Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of c-kit in human osteosarcoma and its relevance as a prognostic marker

Aims: To examine the prognostic relevance of c-kit expression in human osteosarcomas and to evaluate the mutation status in exon 9 and exon 11 of the c-kit gene. Methods: c-kit expression was examined in 100 human osteosarcomas by immunohistochemistry using paraffin embedded tumour tissues, and capillary sequencing of genomic DNA was performed to search for mutations in exons 9 and 11 of the c-kit gene. Results: 20 osteosarcomas showed c-kit expression ranging from 5% to 90% (mean 5.9%; SD 16.74%). Furthermore, DNA sequences of exon 9 and exon 11 of the c-kit gene were not altered in these tumours. Overall and disease free survival analysis did not reveal any differences between patients with osteosarcoma with c-kit expression and those with c-kit negative tumours. Conclusions: C-kit expression is not a prognostic marker in patients with osteosarcoma. The protein expression is not linked to mutations in exon 9 or exon 11 of the c-kit gene. Therefore, these exons may not function as targets for treatment modalities based on the suppression of c-kit tyrosine kinase activity.
Utilization of Methanol plus Hydrogen by Methanosarcina barkeri for Methanogenesis and Growth

Methanosarcina barkeri grew on methanol plus H2. Both substrates were consumed in equimolar amounts. Growth was strictly dependent on the presence of acetate, which was required for the biosynthesis of cellular constituents. Only about 0.4% of the methane produced originated from acetate. By using deuterated methanol, it was demonstrated that methanogenesis from this compound under H2 did not occur via oxidation of methanol to CO2 and subsequent reduction but by direct reduction with H2. Growth yields with methanol plus H2 and with methanol alone were not significantly different: 2.8 g of cells per mol of methanol in mineral medium and 4.6 g of cells per mol of methanol in complex medium, respectively. Growth of M. barkeri on methanol plus H2 depended strictly on the presence of sodium ions in the medium. In the presence of 50 mM K+ the Ks for Na+ was 5 mM.
Influence d'une sélection pour la combativité et l'aptitude à la dominance sur le comportement social et la réactivité émotionnelle des bovins domestiques femelles de la race d'Hérens

La race d'Herens est une race laitiere, dont le caractere belliqueux est a l’ origine de manifestations populaires, aux cours desquelles, les vaches luttent pour etablir une hierarchie. Les animaux de cette race ont ete selectionnes empiriquement depuis des generations pour leur combativite et leur aptitude a la dominance, constituant ainsi un modele original pour l'etude du comportement social chez les bovins domestiques. La premiere partie de ce travail, consacree a l'etude du livre genealogique de la race d'Herens, nous a permis de mettre en evidence l'influence de l'ascendance sur l'aptitude a la dominance, et la compatibilite de la selection avec les objectifs zootechniques de la race. Dans une seconde partie, grâce a l'etude d'un echantillon d'eleveurs, les criteres de choix pour la selection des jeunes veaux femelles en tant que futures combattantes ont ete mis a jour : ils sont essentiellement lies au physique de l'animal. Pour tenter de determiner les reponses a la selection, la troisieme partie de ce travail a ete consacree a une etude comparative des femelles de la race d'Herens (h) avec celles d'une race non selectionnee pour la combativite et l'aptitude a la dominance, soumises a la meme conduite d'elevage, la race brune des alpes (BA). Quel que soit l'âge (6, 10-12, 18 mois ou plus de 4 ans), une aptitude a la dominance superieure des Herens a ete observee, ce qui valide l'interet porte a ce modele. A 6 mois, les veaux h se sont montres plus agressifs, moins tolerants, et plus reactifs dans des situations anxiogenes que les animaux BA. Au contraire, a l'âge adulte, ces differences s'inversent entre les deux races. Parmi les explications possibles de ces differences, on peut citer l'influence d'un stress prenatal important que subiraient les h, l'influence des facteurs endocriniens, ou encore un role different de l'experience sociale pour les deux races. Enfin, dans une quatrieme partie, nous avons tente, par l'etude longitudinale de 28 veaux Herens de 6 a 30 mois, de determiner des indicateurs precoces de la dominance. Les veaux peu reactifs a des situations de neophobie ou d'effet de surprise a 6 mois deviennent des genisses dominantes dans une situation de rencontre avec des animaux non familiers a 30 mois. Ce resultat met en evidence le role primordial de la reactivite emotionnelle dans le developpement de l'aptitude a la dominance chez les bovins domestiques femelles.
Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: protocol detailing observations in a whole of population cohort

