bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRRC15 antibody‐drug conjugates show promise as osteosarcoma therapeutics in preclinical studies
Authors: Slemmons Katherine K. , Mukherjee Sanjit , Meltzer Paul , Purcell James W. , Helman Lee J. 
Published: October 2020

AbstractBackgroundOsteosarcoma (OS), the most common bone tumor in children and adolescents, has high rates of metastasis leading to poor survival. Leucine‐rich repeat containing 15 (LRRC15), a transmembrane protein whose expression is modulated by TGFβ, was recently shown to be highly expressed on the surface of OS tumor cells. Here, we evaluate a novel antibody‐drug conjugate (ADC) targeting LRRC15 in OS human cell lines and murine xenografts. We compare this new ADC, which is conjugated to the anthracycline derivative PNU‐159682 (PNU), to a previously studied LRRC15 ADC that is conjugated to the tubulin inhibitor monomethyl auristatin E (MMAE), since anthracyclines are standard of care in OS.ProcedureWe evaluated LRRC15 expression in OS cells using Western blots and flow cytometry, and analyzed the epigenetic landscape of the LRRC15 locus using chromatin immunoprecipitation. Efficacy of ADCs on cell growth was analyzed by IncuCyte live cell imaging. Intramuscular xenograft tumor growth was assessed by bioluminescence imaging and hematoxylin and eosin staining.ResultsLRRC15‐PNU is more effective at inhibiting growth in vitro and in vivo than an isotype antibody control or the LRRC15‐MMAE ADC in two high LRRC15 expressing OS cell lines. Low expressing cell lines are not sensitive to either ADC. Importantly, cells with low LRRC15 expression are amenable to re‐expression after TGFβ treatment, suggesting a potential to sensitize insensitive OS cells to LRRC15 ADC treatment. In vivo, LRRC15‐PNU had cure rates of 40‐100% in OS xenograft models.ConclusionsOverall, LRRC15‐directed ADCs are a promising new avenue for OS treatment.
Target verification of allyl isothiocyanate on the core subunits of cytochrome c oxidase in Sitophilus zeamais by RNAi
Authors: Zhang Min , Zhang Dan , Ren Jingjing , Pu Shi , Wu Hua , Ma Zhiqing 
Published: October 2020

AbstractBACKGROUNDAllyl isothiocyanate (AITC) is a volatile organic compound with a potent insecticidal activity to the stored‐grain pest Sitophilus zeamais Motschulsky, which severely damages grain storage and container transport worldwide. Our previous study showed that mitochondrial complex IV was the primary target of AITC in adult Sitophilus zeamais. To further verify the targets of AITC, we employed RNA interference (RNAi) by using double‐stranded RNA (dsRNA) to knockdown three core subunits of cytochrome c oxidase (COX)‐I, ‐II and ‐III in 18‐day‐old larvae prior to their exposure to AITC to detect susceptibility changes.RESULTSThe susceptibility of dsRNACOX‐I and ‐II injection treatments to AITC significantly increased at 72 h while the mortality reached up to 85.56% and 67.78%, respectively, and dsRNACOX‐I and dsRNACOX‐II injection showed the same subcellular structural characteristics showing vacuolization and vague mitochondrial cristae and decrease of COX activity during AITC fumigation treatment, suggesting the potential of COX‐I and COX‐II as the targets of AITC. High mortality reached up to 75.55%, 71.88% and 82.22%, respectively, and the phenotype of larvae turning from milky white to dark brown in the thorax and death eventually was confirmed after dsRNACOX‐I, ‐II and ‐III injection.CONCLUSIONCOX‐I and ‐II were elucidated as the potential targets of AITC and dsRNACOX‐I, ‐II and ‐III have the potential to be developed into nucleic acid pesticides for their robust lethal effects and are worth pursuing for improving AITC fumigation activity in Sitophilus zeamais control. © 2020 Society of Chemical Industry
On practical fixed‐time stability of discrete‐time impulsive switched nonlinear systems
Authors: Chen Guopei , Yang Ying , Deng Feiqi 
Published: October 2020

