bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling of substrate access and substrate binding to cephalosporin acylases
Authors: Ferrario Valerio , Fischer Mona , Zhu Yushan , Pleiss Jürgen 
Published: August 2019

AbstractSemisynthetic cephalosporins are widely used antibiotics currently produced by different chemical steps under harsh conditions, which results in a considerable amount of toxic waste. Biocatalytic synthesis by the cephalosporin acylase from Pseudomonas sp. strain N176 is a promising alternative. Despite intensive engineering of the enzyme, the catalytic activity is still too low for a commercially viable process. To identify the bottlenecks which limit the success of protein engineering efforts, a series of MD simulations was performed to study for two acylase variants (WT, M6) the access of the substrate cephalosporin C from the bulk to the active site and the stability of the enzyme-substrate complex. In both variants, cephalosporin C was binding to a non-productive substrate binding site (E86α, S369β, S460β) at the entrance to the binding pocket, preventing substrate access. A second non-productive binding site (G372β, W376β, L457β) was identified within the binding pocket, which competes with the active site for substrate binding. Noteworthy, substrate binding to the protein surface followed a Langmuir model resulting in binding constants K = 7.4 and 9.2 mM for WT and M6, respectively, which were similar to the experimentally determined Michaelis constants KM = 11.0 and 8.1 mM, respectively.
Pharmacologically reversible, loss of function mutations in the TM2 and TM4 inner pore helices of TREK-1 K2P channels
Authors: Al-Moubarak Ehab , Veale Emma L. , Mathie Alistair 
Published: August 2019

AbstractA better understanding of the gating of TREK two pore domain potassium (K2P) channels and their activation by compounds such as the negatively charged activator, flufenamic acid (FFA) is critical in the search for more potent and selective activators of these channels. Currents through wild-type and mutated human K2P channels expressed in tsA201 cells were measured using whole-cell patch-clamp recordings in the presence and absence of FFA. Mutation of the TM2.6 residue of TREK-1 to a phenylalanine (G171F) and a similar mutation of TM4.6 (A286F) substantially reduced current through TREK-1 channels. In complementary experiments, replacing the natural F residues at the equivalent position in TRESK channels, significantly enhanced current. Known, gain of function mutations of TREK-1 (G137I, Y284A) recovered current through these mutated channels. This reduction in current could be also be reversed pharmacologically, by FFA. However, an appropriate length MTS (MethaneThioSulfonate) cross-linking reagent (MTS14) restricted the activation of TREK-1_A286C channels by repeated application of FFA. This suggests that the cross-linker stabilises the channel in a conformation which blunts FFA activation. Pharmacologically reversible mutations of TREK channels will help to clarify the importance of these channels in pathophysiological conditions such as pain and depression.
Characterization of Hailey-Hailey Disease-mutants in presence and absence of wild type SPCA1 using Saccharomyces cerevisiae as model organism
Authors: Muncanovic Daniel , Justesen Mette Heberg , Preisler Sarah Spruce , Pedersen Per Amstrup 
Published: August 2019

AbstractHailey-Hailey disease is an autosomal genetic disease caused by mutations in one of the two ATP2C1 alleles encoding the secretory pathway Ca2+/Mn2+-ATPase, hSPCA1. The disease almost exclusively affects epidermis, where it mainly results in acantholysis of the suprabasal layers. The etiology of the disease is complex and not well understood. We applied a yeast based complementation system to characterize fourteen disease-causing ATP2C1 missense mutations in presence or absence of wild type ATP2C1 or ATP2A2, encoding SERCA2. In our yeast model system, mutations in ATP2C1 affected Mn2+ transport more than Ca2+ transport as twelve out of fourteen mutations were unable to complement Mn2+ sensitivity while thirteen out of fourteen to some extent complemented the high Ca2+requirement. Nine out of fourteen mutations conferred a cold sensitive complementation capacity. In absence of a wild type ATP2C1 allele, twelve out of fourteen mutations induced an unfolded protein response indicating that in vivo folding of hSPCA1 is sensitive to disease causing amino acid substitutions and four of the fourteen mutations caused the hSPCA1 protein to accumulate in the vacuolar membrane. Co-expression of either wild type ATP2C1 or ATP2A2 prevented induction of the unfolded protein response and hSPCA1 mis-localization.
RNA modulates aggregation of the recombinant mammalian prion protein by direct interaction
Authors: Kovachev Petar Stefanov , Gomes Mariana P. B. , Cordeiro Yraima , Ferreira Natália C. , Valadão Leticia P. Felix , Ascari Lucas M. , Rangel Luciana P. , Silva Jerson L. , Sanyal Suparna 
Published: August 2019

