Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct demonstration of discrete Ca2+ microdomains associated with different isoforms of adenylyl cyclase

Ca2+-sensitive adenylyl cyclases (ACs) orchestrate dynamic interplay between Ca2+ and cAMP that is a crucial feature of cellular homeostasis. Significantly, these ACs are highly selective for capacitative Ca2+ entry (CCE) over other modes of Ca2+ increase. To directly address the possibility that these ACs reside in discrete Ca2+ microdomains, we tethered a Ca2+ sensor, GCaMP2, to the N-terminus of Ca2+-stimulated AC8. GCaMP2-AC8 measurements were compared with global, plasma membrane (PM)-targeted or Ca2+-insensitive AC2-targeted GCaMP2. In intact cells, GCaMP2-AC8 responded rapidly to CCE, but was largely unresponsive to other types of Ca2+ rise. The global GCaMP2, PM-targeted GCaMP2 and GCaMP2-AC2 sensors reported large Ca2+ fluxes during Ca2+ mobilization and non-specific Ca2+ entry, but were less responsive to CCE than GCaMP2-AC8. Our data reveal that different AC isoforms localize to distinct Ca2+-microdomains within the plasma membrane. AC2, which is regulated via protein kinase C, resides in a microdomain that is exposed to a range of widespread Ca2+ signals seen throughout the cytosol. By contrast, a unique Ca2+ microdomain surrounds AC8 that promotes selectivity for Ca2+ signals arising from CCE, and optimizes CCE-mediated cAMP synthesis. This direct demonstration of discrete compartmentalized Ca2+ signals associated with specific signalling proteins provides a remarkable insight into the functional organization of signalling microdomains.
Arabidopsis thaliana *

The phenotype appearance of Ar~bidopsis thaliana hairy roots and crown galls their teratomas and regenerated plants were compared. Several differences were found, which correlate with T-DNA differences between Ti and Ri plasmids. The induction of crown galls in Arabidopsis thaliana by Agrobacterium tumefaciens was already demonstrated (AERTS et al. 1979, O~DfCEJ et al. 1984a). A. thaliana has shown an unusual response to crown gall induction; we demonstrated frequent spontaneous differentiation of opine synthesizing plants and the opine synthesizing activity was maintained in succeeding generations (PAvINGEROVA et al. 1983). Like in tobacco crown galls (BEzDEK et al. 1977), A. thaliana crown galls also showed higher resistance to 5-bromdeoxyuridine than untransformed calli (ONDREJ 1983). BEZDI~K and VYSKOT (1981) explain their results in tobacco by modulation of thymidyla te kinase activity due to the increased level of cytokinins. Thymidylate synthase causes debromination of 5-bromdeoxyuridine in situ in crown galls. The peculiarity of A. thaliana crown galls is tha t they are capable of in vitro growth without growth regulators in the light only (OND]~EJ et al. 1984a). Untransformed A. thaliana calli are also capable of in vitro growth without growth regulators in the medium but the growth is slow and transient (ONDREJ et al. 1984b). Agrobacterium rhizogenes brings its T-DNA of the Ri plasmid into plant cell nuclei similarly as A. tumefaciens (CHILTON et al. 1982, WHITE et al. 1982) but most of T-DNA genes on Ri plasmid of A. rhizogenes are different from those on Ti plasmid of A. tumefaciens (WILLMITZER et al. 1982a). Genes for T-DNA transcripts 1 and 2 (WILLMITZER et al. 1982b) which were shown to code for enzymes for biosynthetic pathway of IAA (INzfi et al. 1984) are common in T-DNA of both Ti and Ri plasmids (WILLMITZER et al. 1982a). * Presented at the International Symposium "Plant Growth Regulators" held on June 18-22, 1984 at Liblice, Czechoslovakia.
Toward a generative transformational approach to visual perception

