Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a Structural Determinant Necessary for the Localization and Function of Estrogen Receptor α at the Plasma Membrane

ABSTRACT Estrogen receptors (ER) have been localized to the cell plasma membrane (PM), where signal transduction mediates some estradiol (E2) actions. However, the precise structural features of ER that result in membrane localization have not been determined. We obtained a partial tryptic peptide/mass spectrometry analysis of membrane mouse ERα protein. Based on this, we substituted alanine for the determined serine at amino acid 522 within the E domain of wild-type (wt) ERα. Upon transfection in CHO cells, the S522A mutant ERα resulted in a 62% decrease in membrane receptor number and reduced colocalization with caveolin 1 relative to those with expression of wt ERα. E2 was significantly less effective in stimulating multiple rapid signals from the membranes of CHO cells expressing ERα S522A than from those of CHO cells expressing wt ERα. In contrast, nuclear receptor expression and transcriptional function were very similar. The S522A mutant was also 60% less effective than wt ERα in binding caveolin 1, which facilitates ER transport to the PM. All functions of ERα mutants with other S-to-A substitutions were comparable to those of wt ER, and deletion of the A/B or C domain had little consequence for membrane localization or function. Transfection of ERα S522A into breast cancer cells that express native ER downregulated E2 binding at the membrane, signaling to ERK, and G1/S cell cycle events and progression. However, there was no effect on the E2 transactivation of an ERE-luciferase reporter. In summary, serine 522 is necessary for the efficient translocation and function of ERα at the PM. The S522A mutant also serves as a dominant-negative construct, identifying important functions of E2 that originate from activating PM ER.
MARKET SEGMENTATION STRATEGIES OF MULTIPRODUCT FIRMS

We analyze a multiproduct duopoly and ask whether firms should offer general purpose products or tailor their offerings to fit specific consumer needs. Offering a targeted product has two effects: utility increases for some consumers due to increased fit, whereas utility decreases for others due to increased misfit. Previous work has not considered these two effects jointly and has therefore not been able to capture the tradeoff inherent inmarket segmentation.We show that in addition to the degree of fit andmisfit, the intensity of competition and the fixed cost of offering an additional product determine firms’ market segmentation strategies.
Visible and near infrared resonance plasmonic enhanced nanosecond laser optoporation of cancer cells

In this paper, we report a light driven, non-invasive cell membrane perforation technique based on the localized field amplification by a nanosecond pulsed laser near gold nanoparticles (AuNPs). The optoporation phenomena is investigated with pulses generated by a Nd:YAG laser for two wavelengths that are either in the visible (532 nm) or near infrared (NIR) (1064 nm). Here, the main objective is to compare on and off localized surface plasmonic resonance (LSPR) to introduce foreign material through the cell membrane using nanosecond laser pulses. The membrane permeability of human melanoma cells (MW278) has been successfully increased as shown by the intake of a fluorescent dye upon irradiation. The viability of this laser driven perforation method is evaluated by propidium iodide exclusion as well as MTT assay. Our results show that up to 25% of the cells are perforated with 532 nm pulses at 50 mJ/cm2 and around 30% of the cells are perforated with 1064 nm pulses at 1 J/cm2. With 532 nm pulses, the viability 2 h after treatment is 64% but it increases to 88% 72 h later. On the other hand, the irradiation with 1064 nm pulses leads to an improved 2 h viability of 81% and reaches 98% after 72 h. Scanning electron microscopy images show that the 5 pulses delivered during treatment induce changes in the AuNPs size distribution when irradiated by a 532 nm beam, while this distribution is barely affected when 1064 nm is used.
Emerging Contours of a New Internet World: Shifting Patterns of Adoption, Attitudes and Behaviour

The Internet is young and continues to be a space of rapid innovation, particularly in patterns of access and use. The cultures of the Internet might be more stable, since they are anchored in the values and attitudes of individuals for whom the Internet is but one, often minor, aspect of their everyday life and work. However, the last four decades of this ‘network of networks’ has seen dramatic changes in who has access to this and related information and communication technologies, and how people use and view these technologies. Globally, this paper provides a snapshot of the diffusion and use of the Internet that suggests the emergence of a ‘New Internet World’. We contrast the basic contours of the old and new Internet world that drove a set of research questions about cross-national differences in the values, attitudes, and behaviour of Internet users. Our global survey of users suggested four related themes that synthesize the empirical findings: a shifting centre of gravity in those who use the Internet; the rise of a global culture among Internet users; the reinforcement of core Internet values by users in rapidly developing nations; and the more innovative patterns of use within rapidly developing nations. Together, these trends provide a perspective on the development of a new Internet world, which we hope will trigger further research on these themes.
Adenosine Biosynthesis in the Collecting Duct

