bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auf Lysin zielende, kovalente Inhibitoren
Authors: Pettinger Jonathan , Jones Keith , Cheeseman Matthew D. 
Published: September 2017

AbstractZielgerichtete kovalente Inhibitoren haben in der Wirkstoffentwicklung breite Beachtung gefunden, da sie in der Onkologie eine validierte Methode zur Verhinderung erworbener Resistenzen bieten. Dabei werden die Kristallstrukturen der Komplexe von Proteinen mit niedermolekularen Verbindungen verwendet, um fest bindende Liganden mit passend positionierten elektrophilen Gefechtsköpfen (“warheads”) zu entwickeln. Der Schwerpunkt liegt zwar auf Cysteinresten als Bindungsstellen, aber auch nukleophile Lysinreste können einen Zugang zu irreversibler Inhibierung bieten. Allerdings sind mit dieser Methode wegen der Basizität der ϵ‐Aminogruppe in Lysin eine Reihe spezifischer Herausforderungen verbunden. Wir besprechen hier die wichtigen Grundlagen für die Inhibitorplanung, geben historische Beispiele und stellen neue Entwicklungen vor, die das Potenzial von Lysin als Konjugationsstelle in der Wirkstoff‐Forschung belegen.
Highly Ordered, Ultralong Mn‐Based Nanowire Films with Low Contact Resistance as Freestanding Electrodes for Flexible Supercapacitors with Enhanced Performance
Authors: Zhou Junli , Yu Lin , Deng Yulin , Yang Yin , Hao Zhifeng , Sun Ming 
Published: September 2017

AbstractNanowires (NWs) have attracted considerable scientific interest in fabricating high‐performance electronic and optical devices. In particular, highly ordered NWs could exhibit unique properties such as good intrinsic electrical conductivity and fast electron transportation. In this work, freestanding films from ultralong manganese dioxide/polyaniline (MNW/PANI) coaxial NWs (ca. 200 μm) with a highly ordered structure have been fabricated at the oil/water interface and then used as flexible electrodes. The ultralong MNW/PANI coaxial NWs with highly ordered orientation provide a longer and continuous electron transportation pathway in the electrode compared to disordered NWs, which could greatly reduce the inter‐junction resistance between NWs in a film to achieve a high capacitance. The electrodes based on ordered NWs show a much lower contact resistance (10.8 Ω cm−2) compared with the randomly oriented ones (96.5 Ω cm−2). The thin film supercapacitor (TFSC) based on well‐ordered MNW/PANI NWs possesses mechanical flexibility, a high specific capacitance of 64.54 mF cm−2 (corresponding to 121.77 F g−1 at a mass loading density of 0.53 mg cm−2), a high energy/powder density (44.80 mWh cm−3, 580 mW cm−3), as well as good cycle stability with high capacitance retention (98 %) after 2000 cycles.
Heli(aza)cene: A Helical Molecular Tweezer with Tunable Intra‐ and Intermolecular Charge Transfer
Authors: Kumar Rajesh , Semwal Shrivats , Choudhury Joyanta , Srivastava Aasheesh 
Published: September 2017

AbstractNon‐planar fluorophores offer unique avenues of intra‐ and intermolecular energy transfer not available in their planar counterparts. We have rationally designed a molecular tweezer based on the pyridine‐2,6‐dicarboxamide framework having two structurally similar arms with extended π‐surface. We termed this molecular tweezer as Heli(aza)cene (HAC) due to its spontaneous adoption of helical conformation stabilized by the amide and imine moieties present in it. In the helical conformation, the two arms of HAC are twisted unequally. This asymmetry confers dissimilar electronic character to the two arms and results in intramolecular charge transfer interactions in HAC. Homochiral stacking of the P‐ and the M‐ helices in crystal, and profound redshifting of the emission at higher concentrations of HAC was attributed to intermolecular charge‐transfer interactions in aggregated/crystal state. Exposure of HAC, in solution as well as in the solid state, to Lewis/Brønsted acids results in rapid and vibrant color changes. This is the first example of a π‐layered helical molecule exhibiting tunable intra‐/intermolecular charge‐transfer characteristics.
Cultivation and quantitative single‐cell analysis of Saccharomyces cerevisiae on a multifunctional microfluidic device
Authors: Stratz Simone , Verboket Pascal Emilio , Hasler Karina , Dittrich Petra Stephanie 
Published: September 2017

