Miracle-dz/UniFAR-FTUs huggingface dataset:
Heat shock factor gains access to the yeast HSC82 promoter independently of other sequence-specific factors and antagonizes nucleosomal repression of basal and induced transcription

Transcription in eukaryotic cells occurs in the context of chromatin. Binding of sequence-specific regulatory factors must contend with the presence of nucleosomes for establishment of a committed preinitiation complex. Here we demonstrate that the high-affinity binding site for heat shock transcription factor (HSF) is occupied independently of other cis-regulatory elements and is critically required for preventing nucleosomal assembly over the yeast HSC82 core promoter under both noninducing (basal) and inducing conditions. Chromosomal mutation of this sequence, termed HSE1, erases the HSF footprint and abolishes both transcription and in vivo occupancy of the TATA box. Moreover, it dramatically reduces promoter chromatin accessibility to DNase I and TaqI, as the nuclease-hypersensitive region is replaced by a localized nucleosome. By comparison, in situ mutagenesis of two other promoter elements engaged in stable protein-DNA interactions in vivo, the GRF2/REB1 site and the TATA box, despite reducing transcription three- to fivefold, does not compromise the nucleosome-free state of the promoter. The GRF2-binding factor appears to facilitate the binding of proteins to both HSE1 and TATA, as these sequences, while still occupied, are less protected from in vivo dimethyl sulfate methylation in a deltaGRF2 strain. Finally, deletion of a consensus upstream repressor sequence (URS1), positioned immediately upstream of the GRF2-HSE1 region and only weakly occupied in chromatin, has no expression phenotype, even under meiotic conditions. However, deletion of URS1, like mutation of GRF2, shifts the translational setting of an upstream nucleosomal array flanking the promoter region. Taken together, our results argue that HSF, independent of and dominant among sequence-specific factors binding to the HSC82 upstream region, antagonizes nucleosomal repression and creates an accessible chromatin structure conducive to preinitiation complex assembly and transcriptional activation.
Social Skills in Individuals with Nonverbal Learning Disabilities

Nonverbal learning disability (NLD) is often a highly misunderstood diagnosis. Challenges with the understanding and use of language in social contexts can have significant negative impacts on individuals with this diagnosis, in that they struggle to interpret both nonverbal communication and nonliteral language. Understanding these challenges is critical in order to provide effective intervention. Assessment in these domains provides information about the areas to target for intervention. While individuals with NLD rely heavily on their auditory skills, it is imperative to provide means for them to learn social pragmatic and language skills in order to function in dynamically changing social exchanges. It is often indicated that teaching must occur only through verbal scripting. However, relying solely on this modality will limit students’ abilities to effectively learn to apply targets in real life social situations. Therefore, a balanced approach that strives toward generalization is necessary. This chapter will provide information regarding assessment and intervention practices related to social interactions for individuals with NLD.
Allocation Problem of Repairable and Replaceable Components for a System Reliability using Selective Maintenance: An Integer Solution

In many industrial environments, systems are required to perform a sequence of operations (or missions) with finite breaks between each operation. During these breaks, it may be advantageous to perform repair and replace on some of the system's components. However, it may not be possible to perform all desirable maintenance activities prior to the beginning of the next mission due to limitations on maintenance resources. In this paper we have used the selective maintenance policy for determining the optimum number of repairable and replaceable components to maximize the system's reliability within limited maintenance time and cost. Also we find the optimal maintenance cost and optimal maintenance time for predetermined reliability requirement of the system. A numerical example is presented to illustrate the computational proc edure.
Biogeomorphological effects of leaf accumulations in stepped-bed channels: Exploratory study, Moravskoslezské Beskydy Mountains, Czech Republic

