bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Flow Synthesis of Tumor Neoantigen Peptides for Personalized Immunotherapy
Authors: Truex Nicholas L. , Holden Rebecca L. , Wang Bin-You , Chen Pu-Guang , Hanna Stephanie , Hu Zhuting , Shetty Keerthi , Olive Oriol , Neuberg Donna , Hacohen Nir , Keskin Derin B. , Ott Patrick A. , Wu Catherine J. , Pentelute Bradley L. 
Published: January 2020

AbstractHigh-throughput genome sequencing and computation have enabled rapid identification of targets for personalized medicine, including cancer vaccines. Synthetic peptides are an established mode of cancer vaccine delivery, but generating the peptides for each patient in a rapid and affordable fashion remains difficult. High-throughput peptide synthesis technology is therefore urgently needed for patient-specific cancer vaccines to succeed in the clinic. Previously, we developed automated flow peptide synthesis technology that greatly accelerates the production of synthetic peptides. Herein, we show that this technology permits the synthesis of high-quality peptides for personalized medicine. Automated flow synthesis produces 30-mer peptides in less than 35 minutes and 15- to 16-mer peptides in less than 20 minutes. The purity of these peptides is comparable with or higher than the purity of peptides produced by other methods. This work illustrates how automated flow synthesis technology can enable customized peptide therapies by accelerating synthesis and increasing purity. We envision that implementing this technology in clinical settings will greatly increase capacity to generate clinical-grade peptides on demand, which is a key step in reaching the full potential of personalized vaccines for the treatment of cancer and other diseases.
Atrial fibrillation is associated with lean body mass in postmenopausal women
Authors: Worm Marie S. , Bager Cecilie L. , Blair Joseph P. M. , Secher Niels H. , Riis Bente J. , Christiansen Claus , Nielsen Henning B. 
Published: January 2020

AbstractThis study investigated the association between body composition and risk of atrial fibrillation (AF) in postmenopausal women. In a retrospective analysis we assessed data from 5704 postmenopausal women (age 70.7 ± 6.5 yrs.) who in 1999–2001 participated in The Prospective Epidemiological Risk Factor study with body composition assessed by dual-energy X-ray absorptiometry. Outcomes were obtained from Danish Health Registries and body composition association to risk of AF was evaluated by univariable and multivariable Cox Hazard regression. 850 women developed AF after baseline. High lean body mass was associated with increased risk of AF in multivariable analyses, adjusting for body mass index (BMI), height or weight (adjusted for: BMI, hazard ratio (HR) 1.49, 95% Confidence Interval (1.22–1.80); height, HR 1.27 (1.03–1.56); weight, 1.33 (1.06–1.65)). Height and weight were associated with increased risk of AF in multivariable analyses adjusting for body composition measures. When adjusting for total lean mass, only height remained statistically significant (HR 1.34 (1.09–1.64)). In a cohort of elderly Caucasian women, high lean body mass, height and weight were associated with increased risk of AF and the variables remained significant after adjusting for age and other known risk factors of AF.
Binding of myeloperoxidase to the extracellular matrix of smooth muscle cells and subsequent matrix modification
Authors: Cai Huan , Chuang Christine Y. , Hawkins Clare L. , Davies Michael J. 
Published: January 2020

AbstractThe extracellular matrix (ECM) of tissues is susceptible to modification by inflammation-associated oxidants. Considerable data support a role for hypochlorous acid (HOCl), generated by the leukocyte-derived heme-protein myeloperoxidase (MPO) in these changes. HOCl can modify isolated ECM proteins and cell-derived matrix, with this resulting in decreased cell adhesion, modulated proliferation and gene expression, and phenotypic changes. Whether this arises from free HOCl, or via site-specific reactions is unresolved. Here we examine the mechanisms of MPO-mediated changes to human coronary smooth muscle cell ECM. MPO is shown to co-localize with matrix fibronectin as detected by confocal microscopy, and bound active MPO can initiate ECM modification, as detected by decreased antibody recognition of fibronectin, versican and type IV collagen, and formation of protein carbonyls and HOCl-mediated damage. These changes are recapitulated by a glucose/glucose oxidase/MPO system where low continuous fluxes of H2O2are generated. HOCl-induced modifications enhance MPO binding to ECM proteins as detected by ELISA and MPO activity measurements. These data demonstrate that MPO-generated HOCl induces ECM modification by interacting with ECM proteins in a site-specific manner, and generates alterations that increase MPO adhesion. This is proposed to give rise to an increasing cycle of alterations that contribute to tissue damage.
Dopamine-induced calcium signaling in olfactory bulb astrocytes
Authors: Fischer Timo , Scheffler Paula , Lohr Christian 
Published: January 2020