Shepard's notion of “internalisation” is better interpreted as a simile than a metaphor. A fractal encoding model of visual perception is sketched, in which image elements are transformed in such a way as to maximise symmetry with the current input. This view, in which the transforming system embodies what has been internalised, resolves some problems raised by the metaphoric interpretation. [Hecht; Shepard]
A Novel Mode of Gleevec Binding Is Revealed by the Structure of Spleen Tyrosine Kinase*

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase required for signaling from immunoreceptors in various hematopoietic cells. Phosphorylation of two tyrosine residues in the activation loop of the Syk kinase catalytic domain is necessary for signaling, a phenomenon typical of tyrosine kinase family members. Syk in vitro enzyme activity, however, does not depend on phosphorylation (activation loop tyrosine → phenylalanine mutants retain catalytic activity). We have determined the x-ray structure of the unphosphorylated form of the kinase catalytic domain of Syk. The enzyme adopts a conformation of the activation loop typically seen only in activated, phosphorylated tyrosine kinases, explaining why Syk does not require phosphorylation for activation. We also demonstrate that Gleevec (STI-571, Imatinib) inhibits the isolated kinase domains of both unphosphorylated Syk and phosphorylated Abl with comparable potency. Gleevec binds Syk in a novel, compact cis-conformation that differs dramatically from the binding mode observed with unphosphorylated Abl, the more Gleevec-sensitive form of Abl. This finding suggests the existence of two distinct Gleevec binding modes: an extended, trans-conformation characteristic of tight binding to the inactive conformation of a protein kinase and a second compact, cis-conformation characteristic of weaker binding to the active conformation. Finally, the Syk-bound cis-conformation of Gleevec bears a striking resemblance to the rigid structure of the nonspecific, natural product kinase inhibitor staurosporine.
Low-Income Immigrant Pupils Learning Vocabulary through Digital Picture Storybooks.

Children from immigrant, low-income families in the Netherlands start school with a limited vocabulary in the language of instruction; therefore, this places them at risk for developing reading difficulties. Exposure to books is assumed to reduce their 2nd language (L2) vocabulary disadvantage. In this experiment, we examined the effects of video storybooks on the receptive and expressive vocabularies of 5-year-old children. Children (N = 92) were exposed repeatedly to the digital storybook. The story was presented with either static or video images. Children in the control condition played with a nonverbal computer game. Children's receptive and expressive book-based vocabularies were assessed. Results reveal that children learned words receptively and expressively; however, the children seldom learned the same words both ways. Both treatments benefited receptive and expressive vocabularies; however, readings with the addition of video were found to be especially effective for expressive L2 vocabulary acquisition.
Probabilistic reasoning

Many decisions are based on beliefs concerning the likelihood of uncertain events such as the outcome of an election, the guilt of a defendant, or the future value of the dollar. These beliefs are usually expressed in statements such as "1 think that . ," "chances are . ," "it is unlikely that . ," and so forth. Occasionally, beliefs concerning uncertain events are expressed in numerical form as odds or subjective probabilities. What determines such beliefs? How do people assess the probability of an uncertain event or the value of an uncertain quantity? This article shows that people rely on a limited number of heuristic principles which reduce the complex tasks of assessing probabilities and predicting values to simpler judgmental operations. In general, these heuristics are quite useful, but sometimes they lead to severe and systematic errors. The subjective assessment of probability resembles the subjective assessment of physical quantities such as distance or size. These judgments are all based on data of limited validity, which are processed according to heuristic rules. For example, the apparent distance of an object is determined in part by its clarity. The more sharply the object is seen, the closer it appears to be. This rule has some validity, because in any given scene the more distant objects are seen less sharply than nearer objects. However, the reliance on this rule leads to systematic errors in the estimation of distance. Specifically, distances are often overestimated when visibility is poor because the contours of objects are blurred. On the other hand, distances are often underestimated when visibility is good because the objects are seen sharply. Thus, the reliance on clarity as an indication of distance leads to common biases.
Perception of Assimilation of Voice as a Function of Segmental Duration and Linguistic Context

