bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects
Authors: Abadi Asal Jalal , Mirzaei Sepideh , Mahabady Mahmood Khaksary , Hashemi Farid , Zabolian Amirhossein , Hashemi Fardin , Raee Pourya , Aghamiri Shahin , Ashrafizadeh Milad , Aref Amir Reza , Hamblin Michael R. , Hushmandi Kiavash , Zarrabi Ali , Sethi Gautam 
Published: October 2021

AbstractCurcumin is a phytochemical isolated from Curcuma longa with potent tumor‐suppressor activity, which has shown significant efficacy in pre‐clinical and clinical studies. Curcumin stimulates cell death, triggers cycle arrest, and suppresses oncogenic pathways, thereby suppressing cancer progression. Cisplatin (CP) stimulates DNA damage and apoptosis in cancer chemotherapy. However, CP has adverse effects on several organs of the body, and drug resistance is frequently observed. The purpose of the present review is to show the function of curcumin in decreasing CP's adverse impacts and improving its antitumor activity. Curcumin administration reduces ROS levels to prevent apoptosis in normal cells. Furthermore, curcumin can inhibit inflammation via down‐regulation of NF‐κB to maintain the normal function of organs. Curcumin and its nanoformulations can reduce the hepatoxicity, neurotoxicity, renal toxicity, ototoxicity, and cardiotoxicity caused by CP. Notably, curcumin potentiates CP cytotoxicity via mediating cell death and cycle arrest. Besides, curcumin suppresses the STAT3 and NF‐ĸB as tumor‐promoting pathways, to enhance CP sensitivity and prevent drug resistance. The targeted delivery of curcumin and CP to tumor cells can be mediated nanostructures. In addition, curcumin derivatives are also able to reduce CP‐mediated side effects, and increase CP cytotoxicity against various cancer types.
Life cycle assessment (LCA) of PET and PLA bottles for the packaging of fresh pasteurised milk: The role of the manufacturing process and the disposal scenario
Authors: Desole Maria Pia , Aversa Clizia , Barletta Massimiliano , Gisario Annamaria , Vosooghnia Alireza 
Published: October 2021

AbstractEnvironmental protection issues are at the forefront of the vast majority of the media and public opinion. The study in question revealed the life cycle of a product commonly used in the home, the bottle of fresh pasteurised milk. The materials used for the manufacturing of the bottles are PET (PolyEthylene Terephthalate), plastic derived from fossil resources, and PLA (PolyLactic Acid), bioplastic derived from sugar cane, therefore from renewable resources. The life cycle of the bottles was carried out by highlighting the extraction phase of raw materials, the production of polymer, bottle, other packaging and distribution of milk and lastly, final disposal, excluding the phase of use, not significant for the purposes of this study. The studies were focused on two disposal scenarios, the current scenario and the one that is likely to take place in 10 years. In the current disposal scenario, there is no clear reduction in environmental impact from the comparison of the materials examined. With reference to the 2030 disposal scenario, the PLA turns out to be much more environmentally friendly.
Sustainable innovation among small businesses: The role of digital orientation, the external environment, and company characteristics
Authors: Nasiri Mina , Saunila Minna , Rantala Tero , Ukko Juhani 
Published: October 2021

AbstractThis study aimed to identify the internal and external environments of a company that affect sustainable innovation in such small enterprises by examining the circumstances under which small enterprises are likely to engage in sustainable innovation. The results of this study demonstrate that companies with high levels of digital orientation in their operations contributed more to sustainable innovation than those without such high levels. In addition, in the external environment, factors that include market and technological turbulence have a negative effect on sustainable innovation. However, the adoption of sustainable innovation was not significantly impacted by market turbulence. Furthermore, certain company characteristics, such as size and maturity, do not determine the contribution of a company's internal and external environments to sustainable innovation.
On the use of principal component analysis in the entropy based detection of denial‐of‐service attacks
Authors: Basicevic Ilija , Blazic Nikola , Ocovaj Stanislav 
Published: October 2021