SummaryIn this note, the practical fixed‐time stability (PFTS) for discrete‐time impulsive switched nonlinear (DISN) systems is investigated. Firstly, the concept of PFTS is introduced for discrete‐time nonlinear (DN) systems, and two sufficient conditions are proposed to verify the PFTS of DN systems by using the positive‐order Lyapunov function. Then, the obtained results are extended to study the PFTS of DISN systems, two stability conditions are given by combining range dwell time and multiple positive‐order Lyapunov functions. Finally, some further discussions on the relaxation of stability conditions are also provided. Two numerical examples are given to illustrate the theoretical results.
Switch from Polymorphic to Homogenous Self‐Assembly of Virus‐Like Particles of Simian Virus 40 through Double‐Cysteine Substitution
Authors: Xu Chengchen , Zhu Weiwei , Mao Hanjing , Zhang Wenjing , Yin Gen‐Quan , Zhang Xian‐En , Li Feng 
Published: October 2020

AbstractSelf‐assembled virus‐like particles (VLPs) hold great potential as natural nanomaterials for applications in many fields. For such purposes, monodisperse size distribution is a desirable property. However, the VLPs of simian virus 40 (SV40), a representative VLP platform, are characterized by polymorphism. In an attempt to eliminate the polymorphism, 15 mutants of the VLP subunit (VP1) are constructed through the substitution of double cysteines at the VP1 pentamer interfaces, generating a group of VLPs with altered size distributions. One of the mutants, SS2 (L102C/P300C), specifically forms homogenous T = 1‐like tiny VLPs of 24 ± 3 nm in diameter. Moreover, the stability of the SS2 VLPs is markedly enhanced compared with that of wild‐type VLPs. The homogeneous self‐assembly and stability enhancement of SS2 VLPs can be attributed to the new disulfide bonds contributed by Cys102 and Cys300, which are identified by mass spectrometry and explored by molecular dynamics simulations. Endocytosis inhibition assays indicate that SS2 VLPs, like the polymorphic wild‐type VLPs, preserve the multipathway feature of cellular uptake. SS2 VLPs may serve as an evolved version of SV40 VLPs in future studies and applications. The findings of this work would be useful for the design and fabrication of VLP‐based materials and devices.
Kinetics and Molecular Docking Studies of Activating Effect of Canna edulis Ker Residue Lignin on the Activity of Lipase
Authors: Xie Fan , Gong Shengxiang , Zhang Wei , Wang Zhengwu 
Published: October 2020

AbstractIn a previous study, abundant lignin is found in the residues of Canna edulis (C. edulis) ker and showed a strong inhibitory effect on α‐glucosidase and a promoting effect on α‐amylase. In this study, the interaction kinetics, thermodynamic parameters, secondary structure, reaction site, and molecular docking are analyzed. C. edulis residues lignin present an activity promotion effect on pancreatic lipase (promoted 90% of lipase activity) through hydrogen bonding and hydrophobic interaction. The temperature increase from 298 to 310 K promotes the reaction between lignin and pancreatic lipase. The isolated lignin forms a 1:1 complex with the pancreatic lipase to quench its fluorescence. The presence of lignin changes the β‐turn structure of the pancreatic lipase molecule to influence its activity. Further, the binding site of the lignin molecule on the pancreatic lipase molecule is the phenolic hydroxyl group on the guaiacyl group. The lignin molecule binds closely to the active site of the pancreatic lipase molecule. These results provide new insight into the effect of C. edulis residues lignin on fat metabolism.
Experimental study on shear behavior of two‐way hollow core precast panel shear wall with vertical connection
Authors: Chu Mingjin , Xiong Chen , Liu Jiliang , Sun Zhijuan 
Published: October 2020

SummaryThe two‐way hollow core precast panel (TWHCPP) exhibits good seismic performance. In this study, the shear behavior of the TWHCPP shear wall with vertical connections was investigated. Specifically, five shear wall specimens, which comprised one cast‐in‐place shear wall, one TWHCPP shear wall without vertical connections, and three TWHCPP shear walls with vertical connections, were investigated experimentally. The TWHCPP shear walls were also modeled through numerical simulation. The experimental and numerical results indicate that the TWHCPP shear wall specimens with vertical connections exhibit monolithic load‐bearing mechanisms before the peak point, which is similar to the cast‐in‐place shear wall specimen. When the peak point of the TWHCPP shear wall specimen was attained, vertical slits were formed in the vertical connection and major vertical crack regions, which divided the shear wall panel into multiple vertical concrete straps. Subsequently, the load‐bearing mechanism of the TWHCPP shear wall transformed to multiple vertical concrete straps working cooperatively with transverse reinforcements. Therefore, the brittle diagonal tension failure mode could be avoided, and a good hysteretic performance could be achieved. The outcomes of this study are expected to provide a useful reference for the application of the TWHCPP shear wall.
Remote active control of nanoengineered materials for dynamic nanobiomedical engineering
Authors: Kim Yuri , Choi Hyojun , Shin Jeong Eun , Bae Gunhyu , Thangam Ramar , Kang Heemin 
Published: October 2020

