bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering a human IgG2 antibody stable at low pH
Authors: Saito Seiji , Namisaki Hiroshi , Hiraishi Keiko , Takahashi Nobuaki , Iida Shigeru 
Published: March 2020

AbstractIgG2 subclass antibodies have unique properties that include low effector function and a rigid hinge region. Although some IgG2 subclasses have been clinically tested and approved for therapeutic use, they have a higher propensity than IgG1 for aggregation, which can curtail or abolish their biological activity and enhance their immunogenicity. In this regard, acid‐induced aggregation of monoclonal antibodies during purification and virus inactivation must be prevented. In the present study, we replaced the constant domain of IgG2 with that of IgG1, using anti‐2,4‐dinitrophenol (DNP) IgG2 as a model antibody, and investigated whether that would confer greater stability. While the anti‐DNP IgG2 antibody showed significant aggregation at low pH, this was reduced for the IgG2 antibody containing the IgG1 CH2 domain. Substituting three amino acids within the CH2 domain—namely, F300Y, V309L, and T339A (IgG2_YLA)—reduced aggregation at low pH and increased CH2 transition temperature, as determined by differential scanning calorimetric analysis. IgG2_YLA exhibited similar antigen‐binding capacity to IgG2, low affinity for FcγRIIIa, and low binding ability to C1q. The same YLA substitution also reduced the aggregation of panitumumab, another IgG2 antibody, at low pH. Our engineered human IgG2 antibody showed reduced aggregation during bioprocessing and provides a basis for designing improved IgG2 antibodies for therapeutic applications.
Surgical treatment of micronodular thymoma with lymphoid stroma
Authors: Kang Min Kyun , Kang Do Kyun , Hwang Youn‐Ho , Kim Ji Yeon 
Published: March 2020

AbstractThis case was about a 71‐year‐old man presented to our clinic for an anterior mediastinal mass found on routine chest computed tomography (CT). CT scan showed a lobulating contoured mass in the anterior mediastinum. A preliminary diagnosis was thymoma. The patient underwent subxiphoid uniportal video‐assisted thoracoscopic surgery for the extended thymectomy and complete excision of the tumour. The pathological examination showed a micronodular thymoma with lymphoid stroma (MTWLS). In conclusion, this report described an extremely rare tumour, MTWLS, and MTWLS might be considered in the differential diagnosis of mediastinal tumour, especially thymoma.
Business strategy, stock price informativeness, and analyst coverage efficiency
Authors: Zhang Rongrong 
Published: March 2020

AbstractWe examine how business strategy affects stock price informativeness which in turn influences analyst coverage efficiency. Using stock price synchronicity and the probability of informed trading as proxies for stock price informativeness, we show that stock prices of prospectors are less informative than those of defenders. Next, we explore two channels through which business strategy influences analyst coverage efficiency. We first test and find support for an information transfer channel, i.e., the higher stock price synchronicity of prospectors facilitates more information transfer by analysts, resulting in higher analyst coverage efficiency of prospectors than defenders. Next, we test and find support for an informed trading channel, i.e., the higher probability of informed trading on stocks of defenders intensifies competition between informed traders and analysts. Such competition adversely affects analyst coverage efficiency, leading to lower analyst coverage efficiency of defenders than prospectors. Our findings are robust to an array of robustness checks including 2SLS/IV tests, differences‐in‐difference tests, and high‐tech industry sensitivity analyses.
A review and meta‐analysis of the agricultural potential of struvite as a phosphorus fertilizer
Authors: Hertzberger Allan J. , Cusick Roland D. , Margenot Andrew J. 
Published: March 2020

