Miracle-dz/UniFAR-FTUs huggingface dataset:
Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients

Objective Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS. Design A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial. Methods The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing. Results Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence. Conclusions BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment. Trial Registration UMIN Clinical Trials UMIN000008527
Semi-automatische Überwachung von Zielsystemen

A heat convection barrier particularly adapted for use with greenhouses and warehouses consists of a series of inflatable tubes which are suspended beneath the roof of a structure and inflated into contact with each other to form a barrier against heat loss through the roof. Each of the tubes includes an integrally formed seam by which the tubes are suspended beneath the roof and an inflatable main body portion, and the tubes are spaced from each other a distance less than the inflated diameters of the main body portions so that when they are inflated they contact each other and form a continuous barrier. One end of each of the tubes is tied off and the opposite ends are split and wrapped about an apertured conduit and a low pressure fan or blower communicates with one end of the conduit to inflate the tubes. When it is desired to heat the roof of the structure to, for example, eliminate snow loads, the fan or blower may be turned off, allowing the tubes to deflate so that warm air may pass upwardly between the deflated tubes and contact the roof. Alternatively a conduit can be inserted between an adjacent pair of inflated tubes to permit warm air to be pumped into the space between the roof and the tubes.
GAPE‐LIMITED PREDATORS AS AGENTS OF SELECTION ON THE DEFENSIVE MORPHOLOGY OF AN INVASIVE INVERTEBRATE

Invasive species have widespread and pronounced effects on ecosystems and adaptive evolution of invaders is often considered responsible for their success. Despite the potential importance of adaptation to invasion, we still have limited knowledge of the agents of natural selection on invasive species. Bythotrephes longimanus, a cladoceran zooplankton, invaded multiple Canadian Shield lakes over the past several decades. Bythotrephes have a conspicuous caudal process (tail spine) that provides a morphological defense against fish predation. We measured viability selection on the longest component of the Bythotrephes spine, the distal spine segment, through a comparison of the lengths of first and second instar Bythotrephes collected from lakes differing in the dominance of gape‐limited predation (GLP) and nongape‐limited predation (NGLP) by fish. We found that natural selection varied by predator gape‐limitation, with strong selection (selection intensity: 0.20–0.79) for increased distal spine length in lakes dominated by GLP, and no significant selection in lakes dominated by NGLP. Further, distal spine length was 17% longer in lakes dominated by GLP, suggesting the possibility of local adaptation. As all study lakes were invaded less than 20 years prior to our collections, our results suggest rapid divergence in defensive morphology in response to selection from fish predators.
Sequences from sea urchin TU transposons are conserved among multiple eucaryotic species, including humans

Sequences homologous to various structural domains of the Strongylocentrotus purpuratus TU family of transposons are present in sea urchin species closely related to S. purpuratus and were found in close proximity to each other in linkage patterns that differed for different species. Sequence homologs of the inverted repeat outer domain (IVR-OD) segment were, in addition, present in a sea urchin related only distantly to S. purpuratus and in all other eucaryotic organisms surveyed. In humans, a polymorphic hybridization pattern was seen for genomic DNA obtained from different individuals. Sequence comparisons revealed that repeated sequence motifs similar to those making up the 15-base-pair direct repeat unit of the IVR-OD domain of the TU elements exist in the IVRs of transposons identified in Drosophila melanogaster and maize and in the transcription control regions of certain eucaryotic viral and cellular genes. The remarkable evolutionary conservation of IVR-OD homologs may reflect a biological role for these sequences in DNA transposition, the regulation of gene expression, or both.
Intelligence Test Scores from Infancy to Adulthood for a Craniopagus Twin Pair Neurosurgically Separated at 4 Months of Age

Long-term effects in a neurosurgically separated twin pair were illuminated by standard psychological test scores obtained over a period from 2 to 38 years of age. Interdigitation of the gyri of their right frontal lobes had necessitated separation in two stages at 4 months of age. One twin clearly suffered some brain injury and showed some impairment during the testing at 5 years of age. The scores of both twins rose at the adult testing. The brighter twin has an IQ comparable to that of the mother. The unique data set is a kind of model for long-term assessment of early brain surgery, particularly with craniopagus twins.
Limits of preservation of samples for urine strip tests and particle counting