AbstractIt is well established that astrocytes respond to the major neurotransmitters glutamate and GABA with cytosolic calcium rises, whereas less is known about the effect of dopamine on astroglial cells. In the present study, we used confocal calcium imaging in mouse brain slices of the olfactory bulb, a brain region with a large population of dopaminergic neurons, to investigate calcium signaling evoked by dopamine in astrocytes. Our results show that application of dopamine leads to a dose-dependent cytosolic calcium rise in astrocytes (EC50 = 76 µM) which is independent of neuronal activity and mainly mediated by PLC/IP3-dependent internal calcium release. Antagonists of both D1- and D2-class dopamine receptors partly reduce the dopaminergic calcium response, indicating that both receptor classes contribute to dopamine-induced calcium transients in olfactory bulb astrocytes.
Reclamation of hexavalent chromium using catalytic activity of highly recyclable biogenic Pd(0) nanoparticles
Authors: Tripathi R. M. , Chung Sang J. 
Published: January 2020

AbstractHexavalent chromium is extremely toxic and increasingly prevalent owing to industrialisation, thereby posing serious human health and environmental risks. Therefore, new approaches for detoxifying high concentrations of Cr (VI) using an ultralow amount of catalyst with high recyclability are increasingly being considered. The catalytic conversion of Cr (VI) into Cr (III) was previously reported; however, it required a large amount of catalyst to reduce a low concentration of Cr (VI); further, pH adjustment and catalyst separation had to be performed, causing issues with large-scale remediation. In this study, an unprecedented eco-friendly and cost-effective method was developed for the synthesis of Pd nanoparticles (PdNPs) with a significantly narrow size distribution of 3–25 nm. PdNPs demonstrated the presence of elemental Pd with the zero oxidation state when analysed by energy-dispersive X-ray analysis and X-ray photoelectron spectroscopy. The PdNPs could detoxify a high concentration of Cr (VI), without the need to adjust the pH or purify the nanoparticles for reusability. The reusability of the PdNPs for the catalytic conversion of Cr (VI) into Cr (III) was >90% for subsequent cycles without the further addition of formic acid. Thus, the study provides new insights into the catalytic reclamation of Cr (VI) for industrial wastewater treatment.
Tunable Electronic, Optical, and Thermal Properties of two- dimensional Germanene via an external electric field
Authors: Chegel Raad , Behzad Somayeh 
Published: January 2020

AbstractIn this paper, we present a tight-binding model based on DFT calculations for investigation the electronic and optical properties of monolayer Germanene. The thermal properties are investigated using Green function method. The required tight binding parameters including the onsite energies and third nearest neighbors hopping and overlap integrals are obtained based on our DFT calculations. Germanene is a semiconductor with zero band gap and linear band dispersion around the K point. The band gap opening occurs in the presence of bias voltage. The band gap is increased linearly with increase of the bias voltage strength. The tight binding results for position of the two first peaks in the optical Infrared region is same with the DFT results. By applying and increasing bias voltage, the dielectric function shows the blue shift by reduction the peak intensity in the energy range E < 1 eV. The thermal conductivity and heat capacity increase with increasing the temperature due to the increasing of thermal energy of charge carriers and excitation them to the conduction bands. The thermal properties of Germanene in the absence of bias U = 0 is larger than that U ≠ 0 and they decrease by further bias strength increasing, due to the increasing band gap with bias.
Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models
Authors: Ando Kentaro , Wada Takeshi , Cao Xin 
Published: January 2020

