Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization by [3H]Dihydroergocryptine Binding of Alpha‐Adrenergic Receptors in Neuroblastoma × Glioma Hybrid Cells

Abstract: [3H]Dihydroergocryptine ([3H]DHE) was shown to bind to sites in membranes from neuroblastoma × glioma hybrid cells (NG 108‐15) that had the characteristics expected of α‐adrenergic receptors. The binding was saturable with 0.3 pmol [3H]DHE bound per mg of protein and of high affinity, with an apparent dissociation constant (KD) of 1.8 nM. The specificity of the binding site for various ligands was more similar to that of α2 receptors than to that of α1. No specific binding of [3H]WB‐4101 was found in the membranes derived from NG 108 cells. This finding also indicated that the [3H]DHE binding site in the cell is the α2 receptor. GTP lowered the affinity of agonists for the [3H]DHE binding site, although the nucleotide hardly affected the affinity of antagonists, including [3H]DHE.
‘Oh God, not a Palliative’: out-of-hours general practitioners within the domain of palliative care

To date, the experiences of out-of-hours general practitioners with regard to palliative care patients and their management are yet to be evaluated, since the new General Medical Services contract came into force. In 2007 the National Institute for Health Research highlighted the need to identify factors that improve and hinder the delivery of optimum palliative out-of-hours care. By interviewing general practitioners who work out-of-hours shifts, this project explored factors influencing confidence in dealing with symptom control and palliative care provision outside regular working hours. Face-to-face semi-structured interviews were conducted with nine out-of-hours general practitioners employed by Serco. Interviews were conducted by a specialist doctor in palliative care who had in the past worked as an out-of-hours general practitioner. Interviews were analysed using Interpretative Phenomenological Analysis. General practitioners expressed concerns relating to constraints within the system provided by the private company-owned out-of-hours provider. Data from interviews was thematically very rich and brought out many different subject areas, some similar to previous interviews, some different. Sub-themes related to the process-driven aspects of working in out-of-hours: • Motivation • Time-pressure constraints and continuity • The out-of-hours doctor within the domain of palliative care • Isolation within system General practitioners stated that their motivation was mainly financial. There was clear concern about the lack of continuity, and inadequacy of notes and follow-up, and there was a demonstrated need for more learning on the topic of palliative care. Pressure from the out-of-hours provider to see more patients was felt to be oppositional with the need to spend adequate time with this vulnerable patient group. General practitioners felt as unwanted strangers who were viewed with suspicion by patients and carers in palliative care situations. It was clear that most of the doctors interviewed felt a strong sense of isolation when working out-of-hours shifts, and some felt less inclined to contact specialist palliative care services.
The biological significance of acoustic stimuli determines ear preference in the music frog

ABSTRACT Behavioral and neurophysiological studies support the idea that right ear advantage (REA) exists for perception of conspecific vocal signals in birds and mammals. Nevertheless, few studies have focused on anuran species that typically communicate through vocalization. The present study examined the direction and latencies of orientation behaviors in Emei music frogs (Babina daunchina) produced in response to six auditory stimuli emitted by a speaker placed directly behind the subjects. The stimuli included male advertisement calls produced from within burrow nests, which have been shown to be highly sexually attractive (HSA), calls produced from outside burrows, which are of low sexual attractiveness (LSA), screech calls produced when frogs are attacked by snakes, white noise, thunder and silence. For all sound stimuli except the screech, the frogs preferentially turned to the right. Right ear preference was strongest for HSA calls. For the screech and thunder stimuli, there was an increased tendency for subjects to move further from the speaker rather than turning. These results support the idea that in anurans, right ear preference is associated with perception of positive or neutral signals such as the conspecific advertisement call and white noise, while a left ear preference is associated with perception of negative signals such as predatory attack. Highlighted Article: Right ear advantage is demonstrated behaviorally in an anuran through an orientation task, which shows that differences in bio-significance induce variable responses, suggesting orientations are affected by mating strategy and emotion processing.
Environmental Influences on Kelp Performance across the Reproductive Period: An Ecological Trade-Off between Gametophyte Survival and Growth?

