bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Intracellular Protein Degradation as a Potential Therapeutic Strategy
Authors: Schneekloth A.R. , Crews C.M. 
Published: November 2010

Here we describe the development of a broadly applicable method for small molecule-mediated post-translational protein degradation known as PROteolysis TArgeting Chimeric molecules (PROTACs). This technique utilizes the Ubiquitin Proteasome System (UPS) that controls protein half-life through targeted degradation. The UPS functions by tagging proteins with a polyubiquitin chain, which facilitates their recognition and subsequent degradation in the 26S proteasome. PROTACs are heterobifunctional molecules that will target a specific protein for degradation via the UPS, by forming a complex between the target protein and an E3 ubiquitin ligase. The PROTAC is comprised of a recognition element for the target, a linker, and a recognition element for an E3 ligase. Following addition to cells, a PROTAC brings the targeted protein and E3 ligase into close physical proximity, facilitating the polyubiquitination of the target, and its subsequent recognition and degradation by the proteasome.
A number of different PROTACs, described herein, have been designed and successfully implemented, with considerable diversity in both the target protein and the E3 ligase component. This method has the potential to be useful as both a tool for understanding the role of specific proteins in cellular pathways, and also as a therapeutic designed to specifically eliminate disease-causing proteins from the cell.
Post-transcriptional and post-translational regulation of Bcl2
Authors: Willimott Shaun , Wagner Simon D. 
Published: December 2010

Bcl2 is an important pro-survival protein that has an essential function in normal immunity and whose constitutive expression leads to the development of lymphomas. Although transcriptional control of Bcl2 has been reported, increasing evidence suggests an important component of Bcl2 regulation is post-transcriptional. Phosphorylation of Bcl2 has been shown to enhance activity to allow response to extracellular growth-factor-mediated signals. Bcl2 mRNA contains regulatory elements in both its 5′- and 3′-UTRs (untranslated regions). An IRES (internal ribosome entry sequence) in the 5′-UTR permits continued translation in the presence of cellular stresses that reduce cap-dependent translation. The 3′-UTR of Bcl2 mRNA is 5.2 kb in length and contains multiple predicted miRNA (microRNA) and RNA-BP (RNA-binding protein)-binding sites. miR-15a and miR-16-1 have been found to inhibit Bcl2 expression in B-cells, whereas the RNA-BP nucleolin has been shown to increase Bcl2 expression by binding to the 3′-UTR and enhancing mRNA stability. Both decreased expression of miR-15a and miR-16-1 and increased nucleolin have been shown to be associated with increased Bcl2 expression and resistance to apoptosis in the common human disease, chronic lymphocytic leukaemia. miRNA-based therapeutic approaches to treat cancer are emerging. Bcl2 is highly regulated by miRNAs and is therefore an excellent candidate for such approaches.
piggyBac‐mediated transposition in Drosophila melanogaster: an evaluation of the use of constitutive promoters to control transposase gene expression
Authors: Li X. , Heinrich J. C. , Scott M. J. 
Published: November 2010

AbstractTransgenic non‐Drosophilid insects have been made using insect transposable elements that have a broad host range such as the piggyBac element. However, the success rate is often low. Previous piggyBac helper plasmids have used either the piggyBac or the hsp70 promoter from Drosophila melanogaster to control expression of the transposase gene. Here we show that plasmids with the piggyBac transposase gene regulated by constitutive promoters can be effective ‘helpers’ for mediating transposition in D. melanogaster. We also present preliminary evidence on the use of an RNA helper that encodes the transposase. Our results suggest that for germ‐line transformation of non‐Drosophilid insects it may be advantageous to isolate a constitutive promoter from the species of interest to control transposase expression.
Language variation and linguistic description in 16th-century France
Authors: Kibbee Douglas A. 
Published: November 2010