AbstractThe low water solubility of struvite is thought to limit its agronomic utility as a phosphorus (P) fertilizer compared with highly soluble P fertilizers. Furthermore, struvite's fertilizer potential is complicated by its hypothesized soil pH‐dependent solubility, crop‐specific interactions, and limited availability of struvite‐derived N, which may explain conflicting reports of crop responses to struvite compared with conventional P fertilizers. A systematic literature review and meta‐analysis was conducted to evaluate the effects of soil pH, soil test P (STP), P rate, struvite particle size, and struvite‐derived N on crop aboveground biomass, P concentration, P uptake, and N uptake. Struvite‐fertilized plants yielded higher biomass, P concentration, and P uptake compared with ammonium phosphates, and superphosphates in soils with pH < 6 and crop responses decreased with increasing pH. Crop responses to struvite were inversely related to experiment duration to soil mass ratios (d kg−1) used in greenhouse studies, opposite to the hypothesized benefit of more roots per unit soil on struvite dissolution. The proportion of total N applied derived from struvite increased with increasing struvite‐P application rate and was inversely related to total N uptake, likely due to the increased crop reliance on slowly available struvite‐N. Crop responses were potentially overestimated by high STP and/or P rates and underestimated due to N limitation from large proportions of total N applied derived from struvite. Evaluations of struvite collectively indicate its efficacy as a P fertilizer is affected by soil pH and its contribution to total N application.
“All‐in‐One” Gel System for Whole Procedure of Stem‐Cell Amplification and Tissue Engineering
Authors: He Qiulin , Liao Youguo , Zhang Jingwei , Yao Xudong , Zhou Wenyan , Hong Yi , Ouyang Hongwei 
Published: March 2020

AbstractMicrosphere (MS)‐based systems provides great advantages for cell expansion and transplantation due to their high surface‐to‐volume ratio and biomimetic environment. However, a MS‐based system that includes cell attachment, proliferation, passage, harvest, cryopreservation, and tissue engineering together has not been realized yet. An “all‐in‐one” gel MS‐based system is established for human adipose‐derived mesenchymal stem cells (hADSCs), realizing real 3D culture with enhanced expansion efficiency and simplified serial cell culture operations, and construction of macrotissues with uniform cell distribution and specific function. A 3D digital light‐processing technology is developed to fabricate gel MSs in an effective way. The printed MSs present a suitable environment with rough surface architecture and the mechanical properties of soft tissues, leading to high cell viability, attachment, proliferation, activity, and differentiation potential. Further, convenient standard operation procedures, including cell passage, detachment, and cryopreservation, are established for cell culture on the gel MSs. Finally, hADSCs‐loaded gel MSs form macrotissues through a “bottom‐up” approach, which demonstrates the potential applications for tissue engineering. These findings exhibit the feasibility and beauty of “all‐in‐one” stem cell culture and tissue engineering system.
Single‐Molecule Manipulation in Zero‐Mode Waveguides
Authors: Schendel Leonard C. , Bauer Magnus S. , Sedlak Steffen M. , Gaub Hermann E. 
Published: March 2020

AbstractThe mechanobiology of receptor–ligand interactions and force‐induced enzymatic turnover can be revealed by simultaneous measurements of force response and fluorescence. Investigations at physiologically relevant high labeled substrate concentrations require total internal reflection fluorescence microscopy or zero mode waveguides (ZMWs), which are difficult to combine with atomic force microscopy (AFM). A fully automatized workflow is established to manipulate single molecules inside ZMWs autonomously with noninvasive cantilever tip localization. A protein model system comprising a receptor–ligand pair of streptavidin blocked with a biotin‐tagged ligand is introduced. The ligand is pulled out of streptavidin by an AFM cantilever leaving the receptor vacant for reoccupation by freely diffusing fluorescently labeled biotin, which can be detected in single‐molecule fluorescence concurrently to study rebinding rates. This work illustrates the potential of the seamless fusion of these two powerful single‐molecule techniques.
Zinc Oxide Particles Catalytically Generate Nitric Oxide from Endogenous and Exogenous Prodrugs
Authors: Yang Tao , Fruergaard Anne Sofie , Winther Anna K. , Zelikin Alexander N. , Chandrawati Rona 
Published: March 2020

AbstractNitric oxide (NO) is a potent biological molecule that contributes to a wide spectrum of physiological processes. However, the full potential of NO as a therapeutic agent is significantly complicated by its short half‐life and limited diffusion distance in human tissues. Current strategies for NO delivery focus on encapsulation of NO donors into prefabricated scaffolds or an enzyme‐prodrug therapy approach. The former is limited by the finite pool of NO donors available, while the latter is challenged by the inherent low stability of natural enzymes. Zinc oxide (ZnO) particles with innate glutathione peroxidase and glycosidase activities, a combination that allows to catalytically decompose both endogenous (S‐nitrosoglutathione) and exogenous (β‐gal‐NONOate) donors to generate NO at physiological conditions are reported. By tuning the concentration of ZnO particles and NO prodrugs, physiologically relevant NO levels are achieved. ZnO preserves its catalytic property for at least 6 months and the activity of ZnO in generating NO from prodrugs in human serum is demonstrated. The ZnO catalytic activity will be beneficial toward generating stable NO release for long‐term biomedical applications.
A review of freely accessible global datasets for the study of floods, droughts and their interactions with human societies
Authors: Lindersson Sara , Brandimarte Luigia , Mård Johanna , Di Baldassarre Giuliano 
Published: March 2020

