bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional antibody characterization via direct structural analysis and information‐driven protein–protein docking
Authors: Depetris Rafael S. , Lu Dan , Polonskaya Zhanna , Zhang Zhikai , Luna Xenia , Tankard Amari , Kolahi Pegah , Drummond Michael , Williams Chris , Ebert Maximilian C. C. J. C. , Patel Jeegar P. , Poyurovsky Masha V.
Published: November 2021

Detailed description of the mechanism of action of the therapeutic antibodies is essential for the functional characterization and future optimization of potential clinical agents. We recently developed KD035, a fully human antibody targeting vascular endothelial growth factor receptor 2 (VEGFR2). KD035 blocked VEGF‐A, and VEGF‐C‐mediated VEGFR2 activation, as demonstrated by the in vitro binding and competition assays and functional cellular assays. Here, we report a computational model of the complex between the variable fragment of KD035 (KD035(Fv)) and the domains 2 and 3 of the extracellular portion of VEGFR2 (VEGFR2(D2‐3)). Our modeling was guided by a priori experimental information including the X‐ray structures of KD035 and related antibodies, binding assays, target domain mapping and comparison of KD035 affinity for VEGFR2 from different species. The accuracy of the model was assessed by molecular dynamics simulations, and subsequently validated by mutagenesis and binding analysis. Importantly, the steps followed during the generation of this model can set a precedent for future in silico efforts aimed at the accurate description of the antibody–antigen and more broadly protein–protein complexes.
Bioproduction of (Z,E)‐9,12‐tetradecadienyl acetate (ZETA), the major pheromone component of Plodia, Ephestia, and Spodoptera species in yeast
Authors: Ding Bao‐Jian , Wang Hong‐Lei , Al‐Saleh Mohammed Ali , Löfstedt Christer , Antony Binu
Published: November 2021

BACKGROUND

(Z,E)‐9,12‐tetradecadienyl acetate (ZETA, Z9,E12‐14:OAc) is a major sex pheromone component for many stored‐product moth species. This pheromone is used worldwide for mating disruption, detection, monitoring, and mass trapping in raw and processed food storage facilities. In this study, we demonstrate the biological production of ZETA pheromone by engineered yeast Saccharomyces cerevisiae.

RESULTS

We mined the pheromone gland transcriptome data of the almond moth, Ephestia (Cadra) cautella (Walker), to trace a novel E12 fatty acyl desaturase and expressed candidates heterologously in yeast and Sf9 systems. Furthermore, we demonstrated a tailor‐made ZETA pheromone bioproduction in yeast through metabolic engineering using this E12 desaturase, in combination with three genes from various sources coding for a Z9 desaturase, a fatty acyl reductase, and an acetyltransferase, respectively. Electrophysiological assays (gas chromatography coupled to an electroantennographic detector) proved that the transgenic yeast‐produced ZETA pheromone component elicits distinct antennal responses.

CONCLUSION

The reconstructed biosynthetic pathway in yeast efficiently produces ZETA pheromone, leaves an undetectable level of biosynthetic intermediates, and paves the way for the economically competitive high‐demand ZETA pheromone's bioproduction technology for high‐value storage pest control.
Magneto‐Optical Sensing Beyond the Shot Noise Limit
Authors: Pai Yun‐Yi , Marvinney Claire E. , Hua Chengyun , Pooser Raphael C. , Lawrie Benjamin J.
Published: November 2021

Magneto‐optical sensors including spin noise spectroscopies and magneto‐optical Kerr effect microscopies are now ubiquitous tools for materials characterization that can provide new understanding of spin dynamics, hyperfine interactions, spin‐orbit interactions, and charge‐carrier g‐factors. Both interferometric and intensity‐difference measurements can provide photon‐shot‐noise‐limited sensitivity, but further improvements in sensitivity with classical resources require either increased laser power that can induce unwanted heating and electronic perturbations or increased measurement times that can obscure out‐of‐equilibrium dynamics and slow experimental throughput. Proof‐of‐principle measurements have already demonstrated quantum enhanced spin noise measurements with a squeezed readout field that are likely to be critical to the nonperturbative characterization of spin excitations in quantum materials that emerge at low temperatures. Here, a truncated nonlinear interferometric readout for low‐temperature magneto‐optical Kerr effect and related magneto‐optical microscopies that is accessible with today's quantum optical resources is proposed. 10 sensitivity is achievable with optical power as small as 1 µW. As a result, measurements may be performed at temperatures as low as 83 mK in commercially available dilution refrigerators. This combination of high sensitivity and low operating temperature is impossible to achieve with any classical measurement. The quantum advantage for the proposed measurements persists even in the limit of large loss and small squeezing parameters.
Sharpness of the phase transition for parking on random trees
Authors: Contat Alice
Published: November 2021

Recently, a phase transition phenomenon has been established for parking on random trees. We extend the results of Curien and Hénard on general Bienaymé–Galton–Watson trees and allow different car arrival distributions depending on the vertex outdegrees. We then prove that this phase transition is sharp by establishing a large deviations result for the flux of exiting cars. This has consequences on the offcritical geometry of clusters of parked spots which displays similarities with the classical Erdős–Renyi random graph model.
Teacher enactment of the crosscutting concepts in next generation science classrooms
Authors: Marckwordt Jasmine , Nguyen Kimberly , Z. Boxerman Jonathan , Iveland Ashley
Published: November 2021