AbstractRecent studies have proposed that nucleic acids act as potential cofactors for protein aggregation and prionogenesis. By means of sedimentation, transmission electron microscopy, circular dichroism, static and dynamic light scattering, we have studied how RNA can influence the aggregation of the murine recombinant prion protein (rPrP). We find that RNA, independent of its sequence, source and size, modulates rPrP aggregation in a bimodal fashion, affecting both the extent and the rate of rPrP aggregation in a concentration dependent manner. Analogous to RNA-induced liquid-liquid phase transitions observed for other proteins implicated in neurodegenerative diseases, high protein to RNA ratios stimulate rPrP aggregation, while low ratios suppress it. However, the latter scenario also promotes formation of soluble oligomeric aggregates capable of seeding de novo rPrP aggregation. Furthermore, RNA co-aggregates with rPrP and thereby gains partial protection from RNase digestion. Our results also indicate that rPrP interacts with the RNAs with its N-terminus. In summary, this study elucidates the proposed adjuvant role of RNA in prion protein aggregation and propagation, and thus advocates an auxiliary role of the nucleic acids in protein aggregation in general.
Long-range vortex transfer in superconducting nanowires
Authors: Córdoba Rosa , Orús Pablo , Jelić Željko L. , Sesé Javier , Ibarra Manuel Ricardo , Guillamón Isabel , Vieira Sebastián , Palacios Juan José , Suderow Hermann , Milosević Milorad V. , De Teresa José María 
Published: August 2019

AbstractUnder high-enough values of perpendicularly-applied magnetic field and current, a type-II superconductor presents a finite resistance caused by the vortex motion driven by the Lorentz force. To recover the dissipation-free conduction state, strategies for minimizing vortex motion have been intensely studied in the last decades. However, the non-local vortex motion, arising in areas depleted of current, has been scarcely investigated despite its potential application for logic devices. Here, we propose a route to transfer vortices carried by non-local motion through long distances (up to 10 micrometers) in 50 nm-wide superconducting WC nanowires grown by Ga+ Focused Ion Beam Induced Deposition. A giant non-local electrical resistance of 36 Ω has been measured at 2 K in 3 μm-long nanowires, which is 40 times higher than signals reported for wider wires of other superconductors. This giant effect is accounted for by the existence of a strong edge confinement potential that hampers transversal vortex displacements, allowing the long-range coherent displacement of a single vortex row along the superconducting channel. Experimental results are in good agreement with numerical simulations of vortex dynamics based on the time-dependent Ginzburg-Landau equations. Our results pave the way for future developments on information technologies built upon single vortex manipulation in nano-superconductors.
Utilizing polarization-selective mode shaping by chalcogenide thin film to enhance the performance of graphene-based integrated optical devices
Authors: Nikbakht Hamed , Latifi Hamid , Parsanasab Gholam-Mohammad , Taghavi Majid , Riyahi Maryam 
Published: August 2019