AbstractThis paper investigates some possibilities for the use of the principal component analysis (PCA) algorithm in the detection of denial‐of‐service (DoS) attacks. Two simple traffic features that are widely used for the detection of DoS attacks are source and destination ports of packets. In this paper, we show that by using only the principal component of these two features as the input for detection a powerful detector can be built. Shannon entropy formula and two generalized entropy formulas have been used in combination with PCA. The input dataset is generated in an emulation testbed. The type of attack that is investigated is SYN flood.
Experimental study on durability of basalt fiber concrete after elevated temperature
Authors: Lu Limin , Han Fei , Wu Shaohua , Qin Yuwen , Yuan Guanglin , Doh Jeung‐Hwan 
Published: October 2021

AbstractThe durability of concrete material after exposure to elevated temperatures is important for the serviceability prediction of concrete structures in a fire disaster scenario. Existing researches show that an appropriate amount of basalt fiber can significantly improve the splitting tensile strength and chloride penetration resistance of concrete. However, the mechanical properties of basalt fiber concrete after elevated temperatures and its durability properties are still not clear. In this paper, the mechanical properties, carbonization law, and chloride ion penetration law of ordinary concrete and basalt fiber concrete under high temperatures are studied. The concept of a burnt layer for concrete exposed to elevated temperatures is proposed, and the thickness of this burnt layer for concrete under different temperatures was measured. The results show that the addition of basalt fiber can inhibit the carbonization of concrete at elevated temperatures, diminish the thickness of the burnt layer, and significantly improve the chloride penetration resistance of concrete.
Prediction model for maximum shear displacement of pipe joints with preexisting defects based on finite element–multiple nonlinear regression method
Authors: Li Bin , Fang Hongyuan , Zhang Xijun , Yang Kangjian , Dong Boyuan , Pang Gaozhao , Zhai Kejie 
Published: October 2021

AbstractUnder the coupling effect of the defects inside and around pipes, the shear displacement of the joints of old concrete pipes fallen into disrepair usually shows an accelerated deterioration trend, and its excessive value can lead to structural damage or fluid leakage. Therefore, developing a prediction model for the maximum shear displacement of concrete drainage pipe joints with preexisting defects is of crucial significance. To this end, this work selects internal corrosion and erosion voids as the typical defects inside and around old pipes, establishes 300 sets of three‐dimensional fine finite element (FE) models of the concrete drainage pipes with corrosion and void, and verifies the reliability of the developed FE model by the full‐scale tests. Based on the verified FE data, a prediction model is successfully proposed for the assessment of the maximum shear displacement of the concrete drainage pipe joints with corrosion and void defects. Moreover, parameter sensitivity analysis is carried out to reveal their relative contribution to the maximum shear displacement of pipe joints. The results show that the model proposed herein has the ability to accurately predict the maximum shear displacement of the pipe joints. The maximum and minimum relative error between the value predicted by the proposed model and the one computed by the FE model is also 12.4% and 4.8% respectively. Moreover, the traffic load with a contribution of 28.7% has the greatest impact on the maximum shear displacement of pipe joints.
COVID-19: A Trigger for Innovations in Insurance?
Authors: Boado-Penas María del Carmen , Eisenberg Julia , Şahin Şule 
Published: October 2021

AbstractThis chapter gives an overview of the consequences of the novel coronavirus, COVID-19 on the insurance branch. The main problems caused by the pandemic on the commercial insurance, and in particular, on the business interruption and possible innovations are discussed. The aim is to prepare the reader for the following chapters specifically by demonstrating connections between different aspects of modelling a pandemic. These models are necessary to create new insurance products supplementing governments’ actions in response to a pandemic.
Diagnostic Tests and Procedures During the COVID-19 Pandemic
Authors: Dunbar Sherry A. , Tang Yi-Wei 
Published: October 2021

