation of important constructs like iterators. This paper argues that the right way to solve the problem is to allow objects of classes defined in the same module to have privileged access to each other's representations; we show how to do this for inner classes. This approach allows programmers to express constructs like iterators and yet supports local reasoning about the correctness of the classes, because a class and its inner classes together can be reasoned about as a module. The paper also sketches how we use our variant of ownership types to enable efficient software upgrades in persistent object stores.
The rat anococcygeus muscle and its response to nerve stimulation and to some drugs

1 A new smooth muscle preparation, the rat anococcygeus muscle, is described. The muscle is paired, thin, consists of smooth muscle only and the muscle cells are organized in parallel bundles. It has a dense adrenergic innervation distributed throughout the muscle but apparently no cholinergic innervation. The muscles are easily isolated. 2 The muscle contracts to noradrenaline, acetylcholine, furmethide, 5‐hydroxytryptamine, but not to histamine. Isoprenaline produces contraction at high concentrations. The effects of noradrenaline and acetylcholine are blocked by phentolamine and atropine respectively. The response to isoprenaline is little affected by propranolol. 3 The muscle contracts in response to field stimulation or stimulation of extrinsic nerves. This response is completely blocked by phentolamine but unaffected by hexamethonium or atropine. 4 Guanethidine 10−6–5 × 10−6M blocks the motor response to nerve stimulation and potentiates that to noradrenaline. Higher concentrations of guanethidine raise tone. In the presence of raised tone, field stimulation produces an inhibitory response insensitive to hexamethonium but abolished by tetrodotoxin 2 × 10−7 g/ml. This inhibitory response to stimulation can also be shown after other drugs which raise tone. 5 The inhibitory response to nerve stimulation is not mimicked by acetylcholine, isoprenaline or ATP, nor blocked by atropine, phentolamine, phenoxybenzamine, propranolol, hexamethonium or lysergic acid diethylamide.
Exosomal lipids induce human pancreatic tumoral MiaPaCa-2 cells resistance through the CXCR4-SDF-1α signaling axis

We previously reported that exosomes secreted by human pancreatic tumor cells induce cell death through the inhibition of the Notch-1 survival pathway (Ristorcelli et al., 2009). We demonstrated that exosomal lipids evoked apoptosis of human pancreatic cancer SOJ-6 cells. Based on the lipid composition of efficient exosomes we designed Synthetic Exosome-Like Nanoparticles (SELN) in which the ratio ordered lipids versus disordered lipids was equal to 6.0 (SELN6.0). These SELN decreased SOJ-6 cells survival by inhibiting the Notch-1 pathway. However MiaPaCa-2 cells were resistant to exosomes (Ristorcelli et al., 2008) and to SELN6.0 (Beloribi et al.,2012). In this paper we aimed at deciphering the reason(s) of this resistance. We observed, in presence of SELN6.0, that the expression of the Notch IntraCytoplasmic Domain (NICD) decreases in MiaPaCa-2 cells but neither Hes-1, the nuclear target of NICD, nor the ratio Bax/Bcl-2 were affected. We further showed that in MiaPaCa-2 cells SELN6.0 induced the activation of NF-kB, which promotes the expression and the secretion of SDF-1α. This chemokine interacts with its receptor CXCR4 on MiaPaCa-2 cells and activates the Akt survival pathway protecting cells from death. This activation process promoted by exosomal lipids could have implications in tumor progression and drug resistance.
Timing synchronization and frequency offset estimation for Ultra-Wideband (UWB) Multi-Band OFDM systems