SummaryThe first French grammarians to consider the French language condemned variation – historical variation, geographical variation, and sociolinguistic variation. For the French language to be first among vernacular languages, it had to have fixity, to be governed by absolute rules. How can one determine if a lexical item, pronunciation feature, or morphological feature should be accepted? Some would study the best authors, but the list of such authors is a matter of debate. Others would define the ‘true French’ geographically, but they tend to choose their own regions. Ultimately, the choice depends on a sense of ‘usage’ which is in harmony with the ‘naïve puissance’ of the language, the pursuit of which may ultimately lead to a reunification of word and object, a unity lost at the Tower of Babel. The grammarians’ attacks on variation serve biblical as well as political destiny.
Phonetics and phonology 1949–1989
Authors: Sara Solomon I. 
Published: November 2010

Summary
Phonetics and Phonology have had noticeable developments in the last forty years: phonetics from the articulatory descriptions of sounds of Pike’s Phonetics (1943), to a physiological set of distinctive features of Chomsky & Halle’s The Sound Pattern of English (1968); the acoustic displays of Potter’s Visible Speech (1947) to a set of acoustic distinctive features in Jakobson, Fant, Halle’s Preliminaries (1951). Suprasegmental characterizations have developed from impressionistic labels of tone, stress, length and intonation to an experimentally quantifiable set of parameters characterizing these aspects of speech in a unified manner in Lehiste’s Suprasegmentals (1970). Phonology progressed from the autonomous to the integrated, and from the structural to the transformational/generative, from Pike’s Phonemics (1947), and Trubetzkoy’s Grundzüge (1939) to a complex system of levels/tiers/strata that represent speech in a more detailed, holistic and integrated manner. Current approaches recognize not only the features and segments of the speech continuum, but the rules that organize these into the phonological system. Approaches to the explanation of this organization have been many: the segmental/sequential approach of American phonemicists, Praguian phonologists and early generativists developed into a phonological component that consists of segments, organized into syllables that pattern into rhythmic feet which constitute the geometry of the sequence as a multi level/tier/stratum. These developments are all considered generative, but labelled Natural-Generative, Autosegmental-Genera-tive, Non-Linear-Generative, Metrical-Generative, etc. ‘Generative’ is kept to maintain the twin characteristics of being integrated and rule governed. There has been a shift in the paradigm: from segments to features and from structural to transformational with significant developments in both paradigms in the last forty years.
The beginnings of phonology in Italy
Authors: Albano Leoni Federico 
Published: November 2010

Summary
It is known that structural phonology (and, more generally, structural linguistics) began in Italy later than in other European countries. In the general opinion, this was due to the hegemony of Benedetto Croces’s philosophy during the years between World War I and his death in 1952. This paper shows how an early attempt to give a structural description of Italian phonology (Porru 1939) encountered an exceptionally harsh review (Pisani 1939), which appears to have been motivated more by personal and academic considerations than by philosophical or theoretical grounds. The authority of Pisani seemed to discourage any other attempt by Italian linguists to join European structuralism until about 1950. In fact, in that year two articles appeared (by no other than Pisani and by Devoto) which seemed to mark the end of a prohibition. The conclusion that may be drawn from this episode is that the development of sciences depends not only on general theoretical and cultural frames but also on actions and choices of individuals.
‘Core’ and ‘Periphery’ in Historical Perspective
Authors: Joseph John E. 
Published: November 2010

SummaryThis article traces the changing fortunes of Chomsky’s concepts of ‘core’ and ‘periphery’, from the beginnings of Government and Binding Theory in the late 1970s to the incipient minimalism of the early 1990s. Ten different characterizations of core and periphery are found in Chomsky’s work of the period, which alternatively questions the need for the distinction and promotes it to central theoretical status. Core and periphery are found to pertain to several different conceptual and phenomenological levels: universality, systematicity, typology, and historicity. Furthermore, they covertly recapitulate some of the oldest dichotomies of linguistic thought: nature/convention, analogy/anomaly, synchronic/diachronic, and marked/unmarked. The conclusions reached support recent changes in the theory which greatly reduce the prominence of the core/periphery distinction.
Las Osservationi de Giovanni Miranda
Authors: Blanch Juan M. Lope 
Published: November 2010