AbstractCells dynamically interact with native nanostructured extracellular matrix at a molecular level in vivo. Developing remotely and actively controllable nanoengineered biomaterials can manipulate and unravel complex cell‐material interactions that dynamically occur in the nanoscale in vivo. In this review, we discuss emerging advances in a myriad of recent nanoengineering technologies to design remotely manipulable materials that enable dynamic nanobiomedical engineering at the molecular level. In particular, we focus on remote active stimuli, such as magnetic fields, light, in situ self‐assembly, and ultrasound, to manipulate dynamic cell‐material interactions in both in vitro and in vivo settings. Remote active control can be particularly appealing with targeting capability for particular locations at any prescribed time points with a degree of reversibility. The unique remote controllability enables the regulation of cellular signaling, adhesion, differentiation, and polarization; cell, drug, and gene delivery; and in situ self‐assembly. These materials allow the remote control in regenerative medicine, immunotherapy, cancer therapy, and biocatalysis as well as mechanistic studies on dynamic nanoscale cell‐material interactions. We also highlight current challenges in the remote active control, such as reproducibility, tissue‐penetrative capability, noninvasive surgery, spatial localization, and temporal variation. Albeit remotely and actively controllable nanoengineered biomaterials are in the nascent stage of development, they can evolve into multiresponsive, reversible, and cost‐effective three‐dimensional systems with safe and convenient long‐term control at the cell, tissue, and organ level toward clinical patient‐tailorable on‐demand therapy.
The ILO and Transformation of Labour Law
Authors: Liukkunen Ulla 
Published: October 2020

AbstractThe article explores some of the biggest challenges to the ILO caused by globalization and altering of the collective labour rights scene. It examines the recent transformation of collective bargaining regimes at national and transnational level and the consequences for normativities that characterize the relationship between labour law and the system of international labour standards. Domestic bargaining regimes are influenced by decentralization whereas in a transnational setting, with the phenomena of contractual arrangements between multinational enterprises and trade unions or other employee representatives, transnational collectivization of labour law is occurring. The process of transnationalization of labour law affects the traditional labour law paradigm with profound consequences for our understanding of the purpose and role of labour law. The transformation of labour law highlights regulatory developments that require reinforcement of the role of fundamental labour rights. Building a perspective on major global challenges to the ILO at the beginning of its second centenary requires an assessment of the labour question in terms of flexibility and vulnerabilities. This raises the question of inclusivity, calling for the ILO decent work agenda, employment creation, social protection, rights at work and social dialogue, all to be more firmly integrated in global regulatory approaches to work.
How to Improve Monitoring and Enforcement of International Labour Standards?
Authors: Waas Bernd 
Published: October 2020

AbstractThis paper presents the existing system of monitoring international labour standards within the ILO, and then discusses how this system could be improved. The author suggests increased and improved cooperation between the relevant international organizations and an intensification of the dialogue between courts and other supervisory bodies, insofar as they are responsible for ensuring compliance with international standards. In addition, the question of whether and in what way the European Union could make a further contribution in this respect is examined. Finally, the role of the private sector is examined in more detail.
Reading Aloud in Human-Computer Interaction: How Spatial Distribution of Digital Text Units at an Interactive Tabletop Contributes to the Participants’ Shared Understanding
Authors: Heuser Svenja , Arend Béatrice , Sunnen Patrick 
Published: October 2020

AbstractThis paper is concerned with how the spatial distribution of written informings in a serious game activity at an interactive tabletop (ITT) induces participants to read aloud interactionally relevant information to each other in the process of co-constructing a shared understanding.Engaging in an unfamiliar game activity, the participants are all equally dependent on written informings from the interface that serve as a game manual and provide crucial information for jointly achieving the game task(s). When it comes to making use of these written informings, we find the participants to read them aloud, making them accountable within the group.Our findings from multimodal video analysis of two reading-aloud cases suggest that the written informing’s directionality and distribution (here, either designed as ‘distributed’ or ‘shared’ among the interface) regulate the participants’ access to information. And that participants who cannot visually access the information they are interested in reading (aloud) co-organize fine-grained joint successive actions build on and actualized by read-aloud utterances. These joint actions allow them to align their orientation and share their understanding of game activity-relevant content.
T duality and Wald entropy formula in the Heterotic Superstring effective action at first-order in α′
Authors: Elgood Zachary , Ortín Tomás 
Published: October 2020