Most kelps (order Laminariales) exhibit distinct temporal patterns in zoospore production, gametogenesis and gametophyte reproduction. Natural fluctuations in ambient environmental conditions influence the intrinsic characteristics of gametes, which define their ability to tolerate varied conditions. The aim of this work was to document seasonal patterns in reproduction and gametophyte growth and survival of Ecklonia radiata (C. Agardh) J. Agardh in south-western Australia. These results were related to patterns in local environmental conditions in an attempt to ascertain which factors explain variation throughout the season. E. radiata was fertile (produced zoospores) for three and a half months over summer and autumn. Every two weeks during this time, gametophytes were grown in a range of temperatures (16–22°C) in the laboratory. Zoospore densities were highly variable among sample periods; however, zoospores released early in the season produced gametophytes which had greater rates of growth and survival, and these rates declined towards the end of the reproductive season. Growth rates of gametophytes were positively related to day length, with the fastest growing recruits released when the days were longest. Gametophytes consistently survived best in the lowest temperature (16°C), yet exhibited optimum growth in higher culture temperatures (20–22°C). These results suggest that E. radiata releases gametes when conditions are favourable for growth, and E. radiata gametophytes are tolerant of the range of temperatures observed at this location. E. radiata releases the healthiest gametophytes when day length and temperature conditions are optimal for better germination, growth, and sporophyte production, perhaps as a mechanism to help compete against other species for space and other resources.
Comprehensive analysis of gene expression patterns in Friedreich's ataxia fibroblasts by RNA sequencing reveals altered levels of protein synthesis factors and solute carriers

ABSTRACT Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease usually caused by large homozygous expansions of GAA repeat sequences in intron 1 of the frataxin (FXN) gene. FRDA patients homozygous for GAA expansions have low FXN mRNA and protein levels when compared with heterozygous carriers or healthy controls. Frataxin is a mitochondrial protein involved in iron–sulfur cluster synthesis, and many FRDA phenotypes result from deficiencies in cellular metabolism due to lowered expression of FXN. Presently, there is no effective treatment for FRDA, and biomarkers to measure therapeutic trial outcomes and/or to gauge disease progression are lacking. Peripheral tissues, including blood cells, buccal cells and skin fibroblasts, can readily be isolated from FRDA patients and used to define molecular hallmarks of disease pathogenesis. For instance, FXN mRNA and protein levels as well as FXN GAA-repeat tract lengths are routinely determined using all of these cell types. However, because these tissues are not directly involved in disease pathogenesis, their relevance as models of the molecular aspects of the disease is yet to be decided. Herein, we conducted unbiased RNA sequencing to profile the transcriptomes of fibroblast cell lines derived from 18 FRDA patients and 17 unaffected control individuals. Bioinformatic analyses revealed significantly upregulated expression of genes encoding plasma membrane solute carrier proteins in FRDA fibroblasts. Conversely, the expression of genes encoding accessory factors and enzymes involved in cytoplasmic and mitochondrial protein synthesis was consistently decreased in FRDA fibroblasts. Finally, comparison of genes differentially expressed in FRDA fibroblasts to three previously published gene expression signatures defined for FRDA blood cells showed substantial overlap between the independent datasets, including correspondingly deficient expression of antioxidant defense genes. Together, these results indicate that gene expression profiling of cells derived from peripheral tissues can, in fact, consistently reveal novel molecular pathways of the disease. When performed on statistically meaningful sample group sizes, unbiased global profiling analyses utilizing peripheral tissues are critical for the discovery and validation of FRDA disease biomarkers. Summary: Transcriptome profiling of Friedreich's ataxia fibroblasts by RNA sequencing reveals that this peripheral tissue can be used as a disease model for gene expression biomarker discovery.
Effect of Phase of Menstrual Cycle on Insulin Sensitivity, Peripheral Blood Flow and Cardiovascular Responses to Hyperinsulinaemia in Young Women with Type 1 Diabetes

