bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin acts as an atypical KCNQ1/KCNE1‐current activator and reverses long QT in insulin‐resistant aged rats by accelerating the ventricular action potential repolarization through affecting the β3‐adrenergic receptor signaling pathway
Authors: Olgar Yusuf , Durak Aysegul , Bitirim Ceylan V. , Tuncay Erkan , Turan Belma 
Published: October 2021

AbstractInsufficient‐heart function is associated with myocardial insulin resistance in the elderly, particularly associated with long‐QT, in a dependency on dysfunctional KCNQ1/KCNE1‐channels. So, we aimed to examine the contribution of alterations in KCNQ1/KCNE1‐current (IKs) to the aging‐related remodeling of the heart as well as the role of insulin treatment on IKsin the aged rats. Prolonged late‐phase action potential (AP) repolarization of ventricular cardiomyocytes from insulin‐resistant 24‐month‐old rats was significantly reversed by in vitro treatment of insulin or PKG inhibitor (in vivo, as well) via recovery in depressed IKs. Although the protein level of either KCNQ1 or KCNE1 in cardiomyocytes was not affected with aging, PKG level was significantly increased in those cells. The inhibited IKsin β3‐ARs‐stimulated cells could be reversed with a PKG inhibitor, indicating the correlation between PKG‐activation and β3‐ARs activation. Furthermore, in vivo treatment of aged rats, characterized by β3‐ARs activation, with either insulin or a PKG inhibitor for 2 weeks provided significant recoveries in IKs, prolonged late phases of APs, prolonged QT‐intervals, and low heart rates without no effect on insulin resistance. In vivo insulin treatment provided also significant recovery in increased PKG and decreased PIP2 level, without the insulin effect on the KCNQ1 level in β3‐ARs overexpressed cells. The inhibition of IKsin aged‐rat cardiomyocytes seems to be associated with activated β3‐ARs dependent remodeling in the interaction between KCNQ1 and KCNE1. Significant recoveries in ventricular‐repolarization of insulin‐treated aged cardiomyocytes via recovery in IKsstrongly emphasize two important issues: (1) IKscan be a novel target in aging‐associated remodeling in the heart and insulin may be a cardioprotective agent in the maintenance of normal heart function during the aging process. (2) This study is one of the first to demonstrate insulin's benefits on long‐QT in insulin‐resistant aged rats by accelerating the ventricular AP repolarization through reversing the depressed IKsvia affecting the β3‐ARs signaling pathway and particularly affecting activated PKG.
Human leukocyte antigen class I association with occult hepatitis B virus infection in the Shaanxi Han group: Analysis at the haplotype level
Authors: Wang Tianju , Qi Jun , Li Hengxin , Chen Liping , Liu Sheng , Shen Chunmei 
Published: October 2021

AbstractBackgroundHuman leucocyte antigen (HLA) class I genes and haplotypes correlate with hepatitis B virus (HBV) infection. Occult HBV infection (OBI), a special type of chronic HBV infection, is defined as HBV surface antigen negative patients with or those without serologic markers by the means of HBV DNA detection in human plasma or in liver tissue by a diagnostic test. So far, the associations of HLA I haplotypes with OBI have not been reported previously in China.MethodsA case–control study between 107 OBI subjects and 280 healthy controls from blood donors in the Blood Center of the Shaanxi Province was conducted in the present association analysis. The HLA‐A, ‐B and ‐C loci of case–control subjects were detected and genotyped by polymerase chain reaction‐sequence based typing. The HLA‐A, ‐B and ‐C haplotypic frequencies were calculated by the maximum likelihood method.ResultsThe HLA‐A*33:03‐C*07:01G (pc = 0.039, odds ratio [OR] = 8.996, 95% confidence interval [CI] = 1.825–44.338), B*44:03‐C*07:01G (pc = 0.0069, OR = 12.000, 95% CI = 2.507–57.436) and A*33:03‐B*44:03‐C*07:01G (pc = 0.04, OR = 7.094, 95% CI = 1.387–36.288) haplotypes showed a a significant positive association with OBI. Independent effects demonstrated that HLA‐B*44:03 and HLA‐C*07:01G gave the main contribution to risk, whereas HLA‐A*33:03 was associated only by linkage disequilibrium.ConclusionsThis present study is the first to demonstrate that HLA I haplotypes are associated with OBI in the Shaanxi Han population. The present results suggest that HLA‐B*44:03‐C*07:01G might be a potential risk factor for OBI.Comparisons of the frequencies of HLA I haplotypes at high resolution were made between OBI from northern Chinese Han and controls. Frequencies of HLA‐A‐B, A‐C, B‐C, A‐B‐C between the OBI group (gray column) and the control group (blank column) were compared. Haplotypes with p < 0.05 in either group were shown. p values for multiple comparisons (pc) were corrected by Bonferroni correction (*pc < 0.05).
Design, synthesis, biological evaluation, and molecular docking studies of some novel N,N‐dimethylaminopropoxy‐substituted aurones
Authors: Kumar Gourav , Saroha Bhavna , Kumar Ramesh , Kumari Meena , Dalal Sunita , Kumar Suresh 
Published: October 2021

