Miracle-dz/UniFAR-FTUs huggingface dataset:
Promotion of epithelial–mesenchymal transition and tumor growth by 17β‐estradiol in an ER+/HER2+ cell line derived from human breast epithelial stem cells

A tumorigenic cell line with estrogen receptor and HER2 expression (ER/HER2+), R2N1d, was developed from a human breast epithelial cell type with stem cell characteristics in a growth factor/hormone‐deprived cell culture condition. This study was undertaken to test whether tumor growth and other biological effects could be induced by estrogen in this cell line. The results clearly show that estrogen treatment greatly promoted the tumor growth of R2N1d cells in immune‐deficient mice. Estrogen treatment of R2N1d cells in vitro was also found to induce other phenotypic changes related to breast carcinogenesis, that is, 1) the induction of epithelial–mesenchymal transition (EMT) shown by molecular and functional marker changes; 2) a significant increase of the CD44high/CD24−/low stem cell population; 3) the enhancement of cell growth rate and colony‐forming ability; and 4) the acquisition of metastatic ability, that is, increased cell migration and invasiveness. From these results, we conclude that 1) estrogen could induce EMT and cancer stem cells and promote tumor growth in ER+/HER2+ cells known to be derived from human breast epithelial stem cells, and 2) normal stem cells could give rise to cancer stem cells.
Dual signaling by innate and adaptive immune receptors is required for TLR7-induced B-cell–mediated autoimmunity

Toll-like receptor 7 (Tlr7) has been linked to systemic lupus disease incidence in humans and mice, but how TLR7 potentiates autoimmunity is unclear. We used a Tlr7 transgenic (tg) mouse model to investigate the cellular and molecular events required to induce spontaneous autoimmunity through increased TLR7 activity. We determined that Tlr7 exerts B-cell–intrinsic effects in promoting spontaneous germinal center (GC) and plasmablast B-cell development, and that these B-cell subsets are dependent on T-cell–derived signals through CD40L and SLAM-associated protein (SAP), but not IL-17. Antigen specificity also factored into TLR7-induced disease, as both a restricted T cell receptor (TCR) specificity and MHC haplotype H2k/k protected Tlr7tg mice from spontaneous lymphocyte activation and autoantibody production. Inflammatory myeloid cell expansion and autoimmunity did not develop in Tlr7tgIgH−/− mice, suggesting either that spontaneous TLR7 activation does not occur in dendritic cells, or, if it does occur, cannot drive these events in the absence of B-cell aid. These data indicate that autoimmune disease in Tlr7tg mice is contingent upon B cells receiving stimulation both through innate pathways and T-cell–derived signals and suggest a codependent relationship between B cells and T cells in the development of autoimmunity.
ADM-Aeolus: The first space-based high spectral resolution Doppler Wind Lidar

The 'Living Planet Programme' of the European Space Agency (ESA) is gaining momentum. Six Earth Explorer missions are currently being implemented including ADM- Aeolus, ESA's Doppler Wind Lidar (DWL) mission. The Aeolus mission will demonstrate the capability of a space- borne high spectral resolution DWL to accurately measure wind profiles in the troposphere and the lower stratosphere (0- 30 km). The Mission thus addresses one of the main identified deficiencies of the current Global Observing System (GOS). From the backscattered frequency-shifted laser light it will be possible to obtain about 3,000 globally distributed horizontal line-of-sight (HLOS) wind profiles daily. The accuracy of the Aeolus winds, in cloud-free regions and above thick clouds, is expected to be comparable to that of radiosonde wind measurements. Additional geophysical products that will be retrieved from the Aeolus measurements are cloud and aerosol optical properties. Aeolus HLOS wind profiles will find wide application in Numerical Weather Prediction (NWP) and climate studies, improving the accuracy of numerical weather forecasting, advancing our understanding of tropical dynamics and processes relevant to climate variability and climate modelling. Impact experiments, assimilating synthetic Aeolus wind data into operational NWP models, have already been performed. One focus has been the forecast performance in regions known to be particularly sensitive to the accuracy of the initial conditions. The tentative results show that the largest benefits from Aeolus HLOS winds can be expected over the oceans and in the Tropics. In view of other lidar missions in space, the potential of a long-term database of cloud and aerosol optical properties is being studied. An additional topic is the potential benefit of wind profile observations in the lower stratosphere. Ground-based and airborne campaigns are being prepared for the validation of the Aeolus Airborne Demonstrator (A2D) - a high spectral resolution DWL instrument with technology very similar to Aeolus. This paper provides an overview of the Aeolus mission, the science and application activities being performed in support of the mission and the potential benefit of such observations in a wider context.
Cereal transformation through particle bombardment.