This exploratory qualitative study examined science teacher enactment of crosscutting concepts (CCCs), a core aspect of Next Generation Science Standards (NGSS) three‐dimensional learning, which also includes disciplinary core ideas and science and engineering practices (SEPs). We collected naturalistic observational and interview data from 13 California teachers involved in a major NGSS implementation initiative and analyzed this data by applying four roles of the CCCs in instruction as described by Rivet et al. (2016). The roles these conceptual resources play are: lens, bridge, tool, and rules of the game. Using this schema, we provide thick description of teachers' different purposes for, modes of, and challenges in using CCCs in their instruction. Naturalistic observations provided information about how teachers were using CCCs in their classrooms while interview data revealed the opportunities and challenges teachers perceived in CCC enactment, both of which are little addressed within the emerging body of CCC research. Teachers received extensive professional development (PD) on the NGSS but nevertheless identified CCC enactment as particularly challenging. For this reason, we suggest the four roles of the CCCs, which were indeed reflected in our data set, could be a helpful framework for making the CCCs more accessible and understandable to teachers, and thus more likely to be incorporated into everyday science instruction to enhance student learning. We envision future use of this framework as an epistemic heuristic having the potential to bring more clarity to CCC enactment for researchers, teachers, curriculum developers, and PD providers.
Same‐sex marriage laws, LGBT hate crimes, and employment discrimination charges
Authors: Nikolaou Dimitrios
Published: November 2021

The impact of same‐sex marriage laws on the victimization of sexual minorities has not received much attention in the literature. Using state‐level panel data within a difference‐in‐differences framework, I examine how the legalization of same‐sex marriage affects hate crimes. The results show that same‐sex marriage laws decrease sexual orientation‐motivated hate crimes, with stronger effects on gay men. This is consistent with the laws increasing tolerance toward and acceptance of lesbian, gay, bisexual, and transgender individuals, further supported by complementary analysis from Google Trends data. This is also the first study to examine the effects of marriage equality on allegations of employment discrimination due to sexual orientation based on information from the U.S. Equal Employment Opportunity Commission. The findings support that marriage equality laws have an additional beneficial effect: the laws not only decrease hate crimes, but they also decrease the incidence of employment discrimination (at worst, the laws do not affect discriminatory practices).
Sulfonyl and Carbonyl Groups in MSTC Effectively Improve the Performance and Stability of Perovskite Solar Cells
Authors: Zhou Ruonan , Liu Xingchong , Li Haimin , Wang Hanyu , Ouyang Yukun , Gong Xiaoli , Peng Xian , Luo Huxin , Ni Yafei , Zou Wenjing , Lei Yue
Published: November 2021

Intrinsic defects are key factors that would affect the performance and stability of perovskite solar cells (PSCs). Herein, a sulfonamides additive, methyl 3‐sulfamoyl‐2‐thiophenecarboxylate (MSTC), is introduced into the PbI2 or FAI/MACl/MABr precursor solution, to prepare high‐quality PSCs with a two‐step method. After the addition of MSTC, all the devices show enhanced performance. With optimized MSTC incorporated into PSCs, the champion power conversion efficiency (PCE) of the PSCs is increased from 19.19% to 22.14%, and the stability is also improved. The MSTC‐FAI based device can still maintain 89% of its initial PCE compared to 68% of the control one after 15 days in ambient condition under relative humidity of 40–50% at room temperature in dark. Test results reveal that amido group in MSTC would coordinate with PbI2 or FAI through hydrogen bonding (NH···I), thus effectively enhancing the performance of devices. Nevertheless, the sulfonyl and carbonyl groups in MSTC would coordinate with the FAI precursor through chemical bond of COS and COC. And with the hydrogen bonding connection between MSTC and FAI, the inherent defects in the MSTC‐FAI based device are effectively suppressed, leading to the enhanced photovoltaic performance.
Quinary Nanocrystal‐Based Passivation Strategy for High Efficiency and Stable Perovskite Photovoltaics
Authors: Ozturk Teoman , Sarilmaz Adem , Akin Seckin , Dursun Huseyin , Ozel Faruk , Akman Erdi
Published: November 2021

Despite the rapid progress of perovskite materials in emerging perovskite photovoltaic devices, they still suffer from the polycrystalline nature associated with grain boundaries (GBs) which are vulnerable to moisture permeation and/or ion migration. Besides, charge carrier recombination of GBs through defect states plays a crucial role in restricting the performance and stability of perovskite photovoltaics. To address such detrimental issues, quinary kesterite nanocrystals, namely Cu2NiSn(S,Se)4 (CNTSSe), having narrow size distribution below 10 nm by a facile hot‐casting method are rationally designed and employed as a passivation agent for the GBs/surface of perovskite films. This passivation strategy greatly reduces defect states at perovskite GBs and promotes continuity between adjacent grains, resulting in accelerated hole transport ability and suppressed interfacial recombination. Thereupon, champion power conversion efficiency of 20.8% (20.5 ± 0.3% in average) (Cs0.05(FA0.90MA0.10)0.95Pb(I0.90Br0.10)3), 18.9% (MAPbI3), and 18.7% (FAPbI3) is achieved with a negligible hysteresis and outstanding stability by retaining over 85% of initial performance under ambient conditions with continuous illumination over 900 h. Herein, not only a universal approach to effectively passivate the GBs of the perovskite films by inorganic nanocrystals is presented, but also a deep understanding of detrimental defects on the photovoltaic performance and stability of perovskite solar cells is ensured.
Modulation of Vertical Component Distribution for Large‐Area Thick‐Film Organic Solar Cells
Authors: Zhang Lin , Yang Shuzhi , Ning Bocheng , Yang Fang , Deng Wen , Xing Zhi , Bi Zhaozhao , Zhou Ke , Zhang Yong , Hu Xiaotian , Yang Bin , Yang Junliang , Zou Yingping , Ma Wei , Yuan Yongbo
Published: November 2021