AbstractHigh refractive index (RI) thin films are capable of pulling waveguide mode profiles towards themselves. In this study, it is shown that by applying high RI coatings with specific thicknesses on the side of optical waveguides, significantly different mode profiles for orthogonal polarizations can be achieved. This phenomenon, that we call it polarization-selective mode shaping, can be extensively used in the enhancement of polarization-dependent integrated optical devices. As an illustrating application, a tri-layer structure consisting of poly(methyl methacrylate)/graphene/chalcogenide on a side-polished fiber is designed to realize an extremely high extinction ratio polarizer. This structure changes the mode profiles in a way that the attenuation of TE mode is maximized, while the power carried by the TM mode remains relatively constant. Simulations and experimental characterizations confirm that polarization-selective mode shaping coordinates four loss mechanisms to maximize the extinction ratio and minimize the insertion loss of the polarizer. The fabricated polarizer is examined in the O, C, and L telecommunication frequency bands. This configuration achieves the high extinction ratio of 51.3 dB and its maximum insertion loss in the tested wavelengths is 1.79 dB. The proposed polarizer has been compared with other state-of-the-art polarizers in the conclusion section which shows its superiority.
Physical multimorbidity and subjective cognitive complaints among adults in the United Kingdom: a cross-sectional community-based study
Authors: Jacob Louis , Haro Josep Maria , Koyanagi Ai 
Published: August 2019

AbstractOur goal was to examine the association between physical multimorbidity and subjective cognitive complaints (SCC) using UK nationally representative cross-sectional community-based data, and to quantify the extent to which a broad range of mainly psychological and behavioral factors explain this relationship. Data from the 2007 Adult Psychiatric Morbidity Survey were analyzed [N = 7399 adults, mean (SD) age 46.3 (18.6) years, 48.6% men]. Multimorbidity was defined as ≥2 physical diseases. SCC included two different cognitive constructs: subjective concentration and memory complaints. Multivariable logistic regression and mediation analyses were conducted. Multimorbidity was associated with higher prevalence of subjective concentration (30.7% vs. 17.3%) and memory complaints (42.8% vs. 22.9%) compared to no multimorbidity. In the regression model adjusted for sociodemographics, multimorbidity was associated with subjective concentration (OR = 2.58; 95% CI = 2.25–2.96) and memory complaints (OR = 2.34; 95% CI = 2.08–2.62). Sleep problems, stressful life events and any anxiety disorder explained 21–23%, 20–22% and 14–15% of the multimorbidity-SCC association, respectively. Multimorbidity and SCC are highly co-morbid. The utility of SCC screening in identifying individuals at high risk for future cognitive decline among individuals with multimorbidity should be assessed.
Interference-free Detection of Lipid-laden Atherosclerotic Plaques by 3D Co-registration of Frequency-Domain Differential Photoacoustic and Ultrasound Radar Imaging
Authors: Choi Sung Soo Sean , Lashkari Bahman , Mandelis Andreas , Weyers Jill J. , Boyes Aaron , Foster Stuart F. , Alves-Kotzev Natasha , Courtney Brian 
Published: August 2019

AbstractAs lipid composition of atherosclerotic plaques is considered to be one of the primary indicators for plaque vulnerability, a diagnostic modality that can sensitively evaluate their necrotic core is highly desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection modality that provides lipid-specific chemical information of arterial walls. Within the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications because lipid exhibits a strong absorption peak at that wavelength. However, other arterial tissues also show some degree of absorption near 1210 nm and generate undesirable interfering PA signals. In this study, a novel wavelength-modulated Intravascular Differential Photoacoustic Radar (IV-DPAR) modality was introduced as an interference-free detection technique for a more accurate and reliable diagnosis of plaque progression. By using two low-power continuous-wave laser diodes in a differential manner, IV-DPAR could efficiently suppress undesirable absorptions and system noise, while dramatically improving system sensitivity and specificity to cholesterol, the primary ingredient of plaque necrotic core. When co-registered with intravascular ultrasound imaging, IV-DPAR could sensitively locate and characterize the lipid contents of plaques in human atherosclerotic arteries, regardless of their size and depth.
The clinical value and safety of ECG-gated dipyridamole myocardial perfusion imaging in patients with aortic stenosis
Authors: Liu Fang-Shin , Wang Shan-Ying , Shiau Yu-Chien , Wu Yen-Wen 
Published: August 2019