The review focuses on experiments that lead to stable transformation in cereals using microprojectile bombardment. The discussion of biological factors that affect transformation examines target tissues and vector systems for gene transfer. The vector systems include reporter genes, selectable markers, genes of agronomic interest, and vector constructions. Other topics include physical parameters that affect DNA delivery, selection of stably transformed cells and plant regeneration, and analysis of gene expression and transmission to the progeny.
Developmental Analysis of CNS Pathology in the Lysosomal Storage Disease &agr;-Mannosidosis

The lysosomal storage disease &agr;-mannosidosis is due to absence or defective function of lysosomal &agr;-mannosidase, resulting in primary storage of undegraded mannose-rich oligosaccharides. Disease has been described in humans, cattle, cats, mice, and guinea pigs and is characterized in all species by progressive neurologic deterioration and premature death. We analyzed the neurodegenerative processes relative to clinical disease in &agr;-mannosidosis guinea pigs as a human disease model, from birth to end-stage disease. Before the onset of obvious neurologic abnormalities at 2 months, we observed widespread neuronal lysosomal vacuolation including secondary accumulation of GM3 ganglioside, widespread axonal spheroids, and reduced myelination of white matter. Histopathologic changes subsequently showed rapid progression in severity in a pattern common to a number of different lysosomal storage disorders, with additional abnormalities including accumulation of GM2 ganglioside and cholesterol, astrogliosis, neuron loss particularly in the cerebellum, and activation and infiltration of the CNS with microglia/macrophages. End-stage clinical disease was seen at 10 to 14 months of age. Our findings show that complex neuropathologic changes in &agr;-mannosidosis guinea pigs are already present at birth, before clinical changes are evident, and similar events are likely to occur in patients with this disorder.
Planktonic dispersal dampens temporal trophic cascades in pond metacommunities.

Trophic cascades, in which changes in predation affect the biomass of lower trophic levels, vary substantially in strength and incidence. Most work to explain this variation has focused on local factors and has ignored larger regional effects. To study how metacommunity dynamics can alter trophic cascades, we constructed mesocosm metacommunities consisting of three pond communities with heterogeneous levels of fish predation and examined how planktonic dispersal rate (5-140% per week) affected biomass partitioning. Two of the three communities differed continually in the occurrence of fish and supported different but constant environments in a 'spatial trophic cascade,' while the third community supported temporally variable fish occurrence in a 'temporal trophic cascade. ' We find that the presence, but the not the magnitude, of dispersal dampens temporal trophic cascades through an increase in grazer biomass. In contrast, dispersal has no effect on the strength of spatial cascades due to strong sorting pressures in the communities with constant presence or absence of fish as top predators.
Immunoglobulin A myeloma presenting with laryngeal obstruction

This dilemma regarding surrogacy represents another example of " quick fire" legislation as described by Justice Michael Kirby. Not only did the Infertility (Medical Procedures) Act contain legislativeambiguity surrounding a number of key words (for example, " embryo" and "fertilization") which have forced amendments to embryo-research sections, but also it is unnecessarily detailed in other sections that inadvertently have proclaimed in-vitro fertilization surrogacy as unlawful. It is to be hoped that further amendments to these relevant sections will, in time, reverse this legal paradox. John Leeton. FRACOG Monas h University Department or Obstetrics and Gynaecology Mona sh Medical Centre 246 Clayton Road , Clayton, VIC 3168
Supplier relationships in regulated industries: longitudinal study on energy distribution

The article attempts to analyse the transformation of procurement management with Finnish electricity distribution network operators regarding the maintenance and construction of distribution networks. We aim to provide insights into their portfolio frameworks the dynamics of which are illustrated using a longitudinal case-based study. The case study is based on archival analysis and interviews. The article demonstrates how the competitive changes through regulation, supply market evolution and supply decisions are interlinked. The appropriateness of: 1) the strategic value of functions; 2) transaction risks; 3) the performance view of portfolio models is evaluated from a theoretical viewpoint. Our findings suggest that supply management changes along with relationship management on high strategic value, comparative performance and the transaction costs of externalised activities. Indeed, the study shows that procurement management becomes less sensitive to portfolio attributes if specialised service providers are able to build attractive offerings.
An Education And Training Framework For Disaster Risk Management In Banks

