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Potassium channels play a crucial role in the physiology of all living organisms. They maintain the membrane potential and are involved in electrical signaling, pH homeostasis, cell-cell communication and survival under osmotic stress. Many prokaryotic potassium channels and members of the eukaryotic Slo channels are regulated by tethered cytoplasmic domains or associated soluble proteins, which belong to the family of regulator of potassium conductance (RCK). RCK domains and subunits form octameric rings, which control ion gating. For years, a common regulatory mechanism was suggested: ligand-induced conformational changes in the octameric ring would pull open a gate in the pore via flexible linkers. Consistently, ligand-dependent conformational changes were described for various RCK gating rings. Yet, recent structural and functional data of complete ion channels uncovered that the following signal transduction to the pore domains is divers. The different RCK-regulated ion channels show remarkably heterogeneous mechanisms with neither the connection from the RCK domain to the pore nor the gate being conserved. Some channels even lack the flexible linkers, while in others the gate cannot easily be assigned. In this review we compare available structures of RCK-gated potassium channels, highlight the similarities and differences of channel gating, and delineate existing inconsistencies. [ABSTRACT FROM AUTHOR]

This paper addresses the (inter)subjective functions of progressive aspect in Dutch. While the aspectual profile of the various Dutch progressive constructions has received considerable attention in the last few years, much less attention has been paid to their non-aspectual uses. As we will demonstrate in this paper on the basis of a corpus study of spoken Dutch, complemented with native-speaker elicitations, the Dutch progressive constructions can be specifically recruited to express (inter)subjective meanings such as surprise, irritation and intensity, and they differ in this respect from their simplex counterparts. Our analysis of progressive aspect in terms of backgrounded boundaries provides an explanation for (i) the general association of progressive aspect with (inter)subjectivity and (ii) our observation that some Dutch progressive constructions are more prone to such (inter)subjective exploitation than others. This semantic account also underlies the last part of this contribution, in which we discuss cases of what we call "(inter)subjective reinforcement" in complex progressive constructions, that is, the embedding of progressive constructions in other constructions that are also semantically affiliated to (inter)subjectivity (e.g. the perfect, gaan/komen 'go/come', modals and the bare infinitive construction), which has been largely neglected in the literature. [ABSTRACT FROM AUTHOR]

Twenty years ago, »homosexuality« was only disputed by Rabbis and their scholars, but today LGBT-people are part of daily Jewish life, even in some orthodox communities. Despite the fact that modern Zionism and the sexual reform movement were founded at almost the same time, the two parties were, for many decades, never in accordance. Apparently neither male nor female »sexual in-betweens« fitted into a modern Zionistic culture or orthodox communities. This changed in 1980s due to HIV/AIDS and the success of sexual reform movements in the Western world. Today, the difference between rich and poor seems to be much more important than the question of hetero- or homosexuality. [ABSTRACT FROM AUTHOR]

Genome-wide sequencing enables evaluation of associations between traits and combinations of variants in genes and pathways. But such evaluation requires multi-locus association tests with good power, regardless of the variant and trait characteristics. And since analyzing families may yield more power than analyzing unrelated individuals, we need multi-locus tests applicable to both related and unrelated individuals. Here we describe such tests, and we introduce SKAT-X, a new test statistic that uses genome-wide data obtained from related or unrelated subjects to optimize power for the specific data at hand. Simulations show that: a) SKAT-X performs well regardless of variant and trait characteristics; and b) for binary traits, analyzing affected relatives brings more power than analyzing unrelated individuals, consistent with previous findings for single-locus tests. We illustrate the methods by application to rare unclassified missense variants in the tumor suppressor gene BRCA2, as applied to combined data from prostate cancer families and unrelated prostate cancer cases and controls in the Multi-ethnic Cohort (MEC). The methods can be implemented using open-source code for public use as the R-package GATARS (Genetic Association Tests for Arbitrarily Related Subjects) . [ABSTRACT FROM AUTHOR]