AbstractCancer chemotherapies have improved prognosis in cancer patients, resulting in a large and rapidly increasing number of cancer survivors. “Onco-cardiology” or “cardio-oncology” is a new discipline for addressing the unanticipated cardiac side effects of newly developed cancer drugs. Lapatinib, a tyrosine kinase inhibitor suppressing the epidermal growth factor receptor and ErbB2, has been used in advanced or metastatic breast cancer treatment. Reportedly, lapatinib has induced cardiovascular adverse events including QT-interval prolongation and heart failure. However, they have not been predicted by preclinical studies. Hence, a new method to assess the tyrosine kinase inhibitor-induced adverse effects needs to be established. Here, we intravenously administered lapatinib to halothane-anaesthetised dogs, evaluating cardiohemodynamic, electrophysiological, and echocardiographic profiles for pharmacological safety assessments. We intravenously administered lapatinib to chronic atrioventricular block beagle dogs to assess its proarrhythmic potential. The therapeutic concentration of lapatinib significantly increased total peripheral vascular resistance, QT, QTc, monophasic action potential (MAP)90(sinus), MAP90(CL400), effective refractory period, and plasma concentration of cardiac troponin I (cTnI), suggesting that lapatinib prolonged the ventricular repolarization without inducing lethal ventricular arrhythmia. Careful monitoring of plasma cTnI concentration and an electrocardiogram could be supportive biomarkers, predicting the onset of lapatinib-induced cardiovascular adverse events.
Influence of temperature change in donor corneas on postoperative endothelium cell density following endothelial transplantation
Authors: Kakisu Koji , Yamaguchi Takefumi , Shimazaki Jun 
Published: January 2020

AbstractTo examine the influence on postoperative endothelial cell density (ECD) caused by preoperative temperature change from 4 °C to room temperature in donor corneas for Descemet stripping automated endothelial keratoplasty (DSAEK). This retrospective, case-controlled comparison of 100 eyes that underwent DSAEK using imported donor corneas transferred from an overseas eye bank (SightLife, Seattle, WA, USA). Fifty donor corneas experienced temperature reversal for ECD measurement (TR group), and postoperative outcomes were compared with 50 disease-matched cases that did not experience temperature changes before DSAEK (NTR group). The main outcome measure was endothelial cell loss and reduction rate of ECD at 1, 3, and 6 months following DSAEK. ECD at 3 months following DSAEK was significantly less in the TR group (1458 ± 494/mm2) than in the NTR group (1696 ± 374/mm2; P = 0.014), though ECD at 6 months was not significantly less in the TR group. The reduction rate of ECD at 3 months was greater in the TR group (42.3% ± 17.2%) than in the NTR group (35.7% ± 14.2%; P = 0.044), though reduction rate of ECD at 6 months was not significantly less in the TR group. We found that preoperative temperature change in donor corneas may adversely affect ECD following DSAEK.
Sensing mechanism of a ratiometric near-infrared fluorescent chemosensor for cysteine hydropersulfide: Intramolecular charge transfer
Authors: Sun Xiaofei , Gao Aihua , Zhang Hongxing 
Published: January 2020

AbstractPrevious studies have shown that the cysteine hydropersulfide (Cys-SSH) as the sulfur donor is crucial to sulfur-containing cofactors synthesis. Recently, a selective and sensitive near-infrared ratiometric fluorescent chemosensor Cy-DiSe has been designed and synthesized to detect Cys-SSH spontaneously. Herein, by means of the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) approaches, the sensing mechanism has been thoroughly explored. According to our calculations, the experimental data have been reproduced. The results indicate the intramolecular charge transfer (ICT) is the reason for changes in fluorescence wavelengths. Compared with the chemosensor Cy-DiSe, the larger energy gap of Cy induced by ICT mechanism leads to the blue-shift of the absorption and emission spectra, which guarantees that Cy-DiSe can become a ratiometric fluorescent chemosensor to detect Cys-SSH.
Quantum read-out for cold atomic quantum simulators
Authors: Gluza M. , Schweigler T. , Rauer B. , Krumnow C. , Schmiedmayer J. , Eisert J. 
Published: January 2020