Background The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia. Methods/design Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research. Ethics and dissemination Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments.
Generalized MGF of Beckmann Fading With Applications to Wireless Communications Performance Analysis

The Beckmann distribution is a general multipath fading model for the received radio signal in the presence of a large number of scatterers, which can thence be modeled as a complex Gaussian random variable where both the in-phase and quadrature components have arbitrary mean and variance. However, the complicated nature of this distribution has prevented its widespread use and relatively few analytical results have been reported for this otherwise useful fading model. In this paper, we derive a closed-form expression for the generalized moment-generating function (MGF) of the signal-to-noise ratio (SNR) of Beckmann fading, which permits to circumvent the inherent analytical complexity of this model. This is a new and useful result, as it is a key for evaluating several important performance metrics of different wireless communication systems and also permits to readily compute the moments of the output SNR. Thus, we obtain simple exact expressions for the energy detection performance in Beckmann fading channels, both in terms of the receiver operating characteristic (ROC) curve and of the area under ROC curve. We also analyze the outage probability in interference limited systems affected by Beckmann fading, as well as the outage probability of secrecy capacity in wiretap Beckmann fading channels. Monte Carlo simulations have been performed to validate the derived expressions.
NMU signaling promotes endometrial cancer cell progression by modulating adhesion signaling

Neuromedin U (NMU) was originally named based on its strong uterine contractile activity, but little is known regarding its signaling/functions in utero. We identified that NMU and one of its receptors, NMUR2, are not only present in normal uterine endometrium but also co-expressed in endometrial cancer tissues, where the NMU level is correlated with the malignant grades and survival of patients. Cell-based assays further confirmed that NMU signaling can promote cell motility and proliferation of endometrial cancer cells derived from grade II tumors. Activation of NMU pathway in these endometrial cancer cells is required in order to sustain expression of various adhesion molecules, such as CD44 and integrin alpha1, as well as production of their corresponding extracellular matrix ligands, hyaluronan and collagen IV; it also increased the activity of SRC and its downstream proteins RHOA and RAC1. Thus, it is concluded that NMU pathway positively controls the adhesion signaling-SRC-Rho GTPase axis in the tested endometrial cancer cells and that changes in cell motility and proliferation can occur when there is manipulation of NMU signaling in these cells either in vitro or in vivo. Intriguingly, this novel mechanism also explains how NMU signaling promotes the EGFR-driven and TGFβ receptor-driven mesenchymal transitions. Through the above axis, NMU signaling not only can promote malignancy of the tested endometrial cancer cells directly, but also helps these cells to become more sensitive to niche growth factors in their microenvironment.
Engrafting Costimulator Molecules onto Tumor Cell Surfaces with Chelator Lipids: A Potentially Convenient Approach in Cancer Vaccine Development1

The genetic modification of cells to develop cell-based vaccines and to modulate immune responses in vivo can be risky and inconvenient to perform in clinical situations. A novel chelator lipid, nitrilotriacetic acid di-tetradecylamine (NTA-DTDA) that, via the NTA group has high affinity for 6His peptide, was used to directly anchor recombinant forms of T cell costimulatory molecules containing a C-terminal 6-His sequence onto tumor cell surfaces. Initial experiments using murine P815 tumor cells established the optimum conditions for incorporating NTA-DTDA onto the membranes of cells. P815 cells with incorporated NTA-DTDAbound hexahistidine-(6His)-tagged forms of the extracellular domains of murine B7.1 and CD40 (B7.1-6H and CD40-6H) at very high levels (fluorescence 200–300-fold above background), and both proteins could be anchored onto the cells simultaneously. Significant loss of the anchored or “engrafted” protein occurred through membrane internalization following culture of the cells under physiological conditions, but P815 cells with engrafted B7.1-6H and/or CD40-6H stimulated the proliferation of allogenic and syngeneic splenic T cells in vitro, and generated cytotoxic T cells when used as vaccines in syngeneic animals. Furthermore, the immunization of syngeneic mice with P815 cells engrafted with B7.1-6H or with B7.1-6H and CD40-6H induced protection against challenge with the native P815 tumor. The results indicate that the use of chelator lipids like NTD-DTDA to engraft costimulatory and/or other molecules onto cell membranes could provide a convenient alternative to transfection in the development of cell-based vaccines and for modulation of immune function.
Scavenger receptor B type 1: expression, molecular regulation, and cholesterol transport function