AbstractHere, we present a multifunctional microfluidic device whose integrative design enables to combine cell culture studies and quantitative single cell biomolecule analysis. The platform consists of 32 analysis units providing two key features; first, a micrometer‐sized trap for hydrodynamic capture of a single Saccharomyces cerevisiae (S. cerevisiae) yeast cell; second, a convenient double‐valve configuration surrounding the trap. Actuating of the outer valve with integrated opening results in a partial isolation in a volume of 11.8 nL, i.e. the cell surrounding fluid can be exchanged diffusion‐based without causing shear stress or cell loss. Actuation of the inner ring‐shaped valve isolates the trapped cell completely in a small analysis volume of 230 pL. The device was used to determine the growth rate of yeast cells (S. cerevisiae) under under optimum and oxidative stress conditions. In addition, we successfully quantified the cofactor beta‐nicotinamide adenine dinucleotide phosphate (NAD(P)H) in single and few cells exposed to the different microenvironments. In conclusion, the microdevice enables to analyze the influence of an external stress factor on the cellular fitness in a fast and more comprehensive way as cell growth and intracellular biomolecule levels can be investigated.
Inhibition of fermentation evolution in bread doughs for aroma analyses
Authors: Pico Joana , Bernal José , Nozal María Jesús , Gómez Manuel 
Published: September 2017

AbstractThe inhibition of the residual fermentation in bread doughs, in order to avoid its evolution, could be crucial to achieve reliable qualitative aroma analyses. Several options have emerged up until now, but they present some drawbacks. In this study, a mixture of methyl octanoate and methyl decanoate (Fames) has been suggested as a non‐toxic alternative to the traditional use of mercuric chloride (HgCl2). Rheofermentometric analyses revealed that although HgCl2 is quicker, Fames solution is highly effective in less than 20 min. Moreover, when HgCl2 was added to 90 min fermented dough, it exhibited an unexpected behavior with a high release of CO2 without the generation of ethyl alcohol, which could affect the dough structure. SHS‐GC/MS analyses of ethyl alcohol and 2/3‐methyl‐1‐butanol corroborated the rheofermentometer's results, with a visible reduction in the peak areas and significant differences in the One‐way Anova between Fames doughs and blank doughs. The application of the Fames solution to SPME‐GC/MS‐QTof analyses involved a reduction in the areas regarding the blank without interferences, showing a logical progression of the volatile compounds over the fermentation time, increasing their concentration from 0 to 90 min. This progression was normally lost when the inhibitors were not added, since the yeast acted in an uncontrolled manner due to the changes of temperature during freezing, thawing or chromatographic analyses, leading to wrong aroma results.
Enantioselective syntheses and sensory properties of 2‐Alken‐4‐olides
Authors: Dai Yifeng , Liu Yongguo , Sun Baoguo , Yang Shaoxiang , Tian Hongyu 
Published: September 2017

AbstractA series of optically active 2‐alken‐4‐olides of C6‐C11 were obtained with 89–97% enantiomeric excess (ee) values by the Sharpless asymmetric dihydroxylation (AD) of methyl (E)‐3‐alkenoates, followed by elimination via mesylates. The odor features and thresholds of the enantiomers were determined by means of chiral gas chromatography‐olfactory (GC‐O). The data revealed that all the samples exhibited stereospecific differences in sensory properties. Both enantiomers of 2‐octen‐4‐olide had the two lowest odour thresholds, whereas two enantiomers of 2‐undecen‐4‐olide presented the two highest odour thresholds.
Double‐outlet left ventricle with a bicuspid pulmonary valve and aortic coarctation
Authors: Sun Feifei , Fan Miao , Huang Liping , Ren Weidong , Li Dongyu 
Published: September 2017

AbstractA double‐outlet left ventricle (DOLV) is a rare congenital cardiac malformation. Here, we describe a case of DOLV with bicuspid pulmonary valve, aortic coarctation, and a subpulmonary ventricular septal defect in which both ventricles were well developed. The anatomic features were observed with echocardiography, and the diagnosis was confirmed at surgery. Many variations of DOLV have been described. The features of our case expand the spectrum of this entity and may provide new insight into its complex anatomy.
Levodopa treatment and dendritic spine pathology
Authors: Nishijima Haruo , Ueno Tatsuya , Funamizu Yukihisa , Ueno Shinya , Tomiyama Masahiko 
Published: September 2017

ABSTRACTParkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission. Recent studies using rodent models have reported dendritic spine head enlargement in the caudate‐putamen, nucleus accumbens, primary motor cortex, and prefrontal cortex in cases where chronic levodopa treatment following dopaminergic denervation induced dyskinesia‐like abnormal involuntary movement. Hypertrophy of spines results from insertion of alpha‐amino‐2,3‐dihydro‐5‐methyl‐3‐oxo‐4‐isoxazolepropanoic acid receptors into the postsynaptic membrane. Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa‐induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. This synaptic plasticity may be one of the mechanisms underlying the priming of levodopa‐induced complications such as levodopa‐induced dyskinesia and dopamine dysregulation syndrome. Drugs that could potentially prevent spine enlargement, such as calcium channel blockers, N‐methyl‐D‐aspartate receptor antagonists, alpha‐amino‐2,3‐dihydro‐5‐methyl‐3‐oxo‐4‐isoxazolepropanoic acid receptor antagonists, and metabotropic glutamate receptor antagonists, are candidates for treatment of levodopa‐induced complications in PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
The Circadian expression of Piezo1, TRPV4, Connexin26, and VNUT, associated with the expression levels of the clock genes in mouse primary cultured urothelial cells
Authors: Ihara Tatsuya , Mitsui Takahiko , Nakamura Yuki , Kanda Mie , Tsuchiya Sachiko , Kira Satoru , Nakagomi Hiroshi , Sawada Norifumi , Hirayama Yuri , Shibata Keisuke , Shigetomi Eiji , Shinozaki Yoichi , Yoshiyama Mitsuharu , Nakao Atsuhito , Takeda Masayuki , Koizumi Schuichi 
Published: September 2017

AimsTo investigate circadian gene expressions in the mouse bladder urothelium to establish an experimental model and study the functions of the circadian rhythm.MethodsThe gene expression rhythms of the clock genes, mechano‐sensors such as Piezo1 and TRPV4, ATP release mediated molecules (ARMM) such as Cx26 and VNUT were investigated in mouse primary cultured urothelial cells (UCs) of wild‐type (WT) and Clock mutant (ClockΔ19/Δ19) mice using quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) and western blotting analysis. The long‐term oscillation of the clock genes in UC was investigated by measuring bioluminescence from UC isolated from Period2luciferase knock‐in mice (Per2::luc) and Per2::luc with ClockΔ19/Δ19 using a luminometer. The mRNA expression rhythms after treatment with Clock short interfering RNA (siRNA) were also measured to compare differences between Clock point mutations and Clock deficiency.ResultsThe UCs from WT mice showed the time‐dependent gene expressions for clock genes, mechano‐sensors, and ARMM. The abundances of the products of these genes also correlated with the mRNA expression rhythms in UCs. The bioluminescence of Per2::Luc in UCs showed a circadian rhythm. By contrast, all the gene expressions rhythms observed in WT mice were abrogated in the ClockΔ19/Δ19 mice. Transfection with Clock siRNA in UCs had the same effect as the Clock mutation.ConclusionsWe demonstrated that the time‐dependent gene expressions, including clock genes, mechano‐sensors, and ARMM, were reproducible in UCs. These findings demonstrated that UCs have the potential to progress research into the circadian functions of the lower urinary tract regulated by clock genes.
The Impact of Power and Civic Engagement in the Decentralized Management of Natural Resources: The Case of Turkey
Authors: Kadirbeyoglu Zeynep 
Published: September 2017

SummaryDecentralization is an extensively discussed topic within academic and institutional circles worldwide. While a common argument for decentralization is that it fosters democratic deepening, counterarguments cautiously point to unequal access to resources and distribution of power as factors that inhibit democratization. This study contributes to the literature on the relationship between decentralization and democratization through a comparative study of Water User Associations in two provinces of Turkey and shows in line with the literature that resource and power inequalities hamper the link between decentralization and democratization. However, as this article shows, civic engagement can generate “countervailing power” that can overcome the negative impact of such inequalities. Copyright © 2017 John Wiley & Sons, Ltd.
Inhibition of retroviral Gag assembly by non-silencing miRNAs promotes autophagic viral degradation
Authors: Qu Na , Ma Zhao , Zhang Mengrao , Rushdi Muaz N , Krueger Christopher J , Chen Antony K 
Published: September 2017