Abstract Background: Preservation of urine samples is important for centralised laboratory services with automated instruments. Methods: A multicentre evaluation was carried out to assess preservative tubes from BD Diagnostics-Pre-analytical Systems and from Greiner Bio-One for test strip reading (documented at the level of remission values), for particle counting by flow cytometers (UF-100) and for visual microscopy. Failures were expressed as percentages of originally positive samples beyond a two-fold change (+100% or –50%) from the original values. Results: The preservative-containing BD Plus C&S plastic, BD Plus UAP and Greiner Stabilur tubes succeeded in preservation of test strip results for 6–24 h (exceptions were glucose and nitrite tests). Greiner boric acid tube showed false negative results in leukocyte, protein and ketone strip tests immediately after adding the preservative. Urine red blood cell counts (with Sysmex UF-100) were preserved for 5 h in BD Plus C&S plastic and Greiner Stabilur tubes (Greiner tubes having clearly larger preservative-related background). Bacteria or white blood cell counting succeeded in BD Plus C&S plastic tubes for 5 or 24 h, respectively, but up to 72 h in Greiner Stabilur tubes. In visual microscopy, the Greiner Stabilur tube was slightly better than the BD Plus C&S plastic tube. Conclusions: Urine specimens can be transported at +20°C on the day of collection if preserved properly. Longer delays need careful planning with current preservatives. Flow cytometry with UF-100 is sensitive to non-dissolved preservative remnants. Clin Chem Lab Med 2008;46:703–13.
A Macroeconomic Model with Financial Panics

This article incorporates banks and banking panics within a conventional macroeconomic framework to analyse the dynamics of a financial crisis of the kind recently experienced. We are particularly interested in characterizing the sudden and discrete nature of banking panics as well as the circumstances that make an economy vulnerable to such panics in some instances but not in others. Having a conventional macroeconomic model allows us to study the channels by which the crisis affects real activity both qualitatively and quantitatively. In addition to modelling the financial collapse, we also introduce a belief driven credit boom that increases the susceptibility of the economy to a disruptive banking panic.
Big People, Little World: The Body Influences Size Perception

Previous research has shown that changes to the body can influence the perception of distances in near space (Witt et al, 2005 Journal of Experimental Psychology: Human Perception and Performance 31 880–888). In this paper, we question whether changes to the body can also influence the perception of extents in extrapersonal space, namely the perception of aperture widths. In experiment 1, broad-shouldered participants visually estimated the size of apertures to be smaller than narrow-shouldered participants. In experiment 2, we questioned whether changes to the body, which included holding a large object, wearing a large object, or simply holding out the arms would influence perceived width. Surprisingly, we found that only when participants' hands were widened was extrapersonal space rescaled. In experiment 3, we explored the boundaries of the effect observed in experiment 2 by asking participants to hold their arms at four different positions in order to determine the arm width at which apertures appeared smaller. We found that arm positions that were larger than the shoulder width made apertures appear smaller. The results suggest that dimensions of the body play a role in the scaling of environmental parameters in extrapersonal space.
Domain adaptation of articulated pose estimation via synthetic pose prior

This paper proposes an articulated pose estimation method based on the pose prior for adaptation that is scene specific. In this research field, various approaches to estimate articulated human pose have been proposed and many researchers have tried to improve pose estimation accuracy for shared datasets. On the other hand, it is not common to use datasets without any labeling for realizing domain adaptation to different scenes even though it is urgently needed. Domain adaptation without labeled data is the key problem because when the user wants to estimate human pose captured in a specific scene, it is too costly to make a labeled dataset for training the estimator. We tackle this problem by proposing the novel approach of using synthetic pose prior, which is made by simulating probable poses in the target scene. We consider the likelihood of human pose distribution generated from various motion capture data sets and environmental knowledge about the scene in addition to training a basic appearance-based pose estimator by using a labeled dataset. Using the likelihood of joint positions specific to the scene, more appropriate results are yielded. In experiments, we adapt an estimator trained by images captured from various perspectives to suit the target images captured from a fixed perspective. As the proposed method takes advantage of the bias caused by fixed perspective, it offers improved estimation accuracy.
Cross-Clade Inhibition of Recombinant Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus SIVcpz Reverse Transcriptases by RNA Pseudoknot Aptamers