Summary
Giovanni Miranda’s Osservationi della Lingua Castigliana (Venice, 1566) was the best pedagogical grammar of Spanish of its time; and since it served as a model to French, English, and German grammarians it was important well beyond Italy. Because it was essentially a practical teaching work, one finds in it few theoretical pronouncements. Theory, however, is not totally absent from his book, as becomes obvious in the discussion of the concept of ‘sentence’ or of the ‘parts of speech’, but as a whole the work deals with questions that were thought to be essential to the learner of a language, mostly morphology and certain peculiarities of Castilian grammar and usage. The work is divided into four parts: I, the article, the noun, the adjective, and the pronoun; II, the verb, whose conjugation is dealt with exhaustively; III, the non-inflectional parts of speech in Spanish; and IV, spelling and pronunciation. Throughout the work the author discusses related semantic, lexical, and phraseological subjects, and uses proverbs, anecdotes, and very short stories to illustrate colloquial usage of Spanish. Miranda’s Osservationi were influenced by Giovanni Mario Alessandri d’Urbino’s Paragone della Lingua Toscana et Castigliana (Naples, 1560). Miranda the format of the Paragone, but greatiy expands on it. The Osservationi della Lingua Castigliana can be said to be the first effective pedagogical grammar of Spanish written for speakers of other languages.
Sobre la formación del corpus de autoridades en la Gramática Española
Authors: Lliteras Poncel Margarita 
Published: November 2010

Summary
In the Spanish tradition, descriptive grammars based both factually and methodologically on a corpus gleaned from identified contemporary sources, mostly taken from literature, do not appear until the several editions (11831–81847) of the grammar of Vicente Salvâ (1786–1849), and later in that of Andrés Bello (11847–1860). A small part of Salvá’s corpus does come from medieval and renaissance authors, but these are used only to illustrate diachronic change in Spanish. Salvá’s empirical and descriptive approach, and that of other 19th-century Spanish and Spanish American grammarians that follow him, leads to specialization within the wider field of grammar and, as is shown here, syntax is the area that profits the most, both in depth and in size or extension. There is no precedent for this grammaticographical tradition in the Renaissance, when a literary corpus is used only for those parts of the texts that traditionally dealt with metrics and versification. Renaissance grammarians derived the authority of their texts from the transfer of the rules of Latin grammar into Spanish, not from the language of the literary canon. During the 18th-century Enlightenment grammars based on a literary corpus begin to appear, but the authors from whose works the corpus is taken are those of a previous (non-contemporary) period. As shown in this article, it is in the 18th century that descriptivism results in an increase in the importance of syntax, although that increment in size is minor by comparison with that which takes place during the 19th century beginning with the works of Salvá.
La historificación de la lingüística histórica
Authors: del Valle José 
Published: November 2010

Summary
The main tenet of this article is that Spanish philologist Ramón Menéndez Pidal’s (1869–1968) theoretical approach to the history of the language, as developed in his Manual de gramática histórica española (1904) and in Orígenes del español (1926), was a result not only of a highly original interpretation of the linguistic theories available to him and a need to improve their explanatory power, but also from an interplay between this theory and the ideological context from which it emerged. This ideological context, which I maintain is critical for the understanding of the full implications of Menéndez Pidal’s linguistic approach, has been assumed by traditional historiography to be outside the scope of linguistics. It is claimed here that the Spanish philologist’s scholarly accomplishments, justly praised by his disciples and hispanists in general, did not occur in a social vacuum, but were instead well entrenched in a specific intellectual, social, and historical context. Menéndez Pidal lived and worked in a period in which Spain, like other 19th-century liberal democracies, was building its identity as a nation-state. In this period, the construction of the Spanish nation was threatened by centrifugal forces (e.g., the articulation of Basque, Catalan, and Galician nationalisms) that challenged Spain’s unitary political and cultural identity. It is precisely against the backdrop of this socio-political landscape that Menéndez Pidal’s use of the neogrammarian model of convergence in the Manual, his scrupulous philological examination of old documents in Orígenes is interpreted – which, for him, offered proof of Castile’s destiny as the leading force in the history of Spain, including his integrative reworking of the phonetic law converting it into a means by which to perceive the unity underlying dialectal variation.
Electronic Prediction Rules for Methicillin-ResistantStaphylococcus aureusColonization
Authors: Robicsek Ari , Beaumont Jennifer L. , Wright Marc-Oliver , Thomson Richard B. , Kaul Karen L. , Peterson Lance R. 
Published: December 2010