AbstractThe role of vasodilator myocardial perfusion imaging (MPI) for aortic stenosis (AS) is controversial due to safety and accuracy concerns. In addition, its utility after aortic valve (AV) interventions remains unclear. Patients with AS who underwent thallium-201-gated dipyridamole MPI using a cadmium-zinc-telluride camera were retrospectively reviewed and divided into three groups: mild AS, moderate-to-severe AS, and prior AV interventions. Patients with coronary artery disease with ≥50% stenosis, severe arrhythmia, left ventricular ejection fraction (LVEF) <40%, left bundle branch block or no follow-up were excluded. Relationships between the severity of AS, clinical characteristics, hemodynamic response, serious adverse events (SAE) and MPI parameters were analyzed. None of the 47 patients had SAE, including significant hypotension or LVEF reduction. The moderate-to-severe AS group had higher summed stress scores (SSSs) and depressed LVEF than the mild AS group, however there were no differences after AV interventions. SSS was positively correlated with AV mean pressure gradient, post-stress lung-heart ratio (LHRs), and post-stress end-diastolic volume (EDVs) (P < 0.05). In multivariate analysis, LHRs and EDVs were independent contributors to SSS. Dipyridamole-induced ischemia and LV dysfunction is common, and dipyridamole stress could be a safe diagnostic tool in evaluation and follow-up in patients with AS.
Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen
Authors: Mosser Eric A. , Chiu Cindy N. , Tamai T. Katherine , Hirota Tsuyoshi , Li Suna , Hui May , Wang Amy , Singh Chanpreet , Giovanni Andrew , Kay Steve A. , Prober David A. 
Published: August 2019

AbstractThe circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.
Effects of deep neuromuscular blockade on the stress response during laparoscopic gastrectomy Randomized controlled trials
Authors: Koo Bon-Wook , Oh Ah-Young , Ryu Jung-Hee , Lee Yea-Ji , Han Ji-Won , Nam Sun-Woo , Park Do-Jung , Seo Kwang-Suk 
Published: August 2019

AbstractMaintaining deep neuromuscular block during surgery improves surgical space conditions. However, its effects on patient outcomes have not been well documented. We examined whether maintaining deep neuromuscular blockade during surgery could decrease the stress response compared to moderate neuromuscular blockade. Patients undergoing laparoscopic gastrectomy were randomly allocated to either the moderate (train-of-four counts of 1–2) or deep (post-tetanic counts of 1–2) neuromuscular blockade group. The primary outcome variable was the postoperative blood level of interleukin-6, and the secondary outcome variables were intraoperative or postoperative blood levels of tumor necrosis factor-α, interleukin-1β, interleukin-8, and C-reactive protein. A total of 96 patients were recruited and 88 (44 in each group) were included in the analyses. The levels of tumor necrosis factor-α and interleukin-1β measured at the end of surgery, interleukin-6 and interleukin-8 measured at 2 h postoperatively, and C-reactive protein measured at 48 h postoperatively were all significantly increased compared to the preoperative values, but there were no differences between the moderate and deep neuromuscular block groups. We found no differences in surgical stress response measured using determining levels of interleukin-6 and other mediators released between the moderate and deep neuromuscular blockade groups in patients undergoing laparoscopic gastrectomy.
Selective and Preferential Separation of Rhodium (III) from Palladium (II) and Platinum (IV) Using a m-Phenylene Diamine-Containing Precipitant
Authors: Matsumoto Kazuya , Yamakawa Sumito , Haga Kazutoshi , Ishibashi Katsuyuki , Jikei Mitsutoshi , Shibayama Atsushi 
Published: August 2019

AbstractAlthough Rh is an industrially important and the most expensive platinum group metal (PGM), the selective and preferential separation of Rh from PGM mixtures still remains as a big challenge. In this work, the separation of Rh (III) from Pd (II) and Pt (IV) in a hydrochloric acid (HCl) solution was studied using am-phenylene diamine-containing precipitant (m-PDA). At high HCl concentrations (6.0–8.0 M), most of the Rh (III) (>90%) was precipitated, and Pd (II) and Pt (IV) were hardly precipitated (<5%). On the other hand, over 85% of Pd (II) and Pt (IV) precipitated along with small amount of Rh (III) (<25%) at low HCl concentrations (1.0–2.0 M). As a consequence,m-PDAenabled selective and preferential precipitation of Rh (III) at high HCl concentrations. XPS and TG analyses revealed that the Rh-containing precipitate is an ion-pair complex composed of one [RhCl6]3−anion and threem-PDAcations. The Rh desorption from the precipitate as well as the recovery ofm-PDAwas successfully achieved using an NH4OH solution. This method is a promising practical approach to Rh recovery.
Amorphous/Nanocrystalline Carbonized Hydrochars with Isomeric Heterogeneous Interfacial Polarizations for High-performance Microwave Absorption
Authors: Qi Yujie , Wei Dongchao , Shi Gui-Mei , Zhang Mu , Qi Yang 
Published: August 2019