ABSTRACT Reverse transcriptase (RT) remains a primary target in therapies directed at human immunodeficiency virus type 1 (HIV-1). RNA aptamers that bind RT from HIV-1 subtype B have been shown to protect human cells from infection and to reduce viral infectivity, but little is known about the sensitivity of the inhibition to amino sequence variations of the RT target. Therefore, we assembled a panel of 10 recombinant RTs from phylogenetically diverse lentiviral isolates (including strains of HIV-1, simian immunodeficiency virus SIVcpz, and HIV-2). After validating the panel by measuring enzymatic activities and inhibition by small-molecule drugs, dose-response curves for each enzyme were established for four pseudoknot RNA aptamers representing two structural subfamilies. All four aptamers potently inhibited RTs from multiple HIV-1 subtypes. For aptamers carrying family 1 pseudoknots, natural resistance was essentially all-or-none and correlated with the identity of the amino acid at position 277. In contrast, natural resistance to aptamers carrying the family 2 pseudoknots was much more heterogeneous, both in degree (gradation of 50% inhibitory concentrations) and in distribution across clades. Site-directed and subunit-specific mutagenesis identified a common R/K polymorphism within the p66 subunit as a primary determinant of resistance to family 1, but not family 2, pseudoknot aptamers. RNA structural diversity therefore translates into a nonoverlapping spectrum of mutations that confer resistance, likely due to differences in atomic-level contacts with RT.
Phosphorylation regulates human OCT4

The transcription factor OCT4 is fundamental to maintaining pluripotency and self-renewal. To better understand protein-level regulation of OCT4, we applied liquid chromatography–MS to identify 14 localized sites of phosphorylation, 11 of which were previously unknown. Functional analysis of two sites, T234 and S235, suggested that phosphorylation within the homeobox region of OCT4 negatively regulates its activity by interrupting sequence-specific DNA binding. Mutating T234 and S235 to mimic constitutive phosphorylation at these sites reduces transcriptional activation from an OCT4-responsive reporter and decreases reprogramming efficiency. We also cataloged 144 unique phosphopeptides on known OCT4 interacting partners, including SOX2 and SALL4, that copurified during immunoprecipitation. These proteins were enriched for phosphorylation at motifs associated with ERK signaling. Likewise, OCT4 harbored several putative ERK phosphorylation sites. Kinase assays confirmed that ERK2 phosphorylated these sites in vitro, providing a direct link between ERK signaling and the transcriptional machinery that governs pluripotency.
Requirement for Transcription Factor NFAT in Interleukin-2 Expression

ABSTRACT The nuclear factor of activated T cells (NFAT) transcription factor is implicated in expression of the cytokine interleukin-2 (IL-2). Binding sites for NFAT are located in the IL-2 promoter. Furthermore, pharmacological studies demonstrate that the drug cyclosporin A inhibits both NFAT activation and IL-2 expression. However, targeted disruption of the NFAT1 and NFAT2 genes in mice does not cause decreased IL-2 secretion. The role of NFAT in IL-2 gene expression is therefore unclear. Here we report the construction of a dominant-negative NFAT mutant (dnNFAT) that selectively inhibits NFAT-mediated gene expression. The inhibitory effect of dnNFAT is mediated by suppression of activation-induced nuclear translocation of NFAT. Expression of dnNFAT in cultured T cells caused inhibition of IL-2 promoter activity and decreased expression of IL-2 protein. Similarly, expression of dnNFAT in transgenic mice also caused decreased IL-2 gene expression. These data demonstrate that NFAT is a critical component of the signaling pathway that regulates IL-2 expression.
PROJECT DESCRIPTION Stabilitiy , Matching and Sensitivity of Flat Beams

The International Linear Collider (ILC) is expected to begin a new era of discovery in elementary particles and high energy physics. To make this new advanced accelerator a reality, many critical R&D needs must be addressed. One of them is the in-depth understanding, and control, of the dynamics of the flat beam that the ILC damping rings are designed to produce. This advanced accelerator will produce beams with an extremely large ratio of horizontal to vertical emittance. In this unprecedent regime of operation, the beam is likely to be extremely sensitive to changes in physical and lattice parameters. Therefore, a tight and robust control of the flat beam is a must to guarantee stability and achieve the desired beam quality and flatness.
Adenoviral expression of protein‐L‐isoaspartyl methyltransferase (PIMT) partially attenuates the biochemical changes in PIMT‐deficient mice