This paper explores a counter-weight to anti-democratic trends suggested by civil society theory: mediating structures (also known as 'intermediate' or 'intermediary' organizations). We look briefly at the range of ways in which the concept has been used in social science and then focus on literature which employs the concept specifically in the context of debates about sustainable democracy We discern from the theoretical literature four distinct functions said to be performed in democracies by mediating structures and we offer case examples of organizations which perform those functions in the contemporary real world. We conclude by providing pointers to how mediating structures might be identified, supported and sustained in the face of anti-democratic trends today. [ABSTRACT FROM AUTHOR]

Gas holdup is one of the most important parameters for characterizing the hydrodynamics of bubble columns. Modeling and design of bubble columns require empirical correlations for precise estimation of gas holdup. Empirical correlations available for prediction of gas holdup (εG) in various non-Newtonian systems for both gas-liquid and gas-liquid-solid bubble columns have been presented in this review. Critical analysis of correlations presented by different researchers has been made considering the findings and pitfalls. As the magnitude of gas holdup depends on many factors, such as physicochemical properties of gas and/or liquid, column geometry, type and design of gas distributors, operating conditions, phase properties, and rheological properties, etc., all of these have been discussed and examined. In order to emphasize the significance, relative importance of parameters such as flow behavior index, consistency index, column diameter, gas flow rate, and density of aqueous carboxymethylcellulose (CMC) solution on gas holdup has been quantified using artificial neural network and Garson's algorithm for an experimental data set of air-CMC solution from the literature. Besides, potential areas for research encompassing operating conditions, column geometry, physical properties, modeling and simulation, rheological properties, flow regime, etc., have been underlined, and the need for developing newer correlations for gas holdup has been outlined. The review may be useful for the modeling and design of bubble columns. [ABSTRACT FROM AUTHOR]

Jacques Derrida beschäftigte sich zeitlebens mit den Fragenstellungen politischer Theologie, wie nicht nur anhand seiner späten Monographie zu Carl Schmitt ersichtlich wird. Auch in seinen stärker unmittelbar politischen Ausführungen spielen diese Überlegungen eine zentrale Rolle. Der Aufsatz stellt die Schmitt-Rezeption und -Kritik Jacques Derridas dar, und wie sich diese Auseinandersetzung im Gerechtigkeitsbegriff niederschlägt, der für das Spätwerk dieselbe Bedeutung erlangt wie die différance für die Frühphase. Die Grundthese dabei lautet, dass die explizite Hinwendung zu Carl Schmitt der theoretischen Konstruktion Derridas und ihren Widersprüchen geschuldet ist, wie sie zugleich jene mythischen Lösungsversuche zeitigte, von denen nicht zuletzt der Gerechtigkeitsbegriff Auskunft gibt. As demonstrated not only by his late monograph on Carl Schmitt, Jacques Derrida grappled with issues of political theology throughout his career. These considerations played a crucial role even in his more directly political statements. In this essay, I discuss Derrida's reception and critique of Carl Schmitt and the imprint it left on his concept of justice, a concept, which was as significant to his later work as the concept of différance was to his earlier endeavours. My basic contention is that Derrida's explicit recourse to Carl Schmitt sprang from his theoretical framework and the contradictions within it. Conversely, it generated the mythological prescriptions, which are evident, not least, in his concept of justice. [ABSTRACT FROM AUTHOR]

The article problematises the current study of pre-modern 'religious choice' and 'religious diversity' by confronting sociological and historical perspectives. A first part analyses current sociological theories of decision-making, which have typically viewed individual religious choices as an innovation of the modern period, and imagined the European Middle Ages as a stark contrast, a "unified Christian culture" (Ernst Troeltsch) without much potential for substantial individual decision-making in religiosis. The article argues that this not only overlooks many instances of religious plurality in the medieval Euro-Mediterranean, but also the high diversity within Christianity. High medieval laypeople were confronted with a growing diversity of innovative religious lifestyles, such as monastic orders or lay religious movements, which were typically framed as legitimate 'options' within Christianity. While some of these options were then hereticised and persecuted, thus reconstituting religious choices as decisions between mutually exclusive 'alternatives', this transformation encountered much protest and resistance. As the case of protest against the inquisition in Bologna in 1299 shows, laypeople often refused to accept the strict boundaries the inquisition wanted them to draw. As the article argues, we should therefore turn the sociological model upside down and look to qualitative rather than quantitative transformations: rather than searching for the 'origins' of religious diversity, plurality or pragmatic tolerance, which were ultimately already present in various forms during the Middle Ages, we might rather focus on the episodic emergence of cultures of decision-making which prescribed mutually exclusive alternatives of truth and error, and therefore enabled persecution. [ABSTRACT FROM AUTHOR]