Thick active layers in organic solar cells (OSCs) have a great promise of enhancing light absorption and providing pinhole‐free films for large‐scale fabrication. Since charge carriers in thick films need a longer transporting path in the vertical direction to the electrode than in thin films, modulation of the active layer morphology in thick films is highly required for effective charge transport. Herein, thin‐film (≈110 nm) and thick‐film (≈300 nm) OSCs based on a PM6:IT‐4 F film are fabricated by blade coating with various additive contents. It is found that the optimized thick‐film device needs more additives than the optimized thin‐film device. The addition of more additives in thick‐films promotes vertical component distribution and enhances the crystallization, resulting in efficient charge transport with reduced charge recombination and electron (or hole) accumulation within the thick active layer. These results are also confirmed by PM6:Y6‐based devices, in which optimized thin‐film and thick‐film devices exhibit power conversion efficiency (PCE) of 16.69% and 14.91% at the additive contents of 0.3% and 0.6%, respectively. Encouragingly, thick‐film device with 0.6% additive has a narrow distribution of PCE values, and high PCEs of 13.94% and 13.05% are obtained for the large‐area (1 cm2) rigid and flexible thick‐film OSCs, showing great application prospect.
Notes on the genus Exostema (Rubiaceae), its limits and sectional subdivision
Authors: Greuter Werner , Rankin‐Rodríguez Rosa
Published: November 2021

Based on recent molecular work by Paudyal & al., the generic limits of the Neotropical woody genus Exostema are reassessed with a view of making them more compatible with traditional, morphology‐based generic concepts. A wide circumscription is favoured, congruent with Paudyal & al.'s “clade B” (the Exostema‐Solenandra‐Coutarea‐Hintonia group). Thus defined, Exostema is a genus with 40 species and five natural sections and incorporates three generic splits that were proposed by Paudyal & al. To minimise nomenclatural disruption, a proposal to conserve the name Exostema Rich. against Coutarea Aubl. has been presented separately. Two new combinations at sectional rank are proposed.
A Chord Recognition Method of Guitar Sound Using Its Constituent Tone Information
Authors: Bando Yoshifumi , Tanaka Motoshi
Published: November 2021

A simple method for identifying musical chords of audio sound played by a guitar is proposed herein. The chord recognition is achieved by comparing similarities between normalized note numbers extracted from the spectrum of the sound and those generated by a database. The database consists of normalized note numbers corresponding to the fundamental frequency of the chord notes, and the database of the chords with different root is shared. The database of five types of the chords were prepared; Major triad, Minor triad, Major seventh, Minor seventh, and Dominant seventh chords. The name of the chord is determined by the root played. Over 800 sounds of the chords played with electric guitars were tested, and the recognition rate showed good performance, which indicates the feasibility of this method. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Tumor suppressor LHX6 upregulation contributes to the inhibitory effect of miR‐346 knockdown on colorectal cancer cell growth
Authors: Li Xianzhe , Zhou Yeqi , Wen Penghao , Yuan Yan , Xiao Zhenghong , Shi Hengwei , Zhou Hailang
Published: November 2021

Colorectal cancer (CRC) is one of the prevalent types of human malignancies and ranks as the second leading cause of cancer‐associated death worldwide. Dysregulated miRNAs have been promulgated as oncogenes or tumor‐suppressive genes participating in the initiation and progression of CRC. A recent study reported that miR‐346 was highly expressed in CRC patients. However, the biological role and underlying mechanism of miR‐346 in CRC remain elusive. qRT‐PCR and western blot assays were employed to detect miR‐346 and LIM homeobox domain 6 (LHX6) expression in CRC cells. Cell proliferation was evaluated by CCK‐8 and BrdU assays. Apoptosis was evaluated by TUNEL assay. The interaction between miR‐346 and LHX6 was assessed by luciferase reporter assay. Results showed that miR‐346 expression was increased and LHX6 expression was reduced in CRC cells. miR‐346 knockdown and LHX6 overexpression inhibited proliferation and promoted apoptosis of CRC cells. Additionally, we found that miR‐346 negatively regulated LHX6 expression in CRC cells by directly targeting LHX6. LHX6 knockdown partially attenuated anti‐miR‐346‐induced proliferation reduction and apoptosis promotion in CRC cells. Furthermore, miR‐346 knockdown inhibited the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway in CRC cells by targeting LHX6. The present study indicated that miR‐346 knockdown repressed cell growth in CRC cells by upregulating LHX6, and this was associated with inactivation of the Akt/mTOR pathway.
Effect of processing conditions and catalyst type on the thermal oxidative degradation mechanisms and melt stability of metallocene and Ziegler‐catalyzed ethylene‐1‐hexene copolymers
Authors: Al‐Malaika Sahar , Daraz Umar , Issenhuth Sylvie
Published: November 2021