Protein‐L‐isoaspartyl methyltransferase (PIMT) is a putative protein repair enzyme, which methylates the α‐carboxyl group of atypical L‐isoaspartyl residues in aged proteins and converts them to normal L‐aspartyl residues. Two splicing variants, PIMT‐I and PIMT‐II, have been reported, although their biological functions and specific subcellular substrates are still to be defined. We and another group have previously showed that PIMT‐deficient mice succumbed to fatal epileptic seizures associated with an abnormal accumulation of isoaspartate (IsoAsp) in the brain. In the present study, we prepared two recombinant adenovirus vectors that contained PIMT‐I or PIMT‐II, respectively, in order to investigate the differential biological roles of PIMT‐I and PIMT‐II. These recombinant viruses differentially conferred PIMT‐I or PIMT‐II expressions in cultured neurons. Biochemical analyses showed that either of PIMT‐I or PIMT‐II effectively repaired the damaged proteins in PIMT‐deficient neurons, but the concomitant expression failed to show an additive effect in the repair of IsoAsp. These results suggested that PIMT‐I and PIMT‐II might share a common biological function and/or subcellular substrates. In addition, we administered an adeno‐PIMT‐I vector into the brain of PIMT‐deficient mice at embryonic day 14.5 by an exo‐utero method to assess the biological effects in vivo. The result showed that recombinant adeno‐PIMT improved the symptoms of PIMT‐deficient mice in vivo, but only partially repaired IsoAsp in damaged proteins. The gene therapy presented in this report provided a better prognosis for the survival of PIMT‐deficient mice than the previously reported anti‐epileptic drug therapy. The results suggested a new reagent for gene therapy applicable to ageing‐associated neurodegenerative disorders. © 2002 Wiley‐Liss, Inc.
Marketing strategies in the wireless telecommunications market: a customers’ perception

This research attempts to examine the main business strategies that may affect customer satisfaction from wireless broadband services and, as a result, business market share measured in terms of customer retention and customer acquisition. A research model is developed where the effect of a number of financial (three) and non-financial (11) factors on customer satisfaction, retention and acquisition is examined. The model has been empirically tested using data gathered from 165 people who use broadband and wireless services and applications. The results show that although financial factors affect users' satisfaction, it is the non-financial factors that mainly affect it. From those, price differentiation, bandwidth, ease of use, empathy, enjoyment and after sales support play the most crucial role. Further, customer satisfaction significantly affects the size of market share hold by a firm, being the main determinant of customer retention, which, in turn, significantly affect (along with customer satisfaction) customer acquisition.
The influence of irrigators' attitudes and objectives on their decision making

Water markets were expected to minimise the socioeconomic impact of reducing irrigators’ water entitlements in Australia’s Namoi Valley by providing a mechanism for reallocating water from inactive license holders to active irrigators. But survey responses show that this is an unlikely scenario as it appears as though there may be a number of influences acting on inactive license holders that are stronger than the desire for economic gain from participating in water markets. This research constructs a typology that aims to provide an explanatory framework for understanding what those influences might be. A better understanding of farmers’ attitudes and objectives; and of the motivations for their behaviour, is likely to lead to better policy design and more successful policy implementation. The implication for policy makers is that reducing irrigators entitlement based on their past usage, rather than equal reductions for all, will cause less disruption within the affected communities as this method places minimum reliance on the market as a reallocation mechanism.
Interactive effects of temperature and drought on cassava growth and toxicity: implications for food security?

Cassava is an important dietary component for over 1 billion people, and its ability to yield under drought has led to it being promoted as an important crop for food security under climate change. Despite its known photosynthetic plasticity in response to temperature, little is known about how temperature affects plant toxicity or about interactions between temperature and drought, which is important because cassava tissues contain high levels of toxic cyanogenic glucosides, a major health and food safety concern. In a controlled glasshouse experiment, plants were grown at 2 daytime temperatures (23 °C and 34 °C), and either well‐watered or subject to a 1 month drought prior to harvest at 6 months. The objective was to determine the separate and interactive effects of temperature and drought on growth and toxicity. Both temperature and drought affected cassava physiology and chemistry. While temperature alone drove differences in plant height and above‐ground biomass, drought and temperature × drought interactions most affected tuber yield, as well as foliar and tuber chemistry, including C : N, nitrogen and cyanide potential (CNp; total cyanide released from cyanogenic glucosides). Conditions that most stimulated growth and yield (well‐watered × high temperature) effected a reduction in tuber toxicity, whereas drought inhibited growth and yield, and was associated with increased foliar and tuber toxicity. The magnitude of drought effects on tuber yield and toxicity were greater at high temperature; thus, increases in tuber CNp were not merely a consequence of reduced tuber biomass. Findings confirm that cassava is adaptable to forecast temperature increases, particularly in areas of adequate or increasing rainfall; however, in regions forecast for increased incidence of drought, the effects of drought on both food quality (tuber toxicity) and yield are a greater threat to future food security and indicate an increasing necessity for processing of cassava to reduce toxicity.