AbstractCoronavirus disease 2019 (COVID-19) has brought a huge impact on global health and the economy. Early and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is essential for clinical intervention and pandemic control. This book chapter addresses the evolving approach to the laboratory diagnosis of COVID-19 covering preanalytical, analytical, and postanalytical steps. The rapidly changing dynamics of the COVID-19 pandemic serve as an example which will be important for laboratories to plan for future pandemics. With the quick identification of the causative pathogen and availability of the genome sequence, it will be possible to develop and implement diagnostic tests within weeks of an outbreak. Laboratories will need to be flexible to continuously adapt to changing testing needs and burdens on the healthcare system, plan mitigation strategies for bottlenecks in testing and workflow due to limitations on resources and supplies, and prepare back-up plans now in order to be better prepared for future pandemics.
Compulsory Licenses and Government Use: Challenges and Opportunities
Authors: Vawda Yousuf A. 
Published: October 2021

AbstractThe compulsory licensing and government use flexibility is potentially the most powerful tool available under the TRIPS Agreement, as amplified by the Doha Declaration, to advance public health objectives. Yet, many lower and middle income countries have shown an apparent reluctance to both incorporate them into their national legislation and then utilise them—except in a relatively small number of cases. This contribution analyses the circumstances surrounding this phenomenon. It outlines the context, historical roots of compulsory licensing and its inclusion on the TRIPS Agreement, recent examples of its utility including in two sub-Saharan countries affected by HIV/AIDS, and offers some recommendations. Among the propositions advanced are that the use of such flexibilities is not an insurmountable problem (as the case of Zimbabwe illustrates) and that in the longer term, public health objectives are best advanced by, among others, amending the TRIPS Agreement to exempt health technologies from the ambit of intellectual property protection, and new, alternative models for rewarding innovation in this field of technology being introduced.
Ein transparentes Modell für einen fairen Preis für innovative Arzneimittel in Europa
Authors: Hendrickx Anne , Kanga-Tona Thomas 
Published: October 2021

Zusammenfassung
Zusammenfassung
Das empfindliche Gleichgewicht zwischen Bezahlbarkeit von Arzneimitteln, Nutzen für Gesundheitssysteme und Patient:innen sowie Einnahmen für die Pharmafirmen hat sich zugunsten letzterer eingependelt. Die europäischen Gesundheitssysteme tun sich schwer damit, Patient:innen zeitnahen Zugang zu neuartigen Arzneimitteln zu ermöglichen, weil deren hohe Preise nicht gerechtfertigt sind. Wie aber verschafft man den Patient:innen Zugang und setzt dabei gleichzeitig Anreize für die Pharmaindustrie, in neue Arzneimittel zu investieren, die die Patient:innen auch wirklich brauchen? In ihrem Modell für eine faire Preisfestsetzung in Europa plädiert die Association Internationale de la Mutualité (AIM) für eine aktivere Rolle der Preisfestsetzungs- und Erstattungsbehörden in Europa bei der Definition und Festsetzung „fairer“ Preise für innovative Arzneimittel. Alternativ zum bisherigen Value-based Pricing schlägt die AIM einen einfachen, aber effektiven Algorithmus vor, der auf die zugrunde liegenden Kosten und den therapeutischen Nutzen abstellt. Wenn man den Gewinn auf ein vernünftiges Maß beschränken und gleichzeitig relevante Innovationen honorieren würde, dann könnte man die Arzneimittelpreise senken und den Patient:innen einen besseren Zugang zu diesen Medikamenten verschaffen. Mit ihrem Modell für eine faire Preisfestsetzung in Europa leistet die AIM einen Beitrag zu einer zentralen Debatte, die die Gesundheitssysteme weltweit in den kommenden Jahren beschäftigen wird.
Ansätze der Heterodoxen Ökonomik
Authors: Mosebach Kai 
Published: October 2021