Polyolefins have traditionally been polymerized via the heterogeneous Ziegler Natta (Z‐N) catalysts since their discovery in the 1950s, but the later developments of the homogeneous single site metallocene/methylaluminoxane (MAO) catalysts have opened the possibility for the synthesis of polyolefin polymers and copolymers (commercialized in the 1990s) with highly defined microstructure and great degree of control of their molecular architecture resulting in some unique beneficial properties compared to their Z‐N counterparts. The main aim of the work reported here was to examine critically the effects of the processing conditions during multipass extrusions on the molecular and rheological characteristics of metallocene‐catalyzed linear low density polyethylene and a Ziegler‐Natta‐based counterpart polymer and on the thermoxidative (in the melt) stability of their melts and their stabilization. Both polymers examined here were based on ethylene‐1‐hexene copolymers and produced by the same manufacturer with similar density and melt index (MI) values. The melt stability and rheological properties of the polymers were determined from melt flow and capillary rheometric measurements. The molecular characteristics were investigated using GPC for molecular weight determination, 13C‐NMR for short chain branching, 1H‐NMR and FTIR for the type and concentration of unsaturation groups, FTIR for carbonyl‐containing compounds and chemical analysis for hydroperoxide determination. The processibility of the two polymers was compared through examination of different processing conditions (die temperatures 210–285°C, screw speeds 50–200 rpm) used for a multipass extrusion process. Further, the effects of the processing conditions on the melt thermoxidation of the differently catalyzed LLDPE polymers were investigated. The results demonstrated that both the catalyst type and the processing conditions have a great effect on both the rheological and the themoxidative behavior of the polymers as well as on the balance between the competing oxidative reactions taking place in the polymer melt, for example, chain scission and crosslinking reactions. The results obtained for the different multipass extrusion conditions of the two polymers have illustrated clearly that the degradation mechanisms during their melt processing are substantially different. The melt degradation route of the Ziegler‐catalyzed polymer was shown to be dominated by chain scission reactions under all the processing conditions examined, and more so at the higher shear rates and temperatures. By contrast, the evidence clearly showed that the metallocene‐catalyzed polymer gave rise to crosslinking reactions that predominated even under the more severe processing conditions, that is, higher temperatures and shear rates.
Pericardial tamponade during balloon pulmonary valvuloplasty in a dog
Authors: Wieser Manuela , Ringer Simone Katja , Baron Toaldo Marco
Published: November 2021

A 4‐month‐old entire male Coton de Tulear dog was referred for balloon valvuloplasty for treatment of severe valvular pulmonic stenosis. During the procedure, when attempting to pass the guide wire into the ventricle, the dog developed cardiac arrest. After initial resuscitation with chest compressions, manual ventilation, adrenaline and intravenous fluids, focused cardiac ultrasound revealed pericardial effusion and cardiac tamponade. Pericardiocentesis resolved the haemodynamic emergency. This case report should raise awareness of pericardial tamponade as a possible complication during pulmonic stenosis balloon valvuloplasty. It describes the clinical signs observed during anaesthesia as well as how to treat it with a positive outcome.
Correction to: Cryopreservation of Potato Shoot Tips for Long-Term Storage
Authors: Vollmer Rainer , Espirilla Janeth , Villagaray Rosalva , Cárdenas José , Castro Mario , Sánchez Juan Carlos , Manrique-Carpintero Norma , Ellis David , Anglin Noelle Lynette
Published: November 2021

Chapter 2 was previously published non-open access. It has now been changed to open access under a CC BY 4.0 license, and the copyright holder updated to ‘The Author(s)’. The book has been updated with this change.
Extracting Einstein from the loop-level double-copy
Authors: Carrasco John Joseph M. , Vazquez-Holm Ingrid A.
Published: November 2021

Abstract

The naive double-copy of (multi) loop amplitudes involving massive matter coupled to gauge theories will generically produce amplitudes in a gravitational theory that contains additional contributions from propagating antisymmetric tensor and dilaton states even at tree-level. We present a graph-based approach that combines the method of maximal cuts with double-copy construction to offer a systematic framework to isolate the pure Einstein-Hilbert gravitational contributions through loop level. Indeed this allows for a bootstrap of pure-gravitational results from the double-copy of massive scalar-QCD. We apply this to construct the novel result of the D-dimensional one-loop five-point QFT integrand relevant in the classical limit to generating observables associated with the radiative effects of massive black-hole scattering via pure Einstein-Hilbert gravity.
Combined SMEFT interpretation of Higgs, diboson, and top quark data from the LHC
Authors:   The SMEFiT collaboration, Ethier Jacob J. , Magni Giacomo , Maltoni Fabio , Mantani Luca , Nocera Emanuele R. , Rojo Juan , Slade Emma , Vryonidou Eleni , Zhang Cen
Published: November 2021

Abstract

We present a global interpretation of Higgs, diboson, and top quark production and decay measurements from the LHC in the framework of the Standard Model Effective Field Theory (SMEFT) at dimension six. We constrain simultaneously 36 independent directions in its parameter space, and compare the outcome of the global analysis with that from individual and two-parameter fits. Our results are obtained by means of state-of-the-art theoretical calculations for the SM and the EFT cross-sections, and account for both linear and quadratic corrections in the 1/Λ2 expansion. We demonstrate how the inclusion of NLO QCD and $$ \mathcal{O} $$
O
(Λ−4) effects is instrumental to accurately map the posterior distributions associated to the fitted Wilson coefficients. We assess the interplay and complementarity between the top quark, Higgs, and diboson measurements, deploy a variety of statistical estimators to quantify the impact of each dataset in the parameter space, and carry out fits in BSM-inspired scenarios such as the top-philic model. Our results represent a stepping stone in the ongoing program of model-independent searches at the LHC from precision measurements, and pave the way towards yet more global SMEFT interpretations extended to other high-pT processes as well as to low-energy observables.
Multipoint correlation functions at phase separation. Exact results from field theory
Authors: Squarcini Alessio
Published: November 2021