Abstract
We consider the compactification on a circle of the Heterotic Superstring effective action to first order in the Regge slope parameter α′ and re-derive the α′-corrected Buscher rules first found in ref. [42], proving the T duality invariance of the dimensionally-reduced action to that order in α′. We use Iyer and Wald’s prescription to derive an entropy formula that can be applied to black-hole solutions which can be obtained by a single non-trivial compactification on a circle and discuss its invariance under the α′-corrected T duality transformations. This formula has been successfully applied to α′-corrected 4-dimensional non-extremal Reissner-Nordström black holes in ref. [21] and we apply it here to a heterotic version of the Strominger-Vafa 5-dimensional extremal black hole.
Emergent Yang-Mills theory
Authors: de Mello Koch Robert , Huang Jia-Hui , Kim Minkyoo , Van Zyl Hendrik J.R. 
Published: October 2020

AbstractWe study the spectrum of anomalous dimensions of operators dual to giant graviton branes. The operators considered belong to the su(2|3) sector of$$ \mathcal{N} $$N= 4 super Yang-Mills theory, have a bare dimension∼ Nand are a linear combination of restricted Schur polynomials withp ∼ O(1) long rows or columns. In the same way that the operator mixing problem in the planar limit can be mapped to an integrable spin chain, we find that our problems maps to particles hopping on a lattice. The detailed form of the model is in precise agreement with the expected world volume dynamics ofpgiant graviton branes, which is a U(p) Yang-Mills theory. The lattice model we find has a number of noteworthy features. It is a lattice model with all-to-all sites interactions and quenched disorder.
Genetisch modifizierte regulatorische T-Zellen: Therapiekonzepte und ihr regulatorischer Rahmen
Authors: Sebe Attila , Anliker Brigitte , Rau Juliane , Renner Matthias 
Published: October 2020

ZusammenfassungAdoptive T‑Zelltherapien sind neuartige Konzepte zur Behandlung verschiedener Krankheiten. CAR-T-Zellen sind dabei als Letztlinientherapie für fortgeschrittene B‑Zelllymphome und die B‑Zellleukämie etabliert und zugelassen. TCR-basierte T‑Zellen als Behandlungsoption verschiedener hämatologischer und solider Tumoren befinden sich in der klinischen Entwicklung. Genetisch modifizierte regulatorische T‑Zellen stehen dagegen noch am Anfang ihrer klinischen Entwicklung zur Induktion von Immuntoleranz in einer Vielzahl von Anwendungsgebieten.In diesem Artikel wird zunächst ein Überblick über die Funktion der regulatorischen T‑Zellen für die Induktion der Immuntoleranz sowie über ihre Rolle im Pathomechanismus bestimmter Immunerkrankungen gegeben und der aktuelle Stand der klinischen Entwicklungen von therapeutischen Ansätzen auf Basis genetisch modifizierter regulatorischer T‑Zellen zusammengefasst. Im Weiteren werden die regulatorisch-wissenschaftlichen Anforderungen und Herausforderungen hinsichtlich Herstellung und Qualitätskontrolle sowie nichtklinischer und klinischer Testung genetisch modifizierter regulatorischer T‑Zellen als Arzneimittel für neuartige Therapien diskutiert.
Studien zu neuen Immuntherapien: Herausforderungen aus Sicht der Ethik
Authors: Paul Norbert W. 
Published: October 2020

ZusammenfassungNeue Immuntherapien werden aufgrund der immer weiter reichenden molekularen Differenzierung von Erkrankungsmustern immer häufiger in sogenannten adaptiven, also fortlaufend an Ergebnisse angepassten Studiendesigns (Umbrella- oder Basket-Studien beziehungsweise Plattformstudien) klinisch erprobt. Der hier vorgelegte Beitrag diskutiert diese Studiendesigns jenseits der Feststellung von Regulierungsbedarf, um ausgehend von typischen Strukturmerkmalen ethische Probleme zu identifizieren und – wo möglich – Lösungsvorschläge zu machen. Neben dem Verhältnis von wissenschaftlichen und sozialen Werten in klinischen Studien werden insbesondere die wissenschaftliche Validität von Evidenz, Fragen des Einschlusses von Studienteilnehmern unter der Bedingung von relativer Unsicherheit, spezifische Herausforderungen für die ethische Bewertung adaptiver Studien sowie die ethischen und praktischen Herausforderungen im Bereich der Patientenaufklärung und -einwilligung in den Blick genommen.
Eine seltene Ursache für das akut blockierte Kniegelenk: die superiore Patellaluxation
Authors: Glasbrenner Johannes , Briese Thorben , Raschke Michael J. , Herbst Elmar , Kittl Christoph 
Published: October 2020

