Advanced Diffusion-Weighted Imaging Sequences for Breast MRI: Comprehensive Comparison of Improved Sequences and Ultra-High B-Values to Identify the Optimal Combination

This study investigated the image quality and choice of ultra-high b-value of two DWI breast-MRI research applications. The study cohort comprised 40 patients (20 malignant lesions). In addition to s-DWI with two m-b-values (b50 and b800) and three e-b-values (e-b1500, e-b2000, and e-b2500), z-DWI and IR m-b1500 DWI were applied. z-DWI was acquired with the same measured b-values and e-b-values as the standard sequence. For IR m-b1500 DWI, b50 and b1500 were measured, and e-b2000 and e-b2500 were mathematically extrapolated. Three readers used Likert scales to independently analyze all ultra-high b-values (b1500-b2500) for each DWI with regards to scan preference and image quality. ADC values were measured in all 20 lesions. z-DWI was the most preferred (54%), followed by IR m-b1500 DWI (46%). b1500 was significantly preferred over b2000 for z-DWI and IR m-b1500 DWI (p = 0.001 and p = 0.002, respectively). Lesion detection was not significantly different among sequences or b-values (p = 0.174). There were no significant differences in measured ADC values within lesions between s-DWI (ADC: 0.97 [±0.09] × 10$^{-3}$ mm$^{2}$/s) and z-DWI (ADC: 0.99 [±0.11] × 10$^{-3}$ mm$^{2}$/s; p = 1.000). However, there was a trend toward lower values in IR m-b1500 DWI (ADC: 0.80 [±0.06] × 10$^{-3}$ mm$^{2}$/s) than in s-DWI (p = 0.090) and z-DWI (p = 0.110). Overall, image quality was superior and there were fewer image artifacts when using the advanced sequences (z-DWI + IR m-b1500 DWI) compared with s-DWI. Considering scan preferences, we found that the optimal combination was z-DWI with a calculated b1500, especially regarding examination time

New statistical potential for quality assessment of protein models and a survey of energy functions

Abstract Background Scoring functions, such as molecular mechanic forcefields and statistical potentials are fundamentally important tools in protein structure modeling and quality assessment. Results The performances of a number of publicly available scoring functions are compared with a statistical rigor, with an emphasis on knowledge-based potentials. We explored the effect on accuracy of alternative choices for representing interaction center types and other features of scoring functions, such as using information on solvent accessibility, on torsion angles, accounting for secondary structure preferences and side chain orientation. Partially based on the observations made, we present a novel residue based statistical potential, which employs a shuffled reference state definition and takes into account the mutual orientation of residue side chains. Atom- and residue-level statistical potentials and Linux executables to calculate the energy of a given protein proposed in this work can be downloaded from http://www.fiserlab.org/potentials. Conclusions Among the most influential terms we observed a critical role of a proper reference state definition and the benefits of including information about the microenvironment of interaction centers. Molecular mechanical potentials were also tested and found to be over-sensitive to small local imperfections in a structure, requiring unfeasible long energy relaxation before energy scores started to correlate with model quality.</p

Die Textualität der Kultur. Gegenstände, Methoden, Probleme der kultur- und literaturwissenschaftlichen Forschung

Im Zuge des sogenannten "cultural turn", der die traditionellen Geisteswissenschaften als Kulturwissenschaften neu bestimmte, sah sich auch die Literaturwissenschaft mit ganz neuen Ansprüchen konfrontiert: Statt sich wie bisher mit literarischen Werken oder Texten des täglichen Gebrauchs zu befassen, sollte sie plötzlich mittels interdisziplinärer Ansätze kulturelle Phänomene aller Art wie Rituale, politische Machtstrukturen oder gesellschaftliche Konstellationen analysieren und erklären. Eine Möglichkeit, das Verhältnis von Text und kulturellem Kontext zu denken, bildet die Vorstellung der Textualität der Kultur, die von Stephen Greenblatt, Louis Montrose und anderen Vertretern des New Historicism unter Bezugnahme auf den Kulturbegriff des Ethnologen Clifford Geertz entwickelt wurde. Geertz versteht Kultur als ein „Netzwerk von bedeutungstragenden Verknüpfungen“ (Geertz 1973), dem ein semiotischer, also ein textueller Charakter eigen ist. Dieses analytische Modell eröffnet die Möglichkeit eines bruchlosen Übergangs zwischen dem Text und dem ihn umgebenden Kontext – eines Übergangs, der in beide Richtungen funktioniert und zudem als "dynamisch" vorgestellt wird: Nicht nur wird der Text als Produkt kultureller Einflüsse angesehen und in einen bereits existierenden Kontext eingeordnet, auch dieser Kontext selbst ist als Zeichengewebe charakterisiert durch seine latenten Bedeutungspotentialen, die erst in der entsprechenden Lektüre aktualisiert und damit realisiert werden. Diese Auffassung von der Textualität der Kultur und der Kulturalität von Texten bildet die gemeinsame methodische Annahme der im vorliegenden Tagungsband versammelten Beiträge.After the "cultural turn" of the 1990s redefined the traditional humanities under the label “Cultural Studies”, literary studies were confronted with new challenges. Suddenly, instead of concentrating mainly on literary works or texts fromeveryday life, they were expected to analyse and explain cultural phenomena such as rituals, structures of power or social constellations, using interdisciplinary methods. One possibility for conceptualizing the relationship between text and context is the notion of the "textuality of culture". This idea was coined by Stephen Greenblatt, Louis Montrose, and other scholars of "the New Historicism," referring to a concept of culture first developed by the ethnologist Clifford Geertz. To Geertz, culture is a “web of significance” of a semiotic and textual nature (Geertz 1973). Assuming a dynamic rather than a static relationship, this analytical model allows for fluent interactions between text and context: No longer is a text just considered to be a product of cultural influences set within a given context. Instead, this context, being a web of signs, was understood to be itself "textual", creating unfulfilled potentials of meaning. Only by being ‘read’ and actualized, are these cultural meanings solidified andthus made real. These notions of the "culturality of texts" and the "textuality of culture" constitute the common methodological assumptions of all the articles assembled in this volume

Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease

Startle disease is a rare, potentially fatal neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden unexpected auditory, visual or tactile stimuli. Mutations in the GlyR alpha(1) subunit gene (GLRA1) are the major cause of this disorder, since remarkably few individuals with mutations in the GlyR beta subunit gene (GLRB) have been found to date. Systematic DNA sequencing of GLRB in individuals with hyperekplexia revealed new missense mutations in GLRB, resulting in M177R, L285R and W310C substitutions. The recessive mutation M177R results in the insertion of a positively-charged residue into a hydrophobic pocket in the extracellular domain, resulting in an increased EC50 and decreased maximal responses of alpha(1)beta GlyRs. The de novo mutation L285R results in the insertion of a positively-charged side chain into the pore-lining 9' position. Mutations at this site are known to destabilize the channel closed state and produce spontaneously active channels. Consistent with this, we identified a leak conductance associated with spontaneous GlyR activity in cells expressing alpha(1)beta(L285R) GlyRs. Peak currents were also reduced for alpha(1)beta(L285R) GlyRs although glycine sensitivity was normal. W310C was predicted to interfere with hydrophobic side-chain stacking between M1, M2 and M3. We found that W310C had no effect on glycine sensitivity, but reduced maximal currents in alpha(1)beta GlyRs in both homozygous (alpha(1)beta(W310C)) and heterozygous (alpha(1)beta beta(W310C)) stoichiometries. Since mild startle symptoms were reported in W310C carriers, this may represent an example of incomplete dominance in startle disease, providing a potential genetic explanation for the 'minor' form of hyperekplexia. (C) 2012 Elsevier Inc. All rights reserved

In search of the ‘great horse’: A zooarchaeological assessment of horses from England (AD 300-1650)

Popular culture presents a deep-rooted perception of medieval warhorses as massive and powerful mounts, but medieval textual and iconographic evidence remains highly debated. Furthermore, identifying warhorses in the zooarchaeological record is challenging due to both a paucity of horse remains relative to other domesticates, and the tendency of researchers to focus on osteological size, which makes it difficult to reconstruct in-life usage of horses and activity related changes. This paper presents the largest zooarchaeological dataset of English horse bones (n = 1964) from 171 unique archaeological sites dating between AD 300 and 1650. Using this dataset alongside a modern comparative sample of known equids (n = 490), we examine trends in size and shape to explore how the skeletal conformation of horses changed through time and reflected their domestic, elite and military roles. In addition to evidencing the generally small stature of medieval horses relative to both earlier and later periods, we demonstrate the importance of accurately exploring the shape of skeletal elements to describe the morphological characteristics of domestic animals. Furthermore, we highlight the need to examine shape variation in the context of entheseal changes and biomechanics to address questions of functional morphology and detect possible markers of artificial selection on past horses

Modes of functional biodiversity control on tree productivity across the European continent

The relative contribution of community functional diversity and composition to ecosystem functioning is a critical question in ecology in order to enable better predictions of how ecosystems may respond to a changing climate. However, there is little consensus about which modes of functional biodiversity are most important for tree growth at large spatial scales. Here we assessed the relative importance of climate, functional diversity and functional identity (i.e. the community mean values of four key functional traits) for tree growth across the European continent, spanning the northern boreal to the southern Mediterranean forests. Using data from five European national forest inventories we applied a hierarchical linear model to estimate the sensitivity of tree growth to changes in climate, functional diversity and functional identity along a latitudinal gradient. Functional diversity was weakly related to tree growth in the temperate and boreal regions and more strongly in the Mediterranean region. In the temperate region, where climate was the most important predictor, functional diversity and identity had a similar importance for tree growth. Functional identity was strongest at the latitudinal extremes of the continent, largely driven by strong changes in the importance of maximum height along the latitudinal gradient

Anti-HIV-1 integrase potency of methylgallate from Alchornea cordifolia using in vitro and in silico approaches:

According to the 2018 report of the United Nations Programme on HIV/AIDS (UNAIDS), acquired immune deficiency syndrome (AIDS), a disease caused by the human immunodeficiency virus (HIV), remains a significant public health problem. The non-existence of a cure or effective vaccine for the disease and the associated emergence of resistant viral strains imply an urgent need for the discovery of novel anti-HIV drug candidates. The current study aimed to identify potential anti-retroviral compounds from Alchornea cordifolia