Disturbances of blood glucose control around the time of menstruation are often reported by women with Type 1 diabetes. To investigate the possibility that such changes may be due to alterations in insulin sensitivity or peripheral blood flow we have studied 9 women with Type 1 diabetes during the follicular and luteal phases of the menstrual cycle. Insulin sensitivity was assessed by the glucose clamp technique with insulin doses of 40 (low dose) and 100 (high dose) mU m−2 min−1. Glucose disposal rates were 2.5 ± 0.3 (mean ± SE) mg kg−1 min−1 during the follicular phase and 3.2 ± 0.3 mg kg−1 min−1 in the luteal phase with low dose insulin, and 5.9 ± 0.4 and 6.4 ± 0.6 mg kg−1 min−1, respectively, with high dose insulin. These differences were not statistically significant. Forearm blood flow, heart rate, and blood pressure were similar during both phases.
Evaluation of 2 Different Reference Planes Used for the Study of Asymmetric Facial Malformations

The purpose of this study was to evaluate if Frankfort plane (FH) and plane passing through the lateral semicircular canals (LS) can be used as reference planes in three-dimensional analysis. Ten patients with facial asymmetry underwent a three-dimensional computed tomography. Computed tomographic images were processed by means of a commercial software and a personal computer to obtain a three-dimensional virtual craniofacial model. The average Frankfort plane and the plane passing through the LS were identified. The distance from the above-mentioned planes to the first upper molar and upper canine cusp was measured. It was not possible to detect an FH plane in any of the patients. Right FH, left FH, average FH, and LS plane were traced. The discrepancies among reference planes were significant in cases with severe asymmetry. A minimal discrepancy was noticed in patients with light asymmetry. In patients with severe asymmetry, the LS plane results in steady, reproducible, detectable, and closer to the patient's anatomy, representing a valid reference plane for three-dimensional computed tomography analysis.
Expression of ΔNp73 Predicts Poor Prognosis in Lung Cancer

Purpose: ΔNp73 is an isoform of the p53 homologue p73, which lacks an NH2-terminal transactivation domain and antagonizes the induction of gene expression by p53/p73. The aim of this study was to detect ΔNp73 expression in lung cancer and to evaluate the relationship between the ΔNp73 expression level and the prognosis of patients with resected lung cancer. Experimental Design: We used immunohistochemistry to analyze the protein expression of ΔNp73 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients and compared the expression level of ΔNp73, clinical variables, and survival outcome. Results: Positive expression of ΔNp73 was detected mainly in the cytoplasm of tumor cells in 77 of 132 patients (58.3%) with lung cancer. The incidence of positive expression of ΔNp73 was 52.2, 50.0, and 70.2% in patients with stage I, II, and III, respectively (P = 0.04). Positive expression of ΔNp73 was associated with gender but not associated with age, histologic type, pathological stage, pathological T status, and pathological N status. Lung cancer patients with positive ΔNp73 expression had a poorer prognosis than those with negative ΔNp73 expression. In addition, multivariate analysis of the clinicopathological characteristics of lung cancer indicated that positive expression of ΔNp73 was a significant independent factor for predicting poor prognosis (P < 0.0001, risk ratio = 3.39). Conclusions: Expression of ΔNp73 may be a useful marker for predicting poor prognosis of patients who underwent resection of lung cancer.
StarPU: a unified platform for task scheduling on heterogeneous multicore architectures