AbstractCarbon allotropes and their derivatives have exhibited superior performances for microwave absorption ascribed to their dielectric attenuation capacity raised from the multiple dipolar configurations. Such characteristics could be achieved by constructing diverse micro/nanoscale architectures, incorporating vacancies and heteroatoms, and composing with heterogeneous components. Alternatively, we herein present a facile approach for the synthesis of carbonized hydrochars, which are composed of dispersed ultrafine nanocrystallines graphite and amorphous matrix. Such a isomeric construction has a high-density interfaces, accompanied with significant interfacial polarizations, leading to the improvement of microwave absorbing capabilities. For carbonized hydrochars, the RLmin value can reach −40.36 dB, and corresponding effective bandwidth is 2 GHz. This work provides a concept for designing microwave absorption materials based on isomeric heterogeneous interfacial polarizations in single-element systems.
Strong optical absorption of a metallic film to induce a lensing effect in the visible region
Authors: Jiang An-Qing , Zang Kai-Yan , Hu Er-Tao , Tu Hua-Tian , Xu Lei , Ren Wen-Shuai , Yoshie Osamu , Lee Young-Pak , Zheng Yu-Xiang , Wang Song-You , Zhao Hai-Bin , Guo Jun-Peng , Wang C. Z. , Ho K. M. , Lynch David. W. , Chen Liang-Yao 
Published: August 2019

AbstractIn this work, the two-dimensional profile of the light transmission through a prism-like metallic film sample of Au was measured at a wavelength of 632.8 nm in the visible intraband transition region to verify that, beyond the possible mechanisms of overcoming the diffraction limit, a strongly nonuniform optical absorption path length of the light traveling in the metal could induce a lensing effect, thereby narrowing the image of an object. A set of prism-like Au samples with different angles was prepared and experimentally investigated. Due to the nonuniform paths of the light traveling in the Au samples, lens-effect-like phenomena were clearly observed that reduced the imaged size of the beam spot with decreasing light intensity. The experimental measurements presented in the work may provide new insight to better understand the light propagation behavior at a metal/dielectric interface.
Perceptual Characteristics of Consonant Production in Apraxia of Speech and Aphasia
Authors: Bislick Lauren , Hula William D. 
Published: August 2019

Purpose
This retrospective analysis examined group differences in error rate across 4 contextual variables (clusters vs. singletons, syllable position, number of syllables, and articulatory phonetic features) in adults with apraxia of speech (AOS) and adults with aphasia only. Group differences in the distribution of error type across contextual variables were also examined.

Method
Ten individuals with acquired AOS and aphasia and 11 individuals with aphasia participated in this study. In the context of a 2-group experimental design, the influence of 4 contextual variables on error rate and error type distribution was examined via repetition of 29 multisyllabic words. Error rates were analyzed using Bayesian methods, whereas distribution of error type was examined via descriptive statistics.

Results
There were 4 findings of robust differences between the 2 groups. These differences were found for syllable position, number of syllables, manner of articulation, and voicing. Group differences were less robust for clusters versus singletons and place of articulation. Results of error type distribution show a high proportion of distortion and substitution errors in speakers with AOS and a high proportion of substitution and omission errors in speakers with aphasia.

Conclusion
Findings add to the continued effort to improve the understanding and assessment of AOS and aphasia. Several contextual variables more consistently influenced breakdown in participants with AOS compared to participants with aphasia and should be considered during the diagnostic process.

Supplemental Material

https://doi.org/10.23641/asha.9701690