Abstract The stepped-bed system, with a step-like longitudinal profile, is typical morphology in steep headwater streams. These systems are created by a series of coarse sediments or instream wood (steps with supercritical flows) interspaced with finer material (forming pools with subcritical flows). In the case of well-developed steps and pools, the resulting channel-reach morphology is referred to as “step-pool” morphology. In this study, we identify a previously undescribed type of step-pool formation, the “foliaged step-pool”, in the high-gradient Stoligy Stream of the Moravskoslezské Beskydy Mountains. The defining feature of this formation is the significant presence of leaves in the step structure. The geometry of the steps and pools was measured and the parameters that characterise the distribution, amount and function of leaves acting in these areas were defined. Statistical results showed differences between non-foliaged and foliaged step-pool formations, in which the latter showed a significant increase in storage level, influencing the channel’s hydrodynamics. Particle-size analyses demonstrated that foliaged step-pool formations had finer sediment in the pools, which indicates that there are differences in sediment transport processes between foliaged and non-foliaged formations. These results offer new insights into stepped-bed and step-pool morphology, providing directions for further research on small streams in deciduous forested regions.
NFATc1 nucleocytoplasmic shuttling is controlled by nerve activity in skeletal muscle

Calcineurin-NFAT signaling has been shown to control activity-dependent muscle gene regulation and induce a program of gene expression typical of slow oxidative muscle fibers. Following Ca2+-calmodulin stimulation, calcineurin dephosphorylates NFAT proteins and induces their translocation into the nucleus. However, NFAT nuclear translocation has never been investigated in skeletal muscle in vivo. To determine whether NFATc1 nucleocytoplasmic shuttling depends on muscle activity, we transfected fast and slow mouse muscles with plasmids coding for an NFATc1-GFP fusion protein. We found that NFATc1-GFP has a predominantly cytoplasmic localization in the fast tibialis anterior muscle but a predominantly nuclear localization in the slow soleus muscle, with a characteristic focal intranuclear distribution. Two hours of complete inactivity, induced by denervation or anaesthesia, cause NFATc1 export out of the nucleus in soleus muscle fibers, whereas electrostimulation of tibialis anterior with a low-frequency tonic impulse pattern, mimicking the firing pattern of slow motor neurons, causes NFATc1 nuclear translocation. The activity-dependent nuclear import and export of NFATc1 is a rapid event, as visualized directly in vivo by two-photon microscopy. The calcineurin inhibitor cain/cabin1 causes nuclear export of NFATc1 both in normal soleus and stimulated tibialis anterior muscle. These findings support the notion that in skeletal muscle NFATc1 is a calcineurin-dependent nerve activity sensor.
The Trump Hypothesis: Testing Immigrant Populations as a Determinant of Violent and Drug‐Related Crime in the United States

Objectives To test the “Trump Hypothesis”: whether immigrants are responsible for higher levels of violent and drug-related crime in the United States, as asserted by Donald Trump in his 2015 presidential campaign announcement. This is achieved using recent crime and immigration data, thus testing the common public perception linking immigrants to crime, and providing an updated assessment of the immigrant-crime nexus. Methods Rates of violent crime and drug arrests by state are pooled for 2012–2014. These are compared against pooled statistics on foreign-born and Mexican nationals living in the United States, as well as estimates of undocumented foreign and undocumented Mexican population by state. The data are analyzed using correlation and multivariate regressions. Results Data uniformly show no association between immigrant population size and increased violent crime. However, there appears to be a small but significant association between undocumented immigrant populations and drug-related arrests. Conclusions Results largely contradict the Trump Hypothesis: no evidence links Mexican or undocumented Mexican immigrants specifically to violent or drug-related crime. Undocumented immigrant associations with drug-related crime are minimal, though significant. The Trump Hypothesis consequently appears to be biased toward rhetoric rather than evidence.
Auditory and Visual Electrophysiology of Deaf Children with Cochlear Implants: Implications for Cross-modal Plasticity

Deaf children who receive a cochlear implant early in life and engage in intensive oral/aural therapy often make great strides in spoken language acquisition. However, despite clinicians’ best efforts, there is a great deal of variability in language outcomes. One concern is that cortical regions which normally support auditory processing may become reorganized for visual function, leaving fewer available resources for auditory language acquisition. The conditions under which these changes occur are not well understood, but we may begin investigating this phenomenon by looking for interactions between auditory and visual evoked cortical potentials in deaf children. If children with abnormal auditory responses show increased sensitivity to visual stimuli, this may indicate the presence of maladaptive cortical plasticity. We recorded evoked potentials, using both auditory and visual paradigms, from 25 typical hearing children and 26 deaf children (ages 2–8 years) with cochlear implants. An auditory oddball paradigm was used (85% /ba/ syllables vs. 15% frequency modulated tone sweeps) to elicit an auditory P1 component. Visual evoked potentials (VEPs) were recorded during presentation of an intermittent peripheral radial checkerboard while children watched a silent cartoon, eliciting a P1–N1 response. We observed reduced auditory P1 amplitudes and a lack of latency shift associated with normative aging in our deaf sample. We also observed shorter latencies in N1 VEPs to visual stimulus offset in deaf participants. While these data demonstrate cortical changes associated with auditory deprivation, we did not find evidence for a relationship between cortical auditory evoked potentials and the VEPs. This is consistent with descriptions of intra-modal plasticity within visual systems of deaf children, but do not provide evidence for cross-modal plasticity. In addition, we note that sign language experience had no effect on deaf children’s early auditory and visual ERP responses.
123I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases

123I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of 123I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of 123I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac 123I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both 123I-ioflupane for the striatum and 123I-MIBG. Despite being a simple index, the H/M ratio of 123I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.
Thermal properties of high-volume fly ash mortars and concretes

As sustainability moves to the forefront of construction, the utilization of high-volume fly ash concrete mixtures to reduce CO2 emissions and cement consumption per unit volume of concrete placed is receiving renewed interest. Concrete mixtures in which the fly ash replaces 50% or more of the Portland cement are both economically and technically viable. This article focuses on a characterization of the thermal properties, namely, specific heat capacity and thermal conductivity, of such mixtures. Both the raw materials and the finished products (mortars and concretes) are evaluated using a transient plane source method. Because the specimens being examined are well hydrated, estimates of the specific heat capacity based on a law of mixtures, with a ‘bound water’ specific heat capacity value being employed for the water in the mixture, provide reasonable predictions of the measured performance. As with most materials, thermal conductivity is found to be a function of density, while also being dependent on whether the aggregate source is siliceous or limestone. The measured values should provide a useful database for evaluating the thermal performance of high-volume fly ash concrete structures.
Late Pleistocene Hystrix (Acanthion) brachyura Linnaeus 1758 from the Fuchsluken Cave Near Saalfeld (Thuringia, Germany) - A Porcupine and Hyena Den and Contribution to their Palaeobiogeography in Europe

Rare Late Pleistocene porcupine remains of Hystrix (Atherurus) brachyura Linnaeus 1758 are described from the Fuchsluken Cave, a small gypsum karst cavity at the Rote Berg on the Giebelstein near Saalfeld (Thuringia, Central Germany). The cave was used during the Eemian and mainly Early Weichselian (around 120.000-75.000 BP) by spotted hyena clans of Crocuta crocuta spelaea (Goldfuss 1823), which imported prey that resulted in a large bone accumulation in and around the cave. It was also used in the short term by porcupines as their den, such as proven for several Eemian to Early Weichselian cave faunas in Central Europe, especially Germany and Czech Republic, recently. In the cave recycled-by-hyenas cracked megafauna bones were found, on which they had chewed all around. These typically nibbled bones with parallel bite scratches were also found at other European caves such as presented here for two more new Hystrix cave sites in the Moravian Karst (Czech Republic) and indirectly prove their presence at more and more cave sites in Central Europe. Here, the recently learned 21 Late Pleistocene porcupine sites with skeletal material and more often the indirect proof by chewed bones are presented in an overview. Nearly all are cave localities, often being small cavities or the entrance parts of small caves were used as porcupine dens, as is proved here in the Fuchsluken Cave near Saalfeld. In many cases the porcupines used hyena dens and recycled their accumulated bone rubbish.
Dynamic and Quantitative Method of Analyzing Service Consistency Evolution Based on Extended Hierarchical Finite State Automata

This paper is concerned with the dynamic evolution analysis and quantitative measurement of primary factors that cause service inconsistency in service-oriented distributed simulation applications (SODSA). Traditional methods are mostly qualitative and empirical, and they do not consider the dynamic disturbances among factors in service's evolution behaviors such as producing, publishing, calling, and maintenance. Moreover, SODSA are rapidly evolving in terms of large-scale, reusable, compositional, pervasive, and flexible features, which presents difficulties in the usage of traditional analysis methods. To resolve these problems, a novel dynamic evolution model extended hierarchical service-finite state automata (EHS-FSA) is constructed based on finite state automata (FSA), which formally depict overall changing processes of service consistency states. And also the service consistency evolution algorithms (SCEAs) based on EHS-FSA are developed to quantitatively assess these impact factors. Experimental results show that the bad reusability (17.93% on average) is the biggest influential factor, the noncomposition of atomic services (13.12%) is the second biggest one, and the service version's confusion (1.2%) is the smallest one. Compared with previous qualitative analysis, SCEAs present good effectiveness and feasibility. This research can guide the engineers of service consistency technologies toward obtaining a higher level of consistency in SODSA.
Participation of women in clinical trials for new drugs approved by the food and drug administration in 2000-2002.