AbstractQuantum simulators allow to explore static and dynamical properties of otherwise intractable quantum many-body systems. In many instances, however, the read-out limits such quantum simulations. In this work, we introduce an innovative experimental read-out exploiting coherent non-interacting dynamics. Specifically, we present a tomographic recovery method allowing to indirectly measure the second moments of the relative density fluctuations between two one-dimensional superfluids, which until now eluded direct measurements. Applying methods from signal processing, we show that we can reconstruct the relative density fluctuations from non-equilibrium data of the relative phase fluctuations. We employ the method to investigate equilibrium states, the dynamics of phonon occupation numbers and even to predict recurrences. The method opens a new window for quantum simulations with one-dimensional superfluids, enabling a deeper analysis of their equilibration and thermalization dynamics.
Association of single nucleotide polymorphisms of MTHFR, TCN2, RNF213 with susceptibility to hypertension and blood pressure
Authors: Liu Shan , Liu Mengwei , Li Qian , Liu Xiuping , Wang Yue , Mambiya Michael , Zhang Kaili , Yang Luping , Zhang Qian , Shang Mengke , Zeng Fanxin , Nie Fangfang , Liu Wanyang 
Published: January 2020

Abstract
Methylenetetrahydrofolate reductase gene (MTHFR), transcobalaminII (TCN2) and ring finger protein 213 (RNF213) are related to homocysteine (Hcy) level and are of great significance for hypertension. We aimed to evaluate the associations of MTHFR (rs1801133, rs1801131, rs9651118), TCN2 (rs117353193) and RNF213 (rs9916351) with hypertension and blood pressure (BP). A total of 953 patients with hypertension and 1103 controls were enrolled. Genotyping was performed by Taqman. Logistic regression analysis indicated that A allele of TCN2 rs117353193 under the dominant model had a significantly protective effect (P=0.045) after adjustment, which showed that AA+GA genotype has a lower risk than GG. Additionally, the average diastolic BP (DBP) (P=0.044) and mean arterial pressure (MAP) (P=0.035) levels were significantly different between genotypes of RNF213 rs9916351. Further pairwise comparison showed that the average systolic BP (SBP) level of the TT genotype carriers were significantly higher than in CC (P=0.024), and the average DBP and MAP levels of the TT genotype carriers were higher than in CT (P=0.044, P=0.012, respectively) and CC (P=0.048, P=0.010, respectively). In the recessive model, the average SBP (P=0.043), DBP (P=0.018) and MAP (P=0.017) levels with the TT genotype carriers were significantly higher than in CT+CC. Multiple linear regression analysis suggested that RNF213 rs9916351 in the recessive model had significant effects on SBP (P=0.025), DBP (P=0.017) and MAP (P=0.010) as a risk factor. However, no associations were observed between MTHFR and hypertension. TCN2 rs117353193 might serve as a protective factor in hypertension, and RNF213 rs9916351 might be a risk factor that is linked to increase BP level in Northeast Chinese population.
Photo-induced protein oxidation: mechanisms, consequences and medical applications
Authors: Fuentes-Lemus Eduardo , López-Alarcón Camilo 
Published: January 2020

Abstract
Irradiation from the sun has played a crucial role in the origin and evolution of life on the earth. Due to the presence of ozone in the stratosphere most of the hazardous irradiation is absorbed, nonetheless UVB, UVA, and visible light reach the earth’s surface. The high abundance of proteins in most living organisms, and the presence of chromophores in the side chains of certain amino acids, explain why these macromolecules are principal targets when biological systems are illuminated. Light absorption triggers the formation of excited species that can initiate photo-modification of proteins. The major pathways involve modifications derived from direct irradiation and photo-sensitized reactions. In this review we explored the basic concepts behind these photochemical pathways, with special emphasis on the photosensitized mechanisms (type 1 and type 2) leading to protein oxidation, and how this affects protein structure and functions. Finally, a description of the photochemical reactions involved in some human diseases, and medical applications of protein oxidation are presented.
The challenge of detecting modifications on proteins
Authors: Smith Lauren Elizabeth , Rogowska-Wrzesinska Adelina 
Published: January 2020