Background.Considerable hospital resources are dedicated to minimizing the number of methicillin-resistantStaphylococcus aureus(MRSA) infections. One tool that is commonly used to achieve this goal is surveillance for MRSA colonization. This process is costly, and false-positive test results lead to isolation of individuals who do not carry MRSA. The performance of this technique would improve if patients who are at high risk of colonization could be readily targeted.Methods.Five MRSA colonization prediction rules of varying complexity were derived in a population of 23,314 patients who were consecutively admitted to a US hospital and tested for colonization. Rules incorporated only prospectively collected, structured electronic data found in a patient's record within 1 day of hospital admission. These rules were tested in a validation cohort of 26,650 patients who were admitted to 2 other hospitals.Results.The prevalence of MRSA at hospital admission was 2.2% and 4.0% in the derivation and validation cohorts, respectively. Multivariable modeling identified predictors of MRSA colonization among demographic, admission-related, pharmacologic, laboratory, physiologic, and historical variables. Five prediction rules varied in their performance, but each could be used to identify the 30% of patients who accounted for greater than 60% of all cases of MRSA colonization and approximately 70% of all MRSA-associated patient-days. Most rules could also identify the 20% of patients with a greater than 8% chance of colonization and the 40% of patients among whom colonization prevalence was 2% or less.Conclusions.We report electronic prediction rules that can fully automate triage of patients for MRSA-related hospital admission testing and that offer significant improvements on previously reported rules. The efficiencies introduced may result in savings to infection control programs with little sacrifice in effectiveness.
Impact of Switching from an Open to a Closed Infusion System on Rates of Central Line–Associated Bloodstream Infection: A Meta-analysis of Time-Sequence Cohort Studies in 4 Countries
Authors: Maki Dennis G. , Rosenthal Victor D. , Salomao Reinaldo , Franzetti Fabio , Rangel-Frausto Manuel Sigfrido 
Published: December 2010

Background.We report a meta-analysis of 4 identical time-series cohort studies of the impact of switching from use of open infusion containers (glass bottle, burette, or semirigid plastic bottle) to closed infusion containers (fully collapsible plastic containers) on central line-associated bloodstream infection (CLABSI) rates and all-cause intensive care unit (ICU) mortality in 15 adult ICUs in Argentina, Brazil, Italy, and Mexico.Methods.All ICUs used open infusion containers for 6–12 months, followed by switching to closed containers. Patient characteristics, adherence to infection control practices, CLABSI rates, and ICU mortality during the 2 periods were compared by χ2test for each country, and the results were combined using meta-analysis.Results.Similar numbers of patients participated in 2 periods (2,237 and 2,136). Patients in each period had comparable Average Severity of Illness Scores, risk factors for CLABSI, hand hygiene adherence, central line care, and mean duration of central line placement. CLABSI incidence dropped markedly in all 4 countries after switching from an open to a closed infusion container (pooled results, from 10.1 to 3.3 CLABSIs per 1,000 central line-days; relative risk [RR], 0.33 [95% confidence interval {CI}, 0.24-0.46];P<.001). All-cause ICU mortality also decreased significantiy, from 22.0 to 16.9 deaths per 100 patients (RR, 0.77 [95% CI, 0.68-0.87];P<.001).Conclusions.Switching from an open to a closed infusion container resulted in a striking reduction in the overall CLABSI incidence and all-cause ICU mortality. Data suggest that open infusion containers are associated with a greatiy increased risk of infusion-related bloodstream infection and increased ICU mortality that have been unrecognized. Furthermore, data suggest CLABSIs are associated with significant attributable mortality.
von Bertalanffy 1.0: a COBRA toolbox extension to thermodynamically constrain metabolic models
Authors: Fleming Ronan M. T. , Thiele Ines 
Published: November 2010