Zusammenfassung
Zusammenfassung
Heterodoxe Ansätze hinterfragen neoklassische Gewissheiten der Arzneimittelversorgung. Dieser Beitrag beschreibt zunächst die besonderen Grundannahmen der heterodoxen (Pharma-)Ökonomik. Im Anschluss daran werden heterodoxe Argumentationslinien dargestellt, welche die hochpreisigen Arzneimittelinnovationen der letzten 10–15 Jahre zu erklären versuchen. Die Kernthese der heterodoxen (Pharma-)Ökonomik ist, dass die großen Pharmaunternehmen aufgrund ihrer Preisführerschaft sich nicht nur die Wertbeiträge staatlicher Forschungs- und Technologieförderung, sondern auch die Innovationskraft von kleinen Start-Up-Unternehmen aneignen, um ihr börsenorientiertes Wachstumsmodell zu verfolgen. Sie nutzen ihre auf Preisführerschaft und immateriellen Vermögenswerten beruhende Marktmacht zur Maximierung ihres Unternehmenswertes und der Kapitalrendite, was – paradoxerweise – ihre Innovationskraft schwächt. Abschließend wird erörtert, welche Schlussfolgerungen die theoretischen Annahmen und empirischen Ergebnisse der heterodoxen Ökonomik bei der Reform des AMNOG-Prozesses nahelegen.
Preisregulierungen im internationalen Vergleich
Authors: Vogler Sabine 
Published: October 2021

Zusammenfassung
Zusammenfassung
Im europäischen und internationalen Vergleich ist das deutsche Preisniveau von Arzneimitteln hoch – insbesondere das von neuen patentgeschützten Medikamenten. Preisregulierungen können dazu beitragen, die nachhaltige Finanzierung des Solidarsystems zu sichern. In diesem Beitrag werden Preisregulierungen im internationalen Umfeld präsentiert. In den meisten europäischen Staaten sind die Herstellerpreise von Arzneimitteln ab Markteintritt reguliert, zumindest für jene Medikamente, deren Kosten jedenfalls teilweise von den (öffentlichen) Zahlern getragen werden. Rabattabkommen (Managed Entry Agreements) sind in vielen Ländern ein gängiger Ansatz, um den Marktzugang zu hochpreisigen Arzneimitteln zu ermöglichen; sie sind allerdings meist intransparent. Neue Beschaffungsmodelle mit einer von der konsumierten Menge unabhängigen Umsatzgarantie für die pharmazeutischen Unternehmer werden in ein paar Ländern pilotiert. Im Rahmen eines integrierten Ansatzes wird Preisregulierung als Teil eines Maßnahmenpakets verstanden, das etwa auch Horizon Scanning und HTA umfasst. In jüngerer Zeit kooperieren Länder mit gemeinsamen Preisverhandlungen bzw. Arzneimittelbeschaffungen.
Beta functions for the duality-invariant sigma model
Authors: Bonezzi Roberto , Codina Tomas , Hohm Olaf 
Published: October 2021

Abstract
The O(d, d) invariant worldsheet theory for bosonic string theory with d abelian isometries is employed to compute the beta functions and Weyl anomaly at one-loop. We show that vanishing of the Weyl anomaly coefficients implies the equations of motion of the Maharana-Schwarz action. We give a self-contained introduction into the required techniques, including beta functions, the Weyl anomaly for two-dimensional sigma models and the background field method. This sets the stage for a sequel to this paper on generalizations to higher loops and α′ corrections.
Time-independence of gravitational Rényi entropies and unitarity in quantum gravity
Authors: Marolf Donald , Wang Zhencheng 
Published: October 2021

Abstract
The Hubeny-Rangamani-Takayanagi surface γHRT computing the entropy S(D) of a domain of dependence D on an asymptotically AdS boundary is known to be causally inaccessible from D. We generalize this gravitational result to higher replica numbers n > 1 by considering the replica-invariant surfaces (aka ‘splitting surfaces’) γ of real-time replica-wormhole saddle-points computing Rényi entropies Sn(D) and showing that there is a sense in which D must again be causally inaccessible from γ when the saddle preserves both replica and conjugation symmetry. This property turns out to imply the Sn(D) to be independent of any choice of any Cauchy surface ΣD for D, and also that the Sn(D) are independent of the choice of boundary sources within D. This is a key hallmark of unitary evolution in any dual field theory. Furthermore, from the bulk point of view it adds to the evidence that time evolution of asymptotic observables in quantum gravity is implemented by a unitary operator in each baby universe superselection sector. Though we focus here on pure Einstein-Hilbert gravity and its Kaluza-Klein reductions, we expect the argument to extend to any two-derivative theory who satisfies the null convergence condition. We consider both classical saddles and the effect of back-reaction from quantum corrections.
Thermodynamics of near BPS black holes in AdS4 and AdS7
Authors: Larsen Finn , Paranjape Shruti 
Published: October 2021