An algorithm based on distinguishing the first significant multipath (FTA) is proposed to address the critical issue of symbol timing synchronization and carrier frequency offset estimation in ultra wideband (UWB) multi-band OFDM (MB-OFDM) systems. FTA pinpoints the frame synchronization sequence and the start of its fast Fourier transform (FFT) window by accumulating multipath energies and then discerning for first significant multipath component through threshold comparison between consecutive accumulated energy samples. Thereafter, the frequency offset (FO) is estimated from phase differences between training symbols. Two channel models (CM), as proposed by IEEE 802.15 channel modeling sub-committee, CM 1: line-of-sight for 0-4 m and CM2: non-line-of-sight for 0-4 m are simulated with 100,000 noisy realizations per threshold. The timing offset mean-squared errors for CM1 is 0.371 OFDM samples and CM2 is 4.548 OFDM samples under a typical signal-to-noise ratio (SNR) of 17 dB for high data rate applications. These are orders of magnitude lower compared to conventional OFDM-extended correlation methods. A maximum likelihood FO estimation algorithm is derived and its performance is compared with FTA simulation results. Variance of the FTA FO estimate approaches that of maximum likelihood FO estimate with a SNR loss of less than 0.5 dB
Survival After the Onset of Congestive Heart Failure in Framingham Heart Study Subjects

BackgroundRelatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting. Methods and ResultsProportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0 ± 10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3 ± 7.6 years in the 1950s, 65.9 ± 7.9 years in the 1960s, 71.6 ± 9.4 years in the 1970s, and 76.4 ± 10.0 years in the 1980s; p<0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26). ConclusionCHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.
Argonaute 2 in dopamine 2 receptor–expressing neurons regulates cocaine addiction

Cocaine is a highly addictive drug that exerts its effects by increasing the levels of released dopamine in the striatum, followed by stable changes in gene transcription, mRNA translation, and metabolism within medium spiny neurons in the striatum. The multiple changes in gene and protein expression associated with cocaine addiction suggest the existence of a mechanism that facilitates a coordinated cellular response to cocaine. Here, we provide evidence for a key role of miRNAs in cocaine addiction. We show that Argonaute 2 (Ago2), which plays an important role in miRNA generation and execution of miRNA-mediated gene silencing, is involved in regulation of cocaine addiction. Deficiency of Ago2 in dopamine 2 receptor (Drd2)–expressing neurons greatly reduces the motivation to self-administer cocaine in mice. We identified a distinct group of miRNAs that is specifically regulated by Ago2 in the striatum. Comparison of miRNAs affected by Ago2 deficiency with miRNAs that are enriched and/or up-regulated in Drd2-neurons in response to cocaine identified a set of miRNAs that are likely to play a role in cocaine addiction.
Edinburgh Research Explorer Genome-Wide Analysis in Swine Associates Corneal Graft Rejection with Donor-Recipient Mismatches in Three Novel Histocompatibility Regions and One Locus Homologous to the Mouse H-3 Locus

In rodents, immune responses to minor histocompatibility antigens are the most important drivers of corneal graft rejection. However, this has not been confirmed in humans or in a large animal model and the genetic loci are poorly characterised, even in mice. The gene sequence data now available for a range of relevant species permits the use of genome-wide association (GWA) techniques to identify minor antigens associated with transplant rejection. We have used this technique in a pre-clinical model of corneal transplantation in semi-inbred NIH minipigs and Babraham swine to search for novel minor histocompatibility loci and to determine whether rodent findings have wider applicability. DNA from a cohort of MHC-matched and MHC-mismatched donors and recipients was analysed for single nucleotide polymorphisms (SNPs). The level of SNP homozygosity for each line was assessed. Genome-wide analysis of the association of SNP disparities with rejection was performed using log-likelihood ratios. Four genomic blocks containing four or more SNPs significantly linked to rejection were identified (on chromosomes 1, 4, 6 and 9), none at the location of the MHC.
Svm-based Phoneme Classification and Lip Shape Refinement in Real-time Lip-synch System

