Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue hyperoxygenation promotes oxidative metabolism in motor unit

Some mutant hemoglobin (Hb) variants are found with lowered O2 affinity. Low oxygen affinity is reported to increase the O2 availability in peripheral tissues (Kunert et al. [1996] Microvasc. Res. 52:58–68). In the present study, we used a mouse model carrying two low‐affinity Hb variants, Titusville and Presbyterian, to evaluate the chronic in vivo influence of lowered oxygen affinity on the neuromuscular system. Our model mice showed an increased voluntary running ability compared with wild‐type littermates. In the tibialis anterior (TA) muscle of mutant mice, the glycolytic fibers were converted to oxidative ones in where the activity of the mitochondrial marker enzyme succinate dehydrogenase (SDH) was up‐regulated. We report that the spinal ventral horn motoneurons innervating TA skeletal fibers also showed higher mitochondrial oxidative enzyme activity. This phenomenon was evidenced by increased SDH activity and electron microscopic (EM) mitochondrial electronic density in these motoneurons. Our data suggest that, as the result of adaptation to the tissue hyperoxygenation, energy metabolism in the neuron–muscle motor unit is augmented and thus function of the motor unit is promoted. © 2005 Wiley‐Liss, Inc.
Improving survival and limiting toxicity: latest advances in treating human epidermal growth factor receptor 2 overexpressing breast cancer

In recent years, new strategies for the treatment of breast cancer have focused on extensive target identification and understanding the expression, regulation and function of critical signaling pathways involved in breast cancer initiation and progression. This has led to significant progress in developing and understanding human epidermal growth factor receptor 2 (HER2)-targeted therapies, which in turn, has translated into significant increases in median survival for patients with HER2-overexpressing breast cancer. It is becoming increasingly difficult to make specific recommendations for the optimal treatment of HER2-overexpressing breast cancer since the field is evolving so rapidly. However, despite the many randomized trials that have been undertaken showing improvement in survival, the current standard treatment for HER2-overexpressing breast cancer continues to revolve around the addition of chemotherapy to a HER2-targeted agent, which in turn, carries substantial toxicities. This article reviews agents that have recently been investigated to treat HER2-overexpressing breast cancers. The goal is ultimately to increase the magnitude and duration of response to trastuzumab-based treatment while minimizing toxicity. Studies addressing length of therapy duration, the superiority and side-effect profile of the different biological drug combinations, and determination of biomarkers of resistance to HER2 therapy will be instrumental in decreasing morbidity and mortality for patients with HER2-overexpressing breast cancer.
Asn441 plays a key role in folding and function of the Na+/I– symporter (NIS)

The Na+/I– symporter (NIS) is a plasma membrane glycoprotein that mediates active I– transport in the thyroid, the first step in the biosynthesis of the iodine‐containing thyroid hormones T3 and T4. Several NIS mutants have been identified as a cause of congenital I– transport defect (ITD), and their investigation has yielded valuable mechanistic information on NIS. Here we report a thorough characterization of the ITD‐causing NIS mutation in which the sixth intracellular loop residues 439‐443 are missing. This mutant protein was intracellularly retained, incompletely glycosylated, and intrinsically inactive. Engineering 5 Ala at positions 439‐443 partially recovered cell surface targeting and activity (~15%). Strikingly, NIS with the sequence 439‐AANAA‐443, in which Asn was restored at position 441, was targeted to the plasma membrane and exhibited ~95% the transport activity of WT NIS. Based on our NIS homology model, we propose that the side chain of N441, a residue conserved throughout most of the SLC5 family, interacts with the main chain amino group of G444, capping the α‐helix of transmembrane segment XII and thus stabilizing the structure of the molecule. Our data provide insight into a critical interhelical interaction required for NIS folding and activity. —Li, W. , Nicola, J. P., Amzel, L. M. , Carrasco, N. , Asn441 plays a key role in folding and function of the Na+/I– symporter (NIS). FASEB J. 27, 3229–3238 (2013). www.fasebj. org
Model Based Clustering of Audio Clips Using Gaussian Mixture Models

The task of clustering multi-variate trajectory data of varying length exists in various domains. Model-based methods are capable of handling varying length trajectories without changing the length or structure. Hidden Markov models (HMMs) are widely used for trajectory data modeling. However, HMMs are not suitable for trajectories of long duration. In this paper, we propose a similarity based representation for multi-variate, varying length trajectories of long duration using Gaussian mixture models. Each trajectory is modeled by a Gaussian mixture model (GMM). The log-likelihood of a trajectory for a given GMM model is used as a similarity score. The scores corresponding to all the trajectories in the given data set and all the GMMs are used to form a score matrix that is used in a clustering algorithm. The proposed model based clustering method is applied on the audio clips which are multi-variate trajectories of varying length and long duration. The performance of the proposed method is much better than the method that uses a fixed length representation for an audio clip based on the perceptual features.
Establishment and characterization of a human gastrointestinal stromal tumour (GIST) xenograft in athymic nude mice.