Abstract The perception of assimilation of ‘voice’ in Dutch two-obstruent clusters across word boundaries was measured as a function of cluster duration. In an experiment employing synthetic speech stimuli the duration of the silent interval of the plosives and of the noise part of the fricatives was varied. The clusters were embedded in three types of linguistic context: sentences, words, and nonsense words. Longer durations gave rise to more ‘voiceless’ percepts, resulting in the perception of more ‘progressive assimilation’, at the expense of ‘regressive assimilation’ and ‘no assimilation’. Nonwords behaved slightly differently from sentences and words. The different response pattern for nonwords is ascribed to a different phonetic context rather than to lexical or phonological factors.
Cultural assumptions in career management: practice implications from Germany

Examines the influence of culture in shaping career models. The research follows the belief that career goals and work strategies are framed by certain presupposed expectations. These ideals are subject to cross‐cultural differences because they are, in part, shaped by nationally grounded beliefs about the nature of work and organizational life. Qualitative data from German managers formed a descriptive basis for practice implications.
Continuous dopaminergic stimulation in Parkinson's disease

Current treatments for Parkinson's disease (PD) are plagued by motor complications. Here these underlying motor complications are briefly reviewed, and strategies to reduce them are discussed.The rationale behind the use of continuous dopaminergic stimulation is highlighted as this is a strategy that may reduce motor complications and improve the quality of life for patients with PD. Copyright © 2007 Wiley Interface Ltd
Action potential fidelity during normal and epileptiform activity in paired soma–axon recordings from rat hippocampus

Although action potential initiation and propagation are fundamental to nervous system function, there are few direct electrophysiological observations of propagating action potentials in small unmyelinated fibres, such as the axons within mammalian hippocampus. To circumvent limitations of previous studies that relied on extracellular stimulation, we performed dual recordings: whole‐cell recordings from hippocampal CA3 pyramidal cell somas and extracellular recordings from their axons, up to 800 μm away. During brief spike trains under normal conditions, axonal spikes were more resistant to amplitude reduction than somatic spikes. Axonal amplitude depression was greatest at the axon initial segment < 150 μm from the soma, and initiation occurred ∼75 μm from the soma. Although prior studies, which failed to verify spike initiation, suggested substantial axonal depression during seizure‐associated extracellular K+ ([K+]o) rises, we found that 8 mm[K+]o caused relatively small decreases in axonal spike amplitude during brief spike trains. However, during sustained, epileptiform spiking induced in 8 mm[K+]o, axonal waveforms decreased significantly in peak amplitude. During epileptiform spiking, bursts of two or more action potentials > 20 Hz failed to propagate in most cases. In normal [K+]o at 25 and 32°C, spiking superimposed on sustained somatic depolarization, but not spiking alone, produced similar axonal changes as the epileptiform activity. These results highlight the likely importance of steady‐state inactivation of axonal channels in maintaining action potential fidelity. Such changes in axonal propagation properties could encode information and/or serve as an endogenous brake on seizure propagation.
The road less travelled: morphology in the optimization of biped robot locomotion

Stable bipedal locomotion has been achieved using coupled evolution of morphology and control of a 5-link biped robot in a physics-based simulation environment. The robot was controlled by a closed loop recurrent neural network controller. The goal was to study the effect of macroscopic, midrange and microscopic changes in mass distribution along the biped skeleton to ascertain whether optimal morphology and control pairs could be discovered. The sensor-motor coupling determined that small changes in morphology manifest themselves as large changes in the performance of the biped, which were exploited by the optimization process. In this way, mechanical design and controller optimization were reduced to a single process, and more mutually optimized designs resulted. This work points to alternative routes for efficient automated and manual biped optimization.
Temporal Conceptual Modelling with DL-Lite