Abstract

We consider near-critical two-dimensional statistical systems with boundary conditions inducing phase separation on the strip. By exploiting low-energy properties of two-dimensional field theories, we compute arbitrary n-point correlation of the order parameter field. Finite-size corrections and mixed correlations involving the stress tensor trace are also discussed. As an explicit illustration of the technique, we provide a closed-form expression for a three-point correlation function and illustrate the explicit form of the long-ranged interfacial fluctuations as well as their confinement within the interfacial region.
A bound on chaos from stability
Authors: Yoon Junggi
Published: November 2021

Abstract

We explore the quantum chaos of the coadjoint orbit action of diffeomorphism group of S1. We study quantum fluctuation around a saddle point to evaluate the soft mode contribution to the out-of-time-ordered correlator. We show that the stability condition of the semi-classical analysis of the coadjoint orbit found in [1] leads to the upper bound on the Lyapunov exponent which is identical to the bound on chaos proven in [2]. The bound is saturated by the coadjoint orbit Diff(S1)/SL(2) while the other stable orbit Diff(S1)/U(1) where the SL(2, ℝ) is broken to U(1) has non-maximal Lyapunov exponent.
Millicharged particles from the heavens: single- and multiple-scattering signatures
Authors: Argüelles Carlos A. , Kelly Kevin J. , Muñoz Víctor M.
Published: November 2021

Abstract

For nearly a century, studying cosmic-ray air showers has driven progress in our understanding of elementary particle physics. In this work, we revisit the production of millicharged particles in these atmospheric showers and provide new constraints for XENON1T and Super-Kamiokande and new sensitivity estimates of current and future detectors, such as JUNO. We discuss distinct search strategies, specifically studies of single-energy-deposition events, where one electron in the detector receives a relatively large energy transfer, as well as multiple-scattering events consisting of (at least) two relatively small energy depositions. We demonstrate that these atmospheric search strategies — especially the multiple-scattering signature — provide significant room for improvement beyond existing searches, in a way that is complementary to anthropogenic, beam-based searches for MeV-GeV millicharged particles. Finally, we also discuss the implementation of a Monte Carlo simulation for millicharged particle detection in large-volume neutrino detectors, such as IceCube.
Quasi-Cauchy quotients and means
Authors: Matkowski Janusz
Published: November 2021

Let $$I\subset {\mathbb {R}}$$

I
⊂
R

be an interval that is closed under addition, and $$ k\in {\mathbb {N}}$$

k
∈
N

, $$k\ge 2\,$$

k
≥
2

. For a function $$f:I\rightarrow \left( 0,\infty \right) $$

f
:
I
→

0
,
∞

such that $$F\left( x\right) :=\frac{f\left( kx\right) }{ kf\left( x\right) }$$

F

x

:
=

f

k
x

k
f

x

is invertible in I, the k-variable function $$ M_{f}:I^{k}\rightarrow I,$$

M
f

:

I
k

→
I
,

$$\begin{aligned} M_{f}\left( x_{1},\ldots ,x_{k}\right) :=F^{-1}\left( \frac{f\left( x_{1}+\cdots +x_{k}\right) }{f\left( x_{1}\right) +\cdots +f\left( x_{k}\right) } \right) , \end{aligned}$$

M
f

x
1

,
…
,

x
k

:
=

F

-
1

f

x
1

+
⋯
+

x
k

f

x
1

+
⋯
+
f

x
k

,

is a premean in I,  and it is referred to as a quasi Cauchy quotient of the additive type of generator f. Three classes of means of this type generated by the exponential, logarithmic, and power functions, are examined. The suitable quasi Cauchy quotients of the exponential types (for continuous additive, logarithmic, and power functions) are considered. When I is closed under multiplication, the quasi Cauchy quotient means of logarithmic and multiplicative type are studied. The equalities of premeans within each of these classes are discussed and some open problems are proposed.
Wire arc additive manufacturing of AA5183 with TiC nanoparticles
Authors: Langelandsvik Geir , Eriksson Magnus , Akselsen Odd M. , Roven Hans J.
Published: November 2021

Aluminium alloys processed by wire arc additive manufacturing (WAAM) exhibit a relatively coarse microstructure with a columnar morphology. A powerful measure to refine the microstructure and to enhance mechanical properties is to promote grain refinement during solidification. Addition of ceramic nanoparticles has shown great potential as grain refiner and strengthening phase in aluminium alloys. Thus, an Al-Mg alloy mixed with TiC nanoparticles was manufactured by the novel metal screw extrusion method to a wire and subsequently deposited by WAAM. Measures to restrict oxidation of magnesium during metal screw extrusion were examined. Purging of CO2 gas into the extrusion chamber resulted in a remarkable reduction in formation of MgO and Mg(OH)2. TiC decomposed to Al3Ti during WAAM deposition, leading to a significant grain refinement of 93% compared to a commercial benchmark. The presence of remaining TiC nanoparticles accounted for an increased hardness of the WAAM material through thermal expansion mismatch strengthening and Orowan strengthening. Exposure of TiC to moisture in air during metal screw extrusion increased the internal hydrogen content significantly, and a highly porous structure was seen after WAAM deposition.
Identifying and decomposing peer effects on decision-making using a randomized controlled trial
Authors: Shimamoto Daichi , Todo Yasuyuki , Kim Yu Ri , Matous Petr
Published: November 2021

