bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pressure‐Accelerated Azide–Alkyne Cycloaddition: Micro Capillary versus Autoclave Reactor Performance
Authors: Borukhova Svetlana , Seeger Andreas D. , Noël Timothy , Wang Qi , Busch Markus , Hessel Volker 
Published: December 2014

AbstractPressure effects on regioselectivity and yield of cycloaddition reactions have been shown to exist. Nevertheless, high pressure synthetic applications with subsequent benefits in the production of natural products are limited by the general availability of the equipment. In addition, the virtues and limitations of microflow equipment under standard conditions are well established. Herein, we apply novel‐process‐window (NPWs) principles, such as intensification of intrinsic kinetics of a reaction using high temperature, pressure, and concentration, on azide–alkyne cycloaddition towards synthesis of Rufinamide precursor. We applied three main activation methods (i.e., uncatalyzed batch, uncatalyzed flow, and catalyzed flow) on uncatalyzed and catalyzed azide–alkyne cycloaddition. We compare the performance of two reactors, a specialized autoclave batch reactor for high‐pressure operation up to 1800 bar and a capillary flow reactor (up to 400 bar). A differentiated and comprehensive picture is given for the two reactors and the three methods of activation. Reaction speedup and consequent increases in space–time yields is achieved, while the process window for favorable operation to selectively produce Rufinamide precursor in good yields is widened. The best conditions thus determined are applied to several azide–alkyne cycloadditions to widen the scope of the presented methodology.
Strongly singular and hypersingular integrals for aeroacoustic incident fields
Authors: Croaker P. , Kessissoglou N. , Marburg S. 
Published: December 2014

SummaryUsing the Burton and Miller formulation to predict the scattering of flow‐induced noise by a body immersed in the flow requires the near‐field pressure and pressure gradient incident on the body. In this paper, Lighthill's acoustic analogy is used to derive formulations for the near‐field pressure and pressure gradient at any point within the flow noise source region, including points on the body. These near‐field formulations involve strongly singular and hypersingular volume and surface integrals. To evaluate these singular integrals, an effective singularity regularization technique is derived. An analytical source distribution is used to demonstrate the accuracy of the method. A cell‐averaged representation of this analytical source distribution, similar to the data stored by computational fluid dynamics solvers, is also created. A piecewise linear, continuous source distribution is generated from these cell‐average values, producing a C0 distribution. A k‐exact reconstruction technique is then used to create high‐order polynomials of the solution variables for each volume cell. These high‐order polynomials are constructed from its cell average value and the average values of the nearby cells. The source distribution created using the k‐exact reconstruction is discontinuous across cell boundaries but exhibits a smooth polynomial distribution within each cell. The near‐field pressure and pressure gradient predicted using these reconstructed source distributions are compared with the results obtained using the analytical distribution. Copyright © 2014 John Wiley & Sons, Ltd.
Targeting of Intravenous Polymeric Nanoparticles by Differential Protein Adsorption
Authors: Staufenbiel Sven , Weise Christoph , Müller Rainer H. 
Published: December 2014

SummaryThe organ distribution of intravenously injected nanoparticles is determined by the composition of the blood protein adsorption pattern occurring after injection. This is exploited in the concept of “differential protein adsorption” for drug targeting, which is briefly discussed. The surface properties of the nanoparticles determine the adsorption patterns, by controlling the surface properties one can generate adsorption patterns required for achieving the desired organ distribution. The efficiency of this principle is shown by reviewing different organ distributions achieved using various polymeric nanoparticles with different surface properties. Surface modification can be obtained by polymer adsorption and can create nanoparticles circulating in the blood, or accumulating in targets such as bone marrow and brain. The protein adsorption patterns were analyzed using two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE). Here, adsorption patterns of dendritic polymer nanoparticles were investigated, where the used polymer was dendritic polyglycerol sulfate. They showed reduced opsonization and preferential adsorption of apolipoprotein A‐I with brain targeting potential. In perspective, the principle of surface property modification by polymer/stabilizer adsorption can be transferred to intravenous drug nanocrystals. A hybrid system of nanocrystal and polymeric nanoparticles is suggested, the polymeric nanoparticle with nanocrystal core.
Preparation of Magneto‐Sensitive Polymer Nanocomposite Microparticles from Copolyesterurethanes via Electrospraying
Authors: Zhang Quanchao , Sauter Tilman , Wang Li , Fang Liang , Kratz Karl , Lendlein Andreas 
Published: December 2014