AbstractIn continuation of our ongoing research on the discovery of novel and potentially bioactive aurones, we have designed and synthesized some novel N,N‐dimethylaminopropoxy‐substituted pyrazole‐based aurones 10(a‐l). These pyrazole‐benzofuranone hybrid compounds were characterized by using their IR, 1H‐NMR, 13C‐NMR, and mass spectrometry data. Compound 10c was used as a model to further explicate the structure of tilted compounds by means of 1H‐1H COSY, 1H‐13C HMQC, 1H‐13C HMBC, 1H‐1H TOCSY, 1H‐1H NOSEY, DEPT‐45°, DEPT‐90°, and DEPT‐135° NMR spectra. The comparative molecular docking study of N,N‐dimethylaminopropoxy‐substituted pyrazole‐based aurones and standard drugs (Ampicillin and Chloramphenicol) against Bacillus subtilis (PDB: 6tzp) active site was performed to determine the binding interactions, binding energy, and orientation of the molecules at the active site of the target protein. Out of these synthesized compounds, five best analogs (10b, 10f, 10h, 10k, and 10l) of docking results were also evaluated for their in vitro antibacterial potential against Bacillus subtilis to validate the docking results.
Polymer Photonic Crystal Waveguides Generated by Femtosecond Laser
Authors: Roth Gian‐Luca , Kefer Stefan , Hessler Steffen , Esen Cemal , Hellmann Ralf 
Published: October 2021

AbstractFemtosecond laser‐based fabrication of integrated photonic crystal waveguides inside of a transparent polymer is reported. In general, the fabrication of waveguides based on femtosecond laser‐induced positive refractive index modifications is feasible. However, in transparent polymers their performance is limited since only minor refractive index changes can be achieved with this technique. These restrictions can be circumvented by generating hexagonal “photonic lattice like” waveguides, which consist of negative refractive index modifications in the cladding, enabling light confinement in the unirradiated core. A comprehensive study on the fabrication of this new class of polymer waveguide is performed as well as a characterization of its numerical aperture, mode field diameter, and attenuation. In addition, integration of Bragg gratings based on positive and negative refractive index modulations within the waveguide's core is studied. Moreover, we highlight that polymer photonic crystal waveguides are compatible with common femtosecond laser‐based internal structuring processes, enabling the creation of monolithic optofluidic devices, which is demonstrated by the fabrication of a Fabry–Pérot interferometer.
Gradient based iterative methods for solving symmetric tensor equations
Authors: Li Tao , Wang Qing‐Wen , Zhang Xin‐Fang 
Published: October 2021

AbstractThe steepest descent and conjugate gradient methods are classical gradient based iterative methods for solving symmetric positive definite linear system . In this article, we are concerned with the numerical solution of the tensor equation by those well‐known iterations in which is an mth order n‐dimensional symmetric tensor. Then we prove that the developed iterative methods converge locally linearly under some appropriate conditions. Finally, some numerical experiments are provided to illustrate the feasibility and effectiveness of the proposed methods.
On a marching level‐set method for extended discontinuous Galerkin methods for incompressible two‐phase flows: Application to two‐dimensional settings
Authors: Smuda Martin , Kummer Florian 
Published: October 2021

AbstractIn this work a solver for two‐dimensional, instationary two‐phase flows on the basis of the extended discontinuous Galerkin (extended DG/XDG) method is presented. The XDG method adapts the approximation space conformal to the position of the interface. This allows a subcell accurate representation of the incompressible Navier‐Stokes equations in their sharp interface formulation. The interface is described as the zero set of a signed‐distance level‐set function and discretized by a standard DG method. For the interface, resp. level‐set, evolution an extension velocity field is used and a two‐staged algorithm is presented for its construction on a narrow‐band. On the cut‐cells a monolithic elliptic extension velocity method is adapted and a fast‐marching procedure on the neighboring cells. The spatial discretization is based on a symmetric interior penalty method and for the temporal discretization a moving interface approach is adapted. A cell agglomeration technique is utilized for handling small cut‐cells and topology changes during the interface motion. The method is validated against a wide range of typical two‐phase surface tension driven flow phenomena in a 2D setting including capillary waves, an oscillating droplet and the rising bubble benchmark.
Bootstrapping octagons in reduced kinematics from A2 cluster algebras
Authors: He Song , Li Zhenjie , Tang Yichao , Yang Qinglin 
Published: October 2021