Abstract
Motivation: In flux balance analysis of genome scale stoichiometric models of metabolism, the principal constraints are uptake or secretion rates, the steady state mass conservation assumption and reaction directionality. Here, we introduce an algorithmic pipeline for quantitative assignment of reaction directionality in multi-compartmental genome scale models based on an application of the second law of thermodynamics to each reaction. Given experimental or computationally estimated standard metabolite species Gibbs energy and metabolite concentrations, the algorithms bounds reaction Gibbs energy, which is transformed to in vivo pH, temperature, ionic strength and electrical potential.
Results: This cross-platform MATLAB extension to the COnstraint-Based Reconstruction and Analysis (COBRA) toolbox is computationally efficient, extensively documented and open source.
Availability: http://opencobra.sourceforge.net
Contact: ronan.mt.fleming@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Granular Packing Influences Bulk Density of DDGS
Authors: Keierleber Christine , Rosentrater Kurt A. 
Published: November 2010

ABSTRACTAs the quantity of ethanol produced continues to increase, the amount of distillers dried grains with solubles (DDGS), the primary coproduct of ethanol manufacturing, has become more widely available. Currently, the main consumer of DDGS is the livestock industry, but new value‐added uses are garnering interest. With the increase in the availability of, and demand for DDGS, transportation has become an important issue because DDGS must be shipped increasingly long distances using railways. Rail transportation is expensive, especially considering the quantities of DDGS that can be loaded onto unit trains. DDGS often has low bulk density and poor flowability characteristics. This study examined compression effects on particle arrangements as quantified by bulk density and compressibility of the DDGS. Mean loose bulk density was 446.18 kg/m3. A linear relationship (R2 = 0.982 for 50 N applied force and R2 = 0.959 for 1 kN applied force) was observed between the applied stress (≈0.0–0.0065 and ≈0.0–0.13 MPa, respectively) and the resulting packed bulk density (≤470.21 and ≤555.03 kg/m3, respectively). Compressive stress increased curvilinearly (R2 = 0.994 for the 50 N load and R2 = 0.997 for the 1 kN load) as the applied strain increased (≈0.0–0.007% and 0.0–24.0%, respectively). As the loading increased, compressibility increased 5.11–19.22%. Bulk restitution after loading was removed was 0.53–0.61. Required storage volume is reduced when the bulk density is increased. But flowability characteristics should improve as the compressibility, and thus the bulk density, of the product is reduced.
Accumulation of Oxygenated Fatty Acids in Oat Lipids During Storage
Authors: Doehlert Douglas C. , Angelikousis Steven , Vick Brady 
Published: November 2010

ABSTRACTOxygenated fatty acids were identified in oat grain by gas chromatography‐mass spectrometry. We hypothesized that most of these were the results of lipoxygenase activity. This hypothesis was tested by measuring concentrations of these compounds after hydrothermal treatments and storage of oat groats or oat flour for 22 weeks at 37°C and 65% relative humidity. Steam treatments inactivated lipases, whereas roasting at 106°C did not. Free fatty acids accumulated quickly in untreated or roasted flour, but not in steamed flour or groats. A total of six hydroxy and epoxy fatty acids were identified. Oxidized fatty acids were found in both esterified lipids and free fatty acids, indicating that lipase action was not necessary for lipid oxidation. More oxidation products were found in flour than in groats, and less were found in the steamed treatments. Lipoperoxygenase appeared to be involved in the formation of oxidation products, although nonenzymatic mechanisms may also operate. Hydroxy‐fatty acids are associated with strongly bitter flavors and are undesirable. Results indicate the importance of enzyme inactivation before storage of processed oat products.