Banks are the most significant financial institutions operating within nation-state and the global financial system. These institutions are exposed to a wide range of operational risks. Disaster risk management is a critical component of the wider operational risk management. The Bank for International Settlements, in conjunction with nation-state prudential regulators, is introducing measures that will require banks to identify, measure and manage operational risks within the context of new capital adequacy requirements. An essential part of any risk management process is education and training. This paper presents a structured education and training framework that will support the achievement of banks’ disaster risk management objectives. The education and training framework comprises three specific programs: (1) an induction/awareness program targeted to all personnel, (2) a contingency planning program – a specialist program for disaster risk management personnel, and (3) an executive program designed for senior management, directors and strategic decision makers.
Effects of Xylitol on survival of mutans Streptococci in mixed-six-species in vitro biofilms modelling supragingival plaque

Xylitol has been claimed to reduce mutans streptococci (MS) in dental plaque by energyconsuming futile metabolic cycles. This study aimed to investigate the effects of xylitol on MS in an in vitro 6-species oral biofilm model. Each multispecies biofilm contained either a laboratory reference strain, a fresh isolate, a xylitol-sensitive or a xylitol-resistant strain of Streptococcus mutans or Streptococcus sobrinus . Biofilms, grown on pellicle-coated hydroxyapatite discs, were fed with a glucose/sucrosesupplemented medium 3 times daily for 45 min and incubated in saliva between feedings. Before or after feeding, biofilms were exposed to either 7.5% xylitol, 7.5% sorbitol or to saliva (control) for 20 min. After 64.5 h, biofilms were harvested and the microbial composition was analysed by non-selective and selective culturing. Strain variability in the ability to colonize biofilms was observed. However, the response patterns in the biofilms to the 4 polyol treatments were similar. None of the MS were inhibited by xylitol provided either before or after feeding. Sorbitol given before feeding did not affect microbial growth whereas sorbitol provided after feeding showed a slight, albeit statistically significant increase in MS counts for some of the tested strains. It did so at the expense of Streptococcus oralis, which decreased in numbers. The present findings do not support the contention that xylitol reduces MS in plaque by futile metabolic cycles. DOI: https://doi.org/10.1159/000322646 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-42218 Accepted Version Originally published at: Giertsen, E; Arthur, R A; Guggenheim, B (2011). Effects of Xylitol on survival of mutans Streptococci in mixed-six-species in vitro biofilms modelling supragingival plaque. Caries Research, 45(1):31-39. DOI: https://doi.org/10.1159/000322646
Why an Asset Pricing Model Fails to Explain the Cross Section of Stock Returns in the Korean Market'

This paper investigates the reason that none of asset pricing models show substantial performance in the Korean market. Based upon previous literature, the main reasons for the failure are categorized into three: transaction costs, investors' irrationality, and missing risk factors. We analyze the difference between the expected return from an asset pricing model and the realized return with respect to three possible reasons for the failure of asset pricing models. By regressing the difference between the expected return and the realized return on proxies of transaction costs, investors' irrationality, and missing risk factors, we find that transaction costs and investors' irrationality are tenaciously disrupting the performance of asset pricing models. We also show that the inferior performance of an asset pricing model from transaction costs and investors' irrationality cannot be improved by just adding more factors in an asset pricing model.
Hydrophobic Motif Phosphorylation Coordinates Activity and Polar Localization of the Neurospora crassa Nuclear Dbf2-Related Kinase COT1

ABSTRACT Nuclear Dbf2p-related (NDR) kinases and associated proteins are recognized as a conserved network that regulates eukaryotic cell polarity. NDR kinases require association with MOB adaptor proteins and phosphorylation of two conserved residues in the activation segment and hydrophobic motif for activity and function. We demonstrate that the Neurospora crassa NDR kinase COT1 forms inactive dimers via a conserved N-terminal extension, which is also required for the interaction of the kinase with MOB2 to generate heterocomplexes with basal activity. Basal kinase activity also requires autophosphorylation of the COT1-MOB2 complex in the activation segment, while hydrophobic motif phosphorylation of COT1 by the germinal center kinase POD6 fully activates COT1 through induction of a conformational change. Hydrophobic motif phosphorylation is also required for plasma membrane association of the COT1-MOB2 complex. MOB2 further restricts the membrane-associated kinase complex to the hyphal apex to promote polar cell growth. These data support an integrated mechanism of NDR kinase regulation in vivo, in which kinase activation and cellular localization of COT1 are coordinated by dual phosphorylation and interaction with MOB2.
A Genetic Algorithm-Based Heuristic For Network Design Of Service Centers With Pick-Up And Delivery Visits Of Mandated Vehicles In Express Delivery Service Industry

In Korean express delivery service market, many domestic companies have been competing fiercely to extend their own market share. The line-haul vehicles operated by the express delivery service companies in Korea in general can be classified into three types depending on the ways their expenses occur; company-owned vehicle, mandated vehicle which is owned by outsider who entrust the company with its operation, and rented vehicle (outsourcing). Actually, most of the line-haul vehicles in express delivery services belong to the mandated vehicle class. Hence, this study suggests an approach to the design of a service network with pick-up and delivery visits for mandated line-haul vehicles with the objective of maximizing the incremental profits of the drivers of the vehicles under the assumption that express delivery service companies operate mandated vehicles only. A heuristic based on genetic algorithm is developed and tested through an example problem.
Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial.