SummarySmall stimuli‐responsive magneto‐sensitive microparticles (<5 μm) have attracted broad interest for biomedical applications, since they can be delivered minimal‐invasively (e.g. via injection) and guided to a specific site or organ, while using their magnetic properties. In addition, such particles can be remotely heated, e.g., for hyperthermia therapy approaches. In this study, we prepared magneto‐sensitive polymer‐based nanocomposite microparticles by electrospraying of a 1,1,1,3,3,3 hexafluoro‐2‐propanol solution containing a mixture of a copolyetheresterurethane (PDC) and magnetic Fe3O4 nanoparticles (MNPs). Thermal gravimetric analysis (TGA) revealed a weight content of 23 ± 0.5 wt‐% MNPs in the PDC magneto‐sensitive nanocomposite microparticles, which was identical with the initial starting composition. Scanning electron microscopy (SEM) results indicated a bimodal particle size distribution for the prepared magneto‐sensitive nanocomposite microparticles around 1.2 ± 0.3 μm and 400 ± 100 nm, respectively. Decreasing the size of the magneto‐sensitive nanocomposite microparticles resulted in an increase in their reduced modulus, which was obtained via nanoindentation testing. The PDC magneto‐sensitive nanocomposite microparticles could be successfully manipulated in dispersion medium suspension with a permanent magnet, demonstrating their magneto‐sensitivity. In addition, the inductive heating capability of the microparticulate nanocomposites could be demonstrated for a thin compression molded test specimen, which could be heated to 44 °C in an alternating magnetic field. The results indicated that such magneto‐sensitive nanocomposite microparticles can be potentially used as magneto‐responsive shape‐memory microparticles for on‐demand and remotely controlled drug delivery.
Job-Related Well-Being Through the Great Recession
Authors: Green Francis , Felstead Alan , Gallie Duncan , Inanc Hande 
Published: December 2014

AbstractWe study how job-related well-being (measured by Warr’s ‘Enthusiasm’ and ‘Contentment’ scales) altered through the Great Recession, and how this is related to changing job quality. Using nationally representative data for Britain, we find that job-related well-being was stable between 2001 and 2006, but then declined between 2006 and 2012. We report relevant changes in job quality. In modelling the determinants of job-related well-being, we confirm several previously-studied hypotheses and present some new findings: downsizing, work re-organisation, decreased choice, and linking pay to organisational performance each reduce well-being; indicators of skills challenge in jobs have more of a positive association with Enthusiasm than with Contentment, while effort has a more negative association with Contentment than with Enthusiasm. Our estimates are largely orthogonal to the effects of personality traits and demographic controls on well-being. Using a standard decomposition, we find that the 2006–2012 fall in job-related well-being is partly accounted for by accelerations in the pace of workplace change, rising job insecurity, increased effort and changing participation.
The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes
Authors: Shin Sung-Young , Kim Taeyong , Lee Ho-Sung , Kang Jun Hyuk , Lee Ji Young , Cho Kwang-Hyun , Kim Do Han 
Published: December 2014

AbstractHow cell fate (survival or death) is determined and whether such determination depends on the strength of stimulation has remained unclear. In this study, we discover that the cell fate of cardiomyocytes switches from survival to death with the increase of β-adrenergic receptor (β-AR) stimulation. Mathematical simulations combined with biochemical experimentation of β-AR signalling pathways show that the gradual increment of isoproterenol (a non-selective β1/β2-AR agonist) induces the switching response of Bcl-2 expression from the initial increase followed by a decrease below its basal level. The ERK1/2 and ICER-mediated feed-forward loop is the hidden design principle underlying such cell fate switching characteristics. Moreover, we find that β1-blocker treatment increases the survival effect of β-AR stimuli through the regulation of Bcl-2 expression leading to the resistance to cell death, providing new insight into the mechanism of therapeutic effects. Our systems analysis further suggests a novel potential therapeutic strategy for heart disease.
Prediction of Metabolic Interactions With Oxycodone via CYP2D6 and CYP3A Inhibition Using a Physiologically Based Pharmacokinetic Model
Authors: Marsousi N , Daali Y , Rudaz S , Almond L , Humphries H , Desmeules J , Samer C F 
Published: December 2014