Adenosine regulates tubular transport in collecting ducts (CDs); however, the sources of adenosine that modulate ion transport in CDs are unknown. The extracellular cAMP-adenosine pathway refers to the conversion of cAMP to AMP by ectophosphodiesterase, followed by metabolism of AMP to adenosine by ecto-5′-nucleotidase, with all steps occurring in the extracellular compartment. The goal of this study was to assess whether the extracellular cAMP-adenosine pathway exists in CDs. Studies were conducted in both freshly isolated CDs and in CD cells in culture (first passage) that were derived from isolated CDs. Purity of CDs was confirmed by microscopy, by Western blotting for aquaporin-1, aquaporin-2, bumetanide-sensitive cotransporter type 1, and thiazide-sensitive cotransporter; and by reverse transcription-polymerase chain reaction for adenosine receptors. Both freshly isolated CDs and CD cells in culture converted exogenous cAMP to AMP and adenosine. In both freshly isolated CDs and CD cells in culture, conversion of cAMP to AMP and adenosine was affected by a broad-spectrum phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine), an ectophosphodiesterase inhibitor (1,3-dipropyl-8-p-sulfophenylxanthine), and a blocker of ecto-5′-nucleotidase (α,β-methylene-adenosine-5′-diphosphate) in a manner consistent with exogenous cAMP being processed by the extracellular cAMP-adenosine pathway. In CD cells in culture, stimulation of adenylyl cyclase increased extracellular concentrations of cAMP, AMP, and adenosine, and these changes were also modulated by the aforementioned inhibitors in a manner consistent with the extracellular cAMP-adenosine pathway. In conclusion, the extracellular cAMP-adenosine pathway is an important source of adenosine in CDs.
Strain Softening with Creep and Exponential Algorithm

A constitutive relation that can describe tensile strain softening with or without simultaneous creep and shrinkage is presented, and an efficient time-step numerical integration algorithm, called the exponential algorithm, is developed. Microcracking that causes strain softening is permitted to take place only within three orthogonal planes. This allows the description of strain softening by independent algebraic relations for each of three orthogonal directions, including independent unloading and reloading behavior. The strain due to strain softening is considered as additive to the strain due to creep, shrinkage and elastic deformation. The time-step formulas for numerical integration of strain softening are obtained by an exact solution of a first-order linear differential equation for stress, whose coefficients are assumed to be constant during the time step but may vary discontinuously between the steps. This algorithm is unconditionally stable and accurate even for very large time steps, and guarantees that the stress is always reduced exactly to zero as the normal tensile strain becomes very large. This algorithm, called exponential because its formulas involve exponential functions, may be combined with the well-known exponential algorithm for linear aging rate-type creep. The strain-softening model can satisfactorily represent the test data available in the literature.
University‐industry collaboration

Purpose – The paper aims to identify the requisite attributes and organisation to be displayed by a research university in order to engage successfully in collaborative research with industry partners.Design/methodology/approach – The conceptual framework contrasts the traditional public funding model against the requirements of the “triple helix” model of government‐university‐industry research funding. The framework supports the exploration of a case study of a long‐standing and successful joint research partnership, the Dundee‐Kinases Consortium, which links a world‐class life sciences research centre and a group of global pharmaceutical companies.Research limitations/implications – The case study provides a starting point, and additional case examinations will confirm the role of resource competences and organisational capabilities in facilitating performance by way of knowledge generation and transfer between partners.Findings – The design and leadership of the consortium achieves vital performance o.
Efficient Verification of Parameterized Cache Coherence Protocols

To address the state explosion problem of parameterized directory based cache protocol in model checking, we put forward the concept of pseudo-cutoff, a bound of the number of nodes which share the same memory block in this paper. Based on the analysis on inherent characteristics of parallel programs, we deduce the pseudo-cutoff value in relaxed consistency Cache-coherent non-uniform memory architecture (CC-NUMA) system under certain conditions. We optimize the state space of parameterized directory-based cache protocol effectively using pseudo-cutoff, and present a new scheme to small probability matter of wide sharing. Experiment results including different system scales show that, the method of protocol model optimization based on pseudo-cutoff could effectively reduce the state space of parameterized cache protocol, accelerates verification speed and improves the capability of verifying large scale Cache protocol.
A Self-occulting Accretion Disk in the SW Sextantis Star DW Ursae Majoris