Cholesterol is required for maintenance of plasma membrane fluidity and integrity and for many cellular functions. Cellular cholesterol can be obtained from lipoproteins in a selective pathway of HDL-cholesteryl ester (CE) uptake without parallel apolipoprotein uptake. Scavenger receptor B type 1 (SR-B1) is a cell surface HDL receptor that mediates HDL-CE uptake. It is most abundantly expressed in liver, where it provides cholesterol for bile acid synthesis, and in steroidogenic tissues, where it delivers cholesterol needed for storage or steroidogenesis in rodents. SR-B1 transcription is regulated by trophic hormones in the adrenal gland, ovary, and testis; in the liver and elsewhere, SR-B1 is subject to posttranscriptional and posttranslational regulation. SR-B1 operates in several metabolic processes and contributes to pathogenesis of atherosclerosis, inflammation, hepatitis C virus infection, and other conditions. Here, we summarize characteristics of the selective uptake pathway and involvement of microvillar channels as facilitators of selective HDL-CE uptake. We also present the potential mechanisms of SR-B1-mediated selective cholesterol transport; the transcriptional, posttranscriptional, and posttranslational regulation of SR-B1; and the impact of gene variants on expression and function of human SR-B1. A better understanding of this unique pathway and SR-B1’s role may yield improved therapies for a wide variety of conditions.
Analysis and Design of a Modular Multilevel Converter With Trapezoidal Modulation for Medium and High Voltage DC-DC Transformers

Conventional dual-active bridge topologies provide galvanic isolation and soft-switching over a reasonable operating range without dedicated resonant circuits. However, scaling the two-level dual-active bridge to higher dc voltage levels is impeded by several challenges among which the high dv/dt stress on the coupling transformer insulation. Gating and thermal characteristics of series switch arrays add to the limitations. To avoid the use of standard bulky modular multilevel bridges, this paper analyzes an alternative modulation technique, where staircase approximated trapezoidal voltage waveforms are produced; thus, alleviating developed dv/dt stresses. Modular design is realized by the utilization of half-bridge chopper cells. This way the analyzed dc-dc transformer employs modular multilevel converters operated in a new mode with minimal common-mode arm currents, as well as reduced capacitor size, hence reduced cell footprint. Suitable switching patterns are developed and various design and operation aspects are studied. Soft-switching characteristics will be shown to be comparable to those of the two-level dual-active bridge. Experimental results from a scaled test rig validate the presented concept.
A probabilistic planning approach to single circuit supply systems

Planning single circuit supply systems has been a challenge for transmission providers for years since the conventional N-1 criterion does not apply. This paper presents a probabilistic planning approach to single circuit supply systems. It is based on historical performance indices, future reliability evaluation and probabilistic economic assessment. A short list of single circuit supply systems for reinforcement is identified first using the criteria of reliability performance (contribution to the improvement of overall system reliability) and probabilistic economic justification. The priority order on the short list is then created using the indices of combined reliability and economic efficiency. The short list with the ranking order provides the essential information for decision makers on the investment direction of single circuit supply systems. An actual utility example is used to demonstrate the application of the presented approach.
Distinct Effects of STAT5 Activation on CD4+ and CD8+ T Cell Homeostasis: Development of CD4+CD25+ Regulatory T Cells versus CD8+ Memory T Cells 1

Using transgenic mice that express a constitutively active version of STAT5b, we demonstrate that STAT5 plays a key role in governing B cell development and T cell homeostasis. STAT5 activation leads to a 10-fold increase in pro-B, but not pro-T, cells. Conversely, STAT5 signaling promotes the expansion of mature αβ T cells (6-fold increase) and γδ and NK T cells (3- to 4-fold increase), but not of mature B cells. In addition, STAT5 activation has dramatically divergent effects on CD8+ vs CD4+ T cells, leading to the selective expansion of CD8+ memory-like T cells and CD4+CD25+ regulatory T cells. These results establish that activation of STAT5 is the primary mechanism underlying both IL-7/IL-15-dependent homeostatic proliferation of naive and memory CD8+ T cells and IL-2-dependent development of CD4+CD25+ regulatory T cells.
A Comparative Study of the Current Cloud Computing Technologies and Offers

Cloud Computing is a powerful and flexible software environment, which delegates the material's management and in which users pay as they go. The migration of enterprise applications on the Cloud is increasing. Most of these applications are available with a standardized access to the business logic through Internet. However, the current cloud offers is not always complying with users' needs. For instance, some providers do not guarantee sufficient resource flexibility and high availability. Other users try to build their own Cloud based on open source technologies. In this work, we conduct a survey on current Cloud providers and technologies in order to help users (1) choosing the better cloud offer that compiles with their needs or (2) building their own Cloud infrastructure with the most suitable open source technologies
Identification and cloning of the bacterial nodulation specificity gene in the Sinorhizobium meliloti--Medicago laciniata symbiosis.