AbstractThe availability of planetary‐scale geospatial datasets that can support the study of water‐related disasters in the Anthropocene is rapidly growing. We review 124 global and free datasets allowing spatial (and temporal) analyses of floods, droughts and their interactions with human societies. Our collection of datasets is available in a descriptive list for download at https://zenodo.org/record/3368882. The purpose of providing an overview of datasets across a wide range of hydrological and socioeconomic variables is to highlight research opportunities across scientific disciplines for the study of the water‐society interplay. Our collection of datasets confirms that the availability of geospatial data capturing hydrological hazards and exposure is far more mature than those capturing vulnerability aspects. We do not only highlight the unprecedented opportunities associated with these global datasets for the study of water‐related disasters in the Anthropocene, but also discuss the challenges associated with their exploitation. These challenges include: (a) time varying datasets advised not to be used in time series analyses; (b) fine spatial resolution datasets advised not to be used in local scale studies; (c), datasets built by a wide variety of data sources prohibiting systematic uncertainty assessments; and (d) datasets built by covariate variables preventing interaction studies.This article is categorized under:
Engineering Water > Planning Water
Engineering Water > Sustainable Engineering of Water
Science of Water > Water Extremes
Are Composition Surveys for Mule Deer Along Roads or From Helicopters Biased? Lessons from the Field
Authors: Conner Mary M. , McKeever Jane S. 
Published: March 2020

ABSTRACTMonitoring sex and age ratios (i.e., population composition) is common practice in deer (Odocoileus spp.) management because these estimates are used to determine population vital rates, as well as assess effects of hunting regulations and other management actions. However, there is longstanding recognition of potential biases in sex and age ratios that can arise from differences in deer behavior and sightability, or from methodological issues, such as using roads for sampling. Biologists often use roads for composition surveys because of convenience and roads are often considered to provide coverage of the sampling area and, consequently, unbiased estimates of sex and age ratios. We tested the long‐standing belief that low‐use roads through mule deer (O. hemionus) winter range provided an unbiased sampling scheme by designing and conducting a random‐route survey in conjunction with the road survey through the same winter range in Round Valley, California, USA, during 2015 and 2016. In addition, we conducted a helicopter survey of the same area in 2016. We found adult male:adult female (buck:doe) ratios were 31–45% greater from the random‐route survey compared with the road survey. There was no difference in buck:doe ratios between road and helicopter surveys, but the random‐route survey had 55% greater buck:doe ratios than the helicopter survey. The helicopter survey also had 2.2–4.7 times greater proportions of unclassified bucks than the road or random‐route surveys. There were no differences in fawn:doe ratios among the 3 survey methods. We conducted additional spatial analyses to determine if the buck:doe ratio was greater along random‐routes because bucks were avoiding roads or because the random‐route survey covered different areas. We found that bucks were not avoiding roads; rather, the roads did not adequately cover the winter range area. There were differences between all 3 methods, but our main message is that the assumption that roads provide adequate coverage of winter range and unbiased estimates of population composition should be evaluated. To evaluate that assumption, we recommend conducting ≥1 survey using random routes and comparing composition estimates with road surveys. Further, if information on buck antler‐class is required for management decisions, a ground survey is preferable to a helicopter survey. © 2020 The Wildlife Society.
Skabiestherapie in Deutschland
Authors: Hackenberg B. , Horváth O. N. , Petachti M. , Schult R. , Yenigün N. , Bannenberg P. 
Published: March 2020

Zusammenfassung
Hintergrund
Therapie der ersten Wahl gemäß Leitlinie ist bei gewöhnlicher Skabies in Deutschland die topische Einmalbehandlung mit Permethrin 5 % Creme. In den letzten Jahren gab es im Zuge zunehmender Skabiesinzidenz vermehrt Meldungen über ein Nachlassen der Wirksamkeit der Standardtherapie.