High-resolution low-temperature X-ray diffraction experiments for doxycycline monohydrate and hydrochloride dihydrate have been performed. Translation-Libration-Screw (TLS) analysis for both crystal forms as well as the data from neutron diffraction experiment for hydrochloride combined with the Hansen-Coppens formalism resulted in precise charge density distribution models for both the zwitterionic monohydrate and a protonated hydrochloride crystal forms. Their detailed topological analysis suggested that the electron structure of doxycycline's amide moiety undergoes significant changes during protonation due to formation of a very strong resonance-assisted hydrogen bond. A notably increased participation of amide nitrogen atom and hydrogen-accepting oxygen atom in the resonance upon doxycycline protonation was observed. A comparison of TLS- and neutron data-derived hydrogen parameters confirmed the experimental neutron data to be vital for proper description of intra- and inter-molecular interactions in this compound. Finally, calculated lattice and interaction energies quantified repulsive Dox-Dox interactions in the protonated crystal form of the antibiotic, relating with a good solubility of doxycycline hydrochloride relative to its hydrate. [ABSTRACT FROM AUTHOR]

Among the fragments of Saint Pachomius edited by Louis T. Lefort there is one that is mirrored in the apophthegmatic tradition in various ways, in terms of language and region (Coptic, Greek, Latin, Ethiopic, and Armenian) as well as in terms of variations in the text itself. It is indeed also part of the Meterikon and there attributed to Melania. It seems that the original form of the saying belongs to Pachomius (in spite of some doubts raised by Samuel Rubenson concerning the quest for the original apophthegms in general), and that it was later adapted to the anchoretic milieu. It has then been enlarged and has been transmitted in both the shorter (Coptic, Greek, Latin, the Meterikon) and the longer version (Greek, Ethiopic, Armenian, and also the Meterikon). While most of the Sayings of the Desert Fathers can be traced down only to the 6th century, when the larger collections were written in Palestine, we have in this case the rare opportunity of following an apophthegm up to its original source, and we know the speaker. [ABSTRACT FROM AUTHOR]

A major feature of Alzheimer's disease (AD) pathology is the plaque composed of aggregated amyloid-β (Aβ) peptide. Although these plaques may have harmful properties, there is much evidence to implicate soluble oligomeric Aβ as the primary noxious form. Aβ oligomers can be generated both extracellularly and intracellularly. Aβ is toxic to neurons in a myriad of ways. It can cause pore formation resulting in the leakage of ions, disruption of cellular calcium balance, and loss of membrane potential. It can promote apoptosis, cause synaptic loss, and disrupt the cytoskeleton. Current treatments for AD are limited and palliative. Much research and effort is being devoted to reducing Aβ production as an approach to slowing or preventing the development of AD. Aβ formation results from the amyloidogenic cleavage of human amyloid precursor protein (APP). Reconfiguring this process to disfavor amyloid generation might be possible through the reduction of APP or inhibition of enzymes that convert the precursor protein to amyloid. [ABSTRACT FROM AUTHOR]

The reactivity of N-2-(2-aminobenzoyl)-N-phenylhydrazinecarbothioamide (1) as an electron donor toward several electron-accepting compounds through electron donor-acceptor interaction has been studied. Thus, upon treatment of 1 with either 1,4-naphthoquinone, 2-dicyanomethyleneindan-1,3-dione, or 2,3-dichloro-1,4-naphthoquinone, the reaction proceeds to give thiadiazino[5,4-b]quinazoline, N-phenylcarbamohydrazonothioate, and thiadiazine-5,10-dione, respectively. Also, the reactivity of compound 1 toward some aldehydes and anhydrides was studied. The products were fully characterized by their spectral data. The mechanisms of formation of the products have been rationalized. [ABSTRACT FROM AUTHOR]

