bluuebunny/crossref_metadata_2025 huggingface dataset:
A powerful software‐defined cyber‐physical system to expand CPS adoption
Authors: Yu Haisheng , Qi Heng , Li Keqiu
Published: July 2019

The cyber‐physical system (CPS) has become a promising direction that can enrich the interaction between people and people, people and objects, objects and objects in the physical world and the virtual world. Because of the development of CPS, the number and types of smart device connected to the Internet has rapidly increased, bringing with it the current issues of flexibility, efficiency, availability, security, and scalability of the Internet‐of‐Things (IoT) network. These problems are caused by the key mechanism of large‐scale distribution to the IoT network. In this article, we propose CPSS inspired by software‐defined networking (SDN) and service‐oriented architecture, which is a powerful software‐defined cyber‐physical system to solve the challenges of broader CPS adoption. CPSS has three complementary modules: application‐as‐a‐service (AAAS), network‐as‐a‐service (NAAS), and infrastructure‐as‐a‐service (IAAS). IAAS collects network information from a different set of controllers and devices and generates a domain‐wide network view. NAAS collects information from different domains and generates a global view, which helps data transmission between different domains and enables seamless switching between applications and infrastructure devices. AAAS provides personalized service for each user. To test CPSS, we develop a prototype system. Our experimental results show that CPSS can effectively control cyber‐physical system, and CPSS has greatly improved network latency, network throughput, and network reliability compared to traditional controller‐controlled CPS.
Verbundträger und Verbunddeckensysteme mit Stegöffnungen
Authors: Claßen Martin , Bielak Jan , Spelter Arne
Published: July 2019

Im Hoch‐ und Industriebau werden immer häufiger Stahl‐Beton‐Verbunddeckensysteme mit hohem Installationsgrad eingesetzt, in denen zur Reduzierung der Bauhöhe die Gebäudetechnik durch Öffnungen in den Trägerstegen geführt wird. Regelungen zur Bemessung von Verbundträgern mit Stegausschnitten sind in der europäischen Normung derzeit allerdings nicht vorhanden und bestehende Ingenieurmodelle aus der Literatur decken die auftretenden Effekte nicht vollständig ab. Hierdurch kann die Querkrafttragfähigkeit des Betongurts, die im Bereich einer Stegöffnung einen wesentlichen Anteil der Gesamttragfähigkeit ausmacht, für die Bemessung nicht angesetzt werden. Im Rahmen des vorliegenden Aufsatzes wird daher ein Modell für Träger mit Öffnungen vorgestellt, das eine mechanisch konsistente Bemessung unter Berücksichtigung aller möglichen Versagensarten ermöglicht. Das Vorgehen wird anhand eines ausführlichen Anwendungsbeispiels veranschaulicht.
Identity-based and anonymous key agreement protocol for fog computing resistant in the Canetti–Krawczyk security model
Authors: Patonico Simone , Braeken An , Steenhaut Kris
Published: July 2019

Fog computing allows to connect the edge of the network, consisting of low cost Internet of Things devices, with high end cloud servers. Fog devices can perform data processing, which can significantly reduce the delay for the application. Moreover, data aggregation can be carried out by fog devices which decrease the bandwidth needed being very important for the wireless part of the communication with the cloud servers. The edge-fog-cloud architecture is currently being rolled out for several applications in the field of connected cars, health care monitoring, etc. In this paper, we propose an identity-based, mutual authenticated key agreement protocol for this fog architecture, in which end device and fog are able to establish a secure communication without leakage of their identities. Only the cloud server is able to control the identities of device and fog. We formally prove that the session keys are also protected in the Canetti–Krawczyk security model, in which adversaries are considered to have access to session state specific information, previous session keys, or long-term private keys. The scheme is very efficient as it only utilises elliptic curve operations and basic symmetric key operations.
Bayesian Comparison of Latent Variable Models: Conditional Versus Marginal Likelihoods
Authors: Merkle Edgar C. , Furr Daniel , Rabe-Hesketh Sophia
Published: July 2019

Typical Bayesian methods for models with latent variables (or random effects) involve directly sampling the latent variables along with the model parameters. In high-level software code for model definitions (using, e.g., BUGS, JAGS, Stan), the likelihood is therefore specified as conditional on the latent variables. This can lead researchers to perform model comparisons via conditional likelihoods, where the latent variables are considered model parameters. In other settings, however, typical model comparisons involve marginal likelihoods where the latent variables are integrated out. This distinction is often overlooked despite the fact that it can have a large impact on the comparisons of interest. In this paper, we clarify and illustrate these issues, focusing on the comparison of conditional and marginal Deviance Information Criteria (DICs) and Watanabe–Akaike Information Criteria (WAICs) in psychometric modeling. The conditional/marginal distinction corresponds to whether the model should be predictive for the clusters that are in the data or for new clusters (where “clusters” typically correspond to higher-level units like people or schools). Correspondingly, we show that marginal WAIC corresponds to leave-one-cluster out cross-validation, whereas conditional WAIC corresponds to leave-one-unit out. These results lead to recommendations on the general application of the criteria to models with latent variables.
Math interest and self‐concept among latino/a students: Reciprocal influences across the transition to middle school
Authors: Denner Jill , Valdes Olivia , Dickson Daniel J. , Laursen Brett
Published: July 2019

Introduction

Psychological factors like math interest and self‐concept typically decline between late childhood and early adolescence; both are key to math achievement. The present study examined the reciprocal interplay between math interest and self‐concept across the transition into middle school, and whether associations are moderated by success attributions.