Utilizing a randomized controlled trial (RCT) in traditional clusters of apparel and textile firms in Vietnam, this paper investigates peer effects on firm managers’ decisions to participate in seminars on export promotion. We invited 131 randomly selected firm representatives to three one-day seminars on export promotion. We use the number of randomly invited peers to identify peer effects. We further decompose the invited peers into peers invited to the same seminar, those invited to the earlier seminars, and those invited to the later seminars. We find that the former has a positive effect on firms' participation, whereas the latter two have no significant effect. These results imply that peer effects on participation primarily arise from the benefits of face-to-face interactions. The presence of positive peer effects suggests that multiple equilibria in terms of the share of participants within each village of firms may emerge, which is also consistent with our observations.
Quo vadis blood protein adductomics?
Authors: Sabbioni Gabriele , Day Billy W.
Published: November 2021

Chemicals are measured regularly in air, food, the environment, and the workplace. Biomonitoring of chemicals in biological fluids is a tool to determine the individual exposure. Blood protein adducts of xenobiotics are a marker of both exposure and the biologically effective dose. Urinary metabolites and blood metabolites are short term exposure markers. Stable hemoglobin adducts are exposure markers of up to 120 days. Blood protein adducts are formed with many xenobiotics at different sites of the blood proteins. Newer methods apply the techniques developed in the field of proteomics. Larger adducted peptides with 20 amino acids are used for quantitation. Unfortunately, at present the methods do not reach the limits of detection obtained with the methods looking at single amino acid adducts or at chemically cleaved adducts. Therefore, to progress in the field new approaches are needed.
An isogeometric mortar method for the coupling of multiple NURBS domains with optimal convergence rates
Authors: Dornisch W. , Stöckler J.
Published: November 2021

We investigate the mortar finite element method for second order elliptic boundary value problems on domains which are decomposed into patches $$\Omega _k$$

Ω
k

with tensor-product NURBS parameterizations. We follow the methodology of IsoGeometric Analysis (IGA) and choose discrete spaces $$X_{h,k}$$

X

h
,
k

on each patch $$\Omega _k$$

Ω
k

as tensor-product NURBS spaces of the same or higher degree as given by the parameterization. Our work is an extension of Brivadis et al. (Comput Methods Appl Mech Eng 284:292–319, 2015) and highlights several aspects which did not receive full attention before. In particular, by choosing appropriate spaces of polynomial splines as Lagrange multipliers, we obtain a uniform infsup-inequality. Moreover, we provide a new additional condition on the discrete spaces $$X_{h,k}$$

X

h
,
k

which is required for obtaining optimal convergence rates of the mortar method. Our numerical examples demonstrate that the optimal rate is lost if this condition is neglected.
Highly sensitive interleukin 6 detection by employing commercially ready liposomes in an LFA format
Authors: Rink Simone , Kaiser Barbara , Steiner Mark-Steven , Duerkop Axel , Baeumner Antje J.
Published: November 2021

Recent years have confirmed the ubiquitous applicability of lateral flow assays (LFA) in point-of-care testing (POCT). To make this technology available for low abundance analytes, strategies towards lower limits of detections (LOD), while maintaining the LFA’s ease of use, are still being sought. Here, we demonstrate how liposomes can significantly improve the LOD of traditional gold nanoparticle (AuNP)–based assays while fully supporting a ready-to-use system for commercial application. We fine-tuned liposomes towards photometric and fluorescence performance on the synthesis level and applied them in an established interleukin 6 (IL-6) immunoassay normally using commercial AuNP labels. IL-6’s low abundance (< 10 pg mL−1) and increasing relevance as prognostic marker for infections make it an ideal model analyte. It was found that liposomes with a high encapsulant load (150 mmol L−1 sulforhodamine B (SRB)) easily outperform AuNPs in photometric LFAs. Specifically, liposomes with 350 nm in diameter yield a lower LOD even in complex matrices such as human serum below the clinically relevant range (7 pg mL−1) beating AuNP by over an order of magnitude (81 pg mL−1). When dehydrated on the strip, liposomes maintained their signal performance for over a year even when stored at ambient temperature and indicate extraordinary stability of up to 8 years when stored as liquid. Whereas no LOD improvement was obtained by exploiting the liposomes’ fluorescence, an extraordinary gain in signal intensity was achieved upon lysis which is a promising feature for high-resolution and low-cost detection devices. Minimizing the procedural steps by inherently fluorescent liposomes, however, is not feasible. Finally, liposomes are ready for commercial applications as they are easy to mass-produce and can simply be substituted for the ubiquitously used AuNPs in the POCT market.

Graphical abstract
Efficacy of the Flow Re-direction Endoluminal Device for cerebral aneurysms and causes of failed deployment
Authors: Suyama Kenichiro , Nakahara Ichiro , Matsumoto Shoji , Suyama Yoshio , Morioka Jun , Hasebe Akiko , Tanabe Jun , Watanabe Sadayoshi , Kuwahara Kiyonori
Published: November 2021

Purpose

The Flow Re-direction Endoluminal Device (FRED) has recently become available for flow diversion in Japan. We have encountered cases that failed to deploy the FRED. In this study, we report our initial experience with the FRED for cerebral aneurysms and clarify the causes of failed FRED deployment.