FK506-binding proteins (FKBPs) belong to a distinct class of immunophilins that interact with immunosuppressants. They use their peptidyl-prolyl isomerase (PPIase) activity to catalyze the cis-trans conversion of prolyl bonds in proteins during protein-folding events. FKBPs also act as a unique group of chaperones. The Drosophila melanogaster peptidyl-prolyl cis-trans isomerase FK506-binding protein of 39 kDa (FKBP39) is thought to act as a transcriptional modulator of gene expression in 20-hydroxyecdysone and juvenile hormone signal transduction. The aim of this study was to analyze the molecular determinants responsible for the subcellular distribution of an FKBP39-yellow fluorescent protein (YFP) fusion construct (YFP-FKBP39). We found that YFPFKBP39 was predominantly nucleolar. To identify the nuclear localization signal (NLS), a series of YFP-tagged FKBP39 deletion mutants were prepared and examined in vivo. The identified NLS signal is located in a basic domain. Detailed mutagenesis studies revealed that residues K188 and K191 are crucial for the nuclear targeting of FKBP39 and its nucleoplasmin-like (NPL) domain contains the sequence that controls the nucleolar-specific translocation of the protein. These results show that FKBP39 possesses a specific NLS in close proximity to a putative helix-turn-helix (HTH) motif and FKBP39 may bind DNA in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Background: Refined encapsulation approaches in dermatotherapy gain increased interest. There is need of reproducible in vitro systems representing disease features to screen drug delivery systems for preclinical assessment. Inflammatory human skin diseases are commonly accompanied by abnormal epidermal differentiation and barrier impairment. Serine proteases (SPs) and their inhibitors play a critical role in such dysfunctional differentiation. SPs also initiate cellular pathways via activation of protease-activated receptors, which contribute to inflammation. Thus, function and activity of SPs should be considered for the design of new therapies of such disorders. Objectives: Herein, we established a novel simplified cell culture model, based on SP-mediated inflammation suitable to assess nanocarriers loaded with anti-inflammatory drugs. Methods: SP-mediated inflammation and the regulatory effect of free or encapsulated dexamethasone were determined by measuring interleukin-6 and interleukin-8 in culture medium of HaCaT (human adult low calcium temperature)-keratinocytes. Additionally, radical formation was analyzed by electron paramagnetic resonance spectroscopy. Cellular uptake of core-multishell nanocarriers was investigated by fluorescence microscopy. Cytotoxicity of all additives was determined by a viability assay. Results: SP-Stimulation of keratinocytes resulted in increased radical production and release of inflammatory cytokines without affecting cell viability. Induced inflammation was successfully downregulated by addition of free or encapsulated dexamethasone. Conclusion: SP-addition can be used as inflammatory stimulus in cell culture to mimic effects of aberrant enzymatic activities found in skin of atopic dermatitis patients. The set-up is appropriate as a preliminary test to examine the effectiveness of new molecules or delivery-systems to counteract serine protease-mediated inflammatory processes prior to skin studies. [ABSTRACT FROM AUTHOR]

This article discusses one item found in the colophons of medieval Hebrew manuscripts copied in Ashkenaz. Some opening and closing scribal formulas were found to be typical of the various cultural expanses of the Jewish world. Here we survey the Hebrew colophons for the closing formula at the end of the copying: » עד שיעלה חמור בסולם « (»until a donkey will go up the ladder«), a formula we found in 228 manuscripts, of which 130 are from Ashkenaz (including the Provence in France) making up over half (57%) of the total manuscripts copied in this area. The rich imagination of the scribes wrought a few changes to the basic formula - not only a donkey »up the ladder« but also other animals and other objects. This formula, which first appears in a thirteenth century manuscript, is tracked in this article up until the middle of the 16th century. We discuss the origin of the formula, whether it is from Jewish or universal cultural sources. »The donkey formula« was used not only in colophons but in Hebrew literary sources as well. The question is whether the scribe used the formula in jest or to express a wish that »nothing bad should happen to him« since »never« will a donkey go up a ladder. There is no definite answer. The formula has spread from Ashkenazic culture to other areas, including Italy, Spain, Byzantium and the Middle East. [ABSTRACT FROM AUTHOR]