OBJECTIVE This study aimed to track the inclusion of women in clinical trials for new drugs approved by the Food and Drug Administration (FDA) between 2000 and 2002 and to evaluate the extent of analyses by sex. METHODS Data were extracted from FDA reviewers' reports, summaries of clinical trials in New Drug Applications (NDAs), and product labeling and organized into a Microsoft Access database. The information collected includes subject enrollment by sex per clinical phase and sex differences in pharmacokinetics, safety, and efficacy as determined by either sponsors or reviewers. RESULTS There were 67 New Molecular Entities (NMEs) approved by the FDA between 2000 and 2002. A total of 397,825 subjects were enrolled in 2,323 clinical trials. If 9 sex-specific NMEs are excluded, 297,697 subjects were enrolled in 1,974 clinical trials. Forty-seven percent of participants were male, 49% were female, and 4% of subjects were not specified. Of the 58 sex-nonspecific products in the study, 71% (41 of 58) of sex analyses were performed either by the sponsor or FDA reviewers. Twenty-five NMEs were found to have sex differences in pharmacokinetics, efficacy or adverse events. However, no recommendation was made to adjust dosage based on sex differences. CONCLUSIONS The percentages of women and men participating in clinical trials varied by year, phase, and product type. However, the overall participation by women and men was comparable, suggesting an improvement in including more women in clinical trials when compared with the previous FDA study evaluating women's participation from 1995 through 1999. As with the previous study, however, a significant underrepresentation of women in early phase trials and in certain areas, such as cardiovascular products, was observed and continues to be an issue of concern. Lack of appropriate analyses by sex should also be noted as an issue of concern.
Cross-cultural Pragmatics : The Semantics of Human Interaction

In a career spanning five decades, Patrick Suppes has pursued a unique approach to the problems of language and learning. This book, with Colleen Crangle, is a reprise of much of the work on the philosophy of language. As the title indicates, the underlying model is of a robot that is to receive instructions (and later also instruction) in ordinary language. The philosophizing is made concrete through software simulations and some simple experiments with a physical robot. Although much of the material has appeared before, it is reworked Into a cohesive whole. Any attempt to deal with such deep issues will involve simplifications, and it is instructive to follow the unfolding of complications. The starting point is quite conventional; attribute grammar with a semantics based on formal logic. But the demands of the robot domain quickly require the introduction of functional semantics for perception and action, which are not analyzed further, and for control primitives. Task requirements also push the authors to abandon the autonomy of syntax and to give a major role to intentionality, contextual readings, and the shared perceptions of speaker and hearer. Thus they are led to many of the core concerns of cognitive semantics and this becomes explicit in a chapter on geometry and spatial prepositions. Traditional issues concerning negation get extended in intriguing ways in the chapter that considers what it means to ask a robot to stop. The work on learning is mostly recent, although the theme goes back to Suppes's original work in mathematical psychology. The model has the robot choose parameters of actions (distance, etc.) from probability distributions that get modified by verbal feedback. The final chapter describes on-going work on the learning of natural language from examples in the robot domain. By postulating pre-existing internal structures for each utterance, the problem is reduced to statistically associating surface forms with internal constructs. This problem is analyzed theoretically and on a small corpus. As in the rest of the book, the work is idiosyncratic. But anyone with a deep interest in the philosophy of language can benefit from following the progression of ideas on some of its most fundamental issues. --Jerome A. Feldman, International Computer Science Institute, Berkeley
Transfer of Cognitive Training across Magnitude Dimensions Achieved with Concurrent Brain Stimulation of the Parietal Lobe

Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity–or the number of items in a set–which is thought to rely on an “approximate number sense” (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components.