bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Trial Assessing the Safety, Pharmacokinetics, and Efficacy During Morning Off of AZ‐009
Authors: Thijssen Eva , den Heijer Jonas , Puibert David , Moss Laurence , Lei Mingzu , Hasegawa David , Keum Kyo , Mochel Ken , Ezzeldin Sharaf Mohammed , Alfredson Tom , Zeng Wenxiang , van Brummelen Emilie , Naranda Tatjana , Groeneveld Geert Jan 
Published: January 2022

ABSTRACTBackgroundInhalation of apomorphine could be a faster‐acting and more user‐friendly alternative to subcutaneous injection for treating off periods in Parkinson's disease (PD).ObjectiveThe aim of this study was to compare the safety and pharmacokinetics of inhaled apomorphine (AZ‐009) with subcutaneous apomorphine (APO‐go PEN) in healthy volunteers (HVs) and to examine the safety, pharmacokinetics, and efficacy of AZ‐009 in patients with PD.MethodsIn part A of this study, eight HVs received 1 mg AZ‐009 and 2 mg subcutaneous apomorphine in a randomized crossover manner. In the subsequent single ascending dose parts in HVs (part B, n = 16) and patients with PD (part C, n = 25), participants were randomized to placebo or AZ‐009 up to 4 mg. In patients, after medication withdrawal, Movement Disorder Society‐Unified Parkinson's Disease Rating Scale part III and on/off states were assessed predose and postdose.ResultsAZ‐009 was rapidly absorbed with peak plasma concentrations at 2 minutes, as compared to 30 minutes for subcutaneous apomorphine. Adverse events for AZ‐009 were comparable to subcutaneous apomorphine, except for mild and transient throat irritation. Adverse events limited AZ‐009 dose escalation in HVs to 3 mg. Patients tolerated up to 4 mg. In patients with PD, 2, 3, and 4 mg AZ‐009 reduced mean Movement Disorder Society‐Unified Parkinson's Disease Rating Scale part III score (standard deviation) by 10.7 (13.6), 12.8 (7.9), and 10.3 (3.7) points, respectively, compared to 4.8 (4.9) after placebo at 10 minutes postdose. The percentage of patients achieving full on within 45 minutes postdose increased dose dependently: 0% (placebo), 17% (2 mg), 50% (3 mg), and 83% (4 mg).ConclusionsAZ‐009 appears to be a rapid‐acting and reasonably well‐tolerated formulation for treating off periods. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Efficiency, safety, and reliability analysis of turbocharging in a large container vessel
Authors: Anantharaman Mohan , Islam Rabiul , Garaniya Vikram , Khan Faisal 
Published: January 2022

AbstractCommercial shipping is currently dominated by mega container vessels. The shipping industry has seen a 10‐fold increase in the size of containers over the last four decades. These vessels are propelled by large marine diesel engines, hereafter referred to as the main engine. The performance of the main engine is determined by its subsystems. An important part of the main engine is the turbocharging system, which contributes to its safety, efficiency, and reliability. In this study, the effectiveness and reliability of the turbocharging system are evaluated. The Australian Maritime College has a Kongsberg Engine Simulator that can produce a variety of malfunctions on a running engine's turbocharging system. Analyzing the results obtained from the simulator determines the efficiency of the turbochargers. The study will provide recommendations for improving the safety of the turbocharging system for better performance to be achieved by the turbochargers, leading to an improvement in the main engine's performance. Last, the reliability of the turbocharging system is evaluated quantitatively using a fault tree analysis and reliability block diagrams. This will enable an optimum maintenance strategy to be established to ensure the safe operation of the vessel.
Event‐based finite‐time H∞ synchronization control for switched complex networks with average dwell time
Authors: Xu Tianlin , Liu Shuai , Wei Guoliang 
Published: January 2022