In this paper, we subject to closer scrutiny one particularly influential recent argument in favour of the long-movement analysis of tough-constructions. Hartman (2011, 2012a, 2012b) discovered that experiencer PPs lead to ungrammaticality in tough-constructions, but not in expletive constructions. He attributes this ungrammaticality to defective intervention of A-movement, a movement step crucially postulated only in the long-movement analysis. He takes this as evidence that tough-constructions are derived via long movement. We make the novel observation that a PP intervention effect analogous to that in tough-constructions also arises in constructions that do not involve A-movement, namely pretty-predicate constructions and gapped degree phrases. Consequently, the intervention effect does not provide an argument for an A-movement step in tough-constructions or for the long-movement analysis, but rather for the base-generation analysis. We develop a uniform account of the intervention effects as a semantic-type mismatch. In particular, we propose that what unifies tough-constructions, pretty-predicate constructions, and gapped degree phrases is that they all have an embedded clause that is a null-operator structure. Introducing an experiencer PP into these constructions creates an irresolvable semantic-type mismatch. As such, we argue for a reassessment of what appears to be a syntactic locality constraint as an incompatibility in the semantic composition. [ABSTRACT FROM AUTHOR]

Piezoelectric microelectromechanical systems (PiezoMEMS) are attractive for developing next generation self-powered microsystems. PiezoMEMS promises to eliminate the costly assembly for microsensors/microsystems and provide various mechanisms for recharging the batteries, thereby, moving us closer towards batteryless wireless sensors systems and networks. In order to achieve practical implementation of this technology, a fully assembled energy harvester on the order of a quarter size dollar coin (diameter = 24.26 mm, thickness = 1.75 mm) should be able to generate about 100 µW continuous power from low frequency ambient vibrations (below 100 Hz). This paper reviews the state-of-the-art in microscale piezoelectric energy harvesting, summarizing key metrics such as power density and bandwidth of reported structures at low frequency input. This paper also describes the recent advancements in piezoelectric materials and resonator structures. Epitaxial growth and grain texturing of piezoelectric materials is being developed to achieve much higher energy conversion efficiency. For embedded medical systems, lead-free piezoelectric thin films are being developed and MEMS processes for these new classes of materials are being investigated. Nonlinear resonating beams for wide bandwidth resonance are also reviewed as they would enable wide bandwidth and low frequency operation of energy harvesters. Particle/granule spray deposition techniques such as aerosol-deposition (AD) and granule spray in vacuum (GSV) are being matured to realize the meso-scale structures in a rapid manner. Another important element of an energy harvester is a power management circuit, which should maximize the net energy harvested. Towards this objective, it is essential for the power management circuit of a small-scale energy harvester to dissipate minimal power, and thus it requires special circuit design techniques and a simple maximum power point tracking scheme. Overall, the progress made by the research and industrial community has brought the energy harvesting technology closer to the practical applications in near future. [ABSTRACT FROM AUTHOR]

The development of a semi-permeable cytoplasmic membrane was a key event in the evolution of microbial proto-cells. As a result, changes in the external osmolarity will inevitably trigger water fluxes along the osmotic gradient. The ensuing osmotic stress has consequences for the magnitude of turgor and will negatively impact cell growth and integrity. No microorganism can actively pump water across the cytoplasmic membrane; hence, microorganisms have to actively adjust the osmotic potential of their cytoplasm to scale and direct water fluxes in order to prevent dehydration or rupture. They will accumulate ions and physiologically compliant organic osmolytes, the compatible solutes, when they face hyperosmotic conditions to retain cell water, and they rapidly expel these compounds through the transient opening of mechanosensitive channels to curb water efflux when exposed to hypo-osmotic circumstances. Here, we provide an overview on the salient features of the osmostress response systems of the ubiquitously distributed bacterium Bacillus subtilis with a special emphasis on the transport systems and channels mediating regulation of cellular hydration and turgor under fluctuating osmotic conditions. The uptake of osmostress protectants via the Opu family of transporters, systems of central importance for the management of osmotic stress by B. subtilis, will be particularly highlighted. [ABSTRACT FROM AUTHOR]