Abstract
Multi-loop scattering amplitudes/null polygonal Wilson loops in $$ \mathcal{N} $$
N
= 4 super-Yang-Mills are known to simplify significantly in reduced kinematics, where external legs/edges lie in an 1 + 1 dimensional subspace of Minkowski spacetime (or boundary of the AdS3 subspace). Since the edges of a 2n-gon with even and odd labels go along two different null directions, the kinematics is reduced to two copies of G(2, n)/T ∼ An−3. In the simplest octagon case, we conjecture that all loop amplitudes and Feynman integrals are given in terms of two overlapping A2 functions (a special case of two-dimensional harmonic polylogarithms): in addition to the letters v, 1 + v, w, 1 + w of A1 × A1, there are two letters v − w, 1 − vw mixing the two sectors but they never appear together in the same term; these are the reduced version of four-mass-box algebraic letters. Evidence supporting our conjecture includes all known octagon amplitudes as well as new computations of multi-loop integrals in reduced kinematics. By leveraging this alphabet and conditions on first and last entries, we initiate a bootstrap program in reduced kinematics: within the remarkably simple space of overlapping A2 functions, we easily obtain octagon amplitudes up to two-loop NMHV and three-loop MHV. We also briefly comment on the generalization to 2n-gons in terms of A2 functions and beyond.
Notes on the post-bounce background dynamics in bouncing cosmologies
Authors: An Ok Song , Kang Jin U , Kim Thae Hyok , Mun Ui Ri 
Published: October 2021

Abstract
We investigate the post-bounce background dynamics in a certain class of single bounce scenarios studied in the literature, in which the cosmic bounce is driven by a scalar field with negative exponential potential such as the ekpyrotic potential. We show that those models can actually lead to cyclic evolutions with repeated bounces. These cyclic evolutions, however, do not account for the currently observed late-time accelerated expansion and hence are not cosmologically viable. In this respect we consider a new kind of cyclic model proposed recently and derive some cosmological constraints on this model.
Exact symmetries and threshold states in two-dimensional models for QCD
Authors: Dempsey Ross , Klebanov Igor R. , Pufu Silviu S. 
Published: October 2021

Abstract
Two-dimensional SU(N) gauge theory coupled to a Majorana fermion in the adjoint representation is a nice toy model for higher-dimensional gauge dynamics. It possesses a multitude of “gluinoball” bound states whose spectrum has been studied using numerical diagonalizations of the light-cone Hamiltonian. We extend this model by coupling it to Nf flavors of fundamental Dirac fermions (quarks). The extended model also contains meson-like bound states, both bosonic and fermionic, which in the large-N limit decouple from the gluinoballs. We study the large-N meson spectrum using the Discretized Light-Cone Quantization (DLCQ). When all the fermions are massless, we exhibit an exact $$ \mathfrak{osp} $$
osp
(1|4) symmetry algebra that leads to an infinite number of degeneracies in the DLCQ approach. More generally, we show that many single-trace states in the theory are threshold bound states that are degenerate with multi-trace states. These exact degeneracies can be explained using the Kac-Moody algebra of the SU(N) current. We also present strong numerical evidence that additional threshold states appear in the continuum limit. Finally, we make the quarks massive while keeping the adjoint fermion massless. In this case too, we observe some exact degeneracies that show that the spectrum of mesons becomes continuous above a certain threshold. This demonstrates quantitatively that the fundamental string tension vanishes in the massless adjoint QCD2 without explicit four-fermion operators.
Warum ist die HPV-Impfung von Jungen sinnvoll?
Authors: Joura Elmar A. , Joura Marie Isolde 
Published: October 2021