Methods

A retrospective data analysis was performed to identify patients treated with the FRED between June 2020 and March 2021. Follow-up digital subtraction angiography was performed at 3 and 6 months and assessed using the O’Kelly-Marotta (OKM) grading scale.

Results

Thirty-nine aneurysms in 36 patients (average age: 54.4 years) were treated with the FRED. The average sizes of the dome and neck were 9.9 mm and 5.2 mm, respectively. In nine patients, additional coiling was performed. In one patient (2.6%), proximal vessel injury caused direct carotid-cavernous fistula during deployment. Ischaemic complications were encountered in one patient (2.6%) with transient symptoms. Angiographic follow-up at 6 months revealed OKM grade C or D in 86.6% of patients. FRED deployment was successful in 35 (92.1%) procedures. In the failure group, the differences between the FRED and the minimum vessel diameter (P = 0.04) and the rate of the parent vessel having an S-shaped curve (P = 0.04) were greater than those in the success group.

Conclusions

Flow diversion using the FRED is effective and safe for treating cerebral aneurysms. The use of the FRED for patients with an S-shaped curve in the parent vessel and oversizing of more than 2 mm should be considered carefully.
A phase 1b study of erlotinib and momelotinib for the treatment of EGFR-mutated, tyrosine kinase inhibitor-naive metastatic non-small cell lung cancer
Authors: Padda Sukhmani K. , Reckamp Karen L. , Koczywas Marianna , Neal Joel W. , Kawashima Jun , Kong Shengchun , Huang Daniel B. , Kowalski Mark , Wakelee Heather A.
Published: November 2021

Introduction

Preclinical evidence suggests the feedforward cytokine loop of interleukin-6/Janus kinases (JAK)/STAT3 plays a role in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) resistance in EGFR-mutated non-small cell lung cancer (NSCLC).

Methods

In this phase 1b study, the JAK1/2 and TANK-binding kinase 1 (TBK1) inhibitor momelotinib was evaluated in combination with erlotinib in patients with EGFR TKI-naive, EGFR-mutated NSCLC. After erlotinib lead-in (50, 75, 100, or 150 mg oral daily [QD]), momelotinib was combined and dose escalated in a 3 + 3 study design. The primary endpoint of maximum tolerated dose (MTD) of momelotinib was determined based on the incidence of dose-limiting toxicities (DLTs) during the first 28-day cycle. Secondary endpoints included efficacy and pharmacokinetics (PK).

Results

Eleven patients were enrolled across 3 dose levels of momelotinib (100 mg QD, 200 mg QD, and 100 mg twice daily [BID]). The MTD was momelotinib 200 mg QD in combination with erlotinib. Two DLTs of grade 4 neutropenia without fever and grade 3 diarrhea occurred at momelotinib 100 mg BID. Most common treatment-emergent adverse events included diarrhea, dry skin, fatigue, and decreased appetite; the vast majority being grades 1–2. The overall response rate was 54.5% (90% CI 27.1–80.0; all partial) and median progression-free survival was 9.2 months (90% CI 6.2–12.4). Momelotinib did not affect the PK of erlotinib.

Conclusions

The JAK1/2 and TBK1 inhibitor momelotinib in combination with erlotinib did not appear to enhance benefit over the historical data of erlotinib monotherapy in patients with EGFR-mutated NSCLC.

ClinicalTrials.gov identifier

NCT02206763.
Automated detection and segmentation of intracranial hemorrhage suspect hyperdensities in non-contrast-enhanced CT scans of acute stroke patients
Authors: Schmitt N. , Mokli Y. , Weyland C. S. , Gerry S. , Herweh C. , Ringleb P. A. , Nagel S.
Published: November 2021

Objectives

Artif
icial intelligence (AI)–based image analysis is increasingly applied in the acute stroke field. Its implementation for the detection and quantification of hemorrhage suspect hyperdensities in non-contrast-enhanced head CT (NCCT) scans may facilitate clinical decision-making and accelerate stroke management.

Methods

NCCTs of 160 patients with suspected acute stroke were analyzed regarding the presence or absence of acute intracranial hemorrhages (ICH) using a novel AI-based algorithm. Read was performed by two blinded neuroradiology residents (R1 and R2). Ground truth was established by an expert neuroradiologist. Specificity, sensitivity, and area under the curve were calculated for ICH and intraparenchymal hemorrhage (IPH) detection. IPH-volumes were segmented and quantified automatically by the algorithm and semi-automatically. Intraclass correlation coefficient (ICC) and Dice coefficient (DC) were calculated.

Results

In total, 79 of 160 patients showed acute ICH, while 47 had IPH. Sensitivity and specificity for ICH detection were 0.91 and 0.89 for the algorithm; 0.99 and 0.98 for R1; and 1.00 and 0.98 for R2. Sensitivity and specificity for IPH detection were 0.98 and 0.89 for the algorithm; 0.83 and 0.99 for R1; and 0.91 and 0.99 for R2. Interreader reliability for ICH and IPH detection showed strong agreements for the algorithm (0.80 and 0.84), R1 (0.96 and 0.84), and R2 (0.98 and 0.92), respectively. ICC indicated an excellent (0.98) agreement between the algorithm and the reference standard of the IPH-volumes. The mean DC was 0.82.

Conclusion

The AI-based algorithm reliably assessed the presence or absence of acute ICHs in this dataset and quantified IPH volumes precisely.

Key Points

• Artificial intelligence (AI) is able to detect hyperdense volumes on brain CTs reliably.