Evaluation of a potential risk of metabolic drug–drug interactions (DDI) is of high importance in the clinical setting. In this study, a physiologically based pharmacokinetic (PBPK) model was developed for oxycodone and its two primary metabolites, oxymorphone and noroxycodone, in order to assess different DDI scenarios using published in vitro and in vivo data. Once developed and refined, the model was able to simulate pharmacokinetics of the three compounds and the DDI extent in case of coadministration with an inhibitor, as well as the oxymorphone concentration variation between CYP2D6 extensive metabolizers (EM) and poor metabolizers (PM). The reliability of the model was tested against published clinical studies monitoring different inhibitors and dose regimens, and all predicted area under the concentration–time curve (AUC) ratios were within the twofold acceptance range. This approach represents a strategy to evaluate the impact of coadministration of different CYP inhibitors using mechanistic incorporation of drug‐dependent and system‐dependent available in vitro and in vivo data.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e152; doi:10.1038/psp.2014.49; published online 17 December 2014
Maternal temperature history activates Flowering Locus T in fruits to control progeny dormancy according to time of year
Authors: Chen Min , MacGregor Dana R. , Dave Anuja , Florance Hannah , Moore Karen , Paszkiewicz Konrad , Smirnoff Nicholas , Graham Ian A. , Penfield Steven 
Published: December 2014

Significance
Seed behavior is known to be highly dependent on the temperature during seed set, but the mechanism is poorly understood. Here we show that the mother plant plays a central role in the control of progeny seed dormancy, integrating long-term temperature memories in fruit tissues using the same pathway that controls flowering time. Regulation of seed coat properties by maternal flowering time pathways effectively passes timing information across generations, aligning progeny behavior with time of year.
MicroRNA408 Is Critical for the HY5-SPL7 Gene Network That Mediates the Coordinated Response to Light and Copper
Authors: Zhang Huiyong , Zhao Xin , Li Jigang , Cai Huaqing , Deng Xing Wang , Li Lei 
Published: December 2014

Abstract
Light and copper are important environmental determinants of plant growth and development. Despite the wealth of knowledge on both light and copper signaling, the molecular mechanisms that integrate the two pathways remain poorly understood. Here, we use Arabidopsis thaliana to demonstrate an interaction between SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7) and ELONGATED HYPOCOTYL5 (HY5), which mediate copper and light signaling, respectively. Through whole-genome chromatin immunoprecipitation and RNA sequencing analyses, we elucidated the SPL7 regulon and compared it with that of HY5. We found that the two transcription factors coregulate many genes, including those involved in anthocyanin accumulation and photosynthesis. Moreover, SPL7 and HY5 act coordinately to transcriptionally regulate MIR408, which results in differential expression of microRNA408 (miR408) and its target genes in response to changing light and copper conditions. We demonstrate that this regulation is tied to copper allocation to the chloroplast and plastocyanin levels. Finally, we found that constitutively activated miR408 rescues the distinct developmental defects of the hy5, spl7, and hy5 spl7 mutants. These findings revealed the existence of crosstalk between light and copper, mediated by a HY5-SPL7 network. Furthermore, integration of transcriptional and posttranscriptional regulation is critical for governing proper metabolism and development in response to combined copper and light signaling.
Transcriptomic Analyses Indicate That Maize Ligule Development Recapitulates Gene Expression Patterns That Occur during Lateral Organ Initiation
Authors: Johnston Robyn , Wang Minghui , Sun Qi , Sylvester Anne W. , Hake Sarah , Scanlon Michael J. 
Published: December 2014