ZusammenfassungUrsprünglich als Impfung gegen Gebärmutterhalskrebs geplant, haben HPV(humane Papillomviren)-Impfungen unsere Erwartungen weit übertroffen. Sie haben das Potenzial, bei Frauen und Männern mindestens 6 Karzinomtypen, deren Vorstufen sowie Genitalwarzen zu verhindern und sogar zu eliminieren. Nach 14 Jahren Anwendung wissen wir, dass HPV-Impfprogramme hocheffektiv sind, frühe Impfung und eine gute Durchimpfungsrate sind wesentlich. Geschlechtsneutrale Impfungen verdoppeln potenziell die Durchimpfungsrate. Das ist vor allem in Ländern mit einer Durchimpfungsrate von < 70 % zur Erlangung eines Herdenschutzes von Bedeutung. Oropharyngeale Karzinome nehmen immer mehr zu, betreffen vor allem Männer und werden durch HPV 16 verursacht. Ebenso werden das Anal- und das Peniskarzinom durch HPV hervorgerufen und sind daher vermeidbar. Ein geschlechtsneutrales HPV-Impfprogramm schützt alle – auch homosexuelle – Männer direkt.
Elevated blood pressure, antihypertensive medications and bone health in the population: revisiting old hypotheses and exploring future research directions
Authors: Canoy D. , Harvey N. C. , Prieto-Alhambra D. , Cooper C. , Meyer H. E. , Åsvold B. O. , Nazarzadeh M. , Rahimi K. 
Published: October 2021

AbstractBlood pressure and bone metabolism appear to share commonalities in their physiologic regulation. Specific antihypertensive drug classes may also influence bone mineral density. However, current evidence from existing observational studies and randomised trials is insufficient to establish causal associations for blood pressure and use of blood pressure–lowering drugs with bone health outcomes, particularly with the risks of osteoporosis and fractures. The availability and access to relevant large-scale biomedical data sources as well as developments in study designs and analytical approaches provide opportunities to examine the nature of the association between blood pressure and bone health more reliably and in greater detail than has ever been possible. It is unlikely that a single source of data or study design can provide a definitive answer. However, with appropriate considerations of the strengths and limitations of the different data sources and analytical techniques, we should be able to advance our understanding of the role of raised blood pressure and its drug treatment on the risks of low bone mineral density and fractures. As elevated blood pressure is highly prevalent and blood pressure–lowering drugs are widely prescribed, even small effects of these exposures on bone health outcomes could be important at a population level.
Tau-Functions and Monodromy Symplectomorphisms
Authors: Bertola M. , Korotkin D. 
Published: October 2021

AbstractWe derive a new Hamiltonian formulation of Schlesinger equations in terms of the dynamical r-matrix structure. The corresponding symplectic form is shown to be the pullback, under the monodromy map, of a natural symplectic form on the extended monodromy manifold. We show that Fock–Goncharov coordinates are log-canonical for the symplectic form. Using these coordinates we define the symplectic potential on the monodromy manifold and interpret the Jimbo–Miwa–Ueno tau-function as the generating function of the monodromy map. This, in particular, solves a recent conjecture by A. Its, O. Lisovyy and A. Prokhorov.
Efficient breeding of industrial brewing yeast strains using CRISPR/Cas9-aided mating-type switching
Authors: Krogerus Kristoffer , Fletcher Eugene , Rettberg Nils , Gibson Brian , Preiss Richard 
Published: October 2021

Abstract
Yeast breeding is a powerful tool for developing and improving brewing yeast in a number of industry-relevant respects. However, breeding of industrial brewing yeast can be challenging, as strains are typically sterile and have large complex genomes. To facilitate breeding, we used the CRISPR/Cas9 system to generate double-stranded breaks in the MAT locus, generating transformants with a single specified mating type. The single mating type remained stable even after loss of the Cas9 plasmid, despite the strains being homothallic, and these strains could be readily mated with other brewing yeast transformants of opposite mating type. As a proof of concept, we applied this technology to generate yeast hybrids with an aim to increase β-lyase activity for fermentation of beer with enhanced hop flavour. First, a genetic and phenotypic pre-screening of 38 strains was carried out in order to identify potential parent strains with high β-lyase activity. Mating-competent transformants of eight parent strains were generated, and these were used to generate over 60 hybrids that were screened for β-lyase activity. Selected phenolic off-flavour positive (POF +) hybrids were further sporulated to generate meiotic segregants with high β-lyase activity, efficient wort fermentation, and lack of POF, all traits that are desirable in strains for the fermentation of modern hop-forward beers. Our study demonstrates the power of combining the CRISPR/Cas9 system with classic yeast breeding to facilitate development and diversification of brewing yeast.