AbstractWe recently reported an unconventional mechanism by which miRNAs inhibit HIV-1 viral production. This occurs when miRNAs bind nonspecifically to the viral structural protein Gag, interfering with viral RNA-mediated Gag assembly at the plasma membrane. Consequently, misassembled viral complexes are redirected into the endocytic pathway where they are delivered to lysosomes for degradation. In this study, we demonstrate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific. Misassembled viral complexes were found to colocalize extensively with LC3 and p62 in late endosomes/lysosomes, demonstrating a convergence of autophagy with functional degradative compartments. Knocking down autophagosome formation machineries reduced this convergence, while treatment with autophagy-inducer rapamycin enhanced the convergence. Furthermore, similar autophagy-dependent nonspecific miRNA inhibition of murine leukemia virus (MLV) assembly was shown. Overall, these results reveal autophagy as a crucial regulator of the retroviral degradation pathway in host cells initiated by nonspecific miRNA-Gag interactions. These findings could have significant implications for understanding how cells may regulate retroviral complex assembly by miRNA expression and autophagy, and raise the possibility that similar regulations can occur in other biological contexts.
Human Rights Experimentalism
Authors: de Búrca Gráinne 
Published: September 2017

AbstractHuman rights in general and the international human rights system in particular have come under increasing attack in recent years. Quite apart from the domestic and global political events since 2016, including an apparent retreat from international institutions, the human rights system has in recent times come in for severe criticism from academic scholars. Amongst the various criticisms levelled have been: (1) the ineffectiveness and lack of impact of international human rights regimes, (2) the ambiguity and lack of specificity of human rights standards, (3) the weakness of international human rights enforcement mechanisms, and (4) the claim to universalism of human rights standards coupled with the hegemonic imposition of these standards on diverse parts of the world. This article responds to several of those criticisms by introducing the idea of experimentalist governance, interpreting key aspects of the functioning of certain international human rights treaties from the perspective of experimentalist governance theory, and surveying a body of recent scholarship on the effectiveness of such treaties. Contrary to the depiction of international human rights regimes as both ineffective and top-down, the article argues that they function at their best as dynamic, participatory, and iterative systems. Experimentalist governance offers a theory of the causal effectiveness of human rights treaties, brings to light a set of features and interactions that are routinely overlooked in many accounts, and suggests possible avenues for reform of other human rights treaty regimes with a view to making them more effective in practice.
Emulating single point bearing faults with the use of an active magnetic bearing
Authors: Corne Bram , Vervisch Bram , Derammelaere Stijn , Knockaert Jos , Desmet Jan 
Published: September 2017

The propagation of evolving mechanical faults in rotating electric machinery and their corresponding signatures in the machines’ electrical signals is still not elucidated thoroughly. This deficiency implies serious obstructions in the development of using those signals as a complete and reliable condition monitoring technology. This study presents a new method to translate single point outer and inner race bearing faults into specific movements of the rotor with respect to the stator. The method contains the excitation of a simplified mass‐spring‐damper bearing model by analytical constructed fault‐related force functions. Furthermore, a novel approach in order to emulate those obtained specific fault‐related rotor movements with the use an experimental test setup is described, dimensioned, simulated and validated. Replacing the drive‐end bearing of the induction machine under test by an active magnetic bearing creates the opportunity to continuously manipulate the rotor's position. The estimated single point bearing fault‐related rotor movements serve as set‐point for the magnetic bearing, resulting in the achievement of a single point bearing fault emulator with high relevance and reproducibility. This study includes experimental results of an emulated single point outer race bearing fault on an 11 kW induction machine.
Die Therapie und Prognose des refraktären und super-refraktären Status epilepticus
Authors: Gollwitzer Stephanie , Hamer Hajo 
Published: September 2017