AbstractDevelopment of multicellular organisms proceeds via the correct interpretation of positional information to establish boundaries that separate developmental fields with distinct identities. The maize (Zea mays) leaf is an ideal system to study plant morphogenesis as it is subdivided into a proximal sheath and a distal blade, each with distinct developmental patterning. Specialized ligule and auricle structures form at the blade-sheath boundary. The auricles act as a hinge, allowing the leaf blade to project at an angle from the stem, while the ligule comprises an epidermally derived fringe. Recessive liguleless1 mutants lack ligules and auricles and have upright leaves. We used laser microdissection and RNA sequencing to identify genes that are differentially expressed in discrete cell/tissue-specific domains along the proximal-distal axis of wild-type leaf primordia undergoing ligule initiation and compared transcript accumulation in wild-type and liguleless1-R mutant leaf primordia. We identified transcripts that are specifically upregulated at the blade-sheath boundary. A surprising number of these “ligule genes” have also been shown to function during leaf initiation or lateral branching and intersect multiple hormonal signaling pathways. We propose that genetic modules utilized in leaf and/or branch initiation are redeployed to regulate ligule outgrowth from leaf primordia.
Word structures of Granada Spanish‐speaking preschoolers with typical versus protracted phonological development
Authors: May Bernhardt B. , Hanson R. , Perez D. , Ávila C. , Lleó C. , Stemberger J. P. , Carballo G. , Mendoza E. , Fresneda D. , Chávez‐Peón M. 
Published: December 2014

AbstractBackgroundResearch on children's word structure development is limited. Yet, phonological intervention aims to accelerate the acquisition of both speech–sounds and word structure, such as word length, stress or shapes in CV sequences. Until normative studies and meta‐analyses provide in‐depth information on this topic, smaller investigations can provide initial benchmarks for clinical purposes.AimsTo provide preliminary reference data for word structure development in a variety of Spanish with highly restricted coda use: Granada Spanish (similar to many Hispano‐American varieties). To be clinically applicable, such data would need to show differences by age, developmental typicality and word structure complexity. Thus, older typically developing (TD) children were expected to show higher accuracy than younger children and those with protracted phonological development (PPD). Complex or phonologically marked forms (e.g. multisyllabic words, clusters) were expected to be late developing.Methods & ProceduresParticipants were 59 children aged 3–5 years in Granada, Spain: 30 TD children, and 29 with PPD and no additional language impairments. Single words were digitally recorded by a native Spanish speaker using a 103‐word list and transcribed by native Spanish speakers, with confirmation by a second transcriber team and acoustic analysis. The program Phon 1.5 provided quantitative data.Outcomes & ResultsIn accordance with expectations, the TD and older age groups had better‐established word structures than the younger children and those with PPD. Complexity was also relevant: more structural mismatches occurred in multisyllabic words, initial unstressed syllables and clusters. Heterosyllabic consonant sequences were more accurate than syllable‐initial sequences. The most common structural mismatch pattern overall was consonant deletion, with syllable deletion most common in 3‐year‐olds and children with PPD.Conclusions & ImplicationsThe current study provides preliminary reference data for word structure development in a Spanish variety with restricted coda use, both by age and types of word structures. Between ages 3 and 5 years, global measures (whole word match, word shape match) distinguished children with typical versus protracted phonological development. By age 4, children with typical development showed near‐mastery of word structures, whereas 4‐ and 5‐year‐olds with PPD continued to show syllable deletion and cluster reduction, especially in multisyllabic words. The results underline the relevance of multisyllabic words and words with clusters in Spanish phonological assessment and the utility of word structure data for identification of protracted phonological development.
Mild hypothermia induces incomplete left ventricular relaxation despite spontaneous bradycardia in pigs
Authors: Schwarzl M. , Alogna A. , Zirngast B. , Steendijk P. , Verderber J. , Zweiker D. , Huber S. , Maechler H. , Pieske B. M. , Post H. 
Published: December 2014