Key points
• CRISPR/Cas9-based mating-type switching was applied to industrial yeast strains.
• Transformed strains could be readily mated to form intraspecific hybrids.
• Hybrids exhibited heterosis for a number of brewing-relevant traits.
The intestinal flora of patients with GHPA affects the growth and the expression of PD-L1 of tumor
Authors: Nie Ding , Fang Qiuyue , Cheng Jianhua , Li Bin , Li Mingxuan , Wang Hongyun , Li Chuzhong , Gui Songbai , Zhang Yazhuo , Zhao Peng 
Published: October 2021

Abstract
Context
Pituitary adenoma (PA) is a common intracranial tumor. The evidence indicates that the tumor immune microenvironment (TIME) is associated with PA and that the intestinal flora influences other tumors' growth through interacting with the TIME. However, how the intestinal microbial flora contributes to the development of PA through the immune response is unknown.

Objective and methods
Here we used high-throughput Illumina MiSeq sequencing targeting the V3−V4 region of the 16S ribosomal RNA gene to investigate the intestinal flora of patients with growth hormone-secreting pituitary adenoma (GHPA), nonfunctional pituitary adenoma (NFPA), and healthy controls. We determined their effects on tumor growth and the TIME. Fecal microbiota transplantation (FMT) was performed after adoptive transfer via peripheral blood mononuclear cells to tumor-bearing nude mice, which allowed the study of the immune response.

Result
We discovered differences in the structures and quantities of intestinal flora between patients with GHPA, patients with NFPA, and healthy controls. After FMT, the intestinal flora of GHPA patients promoted the growth of tumors in mouse models. The number of programmed cell death ligand 1 (PD-L1)-positive cells increased in tumor tissues as well as the extent of infiltration of CD8+ cells. Increased numbers of CD3+CD8+ cells and increased levels of sPD-L1 were detected in peripheral blood.

Conclusion
These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.
Characterizing the surface texture of a dense suspension undergoing dynamic jamming
Authors: Rømcke Olav , Peters Ivo R. , Hearst R. Jason 
Published: October 2021

Abstract
Measurements of the surface velocity and surface texture of a freely propagating shear jamming front in a dense suspension are compared. The velocity fields are captured with particle image velocimetry (PIV), while the surface texture is captured in a separated experiment by observing a direct reflection on the suspension surface with high-speed cameras. A method for quantifying the surface features and their orientation is presented based on the fast Fourier transform of localized windows. The region that exhibits strong surface features corresponds to the the solid-like jammed region identified via the PIV measurements. Moreover, the surface features within the jammed region are predominantly oriented in the same direction as the eigenvectors of the strain tensor. Thus, from images of the free surface, our analysis is able to show that the surface texture contains information on the principle strain directions and the propagation of the jamming front.

Graphic Abstract
The use of deep learning on endoscopic images to assess the response of rectal cancer after chemoradiation
Authors: Haak Hester E. , Gao Xinpei , Maas Monique , Waktola Selam , Benson Sean , Beets-Tan Regina G. H. , Beets Geerard L. , van Leerdam Monique , Melenhorst Jarno 
Published: October 2021

AbstractBackgroundAccurate response evaluation is necessary to select complete responders (CRs) for a watch-and-wait approach. Deep learning may aid in this process, but so far has never been evaluated for this purpose. The aim was to evaluate the accuracy to assess response with deep learning methods based on endoscopic images in rectal cancer patients after neoadjuvant therapy.MethodsRectal cancer patients diagnosed between January 2012 and December 2015 and treated with neoadjuvant (chemo)radiotherapy were retrospectively selected from a single institute. All patients underwent flexible endoscopy for response evaluation. Diagnostic performance (accuracy, area under the receiver operator characteristics curve (AUC), positive- and negative predictive values, sensitivities and specificities) of different open accessible deep learning networks was calculated. Reference standard was histology after surgery, or long-term outcome (>2 years of follow-up) in a watch-and-wait policy.Results226 patients were included for the study (117(52%) were non-CRs; 109(48%) were CRs). The accuracy, AUC, positive- and negative predictive values, sensitivity and specificity of the different models varied from 0.67–0.75%, 0.76–0.83%, 67–74%, 70–78%, 68–79% to 66–75%, respectively. Overall, EfficientNet-B2 was the most successful model with the highest diagnostic performance.ConclusionsThis pilot study shows that deep learning has a modest accuracy (AUCs 0.76-0.83). This is not accurate enough for clinical decision making, and lower than what is generally reported by experienced endoscopists. Deep learning models can however be further improved and may become useful to assist endoscopists in evaluating the response. More well-designed prospective studies are required.