A unicellular marine diatom, Entomoneis sp. MMOGRB 0374S, was isolated as a candidate strain for high production of a polyunsaturated fatty acid (PUFA), arachidonic acid (ARA, 20:4ω6). Its morphological characters were typical for representatives of the genus Entomoneis, e.g. junction line, sigmoid keel and panduriform girdle view. This species was differentiated from other Entomoneis species by its smaller size and denser stria. Phylogenetically, it was distinct from other taxa with a long branch. This relationship was also emphasized by only 94% nucleotide similarity between Entomoneis sp. MMOGRB 0374S and other related species. The biomass concentration reached 182 mg l- 1 at the stationary phase and 229 mg l- 1 after 3 days of nitrogen-limited culture. Lipids were extracted using four methods, and the dichloromethane (DCM) /methanol method was the most effective, yielding 36% of dry biomass at the stationary phase and 40% after 3 days of nitrogen-free culture. Gas chromatography revealed 17 types of fatty acids. ARA was the major component of PUFA and represented between 16% and 19% of the total fatty acids using the four lipid extraction methods, among which DCM/methanol yielded the highest proportion of ARA. Considering the yields of both total lipids and ARA, the DCM/methanol method was the most effective for ARA extraction. [ABSTRACT FROM AUTHOR]

Stroke is a major reason for disability and the second highest cause of death in the world. When a patient is admitted to a hospital, it is necessary to identify the type of stroke, and the likelihood for development of a recurrent stroke, vascular dementia, and depression. These factors could be determined using different biomarkers. Metabolomics is a very promising strategy for identification of biomarkers. The advantage of metabolomics, in contrast to other analytical techniques, resides in providing low molecular weight metabolite profiles, rather than individual molecule profiles. Technically, this approach is based on mass spectrometry and nuclear magnetic resonance. Furthermore, variations in metabolite concentrations during brain ischemia could alter the principal neuronal functions. Different markers associated with ischemic stroke in the brain have been identified including those contributing to risk, acute onset, and severity of this pathology. In the brain, experimental studies using the ischemia/reperfusion model (IRI) have shown an impaired energy and amino acid metabolism and confirmed their principal roles. Literature data provide a good basis for identifying markers of ischemic stroke and hemorrhagic stroke and understanding metabolic mechanisms of these diseases. This opens an avenue for the successful use of identified markers along with metabolomics technologies to develop fast and reliable diagnostic tools for ischemic and hemorrhagic stroke., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

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Chemical modifications of DNA comprise epigenetic mechanisms that contribute to the maintenance of cellular activities and memory. Although the function of 5-methylcytosine (5-mC) has been extensively studied, little is known about the function(s) of relatively rarer and underappreciated cytosine modifications including 5-hydroxymethylcytosine (5-hmC). The discovery that ten-eleven translocation (Tet) proteins mediate conversion of 5-mC to 5-hmC, and other oxidation derivatives, sparked renewed interest to understand the biological role of 5-hmC. Studies examining total 5-hmC levels revealed the highly dynamic yet tissue-specific nature of this modification, implicating a role in epigenetic regulation and development. Intriguingly, 5-hmC levels are highest during early development and in the brain where abnormal patterns of 5-hmC have been observed in disease conditions. Thus, 5-hmC adds to the growing list of epigenetic modifications with potential utility in clinical applications and warrants further investigation. This review discusses the emerging functional roles of 5-hmC in normal and disease states, focusing primarily on insights provided by recent studies exploring the genome-wide distribution of this modification in mammals. [ABSTRACT FROM AUTHOR]

In this paper, we propose a reassessment of Wolof noun morphology and morphosyntax. Wolof is usually said to possess a total of 10 noun classes (8 for the singular, 2 for the plural), marked today exclusively on agreement targets. We provide evidence that two more plural noun classes must be recognized, which have so far been misinterpreted as 'collective' rather than plural: the evidence we provide is morphosyntactic (from verb agreement) as well as morphological (from class-related asymmetries in the paradigm of the indefinite article). As for method, the main thrust of the paper consists in showing that an accurate analysis of the Wolof data must make use of the three distinct notions 'noun class', 'inflectional class' and 'agreement class' (or gender). Under the analysis defended here, Wolof turns out to have a fairly complex gender system, featuring 17 distinct gender values. Our analysis - and especially the discussion of Wolof so-called 'collectives' - also bears on the general theoretical issue of how to establish the values of the number category. [ABSTRACT FROM AUTHOR]