AbstractThis paper investigates the problem of the event‐triggered finite‐time nonfragile synchronization control for a class of discrete time‐delayed complex networks with switched topology. To decrease the unnecessary signal transmission and save control cost, the dynamic event‐triggering scheme is employed in the controller‐to‐actuator channel where the varying triggering threshold is governed by a dynamical equation. The main purpose of this paper is to design a nonfragile synchronization controller such that the synchronization error dynamics satisfies both the finite‐time boundedness and the disturbance rejection level. By constructing appropriate Lyapunov–Krasovskii functional and using the average‐dwell‐time technique, the desired controller gains are acquired in terms of the solution to a set of linear matrix inequalities. Finally, a numerical simulation example is provided to demonstrate the effectiveness of the proposed synchronization controller design scheme.
Stabilizing regions of PID controller for a class of unknown nonlinear non‐affine discrete‐time systems
Authors: Xiong Shuangshuang , Hou Zhongsheng 
Published: January 2022

AbstractBased on the technology of dynamic linearization, the stability regions of PID, PI, PD, and P type controllers are investigated for a class of unknown nonlinear non‐affine discrete‐time systems. An equivalent data model to the unknown nonlinear system is established first through the dynamic linearization technique. Then based on the established data model, the determination of the structure of PID/PI controller has been given by rigorous theoretical derivation. The closed‐loop system is shown to be asymptotically stable for the PID, PI controllers, and the output/input signals of the closed loop system are bounded for the PD and P type controllers with the method of contraction mapping principle. An example of nonlinear non‐affine discrete‐time systems is used to demonstrate its correspondingly stability regions.
THE SAINT MODEL: A DECADE LATER
Authors: Jarner Søren F. , Jallbjørn Snorre 
Published: January 2022

AbstractWhile many of the prevalent stochastic mortality models provide adequate short- to medium-term forecasts, only few provide biologically plausible descriptions of mortality on longer horizons and are sufficiently stable to be of practical use in smaller populations. Among the very first to address the issue of modelling adult mortality in small populations was the SAINT model, which has been used for pricing, reserving and longevity risk management by the Danish Labour Market Supplementary Pension Fund (ATP) for more than a decade. The lessons learned have broadened our understanding of desirable model properties from the practitioner’s point of view and have led to a revision of model components to address accuracy, stability, flexibility, explainability and credibility concerns. This paper serves as an update to the original version published 10 years ago and presents the SAINT model with its modifications and the rationale behind them. The main improvement is the generalization of frailty models from deterministic structures to a flexible class of stochastic models. We show by example how the SAINT framework is used for modelling mortality at ATP and make comparisons to the Lee-Carter model.
Toward an Anti-Maleficent Research Agenda
Authors: Ferdowsian Hope , Fuentes Agustin , Johnson L. Syd M , King Barbara J. , Pierce Jessica 
Published: January 2022

AbstractImportant advances in biomedical and behavioral research ethics have occurred over the past few decades, many of them centered on identifying and eliminating significant harms to human subjects of research. Comprehensive attention has not been paid to the totality of harms experienced by animal subjects, although scientific and moral progress require explicit appraisal of these harms. Science is a public good and the prioritizing within, conduct of, generation of, and application of research must soundly address questions about which research is morally defensible and valuable enough to support through funding, publication, tenure, and promotion. Likewise, educational pathways of re-imagined science are critical.
Activation of the anterior cingulate cortex ameliorates anxiety in a preclinical model of fetal alcohol spectrum disorders
Authors: Hwang Hye M. , Hashimoto-Torii Kazue 
Published: January 2022

AbstractPeople with fetal alcohol spectrum disorders (FASD) are suffered from a wide range of interlinked cognitive and psychological problems. However, few therapeutic options are available for those patients due to limited dissection of its underlying etiology. Here we found that prenatal alcohol exposure (PAE) increases anxiety in mice due to a dysregulated functional connectivity between the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). We also show that chemogenetic activation of excitatory neurons in the ACC reduced this anxiety behavior in the PAE mice. Interestingly, although the level of plasma corticosterone correlated with the increase in anxiety in the PAE, this level was not altered by chemogenetic activation of the ACC, suggesting that the functional connectivity between the ACC and the BLA does not alter the activity of the hypothalamic–pituitary–adrenal axis. Altogether, this study demonstrated that reduced excitation in the ACC is a cause of anxiety in the PAE mice, providing critical insights into the ACC–BLA neural circuit as a potential target for treating anxiety in FASD patients.
Ultra-fast optical ranging using quantum-dash mode-locked laser diodes
Authors: Trocha Philipp , Kemal Juned Nassir , Gaimard Quentin , Aubin Guy , Lelarge François , Ramdane Abderrahim , Freude Wolfgang , Randel Sebastian , Koos Christian 
Published: January 2022