Ziel
Um ein besseres Verständnis von der Wirksamkeit der Skabiestherapie unter Praxisbedingungen zu entwickeln, wurde eine Umfrage mit besonderem Fokus auf die Erstlinientherapie mit Permethrin in dermatologischen Kliniken, Ambulanzen und Hautarztpraxen durchgeführt.

Methoden
In der postalischen Umfrage unter allen in Deutschland dermatologisch tätigen Ärzten wurden die bevorzugten Diagnoseverfahren, die jeweilige Standardinitialbehandlung, die wahrgenommene Wirksamkeit der Permethrin-Therapie, die Häufigkeit und die Gründe für ein mögliches Therapieversagen unter Permethrin und das therapeutische Vorgehen bei Versagen der Initialtherapie erfragt.

Ergebnisse
Die Wirksamkeit von Permethrin wurde von 187 Ärzten im Mittel mit 73 % bewertet. Rund 74 % behandeln weiterhin initial topisch mit 5 %iger Permethrin-Creme. Die am häufigsten genannten Gründe für ein Therapieversagen waren Anwendungsfehler, mangelnde Compliance und unzureichende Hygienemaßnahmen. Daneben wurde der Verdacht auf nachlassende Wirksamkeit, Resistenzentwicklung und Re-Infestationen geäußert. Bei Unwirksamkeit der Initialtherapie entscheiden sich die meisten Ärzte für orales Ivermectin, eine Wiederholung der Permethrin-Therapie oder für eine Kombination aus beidem.

Fazit
Obwohl lokal begrenzt über ein Nachlassen der Wirksamkeit von Permethrin bei Skabies berichtet wird, deuten die Ergebnisse dieser Umfrage weiterhin auf eine gute Wirksamkeit der Erstlinientherapie mit Permethrin 5 % Creme in Deutschland hin.
Pharmacological targeting of α3β4 nicotinic receptors improves peripheral insulin sensitivity in mice with diet-induced obesity
Authors: Jall Sigrid , De Angelis Meri , Lundsgaard Anne-Marie , Fritzen Andreas M. , Nicolaisen Trine S. , Klein Anders B. , Novikoff Aaron , Sachs Stephan , Richter Erik A. , Kiens Bente , Schramm Karl-Werner , Tschöp Matthias H. , Stemmer Kerstin , Clemmensen Christoffer , Müller Timo D. , Kleinert Maximilian 
Published: March 2020

Abstract
Aims/hypothesis
Treatment with the α3β4 nicotinic acetylcholine receptor (nAChR) agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), improves glucose tolerance in diet-induced obese (DIO) mice, but the physiological and molecular mechanisms are unknown.

Methods
DMPP (10 mg/kg body weight, s.c.) was administered either in a single injection (acute) or daily for up to 14 days (chronic) in DIO wild-type (WT) and Chrnb4 knockout (KO) mice and glucose tolerance, tissue-specific tracer-based glucose metabolism, and insulin signalling were assessed.

Results
In WT mice, but not in Chrnb4 KO mice, single acute treatment with DMPP induced transient hyperglycaemia, which was accompanied by high plasma adrenaline (epinephrine) levels, upregulated hepatic gluconeogenic genes, and decreased hepatic glycogen content. In contrast to these acute effects, chronic DMPP treatment in WT mice elicited improvements in glucose tolerance already evident after three consecutive days of DMPP treatment. After seven days of DMPP treatment, glucose tolerance was markedly improved, also in comparison with mice that were pair-fed to DMPP-treated mice. The glycaemic benefit of chronic DMPP was absent in Chrnb4 KO mice. Chronic DMPP increased insulin-stimulated glucose clearance into brown adipose tissue (+69%), heart (+93%), gastrocnemius muscle (+74%) and quadriceps muscle (+59%), with no effect in white adipose tissues. After chronic DMPP treatment, plasma adrenaline levels did not increase following an injection with DMPP. In glucose-stimulated skeletal muscle, we detected a decreased phosphorylation of the inhibitory Ser640 phosphorylation site on glycogen synthase and a congruent increase in glycogen accumulation following chronic DMPP treatment.