Conceptual modelling formalisms such as the Entity-Relationship model (ER) and Unified Modelling Language (UML) have become a de facto standard in database design by providing visual means to describe application domains in a declarative and reusable way. On the other hand, both ER and UML turned out to be closely connected with description logics that are underpinned by formal semantics and thus capable of providing services for effective reasoning over conceptual models; see, e.g., [11, 4]. Temporal conceptual data models (TCMs) [18, 25] have been introduced in the context of temporal databases [20, 15, 13]. In this case, apart from the classical constructs—such as inheritance between classes and relationships, cardinality constraints restricting participation in relationships, and disjointness and covering constraints—temporal constructs are used to capture the temporal behaviour of various components of conceptual schemas. Such constructs can be grouped into 3 categories. Timestamping constraints discriminate between those classes, relationships and attributes that change over time and those that are timeinvariant [28, 18, 16, 6, 25]. Evolution constraints control how domain elements evolve over time by ‘migrating’ from one class to another [19, 23, 26, 25, 3]. We distinguish between qualitative evolution constraints describing generic temporal behaviour, and quantitative ones specifying the exact moment of migration. Temporal cardinality constraints restrict the number of times an instance of a class participates in a relationship. Snapshot cardinality constraints do it at each moment of time, while lifespan cardinality constraints impose restrictions over the entire existence of the instance as a member of the class [27, 22]. Temporal conceptual data models can be encoded in various temporal description logics (TDLs), which have been designed and investigated since the seminal paper [24] with the aim of understanding the computational price of introducing a temporal dimension in DLs; see [21] for a recent survey. A general conclusion one can draw from the obtained results is that—as far as there is nontrivial interaction between the temporal and DL components—TDLs based on full-fledged DLs like ALC turn out to be too complex for effective reasoning (see the end of the introduction for details). The aim of this paper is to tailor ‘minimal’ TDLs that are capable of representing various aspects of TCMs and investigate their computational behaviour. First of all, as the DL component we choose the ‘light-weight’ DL-Lite logic Proc. 23rd Int. Workshop on Description Logics (DL2010), CEUR-WS 573, Waterloo, Canada, 2010.
A Method Comparison and Stressor-Response Experimental Study of Nitrogen and Phosphorus Impacts to Periphyton in Ozark Streams

Stream bioassessment is important for understanding algal-nutrient relationships and the development of scientifically defensible numeric nutrient criteria. However, multiple methods of periphyton data collection are currently used, and little is known about the comparability of resulting datasets. Literature also suggests other factors besides nutrients (i.e. variable grazing, light, and flow) can confound algal-nutrient relationships. A one-year method comparison study and 31-day algal biomass-nutrient manipulative experiment were conducted in the southern Ozarks of Arkansas. The method comparison study was implemented using two common bioassessment procedures (whole-surface and delimiter-reduced periphyton removal) to assess the potential for combining datasets. During the manipulative experiment, cobbles from the Buffalo River Watershed were exposed to a range of phosphorus (P) and nitrogen (N) concentrations during P-only and N + P enrichment periods to evaluate algal biomass responses using recirculating streamside mesocosms. Results of the method comparison study showed no statistical difference between bioassessment procedures for chlorophyll-a (chl-a) and ash-free dry mass (AFDM) (p = 0.123 and p = 0.550, respectively) or any interaction between method and season. Differences in chl-a and AFDM from both methods were detected (p < 0.001 and p = 0.012, respectively) when comparing warmer versus cooler seasons. Temperature-dependent grazing pressures were a potential explanation for the observed seasonal variability in biomass. The experiment revealed a positive linear relationship between benthic chl-a and increasing P and N addition up to 0.2 mg/L P (p < 0.001), with apparent N-limitation observed during the Ponly enrichment period. After 17 days of P-only enrichment, chl-a increased with increasing P concentrations (p < 0.001), ranging from 4.4 to 57.9 mg/m. After 14 additional days of N + P enrichment, mean chl-a had almost tripled across respective treatments, ranging from 13.3 to 171.1 mg/m. Results support the need for controlling N and P in freshwater systems to avoid excessive algal biomass accrual and provide insight into how possible increases in nutrient loading may influence the Buffalo River Watershed, disregarding confounding factors. Overall, both studies further scientific understanding of algal-nutrient relationships and verify the combining of both bioassessment methods for developing regional nutrient criteria and protecting stream designated uses.
Effect of blocking VEGF, hTERT and Bcl-xl by multiple shRNA expression vectors on the human laryngeal squamous carcinoma xenograft in nude mice