OBJECTIVE To compare the bone anabolic drug teriparatide (20 microg/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoid-induced osteoporosis (OP). METHODS This was a 36-month, randomized, double-blind, controlled trial in 428 subjects with OP (ages 22-89 years) who had received > or =5 mg/day of prednisone equivalent for > or =3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety. RESULTS Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N-terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C-terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P = 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P = 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001). CONCLUSION Our findings indicate that subjects with glucocorticoid-induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate.
Human-Robot Interaction Using Affective Cues

This paper presents a closed loop human-robot interaction framework where a robot can infer the implicit affective cues of the human and respond to them appropriately. Affective cues are inferred by the robot in realtime using psychophysiological analysis where the physiological signals are measured through wearable biofeedback sensors. A robot-based basketball game is designed where a robotic "coach" monitors the participant's anxiety to alter the difficulty level of the game in a real-time closed loop manner according to each participant's performance and anxiety. The results are compared with situations when anxiety is not monitored and the game is adapted only according to the performance. Results show that monitoring and responding to affective cues led to higher performance improvement of the majority of the participants under lower anxiety
Comparative Evaluation of Combined-Disk Tests Using Different Boronic Acid Compounds for Detection of Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Clinical Isolates

ABSTRACT The accurate phenotypic detection of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae is an increasing necessity worldwide. We evaluated the performance of boronic acid combined-disk tests using as substrate imipenem or meropenem and as inhibitor of KPC production 300 μg aminophenylboronic acid (APBA), 600 μg APBA, or 400 μg phenylboronic acid (PBA). Tests were considered positive when an increase in the growth-inhibitory zone around a carbapenem disk with KPC inhibitor was 5 mm or greater of the growth-inhibitory zone diameter around the disk containing carbapenem alone. The comparison of the combined-disk tests was performed with 112 genotypically confirmed KPC-possessing Enterobacteriaceae isolates. To measure the specificity of the tests, 127 genotypically confirmed KPC-negative Enterobacteriaceae isolates that were nonsusceptible to at least one carbapenem were chosen for testing. Using disks containing imipenem without and with 300 μg APBA, 600 μg APBA, or 400 μg PBA, 72, 92, and 112 of the KPC producers, respectively, gave positive results (sensitivities, 64.3%, 82.1%, and 100%, respectively). Using disks containing meropenem without and with 300 μg APBA, 600 μg APBA, or 400 μg PBA, 87, 108, and 112 of the KPC producers, respectively, gave positive results (sensitivities, 77.7%, 96.4%, and 100%, respectively). Among KPC producers, the disk potentiation tests using meropenem and PBA demonstrated the largest differences in inhibition zones (P < 0.001). All combined-disk tests correctly identified 124 of the 127 non-KPC producers (specificity, 97.6%). This comparative study showed that PBA is the most effective inhibitor of KPC enzymes, and its use in combined-disk tests with meropenem may give the most easily interpreted results.
Linkage disequilibrium patterns vary with chromosomal location: a case study from the von Willebrand factor region.

Linkage disequilibrium analysis has been used as a tool for analyzing marker order and locating disease genes. Under appropriate circumstances, disequilibrium patterns reflect recombination events that have occurred throughout a population's history. As a result, disequilibrium mapping may be useful in genomic regions of < 1 cM where the number of informative meioses needed to detect recombinant individuals within pedigrees is exceptionally high. Its utility for refining target areas for candidate disease genes before initiating chromosomal walks and cloning experiments will be enhanced as the relationship between linkage disequilibrium and physical distance is better understood. To address this issue, we have characterized linkage disequilibrium in a 144-kb region of the von Willebrand factor gene on chromosome 12. Sixty CEPH and 12 von Willebrand disease families were genotyped for five PCR-based markers, which include two microsatellite repeats and three single-base-pair substitutions. Linkage disequilibrium and physical distance between polymorphisms are highly correlated (rm = -.76; P < .05) within this region. None of the five markers showed significant disequilibrium with the von Willebrand disease phenotype. The linkage disequilibrium/physical distance relationship was also analyzed as a function of chromosomal location for this and eight previously characterized regions. This analysis revealed a general trend in which linkage disequilibrium dissipates more rapidly with physical distance in telomeric regions than in centromeric regions. This trend is consistent with higher recombination rates near telomeres.