We present the ultraviolet spectrum of the SW Sextantis star and nova-like variable DW Ursae Majoris in an optical low state, as observed with the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope (HST). The data are well described by a synthetic white dwarf (WD) spectrum with Teff = 46,000 ± 1000 K, log g = 7.60 ± 0.15, v sin i = 370 ± 100 km s-1, and Z/Z☉ = 0.47 ± 0.15. For this combination of Teff and log g, WD models predict MWD = 0.48 ± 0.06 M☉ and RWD = (1.27 ± 0.18) × 109 cm. Combining the radius estimate with the normalization of the spectral fit, we obtain a distance estimate of d = 830 ± 150 pc. During our observations, DW UMa was approximately 3 mag fainter in V than in the high state. A comparison of our low-state HST spectrum with a high-state spectrum obtained with the International Ultraviolet Explorer shows that the former is much bluer and has a higher continuum level shortward of 1450 Å. Since DW UMa is an eclipsing system, this suggests that an optically thick accretion disk rim blocks our view of the WD primary in the high state. If self-occulting accretion disks are common among the SW Sex stars, we can account for (1) the preference for high-inclination systems within the class and (2) their V-shaped continuum eclipses. Moreover, even though the emission lines produced by a self-obscured disk are generally still double-peaked, they are weaker and narrower than those produced by an unobscured disk. This may allow a secondary line emission mechanism to dominate and produce the single-peaked, optical lines that are a distinguishing characteristic of the SW Sex stars.
Noninvasive 64Cu-ATSM and PET/CT Assessment of Hypoxia in Rat Skeletal Muscles and Tendons During Muscle Contractions

The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer 64Cu-diacetyl bis(N4-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene expression of 2 hypoxia-related genes, hypoxia-inducible factor 1α (HIF1α) and carbonic anhydrase III (CAIII). Methods: Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, 64Cu-ATSM was injected and contractions were continued for 20 min. PET/CT of both hind limbs was performed immediately and 1 h after the contractions. The exercise group (n = 8) performed only muscle contractions as described, whereas the other group, exercise plus cuff (n = 8), in addition underwent cuff-induced hypoxia during the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1α and CAIII using real-time polymerase chain reaction. Results: Immediately after the contractions, uptake of 64Cu-ATSM was significantly increased, by approximately 1.5-fold in muscles and 1.3-fold in tendons, compared with resting conditions. The significant increase was maintained in late PET scans in stimulated muscles and tendons independently of cuff application. In muscles, SUV correlated significantly with gene expression of HIF1α and CAIII, whereas this coherence was not found in tendons. Conclusion: We found enhanced uptake of 64Cu-ATSM in both early and late PET scans, thereby supporting the possibility that 64Cu-ATSM registers exercise-induced transient hypoxia in both skeletal muscles and force-transmitting tendons. The fact that skeletal muscles but not tendons showed upregulation of HIF1α and CAIII could indicate that healthy tendons are less responsive than skeletal muscles to low levels of oxygen.
Status Update

How does the ideology of the digital economy shape the attitudes and experiences of people in the tech world? Based on her ob servation that software companies value profits over political change, former Microsoft researcher and dot-com employee Alice Marwick investigates this question in Status Update: Celebrity, Publicity, and Branding in the Social Media Age , an ethnography of the mid-2000s San Francisco tech scene. Researched at a time when pundits like Time ’s Lev Grossman (2006) declared “You” as the magazine’s “Person of the Year” and prophesized that platforms such as YouTube, Wikipedia, and MySpace were going to “change the world” (see also Benkler, 2006; Shirky, 2008; Tapscott & Williams, 2006), Marwick’s book attempts to clean up the “idealistic cyber drool of the digerati” (Terranova, 2000, p. 44) by providing a more sober account of the critical implications of this so-called social media (Aronczyk, 2014). Combining informant interviews with Twitter’s “micro-celebrities” and participant observations from a seemingly endless number of industry meet-ups, drink ups, and star-studded conferences, Marwick constructs social media as a neoliberal technology of subjectivity that produces social status as the ultimate commodity. Focusing specifi cally on the San Francisco based Twitter as a vital piece of industry infrastructure that facilitates this practice, Marwick argues that the logic of marketing and advertising embedded in social software has infiltrated the ways in which we relate to ourselves and to others, teaching us how to be good corporate citizens along the way. In this nar rative, Marwick’s “characters” are ideal neoliberal subjects. They are young and child less, highly entrepreneurial, and justify consumption only when done in the name of self-improvement or work. They tout the techno-utopian party line of the neighbour ing Silicon Valley, which positions social media as a great equalizer destined to “change the world” (“into one where they’re rich,” quips one of her insiders). While Marwick’s argument that the commercial imperatives of social media are eclipsing its democratic potential is hardly news for critics of the information society and the Internet (Dean, 2009; Garnham, 2004; McChesney, 2013; Schiller, 1999; Webster, 2006), her micro-perspective from the lifeworlds of workers skillfully con structs the San Francisco tech scene as a puzzling set of contradictions. The idealistic techno-libertarianism of Web 2.0, for example, emerges from a peculiar West Coast combination of radical activism and business culture that endorses creativity and re bellion so long as they are profitable. Industry perspectives regarding digital social climbing are similarly perplexing. While many of Marwick’s characters feign a blase attitude or express disdain toward those who take Twitter seriously or use it to self-promote, she keenly observes that most are hyper-vigilant about their own Twitter metrics—such as number of followers, retweets, and mentions—in order to evaluate and display their own level of prestige, in
The hippocampus operates in a threshold manner during spatial source memory