ZusammenfassungEs wird über den Fall eines 56-jährigen Patienten berichtet, der sich ohne Traumaanamnese mit akuter Blockade des Kniegelenks in Streckung vorstellte. Anamnese, klinische Untersuchung und Röntgen führten zur Diagnose einer superioren Patellaluxation. Nach geschlossener Reposition konnte bei beschwerdefreiem Patienten eine Entlassung ohne Hilfsmittel erfolgen. Die Kenntnis dieser seltenen Ursache des akut blockierten Kniegelenks kann helfen, aufwändigere apparative Untersuchungen einzusparen und eine zügige Behandlung und Beschwerdelinderung herbeizuführen.
Dynamic handgrip exercise for the evaluation of mitral valve regurgitation: an echocardiographic study to identify exertion induced severe mitral regurgitation
Authors: Alachkar Mhd Nawar , Kirschfink Annemarie , Grebe Julian , Almalla Mohammad , Frick Michael , Milzi Andrea , Moersen Wiebke , Becker Michael , Marx Nikolaus , Altiok Ertunc 
Published: October 2020

AbstractHandgrip exercise (HG) has been occasionally used as a stress test in echocardiography. The effect of HG on mitral regurgitation (MR) is not well known. This study aims to evaluate this effect and the possible role of HG in the echocardiographic evaluation of MR. 722 patients with MR were included (18% primary, 82% secondary disease). We calculated effective regurgitant orifice area (EROA) and regurgitant volume (RVOL) at rest and during dynamic HG. Increase in MR was defined as any increase in EROA or RVOL. We analyzed the data to identify possible associations between clinical or echocardiographic parameters and the effect of HG on MR. MR increased during dynamic HG in 390 of 722 patients (54%) (∆EROA = 25%, ∆RVOL = 27%). Increase of regurgitation occurred in 66 of 132 patients with primary MR (50%) and in 324 of 580 patients with secondary MR (55%). This increase was associated with larger baseline EROA and RVOL, but it was independent from other clinical or echocardiographic parameters. In secondary MR, dynamic HG led to a reclassification of regurgitation severity from non-severe at rest to severe MR during HG in 104 of 375 patients (28%). There was a significant association between this upgrade in MR classification and higher New York Heart Association (NYHA) class (OR 1.486, 95%-CI 1.138–1.940, p = 0.004). Dynamic HG exercise increases MR in about half of patients independent of the etiology. Dynamic HG may be used to identify symptomatic patients with non-severe secondary MR at rest but severe MR during exercise.
Validation of a new approach for distinguishing anesthetized from awake state in patients using directed transfer function applied to raw EEG
Authors: Juel Bjørn E. , Romundstad Luis , Storm Johan F. , Larsson Pål G. 
Published: October 2020

AbstractWe test whether a measure based on the directed transfer function (DTF) calculated from short segments of electroencephalography (EEG) time-series can be used to monitor the state of the patients also during sevoflurane anesthesia as it can for patients undergoing propofol anesthesia. We collected and analyzed 25-channel EEG from 7 patients (3 females, ages 41–56 years) undergoing surgical anesthesia with sevoflurane, and quantified the sensor space directed connectivity for every 1-s epoch using DTF. The resulting connectivity parameters were compared to corresponding parameters from our previous study (n = 8, patients anesthetized with propofol and remifentanil, but otherwise using a similar protocol). Statistical comparisons between and within studies were done using permutation statistics, a data driven algorithm based on the DTF-parameters was employed to classify the epochs as coming from awake or anesthetized state. According to results of the permutation tests, DTF-parameter topographies were significantly different between the awake and anesthesia state at the group level. However, the topographies were not significantly different when comparing results computed from sevoflurane and propofol data, neither in the awake nor in anesthetized state. Optimizing the algorithm for simultaneously having high sensitivity and specificity in classification yielded an accuracy of 95.1% (SE = 0.96%), with sensitivity of 98.4% (SE = 0.80%) and specificity of 94.8% (SE = 0.10%). These findings indicate that the DTF changes in a similar manner when humans undergo general anesthesia caused by two distinct anesthetic agents with different molecular mechanisms of action.