In this paper, we present a real time lip-synch system that activates 2-D avatar's lip motion in synch with incoming speech utterance. To achieve the real time operation of the system, the processing time was minimized by "merge and split" procedures resulting in coarse-to-fine phoneme classification. At each stage of phoneme classification, the support vector machine (SVM) method was applied to reduce the computational load while maintaining the desired accuracy. The coarse-to-fine phoneme classification, is accomplished via two_stages of feature extraction: in the first stage, each speech frame is acoustically analyzed for three classes of lip opening using Mel Frequency Cepstral Coefficients (MFCC) as a feature; in the second stage, each frame is further refined for detailed lip shape using formant information. The method was implemented in 2-D lip animation and it was demonstrated that the system was effective in accomplishing real-time lip-synch. This approach was tested on a PC using the Microsoft Visual Studio with an Intel Pentium IV 1.4 Giga Hz CPU and 384 MB RAM. It was observed that the methods of phoneme merging and SVM achieved about twice the speed in recognition than the method employing the Hidden Markov Model (HMM). A typical latency time per a single frame observed using the proposed method was in the order of 18.22 milliseconds while an HMM method under identical conditions resulted about 30.67 milliseconds.
An Evaluation of Utility Measurement in Crohn's Disease

Summary: We evaluated the use of utility measurements to assess the quality of life of patients with Crohn's disease. Utility scores were obtained using the Time Trade‐Off (TTO), Standard Gamble, and Visual Analog Scale (VAS) methods in 180 consecutive patients with Crohn's disease. The mean utility scores of patients with a spectrum of disease severity were compared with other measures of disease activity to assess the operating properties of these instruments. All methods of utility estimation yielded lower mean scores in patients with more severe disease. (Remission versus chronically active, therapy resistant disease: TTO 0.96 versus 0.88; Standard Gamble 0.88 versus 0.74; VAS 0.84 versus 0.61). TTO scores were consistently higher than those derived by the other methods (p = 0.001). The utility scores were reliable in patients who were stable (intraclass correlation coefficient 0.55‐0.84), but were less responsive than the Crohn's Disease Activity Index (responsiveness ratio 0.97‐1.3 versus 2.10) to changes in disease severity. Patients with active Crohn's disease have decreased quality of life as measured by utility scores. Although utilities are valid and reliable quality of life assessments, they are less responsive than other measures of outcome used for clinical trials.
Differences in the Association between Segment and Language: Early Bilinguals Pattern with Monolinguals and Are Less Accurate than Late Bilinguals

Early bilinguals often show as much sensitivity to L2-specific contrasts as monolingual speakers of the L2, but most work on cross-language speech perception has focused on isolated segments, and typically only on neighboring vowels or stop contrasts. In tasks that include sounds in context, listeners’ success is more variable, so segment discrimination in isolation may not adequately represent the phonetic detail in stored representations. The current study explores the relationship between language experience and sensitivity to segmental cues in context by comparing the categorization patterns of monolingual English listeners and early and late Spanish–English bilinguals. Participants categorized nonce words containing different classes of English- and Spanish-specific sounds as being more English-like or more Spanish-like; target segments included phonemic cues, cues for which there is no analogous sound in the other language, or phonetic cues, cues for which English and Spanish share the category but for which each language varies in its phonetic implementation. Listeners’ language categorization accuracy and reaction times were analyzed. Our results reveal a largely uniform categorization pattern across listener groups: Spanish cues were categorized more accurately than English cues, and phonemic cues were easier for listeners to categorize than phonetic cues. There were no differences in the sensitivity of monolinguals and early bilinguals to language-specific cues, suggesting that the early bilinguals’ exposure to Spanish did not fundamentally change their representations of English phonology. However, neither did the early bilinguals show more sensitivity than the monolinguals to Spanish sounds. The late bilinguals however, were significantly more accurate than either of the other groups. These findings indicate that listeners with varying exposure to English and Spanish are able to use language-specific cues in a nonce-word language categorization task. Differences in how, and not only when, a language was acquired may influence listener sensitivity to more difficult cues, and the advantage for phonemic cues may reflect the greater salience of categories unique to each language. Implications for foreign-accent categorization and cross-language speech perception are discussed, and future directions are outlined to better understand how salience varies across language-specific phonemic and phonetic cues.