BACKGROUND The majority of gastrointestinal stromal tumours (GISTs) contain oncogenic KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or platelet-derived growth factor-alpha (PDGFRA) receptor tyrosine kinase (TK) mutations and are initially, but only temporarily sensitive to TK inhibitors. The aim of this study was to establish and characterize a human GIST xenograft that could be used for evaluating various molecularly targeted therapies. MATERIALS AND METHODS GIST tissue from four patients was implanted under the skin of athymic nude mice. In one case a tumour line was established. RESULTS The xenograft showed characteristic GIST morphology and exhibited the same mutation profile as that of the patient. CONCLUSION A human GIST xenograft with mutation in KIT exons 11 and 17 has been established and maintained in nude mice for 3 years (13 passages). This model will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.
Use of bacterial magnetosomes in the magnetic hyperthermia treatment of tumours: A review

Abstract We review the most recent and significant results published in the field of magnetotactic bacteria (MTB), in particular data relating to the use of bacterial magnetosomes in magnetic hyperthermia for the treatment of tumours. We review different methods for cultivating MTB and preparing suspensions of bacterial magnetosomes. As well as the production of magnetosomes, we also review key data on the toxicity of the magnetosomes as well as their heating and anti-tumour efficiencies. The toxicity and efficiency of magnetosomes needs to be understood and the risk–benefit ratio with which to evaluate their use in the magnetic hyperthermia treatment of tumours needs to be measured.
Genetic Variation, Simplicity, and Evolutionary Constraints for Function-Valued Traits

Understanding the patterns of genetic variation and constraint for continuous reaction norms, growth trajectories, and other function-valued traits is challenging. We describe and illustrate a recent analytical method, simple basis analysis (SBA), that uses the genetic variance-covariance (G) matrix to identify “simple” directions of genetic variation and genetic constraints that have straightforward biological interpretations. We discuss the parallels between the eigenvectors (principal components) identified by principal components analysis (PCA) and the simple basis (SB) vectors identified by SBA. We apply these methods to estimated G matrices obtained from 10 studies of thermal performance curves and growth curves. Our results suggest that variation in overall size across all ages represented most of the genetic variance in growth curves. In contrast, variation in overall performance across all temperatures represented less than one-third of the genetic variance in thermal performance curves in all cases, and genetic trade-offs between performance at higher versus lower temperatures were often important. The analyses also identify potential genetic constraints on patterns of early and later growth in growth curves. We suggest that SBA can be a useful complement or alternative to PCA for identifying biologically interpretable directions of genetic variation and constraint in function-valued traits.
Parents' knowledge, attitudes, use of pain relief methods and satisfaction related to their children's postoperative pain management: a descriptive correlational study.

AIMS AND OBJECTIVES To examine parents' knowledge about and attitudes towards pain management, use of pain relief strategies and satisfaction with their children's postoperative pain management, as well as the relationships among these variables. BACKGROUND Children's postoperative pain is inadequately managed worldwide. Despite increasing emphasis on parental involvement in children's postoperative pain management, few studies have examined parents' management of their child's postoperative pain in Singapore. DESIGN A descriptive correlational study. METHODS A convenience sample of 60 parents having 6- to 14-year-old children undergoing inpatient elective surgery in a public hospital in Singapore was recruited. Data were collected one day after each child's surgery using the Pain Management Knowledge and Attitudes questionnaire and the Parents' Use of Pain Relief Strategies questionnaire. Descriptive statistics, Mann-Whitney U tests, Kruskal-Wallis tests and Spearman's rank correlation coefficient were used for data analyses. RESULTS Parents displayed moderate levels of knowledge, attitudes and use of pain relief methods in relation to their children's postoperative pain and pain management. They were generally satisfied with the management of their child's postoperative pain. There was significant difference in Parents' Use of Pain Relief Strategies scores between parents with and without previous experience of caring for their hospitalised child. Statistically significant positive correlations were found between parents' knowledge and attitude, knowledge and satisfaction, attitude and satisfaction, knowledge and pain relief strategies, as well as attitude and pain relief strategies. CONCLUSION This study indicates the need to provide parents with more information regarding their children's postoperative pain management. Future studies are needed to develop educational interventions for parents to improve their knowledge and attitudes, which will eventually improve their use of pain relief strategies for their children. RELEVANCE TO CLINICAL PRACTICE Health professionals need to provide more information to equip parents with knowledge and skills regarding paediatric postoperative pain management.
Optimal Reinsurance Policies under the VaR Risk Measure When the Interests of Both the Cedent and the Reinsurer Are Taken into Account