AbstractPost-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.
Expected performances of the Characterising Exoplanet Satellite (CHEOPS)
Authors: Futyan D. , Fortier A. , Beck M. , Ehrenreich D. , Bekkelien A. , Benz W. , Billot N. , Bourrier V. , Broeg C. , Collier Cameron A. , Deline A. , Kuntzer T. , Lendl M. , Queloz D. , Rohlfs R. , Simon A. E. , Wildi F. 
Published: January 2020

Context. The CHaracterising ExOPlanet Satellite (CHEOPS) is a mission dedicated to the search for exoplanetary transits through high precision photometry of bright stars already known to host planets. The telescope will provide the unique capability of determining accurate radii for planets whose masses have already been measured from ground-based spectroscopic surveys. This will allow a first-order characterisation of the planets’ internal structure through the determination of the bulk density, providing direct insight into their composition. By identifying transiting exoplanets with high potential for in-depth characterisation, CHEOPS will also provide prime targets for future instruments suited to the spectroscopic characterisation of exoplanetary atmospheres.
Aims. The CHEOPS simulator has been developed to perform detailed simulations of the data which is to be received from the CHEOPS satellite. It generates accurately simulated images that can be used to explore design options and to test the on-ground data processing, in particular, the pipeline producing the photometric time series. It is, thus, a critical tool for estimating the photometric performance expected in flight and to guide photometric analysis. It can be used to prepare observations, consolidate the noise budget, and asses the performance of CHEOPS in realistic astrophysical fields that are difficult to reproduce in the laboratory.
Methods. The simulator has been implemented as a highly configurable tool called CHEOPSim, with a web-based user interface. Images generated by CHEOPSim take account of many detailed effects, including variations of the incident signal flux and backgrounds, and detailed modelling of the satellite orbit, pointing jitter and telescope optics, as well as the CCD response, noise and readout.
Results. The simulator results presented in this paper have been used in the context of validating the data reduction processing chain, in which image time series generated by CHEOPSim were used to generate light curves for simulated planetary transits across real and simulated targets. Independent analysts were successfully able to detect the planets and measure their radii to an accuracy within the science requirements of the mission: for an Earth-sized planet with an orbital period of 50 days orbiting a Sun-like target with magnitude V = 6, the median measured value of the planet to star radius ratio, Rp/Rs, was 0.00923 ± 0.00054(stat) ± 0.00019(syst), compared to a true input value of 0.00916. For a Neptune-sized planet with an orbital period of 13 days orbiting a target with spectral type K5V and magnitude V = 12, the median measured value of Rp/Rs was 0.05038 ± 0.00061(stat) ± 0.00031(syst), compared to a true input value of 0.05.
Convergence rates of high dimensional Smolyak quadrature
Authors: Zech Jakob , Schwab Christoph 
Published: January 2020

We analyse convergence rates of Smolyak integration for parametric maps u: U → X taking values in a Banach space X, defined on the parameter domain U = [−1,1]N. For parametric maps which are sparse, as quantified by summability of their Taylor polynomial chaos coefficients, dimension-independent convergence rates superior to N-term approximation rates under the same sparsity are achievable. We propose a concrete Smolyak algorithm to a priori identify integrand-adapted sets of active multiindices (and thereby unisolvent sparse grids of quadrature points) via upper bounds for the integrands’ Taylor gpc coefficients. For so-called “(b,ε)-holomorphic” integrands u with b∈lp(∕) for some p ∈ (0, 1), we prove the dimension-independent convergence rate 2/p − 1 in terms of the number of quadrature points. The proposed Smolyak algorithm is proved to yield (essentially) the same rate in terms of the total computational cost for both nested and non-nested univariate quadrature points. Numerical experiments and a mathematical sparsity analysis accounting for cancellations in quadratures and in the combination formula demonstrate that the asymptotic rate 2/p − 1 is realized computationally for a moderate number of quadrature points under certain circumstances. By a refined analysis of model integrand classes we show that a generally large preasymptotic range otherwise precludes reaching the asymptotic rate 2/p − 1 for practically relevant numbers of quadrature points.