In our previous work, we constructed short hairpin RNA (shRNA) expression plasmids that targeted human telomerase reverse transcriptase (hTERT) messenger RNA, and we demonstrated that these vectors could inhibit the growth of cancer cells by 76.5% in vivo. In order to maximize the efficiency and versatility of the vector-based siRNA approach, here we have constructed multiple shRNA expression vectors that simultaneously targeted 3 different genes in cancer cells, and then investigated their effect on human laryngeal squamous carcinoma (Hep-2) in vivo. Materials and methods Short hairpin RNA expression vectors targeting the mRNA of VEGF, hTERT and Bcl-xl were constructed and subsequently transfected by direct injections into the tumors formed by Hep-2 cells implanted in nude mice. The expression of targeted genes as well as apoptosis of tumor cells were evaluated after treatment with multiple shRNA vectors or control vectors. Results We found that expression of multiple shRNAs led to a significant reduction in VEGF, hTERT and Bcl-xl RNA and protein expression. Tumor growth curves showed that those tumors treated with the shRNAs were obviously smaller than control, non-transfected tumors. Analysis at 14 days following the final injection showed a tumor inhibition ratio of 91.2%. However, the control shRNA vectors showed none of these effects. Conclusions Our results demonstrate that the application of vector-based RNAi technology that involves blocking multiple targets will be a promising therapeutic modality in the gene therapy of human cancers. The data strongly suggest that simultaneously blocking multiple genes in human cancers using an RNAi approach should be considered in cancer therapy.
Crises: the price of globalization?

Globalization was once believed to reduce the likelihood of widespread financial crises. Spectacular crises, however, have persisted despite widespread integration of economies, leaving observers to wonder whether crises will coexist with international integration. The author reviews the latest models of financial crises to understand how crises begin and how to contain them. He concludes not only that postcrisis policies are largely ineffective but also that crises will recur.
Augmented-Reality Scratch: A Tangible Programming Environment for Children

In this paper we introduce AR Scratch, the first augmented-reality (AR) authoring environment designed for children. By adding augmented-reality functionality to the Scratch programming platform, this environment allows pre-teens to create programs that mix real and virtual spaces. Children can display virtual objects on a real-world space seen through a camera, and they can control the virtual world through interactions between physical objects. This paper describes the system design process, which focused on appropriately presenting the AR technology to the typical Scratch population (children aged 8-12), as influenced by knowledge of child spatial cognition, programming expertise, and interaction metaphors. Evaluation of this environment is proposed, as well a s foreseeable impacts on the Scratch user community.
Design and GPGPU performance of Futhark's redomap construct

This paper presents and evaluates a novel second-order operator, named 'redomap', that stems from 'map'-'reduce' compositions in the context of the purely-functional array language Futhark, which is aimed at efficient GPGPU execution. Main contributions are: First, we demonstrate an aggressive fusion technique that is centered on the 'redomap' operator. Second, we present a compilation technique for 'redomap' that efficiently sequentializes the excess parallelism and ensures coalesced access to global memory, even for non-commutative 'reduce' operators. Third, a detailed performance evaluation shows that Futhark's automatically generated code matches or exceeds performance of hand-tuned Thrust code. Our evaluation infrastructure is publicly available and we encourage replication and verification of our results.