Optimal forms of reinsurance policies have been studied for a long time in the actuarial literature. Most existing results are from the insurer’s point of view, aiming at maximizing the expected utility or minimizing the risk of the insurer. However, as pointed out by Borch (1969), it is understandable that a reinsurance arrangement that might be very attractive to one party (e.g., the insurer) can be quite unacceptable to the other party (e.g., the reinsurer). In this paper, we follow this point of view and study forms of Pareto-optimal reinsurance policies whereby one party’s risk, measured by its value-at-risk (VaR), cannot be reduced without increasing the VaR of the counter-party in the reinsurance transaction. We show that the Pareto-optimal policies can be determined by minimizing linear combinations of the VaR s of the two parties in the reinsurance transaction. Consequently, we succeed in deriving user-friendly, closed-form, optimal reinsurance policies and their parameter values.
Breast cancer in Nigerian women

A combined retrospective (1971–1980) and prospective (1981–1990) study of the epidemiology, clinical characteristics and pathology of breast cancer in a black African population was carried out. There were 1946 biopsy‐proven cases, with a rate frequency of 33.6 per 100 000 patients per year. The age range was 14‐96 years but 70 per cent of patients were between 26 and 50 years old. The cumulative frequency of cancer was 0.8 per cent at age <20 years and 3.3 per cent at age <25 years: the peak age range for disease was 36–45 years. Of 1842 evaluable patients, 17.2 per cent presented with stages I or II cancer and 73.8per cent with stage III disease. The dominant histopathological type was infiltrating ductal cancer (49.2 per cent), followed by undiferentiated anaplastic carcinoma (33.3 per cent). Burkitt's lymphoma occurred in five patients and developed concurrently and rapidly during lactation in four. The prospective study did not demonstrate that age at menarche or first full‐term pregnancy, duration of breast feeding or parity were risk factors in black women.
Antioxidant and vitamin E transport genes and risk of high‐grade prostate cancer and prostate cancer recurrence

Observational studies suggest an inverse association between vitamin E and risk of prostate cancer, particularly aggressive tumors. However, three large randomized controlled trials have reported conflicting results. Thus, we examined circulating vitamin E and vitamin E‐related genes in relation to risk of high‐grade prostate cancer and prostate cancer recurrence among men initially diagnosed with clinically organ‐confined disease.
Dynamic control plane management for software‐defined networks

Software‐defined network (SDN) is an emerging network paradigm that allows flexible network management by providing programmability from a separated control plane. Because of the centralized management scheme that SDN adopts, intensive control plane overhead incurs as the scale of SDN increases. The control plane overhead is mainly caused by a massive amount of control messages generated during data plane monitoring and reactive flow instantiation. By far, very few works have addressed the overhead issue on reaction flow instantiation; therefore, we mainly focus on alleviating such overhead in this work. To achieve this goal, we propose a new control plane management (CPMan) method. CPMan aims to realize the following two objectives: first, reduce the number of control messages exchanged through the control channel and second, evenly distribute the control workload across multiple controllers to mitigate the potential performance bottleneck. To realize the former, we propose a lightweight feedback loop‐based control scheme, whereas for the latter, we propose a dynamic switch‐to‐controller (DSC) placement scheme. To show the feasibility of our proposal, we implemented a prototype of the two proposed schemes on top of a carrier‐grade SDN controller and validated its performance in an emulated network. We achieved approximately 57.13% overhead reduction with feedback loop‐based control scheme, while achieved approximately 98.68% balance ratio with DSC placement scheme. Copyright © 2016 John Wiley & Sons, Ltd.
Role of muscle tone in peristalsis in guinea‐pig small intestine

1 We investigated the involvement of muscle tone and circular muscle (CM) contraction in peristalsis in isolated guinea‐pig small intestine. 2 A segment of jejunum (≈13 cm) was mounted into a three chambered partitioned bath. Peristaltic waves were initiated in the oral chamber eitherby: (1) infusing fluid into the oral end of the jejunum; the ejected fluid was diverted via a cannula from reaching the intermediate and anal chambers, or by (2) intraluminal balloon distension of the empty oral segment. Tension of the circular muscle was measured in all three chambers. 3 Peristaltic waves elicited by fluid infusion were evoked at an abrupt threshold. 4 In contrast, peristaltic waves elicited by distension could be graded in amplitude according to stimulus intensity. 5 Peristaltic waves evoked in an empty intestine exhibited similar propagation velocities to peristaltic waves associated with fluid propulsion. 6 Nifedipine (200‐400 nM) added to the intermediate chamber to block muscle contraction did not prevent peristaltic waves elicited by either stimulus from propagating into the anal chamber, although their amplitude was attenuated. Nifedipine to the site of stimulation (oral chamber) abolished peristaltic waves generated by either stimulus. 7 Tetrodotoxin (1‐2 μM), or a low Ca2+‐high Mg2+ solution to the intermediate chamber abolished the propagation of peristalsis from the oral to anal chambers. 8 In conclusion, graded peristaltic waves can occur in an empty intestine. Therefore peristalsis is not necessarily an ‘all‐or‐none’ phenomenon. Peristalsis depends on the spread of nervous activity along the bowel, rather than the reactivation of neural circuits caused by displacement of fluid in the lumen. However, local muscle tone and contraction are important for the initiation and maintenance of peristaltic propagation.
Efficacy of Sandostatin® LAR® (long‐acting somatostatin analogue) is similar in patients with untreated acromegaly and in those previously treated with surgery and/or radiotherapy