In the field of HPC, the current hardware trend is to design multiprocessor architectures featuring heterogeneous technologies such as specialized coprocessors (e.g. Cell/BE) or data‐parallel accelerators (e.g. GPUs). Approaching the theoretical performance of these architectures is a complex issue. Indeed, substantial efforts have already been devoted to efficiently offload parts of the computations. However, designing an execution model that unifies all computing units and associated embedded memory remains a main challenge. We therefore designed StarPU, an original runtime system providing a high‐level, unified execution model tightly coupled with an expressive data management library. The main goal of StarPU is to provide numerical kernel designers with a convenient way to generate parallel tasks over heterogeneous hardware on the one hand, and easily develop and tune powerful scheduling algorithms on the other hand. We have developed several strategies that can be selected seamlessly at run‐time, and we have analyzed their efficiency on several algorithms running simultaneously over multiple cores and a GPU. In addition to substantial improvements regarding execution times, we have obtained consistent superlinear parallelism by actually exploiting the heterogeneous nature of the machine. We eventually show that our dynamic approach competes with the highly optimized MAGMA library and overcomes the limitations of the corresponding static scheduling in a portable way. Copyright © 2010 John Wiley & Sons, Ltd.
Current Therapeutic Advances Targeting EGFR and EGFRvIII in Glioblastoma

Epidermal growth factor receptor (EGFR) and EGFRvIII analysis is of current interest in glioblastoma – the most common malignant primary CNS tumor, because of new EGFRvIII vaccine trials underway. EGFR activation in glioblastoma promotes cellular proliferation via activation of MAPK and PI3K–Akt pathways, and EGFRvIII is the most common variant, leading to constitutively active EGFR. This review explains EGFR and EGFRvIII signaling in GBM; describes targeted therapy approaches to date including tyrosine kinase inhibitor, antibody-based therapies, vaccines and pre-clinical RNA-based therapies, and discusses the difficulties encountered with these approaches including pathway redundancy and intratumoral heterogeneity.
Distinct Neural Systems Involved in Agency and Animacy Detection

We designed an fMRI experiment comparing perception of human faces and robotic faces producing emotional expressions. The purpose of our experiment was to investigate engagement of different parts of the social brain by viewing these animate and inanimate agents. Both human and robotic face expressions evoked activity in face-responsive regions in the fusiform gyrus and STS and in the putative human mirror neuron system. These results suggest that these areas mediate perception of agency, independently of whether the agents are living or not. By contrast, the human faces evoked stronger activity than did robotic faces in the medial pFC and the anterior temporal cortex—areas associated with the representation of others' mental states (theory of mind), whereas robotic faces evoked stronger activity in areas associated with perception of objects and mechanical movements. Our data demonstrate that the representation of the distinction between animate and inanimate agents involves areas that participate in attribution of mental stance.
The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury

Abstract Objective To investigate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on intractable neuropathic pain in patients with spinal cord injury (SCI). Design A single center, prospective, randomized, double-blinded, controlled study. Setting SCI rehabilitation unit of university rehabilitation center. Participants Seventeen patients with SCI and chronic neuropathic pain who met the inclusion criteria recruited between April 2010 and January 2012. Interventions Ten daily treatment sessions of real or sham rTMS (30 trains of 10-Hz stimuli for a duration of 5 seconds; a total of 1500 pulses at intensity equal to 110% of the resting motor threshold) was applied over vertex using a ﬁgure-of-8-shaped coil. Outcome measures Pain was assessed with visual analog scale (VAS) at baseline and 10 days, 6 weeks and 6 months after the treatment. Patients’ satisfactions obtained using a 5-point Likert scale at 6 months. Results Both real and sham rTMS provided a significant reduction in the VAS scores (real rTMS group, P = 0.004; sham rTMS group, P = 0.020). Post hoc analysis revealed the significant difference was at 10 days and 6 weeks compared to baseline in the real rTMS group and only at 10 days compared to baseline in the sham rTMS group. Comparison of VAS scores and patient satisfaction did not show any significant difference at each assessment point (P > 0.05). Conclusion Our results demonstrated analgesic effect of rTMS on intractable neuropathic pain in SCI was not superior to placebo. However, middle-term (over 6 weeks) pain relief by rTMS is encouraging and suggests the need for future studies with a larger sample size.
S-Nitrosylation Positively Regulates Ascorbate Peroxidase Activity during Plant Stress Responses1