Medicago laciniata (cut-leaf medic) is an annual medic that is highly nodulation specific, nodulating only with a restricted range of Sinorhizobium meliloti. e.g., strain 102L4, but not with most strains that nodulate Medicago sativa (alfalfa), e.g., strains RCR2011 and Rm41. Our aim was to identify and clone the S. meliloti 102L4 gene implicated in the specific nodulation of M. laciniata and to characterize the adjacent nodulation (nod) region. An 11-kb EcoRI DNA fragment from S. meliloti 102L4 was shown to complement strain RCR2011 for nodulation of M. laciniata. Nucleotide sequencing revealed that this fragment contained nodABCIJ genes whose overall arrangement was similar to those found in strains RCR2011 and Rm41, which do not nodulate M. laciniata. Data for Tn5 mutagenesis of the nodABCIJ region of strain 102L4 suggested that the nodC gene was involved in the specific nodulation of M. laciniata. Tn5 insertions in the nodIJ genes gave mutants with nodulation delay phenotypes on both M. laciniata and M. sativa. Only subclones of the 11-kb DNA fragment containing a functional nodC gene from strain 102L4 were able to complement strain RCR2011 for nodulation of M. laciniata. The practical implications of these findings are discussed in the context of the development of a specific M. sativa - S. meliloti combination that excludes competition for nodulation by bacterial competitors resident in soil.
Haseman and Elston revisited

Haseman and Elston (H‐E) [1972] proposed a method to detect quantitative trait loci by linkage to a marker. The squared sib‐pair trait difference is regressed on the proportion of marker alleles the pair is estimated to share identical by descent: a significantly negative regression coefficient suggests linkage. It has been shown that a maximum likelihood method that directly models the sib‐pair covariance has more power. This increase in power can also be obtained using the H‐E regression procedure by changing the dependent variable from the squared difference to the mean‐corrected product of the sibs' trait values. Multiple sibs in a sibship can be accommodated by allowing for the correlations between pairs of products in a generalized least squares procedure. Multiple trait loci, including epistatic interactions, involve only multiple linear regression. Multivariate traits can use the method of Amos et al. [1990] to find the linear function of the traits that maximizes the evidence for linkage, which now leads more simply to a test of significance. Multiple markers can be the basis of a multipoint analysis. Results of simulation studies for a continuous trait are presented that investigate Type I error and power. A similar general scheme can be used to study affected sib pairs, testing whether their identity by descent sharing probabilities are greater than would be expected in the absence of linkage, and to study other types of relative pairs. Genet. Epidemiol. 19:1–17, 2000. © 2000 Wiley‐Liss, Inc.
Study of myocardial infraction feature extraction using subjective introduction based method

Most of the existing studies on myocardial infraction (MI) feature extraction are based on certain important components. The subjective significance based method was introduced into the feature extraction from an entire ECG segment for the classification in the paper. The method was employed to discriminate the assumed prior class from the other classes and separate each of the classes at the same time. The data in the analysis including healthy control (HC), myocardial infraction in early stage (MIES) and acute myocardial infraction (AMI) was collected from PTB diagnostic ECG database which is the latest public database for various research purposes. The results show that the proposed method can obtain the effective features from the ECGs with 12-leads for the classification purpose.
Comparison of changes in locomotor activity with striatal homovanillic acid and 3,4‐dihydroxyphenylacetic acid concentrations following the bilateral intranigral injection of dopamine agonist drugs in rats

Bilateral injection of apomorphine (2.5 μg) into the substantia nigra zona reticulata of rats reduced both locomotor activity and striatal HVA and DOPAC concentrations. Bilateral injection of dopamine (10 μg) did not affect locomotor activity whereas a higher dose of dopamine (50 μg) enhanced locomotor activity. Striatal HVA and DOPAC concentrations were unchanged following injection of dopamine. Bilateral injection of (±)‐3PPP (0.1 or 2.5 μg) into the zona reticulata of the substantia nigra did not alter locomotor activity while a higher dose (10 μg) enhanced locomotion. Injection of (±)‐3PPP (0.1–10 μg) into the zona reticulata was without effect on striatal HVA or DOPAC concentrations. The bilateral manipulation of nigral dopaminergic neurotransmission alters motor activity and nigrostriatal dopamine turnover in conscious rats. However, the changes in motor activity are not necessarily related to altered nigrostriatal activity, suggesting the involvement of dopamine receptors located at non‐dopaminergic sites within the substantia nigra.