The mixing of magmas of distinct temperature, bulk composition, mineralogy, and physical properties plays a central role in explaining the diversity of magma types on Earth and in explaining the growth of continental and oceanic crust. Magma mixing is also of practical importance. For example, the mixing of distinct magmas has been cited as an important process in creation of economically important horizons in layered intrusions as well as a triggering mechanism for initiation of volcanic eruptions. The motivation for better quantifying the dynamics and thermodynamics of magma mixing and its attendant plutonic and volcanic products is clear. The degree of magma mixing, which spans a continuum from mingling to complete hybridization, depends upon initial and boundary conditions, magma properties, driving forces, and time available for mixing. Magma mingling produces a heterogeneous mixture of discrete clumps of the end-member magmas, whereas complete hybridization involves the thermodynamic equilibration of two distinct magmas to form a third. Qualitatively, mixing occurs via reduction in the size of compositional heterogeneities (i.e., clumps) through stretching and folding by viscous flow, followed by homogenization, once shear has reduced the size of compositional anomalies to diffusive length scales. Quantification of this process relies on two statistical measures: the linear scale of segregation (Λ) defined as the spatial integral of the compositional correlation function related to the size-distribution of the segregated clumps within the mixture, and the intensity of segregation (I) a measure that quantifies how much the composition at each location differs from the average. The mixing dynamics of a layered system are analyzed in terms of the parameters governing mixing (Rayleigh, Lewis, and buoyancy numbers and viscosity ratio) to estimate how the timescale for magma hybridization, tH, compares to solidification, recharge, diffusive, and assimilation timescales. This analysis illustrates that hybridization times can be shorter than or comparable to thermal, solidification, and replenishment timescales; thus, formation of hybridized or nearly hybridized magmas is one anticipated outcome of mixing. The machinery of thermodynamics can be used to compute the hybrid magma state. An exploratory model for the thermochemistry of hybridization is developed based on binary eutectic phase relations and thermodynamics. Eight thermodynamic parameters define the phase diagram and associated energetics, and six parameters (initial temperatures, compositions, mass ratio of mixing magmas, and an enthalpy parameter) are necessary and sufficient to determine the state of hybrid magma uniquely. While relevant combinations of 14 thermodynamic and mixing parameters might suggest that the number of mixing outcomes (i.e., products) is too high to systematize, Monte Carlo simulations using the exploratory model document how millions of arbitrary initial states evolve into five possible final (mixed) states. Such an analysis implies that a magma mixing taxonomy that defines possible mixed product states can be developed and tied to petrologic indicators of mixing. Additional insights gained from this exploratory model that are supported by independent results from a multicomponent, multiphase thermodynamic model of magma mixing (Magma Chamber Simulator) include: (1) the proclivity of invariant point hybrid states, which may explain some instances of compositionally monotonous melts associated with mixed magma eruptions; (2) a surprising thermal effect such that the temperature of hybridized magma can be significantly less than the initial temperature of either of the mixing magmas. This type of magma mixing may result in crystal resorption, thus invalidating an assumption that resorption textures in crystals are typically the result of a magma heating event; (3) illustration of the differing effects of stoped block temperature and composition on hybrid magma temperature and phase state; and (4) illustration of a cessation of crystallization effect that may pertain to the MORB pyroxene "paradox." Differences between adiabatic or R-hybridization and diabatic or RFC-hybridization are also explored. The model can be used to elucidate the thermodynamic principles underlying magma mixing in the hybridization limit. These principles are of general applicability and carry over to more compositionally complicated systems. [ABSTRACT FROM AUTHOR]