ZusammenfassungEin Status epilepticus, der über 60 Minuten andauert und durch die Gabe von Benzodiazepinen und nicht-sedierenden Antikonvulsiva der Stufe 2 nicht beendet werden kann, wird als refraktär bezeichnet. Wenn der Status auch nach i. v.-Anästhetikagabe über 24 Stunden nicht durchbrochen werden kann, wird er als super-refraktär definiert. Zur Therapie des refraktären Status epilepticus (RSE) wird eine Kombination aus nicht-sedierenden Antikonvulsiva und i. v.-Anästhetika eingesetzt; Medikamente der ersten Wahl sind dabei Midazolam, Propofol und Thiopental. Zur Behandlung des super-refraktären Status epilepticus (SRSE) existieren keine klaren evidenz-basierten Empfehlungen, Therapieerfahrungen stützen sich überwiegend auf Einzelfallberichte und kleine Fallserien. Eingesetzt werden Ketamin, Inhalationsanästhetika, Steroide und Immunglobuline. An nicht-medikamentösen Verfahren kommen die ketogene Diät, die Elektrokonvulsionstherapie und die Epilepsiechirurgie in Betracht. Ein neues, vielversprechendes Behandlungskonzept stellt das Neurosteroid Allopregnanolon dar. Die Mortalität des RSE und SRSE hängt von der Ätiologie des Status ab und ist insgesamt deutlich höher als die des nicht-refraktären Status. In publizierten Fallserien lag sie bei ca. 30 % bzw. 50 %.
What Is the Optimal Time to Retest Patients With a Urogenital Chlamydia Infection? A Randomized Controlled Trial
Authors: van der Helm Jannie J. , Koekenbier Rik H. , van Rooijen Martijn S. , Schim van der Loeff Maarten F. , de Vries Henry J.C. 
Published: September 2017

Background

Chlamydia trachomatis is a common, often recurring sexually transmitted infection, with serious adverse outcomes in women. Current guidelines recommend retesting after a chlamydia infection, but the optimum timing is unknown. We assessed the optimal retest interval after urogenital chlamydia treatment.

Methods
A randomized controlled trial among urogenital chlamydia nucleic acid amplification test positive heterosexual clients of the Amsterdam sexually transmitted infection clinic. After treatment, patients were randomly assigned for retesting 8, 16, or 26 weeks later. Patients could choose to do this at home (and send a self-collected sample by mail) or at the clinic. Retest uptake and chlamydia positivity at follow-up were calculated.

Results
Between May 2012 and March 2013, 2253 patients were included (45% men; median age, 23 years; interquartile range, 21–26). The overall uptake proportion within 35 weeks after the initial visit was significantly higher in the 8-week group (77%) compared with the 16- and 26-week groups (67% and 64%, respectively, P < 0.001), and the positivity proportions among those retested were comparable (P = 0.169). The proportion of people with a diagnosed recurrent chlamydia infection among all randomized was similar between the groups (n = 69 [8.6%], n = 52 [7.4%], and n = 69 [9.3%]; P = 0.4).

Conclusions
Patients with a recent urogenital chlamydia are at high risk of recurrence of chlamydia and retesting them is an effective way of detecting chlamydia cases. We recommend inviting patients for a re-test 8 weeks after the initial diagnosis and treatment.
Comparison of Postoperative Pain and Residual Gas Between Restrictive and Liberal Fluid Therapy in Patients Undergoing Laparoscopic Cholecystectomy
Authors: Yao Lei , Wang Yulan , Du Boxiang , Song Jie , Ji Fuhai 
Published: September 2017

Background:
Different fluid regimens are used in the clinical management of perioperative fluid therapy, but there still is the argument about which fluid regimen is better for patients. This study was mainly designed to compare different fluid regimens on postoperative pain and residual gas in patients undergoing laparoscopic cholecystectomy.

Methods:
A total of 100 patients were equally randomized to receive restrictive fluid infusion (n=50) with lactated Ringer (LR) solution 5 mL/kg/h or liberal fluid infusion (n=50), with 30 mL/kg/h lactated Ringer solution. Postoperative pain was evaluated at 1, 6, and 24 hours after surgery using a visual analog scale (VAS). Postoperative subdiaphragmatic residual gas was monitored by x-ray at 24 hours after surgery.

Results:
Patients in the restrictive group had significantly higher VAS pain scores at 6 hours after surgery than those in the liberal group (P=0.009). The incidence of subdiaphragmatic residual gas in the restrictive group was higher than in the liberal group (P=0.045). Patients who had residual gas had higher VAS pain scores than those with no residual gas in the restrictive group at 6 hours after surgery (P=0.02).

Conclusions:
Patients undergoing laparoscopic cholecystectomy with restrictive fluid therapy may suffer more severe postoperative pain than those receiving liberal fluid therapy. It suggests that the higher incidence of subdiaphragmatic residual gas may have occurred with restrictive fluid therapy.