AbstractLaser-based light detection and ranging (LiDAR) is key to many applications in science and industry. For many use cases, compactness and power efficiency are key, especially in high-volume applications such as industrial sensing, navigation of autonomous objects, or digitization of 3D scenes using hand-held devices. In this context, comb-based ranging systems are of particular interest, combining high accuracy with high measurement speed. However, the technical complexity of miniaturized comb sources is still prohibitive for many applications, in particular when high optical output powers and high efficiency are required. Here we show that quantum-dash mode-locked laser diodes (QD-MLLD) offer a particularly attractive route towards high-performance chip-scale ranging systems. QD-MLLDs are compact, can be easily operated by a simple DC drive current, and provide spectrally flat frequency combs with bandwidths in excess of 2 THz, thus lending themselves to coherent dual-comb ranging. In our experiments, we show measurement rates of up to 500 MHz—the highest rate demonstrated with any ranging system so far. We attain reliable measurement results with optical return powers of only – 40 dBm, corresponding to a total loss of 49 dB in the ranging path, which corresponds to the highest loss tolerance demonstrated so far for dual-comb ranging with chip-scale comb sources. Combing QD-MLLDs with advanced silicon photonic receivers offers an attractive route towards robust and technically simple chip-scale LiDAR systems.
Comparing head muscles among Drusinae clades (Insecta: Trichoptera) reveals high congruence despite strong contrasts in head shape
Authors: Zittra Carina , Vitecek Simon , Schwaha Thomas , Handschuh Stephan , Martini Jan , Vieira Ariane , Kuhlmann Hendrik C. , Waringer Johann 
Published: January 2022

AbstractThe subfamily Drusinae (Limnephilidae, Trichoptera) comprises a range of species exhibiting differently shaped head capsules in their larval stages. These correspond to evolutionary lineages pursuing different larval feeding ecologies, each of which uses a different hydraulic niche: scraping grazers and omnivorous shredders sharing rounded head capsules and filtering carnivores with indented and corrugated head capsules. In this study, we assess whether changes in head capsule morphology are reflected by changes in internal anatomy of Drusinae heads. To this end, internal and external head morphology was visualized using µCT methods and histological sections in three Drusinae species—Drusus franzi, D. discolor and D. bosnicus—representing the three evolutionary lineages. Our results indicate that Drusinae head musculature is highly conserved across the evolutionary lineages with only minute changes between taxa. Conversely, the tentorium is reduced in D. discolor, the species with the most aberrant head capsule investigated here. Integrating previous research on Drusinae head anatomy, we propose a fundamental Drusinae blueprint comprising 29 cephalic muscles and discuss significance of larval head capsule corrugation in Trichoptera.
Thin flexible lab-on-a-film for impedimetric sensing in biomedical applications
Authors: Farooq Amina , Hayat Fezan , Zafar Sobia , Butt Nauman Zafar 
Published: January 2022

AbstractMicrofluidic cytometers based on coulter principle have recently shown a great potential for point of care biosensors for medical diagnostics. Here, we explore the design of an impedimetric microfluidic cytometer on flexible substrate. Two coplanar microfluidic geometries are compared to highlight the sensitivity of the device to the microelectrode positions relative to the detection volume. We show that the microelectrodes surface area and the geometry of the sensing volume for the cells strongly influence the output response of the sensor. Reducing the sensing volume decreases the pulse width but increases the overall pulse amplitude with an enhanced signal-to-noise ratio (~ max. SNR = 38.78 dB). For the proposed design, the SNR was adequate to enable good detection and differentiation of 10 µm diameter polystyrene beads and leukemia cells (~ 6–21 µm). Also, a systematic approach for irreversible & strong bond strength between the thin flexible surfaces that make up the biochip is explored in this work. We observed the changes in surface wettability due to various methods of surface treatment can be a valuable metric for determining bond strength. We observed permanent bonding between microelectrode defined polypropylene surface and microchannel carved PDMS due to polar/silanol groups formed by plasma treatment and consequent covalent crosslinking by amine groups. These experimental insights provide valuable design guidelines for enhancing the sensitivity of coulter based flexible lab-on-a-chip devices which have a wide range of applications in point of care diagnostics.
Process intensification for the continuous production of an antimicrobial peptide in stably-transformed Sf-9 insect cells
Authors: Käßer Lukas , Rotter Maximilian , Coletta Luca , Salzig Denise , Czermak Peter 
Published: January 2022