Melanocortin-4 receptor (MC4R) deficiency is the most frequent monogenic form of obesity. The contribution of MC4R mutations to the Slovak population has not been investigated as yet. We screened the coding sequence of the MC4R gene in a cohort of 210 Slovak obese children and adolescents. We identified four different mutations in four patients, giving a mutation detection rate of 0.95%. Of these, three were missense mutations previously identified and characterized by other research groups (p.R7C, p.S127L and p. R305W, respectively). One was a novel nonsense mutation p.W174* detected in a severely obese 7-year-old boy. This mutation was further analyzed in family segregation analysis and exhibited variable penetrance. Two known amino acid polymorphisms (p.V103I and p.I251L) were also identified in seven subjects of our cohort group. We also performed multifactorial statistical analysis to determine the influence of genotypes on standard biochemical blood markers. No significant influence was observed in carriers of DNA variants on tested parameters. We conclude that rare heterozygous MC4R mutations contribute to the onset of obesity only in a few cases in the Slovak population. [ABSTRACT FROM AUTHOR]

Both cell-cell and cell-matrix adhesion are important for epithelial cell differentiation and function. Classical cadherins mediate cell to cell interactions and are potent activators of the signal transducer and activator of transcription (Stat3), thereby offering survival signaling. While the epithelial (E)-cadherin is required for cells to remain tightly associated within differentiated epithelial tissues, cadherin-11 promotes invasion and metastasis, preferentially to the bone. Cell adhesion to the extracellular matrix is mediated through the integrin receptors that bind to the focal adhesion kinase (FAK)/Src complex, thus activating downstream effectors such as Ras/Erk1/2 and PI3k/Akt, but not Stat3. Therefore, at high densities of cultured cells or in epithelial tissues, co-ordinate activation of the complementary cadherin/Stat3 and integrin/ FAK pathways can greatly enhance survival and growth of tumor cells. In neoplastically transformed cells on the other hand, a variety of oncogenes including activated Src or receptor tyrosine kinases, activate both pathways. Still, most single-agent therapies directed against these signaling pathways have proven disappointing in the clinic. Combined targeting of the Src/FAK and Stat3 pathways with inhibitory drugs would be expected to have greater efficacy in inhibiting tumor cell survival, and enhancing sensitivity to conventional cytotoxic drugs for treatment of metastatic disease. [ABSTRACT FROM AUTHOR]

This paper uses conversation analysis to examine when Vietnamese speakers explicitly mark the source of represented talk or thought (RT) and when they may omit the RTs source in narratives in dyadic and multiparty family conversations. In Vietnamese, a pro-drop, non-inflectional language, RTs may be introduced by a verb of speaking and its subject, a verb of speaking without the subject, or no verb of speaking and no subject. The analysis focuses on how these three choices are employed in the sequential organization of narrative series, narrative participation frameworks, and narrative dramatization. The findings contribute to current understandings about source marking through linguistic devices as an interactional practice in conversations in addition to other resources such as voicing and embodied actions. [ABSTRACT FROM AUTHOR]

The social sciences and the humanities consider academic writing a natural skill of all academics. This contribution doubts this position and explains forms and places of academic writing with reference to the organisational factors that demand such contributions. Three aspects are highlighted: First, writing becomes the key tool to learn science at universities. Criteria that need to be explicated for this purpose not only describe, but start to shape science. Second, the results of such pedagogical exercises are used to compare students and institutional performances. Universities become transparent to external observers. Third, disciplinary structures challenge the comparability and controllability of academic texts, which controllers respond to with increasingly elaborate controls. [ABSTRACT FROM AUTHOR]

Sunscreens are used to protect the human skin against harmful effects of solar UV radiation. The most important quantity characterizing sunscreen performance is the sun protection factor (SPF). At the stage of development of new sun protection formulations quick and inexpensive methods for estimation of the UV screening performance are highly desirable. The most convenient approach towards this goal is given by computational simulations. Models for the calculation of the SPF employ the same algorithm as used with in vitro SPF measurements, but replace the transmittance measurement by the calculation of the overall absorbance of the UV filters in an irregular sunscreen film. The simulations require a database with quantitative UV extinction spectra of the relevant UV filters as well as a mathematical description of the film irregularity. The simulation algorithm implies also the consideration of photodegradation properties of the UV filters in the sunscreen composition. Besides using such simulations for designing new sunscreen formulations, the calculations can also support the understanding of sunscreen performance in general. [ABSTRACT FROM AUTHOR]