Conclusions/interpretation
Our data suggest that DMPP acutely induces adrenaline release and hepatic glycogenolysis, while chronic DMPP-mediated activation of β4-containing nAChRs improves peripheral insulin sensitivity independently of changes in body weight via mechanisms that could involve increased non-oxidative glucose disposal into skeletal muscle.
Operational neural networks
Authors: Kiranyaz Serkan , Ince Turker , Iosifidis Alexandros , Gabbouj Moncef 
Published: March 2020

AbstractFeed-forward, fully connected artificial neural networks or the so-called multi-layer perceptrons are well-known universal approximators. However, their learning performance varies significantly depending on the function or the solution space that they attempt to approximate. This is mainly because of their homogenous configuration based solely on the linear neuron model. Therefore, while they learn very well those problems with a monotonous, relatively simple and linearly separable solution space, they may entirely fail to do so when the solution space is highly nonlinear and complex. Sharing the same linear neuron model with two additional constraints (local connections and weight sharing), this is also true for the conventional convolutional neural networks (CNNs) and it is, therefore, not surprising that in many challenging problems only the deep CNNs with a massive complexity and depth can achieve the required diversity and the learning performance. In order to address this drawback and also to accomplish a more generalized model over the convolutional neurons, this study proposes a novel network model, called operational neural networks (ONNs), which can be heterogeneous and encapsulate neurons with any set of operators to boost diversity and to learn highly complex and multi-modal functions or spaces with minimal network complexity and training data. Finally, the training method to back-propagate the error through the operational layers of ONNs is formulated. Experimental results over highly challenging problems demonstrate the superior learning capabilities of ONNs even with few neurons and hidden layers.
The scenario coevolution paradigm: adaptive quality assurance for adaptive systems
Authors: Gabor Thomas , Sedlmeier Andreas , Phan Thomy , Ritz Fabian , Kiermeier Marie , Belzner Lenz , Kempter Bernhard , Klein Cornel , Sauer Horst , Schmid Reiner , Wieghardt Jan , Zeller Marc , Linnhoff-Popien Claudia 
Published: March 2020

AbstractSystems are becoming increasingly more adaptive, using techniques like machine learning to enhance their behavior on their own rather than only through human developers programming them. We analyze the impact the advent of these new techniques has on the discipline of rigorous software engineering, especially on the issue of quality assurance. To this end, we provide a general description of the processes related to machine learning and embed them into a formal framework for the analysis of adaptivity, recognizing that to test an adaptive system a new approach to adaptive testing is necessary. We introduce scenario coevolution as a design pattern describing how system and test can work as antagonists in the process of software evolution. While the general pattern applies to large-scale processes (including human developers further augmenting the system), we show all techniques on a smaller-scale example of an agent navigating a simple smart factory. We point out new aspects in software engineering for adaptive systems that may be tackled naturally using scenario coevolution. This work is a substantially extended take on Gabor et al. (International symposium on leveraging applications of formal methods, Springer, pp 137–154, 2018).
Sex, Reasons, Pro Tanto Wronging, and the Structure of Rape Liability
Authors: Greasley Kate 
Published: March 2020

AbstractSome recent scholarship in the philosophy of criminal law has claimed that sexual penetration ‘per se’—meaning, consensual or otherwise—is pro tanto morally wrong, or that there exist ‘general reasons’ against it. On such a view, penetrative sex is only ever at best justified wrongdoing. When paired with an influential view about the theoretical basis of the offence-defence distinction in criminal law, the apparent implication is that sexual penetration alone ought to constitute the actus reus of rape, with the question of consent relegated to a defence matter. This article firstly sets out some of the difficult upshots of considering all sexual penetration to be pro tanto wrong, particularly when one attends to the full moral entailments of justified wrongdoing. Assuming, arguendo, that sexual penetration is pro tanto wrong, it is also far from clear, I suggest, that consent, of all things, amounts to a justification for penetrative sex. This creates further difficulties for the pro tanto wrong view. Finally, I argue that even if penetrative sex is a pro tanto moral wrong of some kind, it does not follow, as some scholars have suggested, that there is a case for making penetrative sex as such (alongside culpability requirements) the offence element of rape.