Nitric oxide positively regulates a key Arabidopsis peroxidase through S-nitrosylation and enhances resistance to oxidative stresses. Nitric oxide (NO) and reactive oxygen species (ROS) are two classes of key signaling molecules involved in various developmental processes and stress responses in plants. The burst of NO and ROS triggered by various stimuli activates downstream signaling pathways to cope with abiotic and biotic stresses. Emerging evidence suggests that the interplay of NO and ROS plays a critical role in regulating stress responses. However, the underpinning molecular mechanism remains poorly understood. Here, we show that NO positively regulates the activity of the Arabidopsis (Arabidopsis thaliana) cytosolic ascorbate peroxidase1 (APX1). We found that S-nitrosylation of APX1 at cysteine (Cys)-32 enhances its enzymatic activity of scavenging hydrogen peroxide, leading to the increased resistance to oxidative stress, whereas a substitution mutation at Cys-32 causes the reduction of ascorbate peroxidase activity and abolishes its responsiveness to the NO-enhanced enzymatic activity. Moreover, S-nitrosylation of APX1 at Cys-32 also plays an important role in regulating immune responses. These findings illustrate a unique mechanism by which NO regulates hydrogen peroxide homeostasis in plants, thereby establishing a molecular link between NO and ROS signaling pathways.
Publicity, police resources and the effectiveness of random breath testing

Random breath testing (RBT) of drivers by the police was introduced in South Australia in 1981 at a very low level of enforcement. As there was no lasting effect on illegal “drink driving” the resources devoted to RBT were increased in 1987. In the months after this change police doubled the number of drivers tested by RBT. Concurrent with this change in the level of enforcement of RBT was an extensive publicity campaign, which warned drinking drivers of their increased risk of detection by RBT units. A roadside breath alcohol survey, conducted in metropolitan Adelaide late at night to evaluate the effect of these changes, showed a 34% reduction in the proportion of car drivers detected with a blood alcohol concentration at or above the legal limit of 0.08 g/100 mL.
Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro

Phospholipid transfer protein (PLTP) plays a pivotal role in cellular lipid efflux and modulation of lipoprotein metabolism. PLTP is distributed widely in the central nervous system (CNS), is synthesized by glia and neurons, and is active in cerebrospinal fluid (CSF). The aims of this study were to test the hypothesis that patients with Alzheimer's disease (AD) have altered PLTP‐mediated phospholipid transfer activity in CSF, and to examine the potential relationship between PLTP activity and apolipoprotein E (apoE) levels in CSF. We assessed PLTP activity and apoE concentration in CSF of patients with probable AD (n = 50), multiple sclerosis (MS; n = 9), other neurologic diseases (n = 21), and neurologically healthy controls (n = 40). PLTP activity in AD was reduced compared to that in controls (P < 0.001), with approximately half of the AD patients with PLTP activity values below all controls. Patients with MS had lower PLTP activity than AD patients (P < 0.001). PLTP activity was highly correlated with PLTP mass, as estimated by Western blot (r = 0.006; P < 0.01). CSF PLTP activity positively correlated with apoE concentration in AD (R = 0.435; P = 0.002) and controls (R = 0.456; P = 0.003). Anti‐apoE immunoaffinity chromatography and Western blot analyses indicated that some CSF PLTP is associated with apoE‐containing lipoproteins. Exogenous addition of recombinant PLTP to primary human astrocytes significantly increased apoE secretion to the conditioned medium. The findings of reduced PLTP activity in AD CSF, and the observation that PLTP can influence apoE secretion in astrocytes suggest a potential link between alterations in the brain lipid metabolism and AD pathogenesis. © 2005 Wiley‐Liss, Inc.