AbstractAimMild hypothermia (MH) decreases left ventricular (LV) end‐diastolic capacitance. We sought to clarify whether this results from incomplete relaxation.MethodsTen anaesthetized pigs were cooled from normothermia (NT, 38 °C) to MH (33 °C). LV end‐diastolic pressure (LVPed), volume (LVVed) and pressure–volume relationships (EDPVRs) were determined during stepwise right atrial pacing. LV capacitance (i.e. LVVed at LVPed of 10 mmHg, LV VPed10) was derived from the EDPVR. Pacing‐induced changes of diastolic indices (LVPed, LVVed and LV VPed10) were analysed as a function of (i) heart rate and (ii) the ratio between diastolic time interval (t‐dia) and LV isovolumic relaxation constant τ, which was calculated using a logistic fit (τL) and monoexponential fit with zero asymptote (τZ) and nonzero asymptote (τNZ).ResultsMild hypothermia decreased heart rate (85 ± 4 to 68 ± 3 bpm), increased τL (22 ± 1 to 57 ± 4 ms), τZ (26 ± 2 to 56 ± 5 ms) and τNZ (41 ± 1 to 96 ± 5 ms), decreased t‐dia/τ ratios, and shifted the EDPVR leftwards compared to NT (all P < 0.05). During NT, pacing at ≥140 bpm shifted the EDPVR progressively leftwards. During MH, relationships between diastolic indices and heart rate were shifted towards lower heart rates compared to NT. However, relationships between diastolic indices and t‐dia/τ during NT and MH were superimposable.ConclusionWe conclude that the loss of LV end‐diastolic capacitance during MH can be explained at least in part by slowed LV relaxation. MH thereby is an example of incomplete LV relaxation at a spontaneous low heart rate. Caution may be advised, when heart rate is increased in patients treated with MH.
Initial therapy, persistence and regimen change in a cohort of newly treated type 2 diabetes patients
Authors: Grimes Ronan T. , Bennett Kathleen , Tilson Lesley , Usher Cara , Smith Susan M. , Henman Martin C. 
Published: December 2014

AimsThe aim was to describe the utilization of antidiabetic agents, in terms of persistence and regimen change, in the management of a cohort of newly treated type 2 diabetes patients and to investigate associated socio‐demographic and treatment factors.MethodsA population‐based retrospective cohort study was conducted using the national pharmacy claims database in Ireland. Subjects were analyzed for persistence and regimen change. Cox proportional hazards regression examined associations of socio‐demographic and treatment factors on treatment patterns. Hazard ratios (HR) and 95% CIs are presented.ResultsA total of 20947 subjects were identified in the study over a 2 year period. Most were initiated on metformin (76%) or sulphonylureas (22%) and 77% were persistent with therapy 12 months after initiation. The likelihood of non‐persistence was significantly lower in the youngest (40–49 years) age groups (reference 60–69 years) (HR 1.62, 95% CI 1.42, 1.84) and those on sulphonylureas (HR 1.49, 95% CI 1.36, 1.64). The likelihood of receiving a regimen change was significantly lower in the older (80+ years) age groups (HR 0.63, 95% CI 0.56, 0.71), females (HR 0.91, 95% CI 0.86, 0.95), and those with pre‐existing CVD (1 vs. 0 CVD medicines) (HR 0.82, 95% CI 0.74, 0.90), and higher in those on sulphonylureas (HR 1.83, 95% CI 1.73, 1.94).ConclusionsType of treatment, pre‐existing CVD and demographic factors are shown to be associated with the observed treatment patterns. Guideline recommended agents were widely used on treatment initiation though a substantial minority were not initiated on the recommended first line agent. Use of guideline recommended agents was not as evident during treatment progression. Further optimization of initial and subsequent antidiabetic agent prescribing may be possible.
Performance and interpretation of spirometry among Swedish hospitals
Authors: Belfrage Björn , Hansson Anders , Bake Björn 
Published: December 2014

AbstractBackground and AimsIt is unclear to what extent spirometric performance and interpretation is standardized in Sweden. The aim of this study was to find out how spirometry is performed and interpreted in large Swedish hospitals.MethodsIn telephone interviews, technicians and physicians working with lung function measurements at 21 large Swedish hospitals were interviewed about routines for spirometry.ResultsAnswers were obtained from 37 of the 42 departments contacted revealing differences in the spirometric routines. Some departments lack a written method description, and three different prediction equations were used among the departments. Different ways of calculating the forced expiratory volume in 1 s (FEV1)/vital capacity (VC) ratio (FEV%) were found and also differences in performance and interpretation of the reversibility test. When diagnosing chronic obstructive pulmonary disease, none of the departments reported using an individualized diagnostic limit of FEV1/VC based on age, sex and height.ConclusionThere is a need for standardization of performance and interpretation of the spirometry test in Sweden and probably also in other countries.