AbstractThe antibiotic resistance crisis has prompted research into alternative candidates such as antimicrobial peptides (AMPs). However, the demand for such molecules can only be met by continuous production processes, which achieve high product yields and offer compatibility with the Quality-by-Design initiative by implementing process analytical technologies such as turbidimetry and dielectric spectroscopy. We developed batch and perfusion processes at the 2-L scale for the production of BR033, a cecropin-like AMP from Lucilia sericata, in stably-transformed polyclonal Sf-9 cells. This is the first time that BR033 has been expressed as a recombinant peptide. Process analytical technology facilitated the online monitoring and control of cell growth, viability and concentration. The perfusion process increased productivity by ~ 180% compared to the batch process and achieved a viable cell concentration of 1.1 × 107 cells/mL. Acoustic separation enabled the consistent retention of 98.5–100% of the cells, viability was > 90.5%. The recombinant AMP was recovered from the culture broth by immobilized metal affinity chromatography and gel filtration and was able to inhibit the growth of Escherichia coli K12. These results demonstrate a successful, integrated approach for the development and intensification of a process from cloning to activity testing for the production of new biopharmaceutical candidates.
Quasi-perfect vortices generated by Pancharatnam-Berry phase metasurfaces for optical spanners and OAM communication
Authors: Xiang Zhiyuan , Shen Zhe , Shen Yaochun 
Published: January 2022

AbstractOptical vortex (OV) can be used in the fields of optical manipulation and optical communication because of its inherent orbital angular momentum (OAM). The size of the OV ring increases with the correlated topological charge (TC), making the OV with large TC not suitable for optical rotation and short-distance communication. Perfect vortex (PV) has attracted much attention due to that its optical transmission profile is almost independent of TC. In this manuscript, we proposed a method to generate quasi- perfect vortices (Q-PVs) by Pancharatnam–Berry (PB) phase metasurfaces, the so-called Q-PV can be regarded as an annularly focused optical vortex whose focal ring in the focal plane has an angular phase gradient. It has a similar property to PV in that its light profile hardly changes with TC in the focal plane. We demonstrated that the Q-PV can be used for optical spanners that particles are trapped and rotated on the specific orbit. Non-coaxial and coaxial Q-PV arrays were further generated for OAM communication applications. We believe that the proposed Q-PVs has potential applications in optical manipulation and optical communication.
Ultrasensitive detection of SARS-CoV-2 nucleocapsid protein using large gold nanoparticle-enhanced surface plasmon resonance
Authors: Yano Taka-aki , Kajisa Taira , Ono Masayuki , Miyasaka Yoshiya , Hasegawa Yuichi , Saito Atsushi , Otsuka Kunihiro , Sakane Ayuko , Sasaki Takuya , Yasutomo Koji , Hamajima Rina , Kanai Yuta , Kobayashi Takeshi , Matsuura Yoshiharu , Itonaga Makoto , Yasui Takeshi 
Published: January 2022

AbstractThe COVID-19 pandemic has created urgent demand for rapid detection of the SARS-CoV-2 coronavirus. Herein, we report highly sensitive detection of SARS-CoV-2 nucleocapsid protein (N protein) using nanoparticle-enhanced surface plasmon resonance (SPR) techniques. A crucial plasmonic role in significantly enhancing the limit of detection (LOD) is revealed for exceptionally large gold nanoparticles (AuNPs) with diameters of hundreds of nm. SPR enhanced by these large nanoparticles lowered the LOD of SARS-CoV-2 N protein to 85 fM, resulting in the highest SPR detection sensitivity ever obtained for SARS-CoV-2 N protein.
Simultaneous evaluation of intermittency effects, replica symmetry breaking and modes dynamics correlations in a Nd:YAG random laser
Authors: Coronel Edwin D. , da Silva-Neto Manoel L. , Moura André L. , González Iván R. R. , Pugina Roberta S. , Hilário Eloísa G. , da Rocha Euzane G. , Caiut José Maurício A. , Gomes Anderson S. L. , Raposo Ernesto P. 
Published: January 2022