Abstract
We develop the thermodynamics of black holes in AdS4 and AdS7 near their BPS limit. In each setting we study the two distinct deformations orthogonal to the BPS surface as well as their nontrivial interplay with each other and with BPS properties. Our results illuminate recent microscopic calculations of the BPS entropy. We show that these microscopic computations can be leveraged to also describe the near BPS regime, by generalizing the boundary conditions imposed on states.
Alpha and beta myosin isoforms and human atrial and ventricular contraction
Authors: Walklate Jonathan , Ferrantini Cecilia , Johnson Chloe A. , Tesi Chiara , Poggesi Corrado , Geeves Michael A. 
Published: October 2021

AbstractHuman atrial and ventricular contractions have distinct mechanical characteristics including speed of contraction, volume of blood delivered and the range of pressure generated. Notably, the ventricle expresses predominantly β-cardiac myosin while the atrium expresses mostly the α-isoform. In recent years exploration of the properties of pure α- & β-myosin isoforms have been possible in solution, in isolated myocytes and myofibrils. This allows us to consider the extent to which the atrial vs ventricular mechanical characteristics are defined by the myosin isoform expressed, and how the isoform properties are matched to their physiological roles. To do this we Outline the essential feature of atrial and ventricular contraction; Explore the molecular structural and functional characteristics of the two myosin isoforms; Describe the contractile behaviour of myocytes and myofibrils expressing a single myosin isoform; Finally we outline the outstanding problems in defining the differences between the atria and ventricles. This allowed us consider what features of contraction can and cannot be ascribed to the myosin isoforms present in the atria and ventricles.
Stable Multi-Level Monotonic Eroders
Authors: Gács Péter , Törmä Ilkka 
Published: October 2021

AbstractEroders are monotonic cellular automata with a linearly ordered state set that eventually wipe out any finite island of nonzero states. One-dimensional eroders were studied by Gal’perin in the 1970s, who presented a simple combinatorial characterization of the class. The multi-dimensional case has been studied by Toom and others, but no such characterization has been found. We prove a similar characterization for those one-dimensional monotonic cellular automata that are eroders even in the presence of random noise.
Mouse Genome Informatics (MGI): latest news from MGD and GXD
Authors: Ringwald Martin , Richardson Joel E. , Baldarelli Richard M. , Blake Judith A. , Kadin James A. , Smith Cynthia , Bult Carol J. 
Published: October 2021

AbstractThe Mouse Genome Informatics (MGI) database system combines multiple expertly curated community data resources into a shared knowledge management ecosystem united by common metadata annotation standards. MGI’s mission is to facilitate the use of the mouse as an experimental model for understanding the genetic and genomic basis of human health and disease. MGI is the authoritative source for mouse gene, allele, and strain nomenclature and is the primary source of mouse phenotype annotations, functional annotations, developmental gene expression information, and annotations of mouse models with human diseases. MGI maintains mouse anatomy and phenotype ontologies and contributes to the development of the Gene Ontology and Disease Ontology and uses these ontologies as standard terminologies for annotation. The Mouse Genome Database (MGD) and the Gene Expression Database (GXD) are MGI’s two major knowledgebases. Here, we highlight some of the recent changes and enhancements to MGD and GXD that have been implemented in response to changing needs of the biomedical research community and to improve the efficiency of expert curation. MGI can be accessed freely athttp://www.informatics.jax.org.
P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke
Authors: Deshpande Sachin S. , Malik Subash C. , Conforti Pasquale , Lin Jia-di , Chu Yu-Hsuan , Nath Suvra , Greulich Franziska , Dumbach Meike-Ast , Uhlenhaut N. Henriette , Schachtrup Christian 
Published: October 2021

AbstractStroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75NTR−/−) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75NTR−/− NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75NTR abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75NTR−/− NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75NTR−/− NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75NTR abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.