• Sensitivity and specificity are highest for the detection of intraparenchymal hemorrhages.

• Interreader reliability for hemorrhage detection shows strong agreement for AI and human readers.
LncRNAs in domesticated animals: from dog to livestock species
Authors: Lagarrigue Sandrine , Lorthiois Matthias , Degalez Fabien , Gilot David , Derrien Thomas
Published: November 2021

Animal genomes are pervasively transcribed into multiple RNA molecules, of which many will not be translated into proteins. One major component of this transcribed non-coding genome is the long non-coding RNAs (lncRNAs), which are defined as transcripts longer than 200 nucleotides with low coding-potential capabilities. Domestic animals constitute a unique resource for studying the genetic and epigenetic basis of phenotypic variations involving protein-coding and non-coding RNAs, such as lncRNAs. This review presents the current knowledge regarding transcriptome-based catalogues of lncRNAs in major domesticated animals (pets and livestock species), covering a broad phylogenetic scale (from dogs to chicken), and in comparison with human and mouse lncRNA catalogues. Furthermore, we describe different methods to extract known or discover novel lncRNAs and explore comparative genomics approaches to strengthen the annotation of lncRNAs. We then detail different strategies contributing to a better understanding of lncRNA functions, from genetic studies such as GWAS to molecular biology experiments and give some case examples in domestic animals. Finally, we discuss the limitations of current lncRNA annotations and suggest research directions to improve them and their functional characterisation.
End-stage renal disease, calcification patterns and clinical outcomes after TAVI
Authors: Grundmann David , Linder Matthias , Goßling Alina , Voigtländer Lisa , Ludwig Sebastian , Waldschmidt Lara , Demal Till , Bhadra Oliver D. , Schäfer Andreas , Schirmer Johannes , Reichenspurner Hermann , Blankenberg Stefan , Westermann Dirk , Schofer Niklas , Conradi Lenard , Seiffert Moritz
Published: November 2021

Background

Patients with chronic hemodialysis due to end-stage renal disease (ESRD) or severely impaired kidney function (CKD) constitute a relevant share of patients undergoing trans-catheter aortic valve implantation (TAVI). However, data on specific challenges and outcomes remain limited.

Aim

We aimed to characterize this patient population, evaluate clinical results and assess the significance of calcification patterns.

Methods

This retrospective single-center analysis evaluated 2,712 TAVI procedures (2012–2019) according to baseline renal function: GFR < 30 ml/min/1.73m2 (CKD; n = 210), chronic hemodialysis (ESRD; n = 119) and control (CTRL; n = 2383). Valvular and vascular calcification patterns were assessed from contrast-enhanced multi-detector computed tomography. Outcomes were evaluated in accordance with the VARC-2 definitions.

Results

Operative risk was higher in ESRD and CKD vs. CTRL (STS-score 8.4% and 7.6% vs. 3.9%, p < 0.001) and patients with ESRD had more severe vascular calcifications (49.1% vs. 33.9% and 29.0%, p < 0.01). Immediate procedural results were similar but non-procedure-related major/life-threatening bleeding was higher in ESRD and CKD (5.0% and 5.3% vs. 1.6%, p < 0.01). 3-year survival was impaired in patients with ESRD and CKD (33.3% and 35.3% vs. 65.4%, p < 0.001). Multivariable analysis identified ESRD (HR 1.60), CKD (HR 1.79) and vascular calcifications (HR 1.29) as predictors for 3-year and vascular calcifications (HR 1.51) for 30-day mortality.

Conclusion

Patients with ESRD and CKD constitute a vulnerable patient group with extensive vascular calcifications. Immediate procedural results were largely unaffected by renal impairment, yielding TAVI a particularly valuable treatment option in these high-risk operative patients. Mid-term survival was determined by underlying renal disease, cardiovascular comorbidities, and vascular calcifications as a novel risk marker.

Graphical abstract
Assessment of renal glomerulosclerosis and thickness of the carotid intima-media complex as a means of age estimation in Western European bodies
Authors: Lehmann-Leo Carl Daniel , Ramsthaler Frank , Birngruber Christoph G. , Verhoff Marcel A.
Published: November 2021

Introduction

The estimation of age-at-death of unidentified cadavers is a central aspect of the identification process. With increasing age, the incidence of glomerulosclerosis and the thickness of the carotid wall have been observed to also increase. This correlation has been demonstrated in various international histological studies. The aim of our study was to assess whether these correlations also apply to a Western European population.

Methodology

In this retrospective observational study, kidney and common carotid artery samples from 216 cases autopsied at the Institute of Legal Medicine at the Justus-Liebig University in Giessen, Germany, were examined. Only cases with available tissue samples from both body sides were included. Exclusion criteria were poor sample quality and an age younger than 21 years. After histological processing, the tissue samples were assessed and digitally evaluated. Regression and classification analyses were used to investigate the correlation between age-at-death and intima-media thickness and age-at-death and the incidence of renal glomerular sclerosis.

Results

Of the 216 autopsy cases, 183 were included for evaluation. Analysis of the carotid artery segments showed a strong correlation (Pearson correlation coefficient r = 0.887) between the intima-media-complex thickness and chronological age. Classification of the glomerulosclerotic incidence showed a correlation of 37.7–43.1% with the predicted age group.

Discussion

Both the intima-media thickness and the proportion of sclerotic glomeruli can be used to estimate age in Western European cadavers. On the basis of these results, both methods are suited to supplement other already established methods for age-at-death estimation in the identification of an unknown cadaver.