background and objectives Somatostatin analogues have been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly for over 15 years, but debate surrounds their use as primary therapy. Newman suggested that octreotide was equally effective as primary or adjuvant therapy, but the effects of previous surgery/radiotherapy may have led to a preselection bias. In an attempt to eliminate this bias, the efficacy of the depot somatostatin analogue Sandostatin® LAR® as primary and adjuvant therapy has been assessed using GH and IGF‐I levels at diagnosis as baseline values.
Protein kinase C down-regulation, and not transient activation, correlates with melanocyte growth.

The nontumorigenic, immortal line of murine melanocytes, Mel-ab, requires the continual presence of biologically active phorbol esters for growth (R.E. Wilson et al., Cancer Res., 49:711-716, 1989). Comparable treatments of B16 murine melanoma cells result in partial inhibition of cell proliferation. The role of protein kinase C (PKC) in the modulation of growth of cells from these two melanocytic cell lines has been investigated. Significant levels of PKC were present in quiescent Mel-ab cells as determined by Western blotting, whereas no immunoreactive protein was detected in cell extracts from either proliferating Mel-ab or B16.F1 cells. Phosphorylation of a Mr 80,000 protein, which by one- and two-dimensional gel analysis comigrated with the known Mr 80,000 protein substrate of PKC in fibroblasts, was induced in 12-O-tetradecanoylphorbol-13-acetate-stimulated quiescent Mel-ab cells but not in proliferating Mel-ab cells or B16.F1 melanoma cells. Direct measurement of PKC activity in these cells demonstrated a 10-fold greater level of activity in quiescent Mel-ab cells (262 +/- 50 pmol/min/mg SD) compared with growing cells (22.8 +/- 11.8 pmol/min/mg SD). An intermediate level of activity was detected in proliferating B16.F1 melanoma cells (148.5 +/- 20.4 pmol/min/mg SD). The subcellular distribution of PKC was dependent upon the growth state of the cells such that quiescent Mel-ab cells displayed a higher level of activity in the cytosol, whereas growing Mel-ab cells displayed greater activity in the particulate fraction. Like many other transformed lines, B16.F1 melanoma cells constitutively expressed the majority of enzyme activity in the particulate fraction. Measurement of [3H]phorbol ester binding in intact cells paralleled the PKC activation data such that quiescent Mel-ab cells displayed binding of 1612 +/- 147 cpm/10(6) cells, whereas proliferating Mel-ab and B16.F1 melanoma cells displayed binding of 652 +/- 28 and 947 +/- 81 cpm/10(6) cells, respectively. Membrane-permeant diacylglycerol analogues, which activated but did not down-regulate PKC, were devoid of growth-stimulating effects on melanocytes, even in the presence of the specific diacylglycerol kinase inhibitor, R59022. Together, these data show that PKC down-regulation, and not activation, correlates with the growth of melanocytes in culture.
Environmental tobacco smoke, wheezing, and asthma in children in 24 communities.

The association of exposure to environmental tobacco smoke (ETS) at home with asthma and several measures of wheeze was examined among 11,534 children aged 8 to 11 yr in 24 communities in the United States and Canada in 1988 through 1990. Information on the child's respiratory symptoms in the past year and history of exposure to ETS was provided by the child's mother on a questionnaire. After adjusting for potential confounders, children currently exposed to ETS were at greater risk of wheezing with colds (odds ratio [OR] = 1.7; 95% confidence interval [95% CI], 1.4 to 1.9), going to a hospital emergency room for wheeze (OR = 1.6; 95% CI, 1.2 to 2.2), and having persistent wheeze (OR = 1.4; 95% CI, 1.1 to 1.8). The relative odds of these symptoms increased with exposure level, and there was no evidence of a difference in the association with smoking by mother, father, or other adults. In contrast to wheeze symptoms, active doctor-diagnosed asthma and asthma medication use were not significantly associated with ETS exposure at home, possibly reflecting underdiagnosis of asthma, reporting bias, or smoking cessation by parents whose child is labeled asthmatic. We conclude that exposure to ETS is associated with wheezing symptoms, medical therapy for wheezing, and wheezing-related emergency department visits in U.S. and Canadian children.