AbstractRandom lasers (RLs) are remarkable experimental platforms to advance the understanding of complex systems phenomena, such as the replica-symmetry-breaking (RSB) spin glass phase, dynamics modes correlations, and turbulence. Here we study these three phenomena jointly in a Nd:YAG based RL synthesized for the first time using a spray pyrolysis method. We propose a couple of modified Pearson correlation coefficients that are simultaneously sensitive to the emergence and fading out of photonic intermittency turbulent-like effects, dynamics evolution of modes correlations, and onset of RSB behavior. Our results show how intertwined these phenomena are in RLs, and suggest that they might share some common underlying mechanisms, possibly approached in future theoretical models under a unified treatment.
Pcyt2 deficiency causes age-dependant development of nonalcoholic steatohepatitis and insulin resistance that could be attenuated with phosphonoethylamine
Authors: Grapentine Sophie , Singh Rathnesh K. , Basu Poulami , Sivanesan Sugashan , Mattos Gabriela , Oresajo Oreoluwa , Cheema Jasmine , Demeke Wendwesen , Dolinsky Vernon W. , Bakovic Marica 
Published: January 2022

AbstractThe mechanisms of NASH development in the context of age and genetics are not fully elucidated. This study investigates the age-dependent liver defects during NASH development in mice with heterozygous deletion of Pcyt2 (Pcyt2+/−), the rate limiting enzyme in phosphatidylethanolamine (PE) synthesis. Further, the therapeutic potential of the artificial Pcyt2 substrate, phosphonoethylamine (PEA), is examined. Pcyt2+/− were investigated at 2 and 6–8 months (mo) of age and in addition, 6-mo old Pcyt2+/− with developed NASH were supplemented with PEA for 8 weeks and glucose and fatty acid metabolism, insulin signaling, and inflammation were examined. Heterozygous ablation of Pcyt2 causes changes in liver metabolic regulators from young age, prior to the development of liver disease which does not occur until adulthood. Only older Pcyt2+/− experiences perturbed glucose and fatty acid metabolism. Older Pcyt2+/− liver develops NASH characterized by increased glucose production, accumulation of TAG and glycogen, and increased inflammation. Supplementation with PEA reverses Pcyt2+/− steatosis, inflammation, and other aspects of NASH, showing that was directly caused by Pcyt2 deficiency. Pcyt2 deficiency is a novel mechanism of metabolic dysregulation due to reduced membrane ethanolamine phospholipid synthesis, and the artificial Pcyt2 substrate PEA offers therapeutic potential for NASH reversion.
Talking While Signing: The Influence of Simultaneous Communication on the Spoken Language of Bimodal Bilinguals
Authors: Rozen-Blay Or , Novogrodsky Rama , Degani Tamar 
Published: January 2022

Purpose:
This study aimed to examine how speech while sign (simultaneous communication [SimCom]) affects the spoken language of bimodal bilingual teachers and how individual differences in sign-language vocabulary knowledge, SimCom teaching experience, and the ability to perform speech under dual-task conditions explain the variability in SimCom performance.

Method:
Forty experienced teachers of deaf and hard of hearing students participated in a story narration task under different conditions. Speech rate, lexical richness, and syntactic complexity were measured and compared across speech-only versus SimCom conditions. Furthermore, participants' score on a sign-language vocabulary test, their self-reported SimCom teaching experience, and their performance in a dual-task condition were taken as predictors of SimCom narration performance.

Results:
The findings revealed slower speech rate, lower lexical richness, and lower syntactic complexity in the SimCom condition compared with the speech-only condition. Sign-language vocabulary score and SimCom teaching experience explained speech rate and lexical richness. Participant's ability to speak under a dual-task condition did not modulate performance.

Conclusions:
The findings may suggest that the production of the less dominant (sign) language during SimCom entails inhibition of the dominant (spoken) language relative to the speech-only condition. At the same time, the findings are also compatible with the suggestion that SimCom serves as a unique complex communication unit that cannot be reduced to the combination of two languages.