Long-term memory can be based on general familiarity or detailed recollection. Although familiarity is thought to be a continuous/graded process, the nature of recollection is currently under debate. In the present functional MRI spatial source memory study, we evaluated the pattern of activity in the hippocampus to assess whether this region operates in a threshold/all-or-none or a continuous manner during recollection. During the study phase, abstract shapes were presented to the left or right of fixation. During the test phase, old and new shapes were presented at fixation, and participants classified each shape as old-left, old-right, or new, followed by a sure–unsure confidence rating. Accurate spatial memory for old-left shapes produced a single activation in the left hippocampus. The corresponding event-related activation profile revealed a threshold above which old-left-sure responses produced positive activity for old-left but not old-right shapes. This hippocampal activation profile was used to generate a source memory receiver operating characteristic that was adequately fit by a threshold model of recollection but was not adequately fit by a continuous model of recollection. By contrast, there was no evidence of a threshold in the behavioral response profile, which is consistent with previous behavioral source memory receiver operating characteristic results indicating that recollection is a continuous process. The present results indicate that the hippocampus can operate in a threshold manner during spatial source memory and further suggest that this discrete signal is transformed into a continuous process through the operation of other brain regions that also contribute to behavioral performance.
The Tenuous Trade‐off between Risk and Incentives

Empirical work testing for a negative trade‐off between risk and incentives has not had much success: the data suggest a positive relationship between measures of uncertainty and incentives rather than the posited negative trade‐off. I argue that the existing literature fails to account for an important effect of uncertainty on incentives through the allocation of responsibility to employees. When workers operate in certain settings, firms are content to assign tasks to workers and monitor their inputs. By contrast, when the situation is more uncertain, they delegate responsibility to workers but, to constrain their discretion, base compensation on observed output.
Denotational abstract interpretation of logic programs

Logic-programming languages are based on a principle of separation “logic” and “control. ”. This means that they can be given simple model-theoretic semantics without regard to any particular execution mechanism (or proof procedure, viewing execution as theorem proving). Although the separation is desirable from a semantical point of view, it makes sound, efficient implementation of logic-programming languages difficult. The lack of “control information” in programs calls for complex data-flow analysis techniques to guide execution. Since data-flow analysis furthermore finds extensive use in error-finding and transformation tools, there is a need for a simple and powerful theory of data-flow analysis of logic programs. This paper offers such a theory, based on F. Nielson's extension of P. Cousot and R. Cousot's abstract interpretation. We present a denotational definition of the semantics of definite logic programs. This definition is of interest in its own right because of its compactness. Stepwise we develop the definition into a generic data-flow analysis that encompasses a large class of data-flow analyses based on the SLD execution model. We exemplify one instance of the definition by developing a provably correct groundness analysis to predict how variables may be bound to ground terms during execution. We also discuss implementation issues and related work.
Influence of Different Forest System Management Practices on Leaf Litter Decomposition Rates, Nutrient Dynamics and the Activity of Ligninolytic Enzymes: A Case Study from Central European Forests

Leaf litter decomposition is the key ecological process that determines the sustainability of managed forest ecosystems, however very few studies hitherto have investigated this process with respect to silvicultural management practices. The aims of the present study were to investigate the effects of forest management practices on leaf litter decomposition rates, nutrient dynamics (C, N, Mg, K, Ca, P) and the activity of ligninolytic enzymes. We approached these questions using a 473 day long litterbag experiment. We found that age-class beech and spruce forests (high forest management intensity) had significantly higher decomposition rates and nutrient release (most nutrients) than unmanaged deciduous forest reserves (P<0.05). The site with near-to-nature forest management (low forest management intensity) exhibited no significant differences in litter decomposition rate, C release, lignin decomposition, and C/N, lignin/N and ligninolytic enzyme patterns compared to the unmanaged deciduous forest reserves, but most nutrient dynamics examined in this study were significantly faster under such near-to-nature forest management practices. Analyzing the activities of ligninolytic enzymes provided evidence that different forest system management practices affect litter decomposition by changing microbial enzyme activities, at least over the investigated time frame of 473 days (laccase, P<0.0001; manganese peroxidase (MnP), P = 0.0260). Our results also indicate that lignin decomposition is the rate limiting step in leaf litter decomposition and that MnP is one of the key oxidative enzymes of litter degradation. We demonstrate here that forest system management practices can significantly affect important ecological processes and services such as decomposition and nutrient cycling.