Methods

A total of 263 (120 boys, 143 girls) Latino students (Mage = 10.5 years at outset) from an agricultural community in California (USA) completed surveys at three time points, from the end of primary school to the first year of middle school. Surveys measured math self‐concept and math interest, as well as attributions to success in math. Cross‐lagged panel models examined possible bidirectional associations between math self‐concept and math interest, and whether attributions of success moderated these association.

Results

Lower initial levels of math self‐concept anticipated greater declines in math interest, an association that was buffered by attributions of math success. The smallest declines in math interest occurred among adolescents who had both the highest math self‐concept and were most inclined to attribute success in math to internal factors like studying. These associations remained when potential confounding variables (e.g., school grades, conduct problems) were included.

Conclusion

The results replicate, in an understudied sample of Latino/a youth, the oft‐reported link from low math self‐concept to declining interest in math. Unique to this study is evidence of the protection afforded by belief in the efficacy of studying. The findings offer important guidance for teachers and parents seeking to mobilize resources for underperforming students.
Emergency Medical Training for the Commercial Fishing Industry: An Expanded Role for Wilderness Medicine
Authors: Miner Todd , Kincl Laurel D. , Bovbjerg Viktor E. , Vaughan Amelia , Jacobson Kaety
Published: July 2019

This article describes the conception, implementation, and evaluation of a wilderness medicine–based first aid class for the commercial fishing industry. Commercial fishing is a dangerous occupation in the United States. Currently, commercial fishermen often only have access to basic first aid classes. Because of its focus on austere environments, hazardous conditions, and distance from definitive medical care—hallmarks of commercial fisheries—wilderness medicine offers a more appropriate approach to decreasing morbidity and mortality in the industry. A 2-d, 16-h pilot wilderness medicine course for commercial fishermen, Fishermen First Aid and Safety Training (FFAST), conducted for Dungeness crab fishermen, was effective and well received, based on pre- and postcourse knowledge, skill, and attitude surveys. FFAST has been approved by the Coast Guard and is being made more widely available to commercial fishermen in the Pacific Northwest. The FFAST program offers an example of how wilderness medicine can improve safety and emergency medical response for a wide variety of austere environments not traditionally linked to the backcountry.
Case of Georgia v. Russia (I) (Just Satisfaction)
Authors: Ioffe Yulia
Published: July 2019

In Georgia v. Russia (I) (Just Satisfaction), the Grand Chamber of the European Court of Human Rights (ECtHR or Court) ordered the Russian Federation to pay Georgia EUR 10 million as reparation for Russia's “coordinated policy of arresting, detaining and expelling Georgian nationals” in the autumn of 2006 (paras. 51, 80). In so doing, the Court reaffirmed its position from Cyprus v. Turkey (IV) (Just Satisfaction) that financial compensation for non-pecuniary damage can be awarded in interstate cases. Although Georgia v. Russia (I) (Just Satisfaction) marks the development of a new line of ECtHR jurisprudence, it is unlikely that the decision will effectively prevent further mass violations of the European Convention on Human Rights (ECHR or Convention) by the states parties or offer fair compensation to the victims of such violations.
Clinical impact of matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the management of inpatient pneumonia without additional antimicrobial stewardship support
Authors: Porreca Kratz Ann Marie , Sullivan Kaede V. , Gallagher Jason C.
Published: July 2019

We assessed whether implementation of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry without antimicrobial stewardship support would impact antimicrobial utilization and clinical outcomes in inpatient pneumonia. Implementation significantly reduced time to organism identification and time to optimal therapy but did not have a detectable impact on clinical outcomes.
A vortex interaction mechanism for generating energy and enstrophy fluctuations in high-symmetric turbulence
Authors: Yasuda Tatsuya , Kawahara Genta , van Veen Lennaert , Kida Shigeo
Published: July 2019

Turbulent vortex dynamics is investigated in triply periodic turbulent flow with Kida’s high symmetry (Kida, J. Phys. Soc. Japan, vol. 54, 1985, pp. 2132–2136) by means of unstable periodic motion representing both the statistical and dynamical properties of turbulence (van Veen et al., Fluid Dyn. Res., vol. 38, 2006, pp. 19–46). In the periodic motion, the large-scale columnar vortices, the smaller-scale vortices and the large-amplitude axial waves on the large-scale columnar vortices are detected. In terms of mutual dynamical interaction between the large-scale columnar vortices and smaller-scale vortices, we demonstrate a cyclic process of excitation of the axial waves, which leads to large-amplitude fluctuations of the total kinetic energy and enstrophy. This cyclic process is characterised by three distinct phases and is therefore reminiscent of the regeneration cycle of near-wall turbulence structures (Hamilton et al., J. Fluid Mech., vol. 287, 1995, pp. 317–348). Notably, such oscillatory behaviour is observed even in freely decaying turbulence as a consequence of the instantaneous energy transfer from smaller to larger scales.
New skull remains of Phorusrhacos longissimus (Aves, Cariamiformes) from the Miocene of Argentina: implications for the morphology of Phorusrhacidae
Authors: Degrange Federico J. , Eddy Drew , Puerta Pablo , Clarke Julia
Published: July 2019

The giant carnivorous phorusrhacid birdPhorusrhacos longissimus(Aves, Cariamiformes) was first described in 1887 by Florentino Ameghino on the basis of a jaw fragment. The majority of a skull of the species still encased in crumbling rock was preserved only long enough for illustrations to be made by Carlos Ameghino in the field and for a brief description to be written. Skull remains of this species have remained scarce, and few postcranial remains have been figured. Here, we reassess the cranial anatomy of this outstanding ‘terror bird’ species taking into account data from a newly discovered skull. An additional specimen of a well-preserved dorsal vertebra referable to Phorusrhacinae is also described from a separate locality within the Miocene Santa Cruz Formation (late early Miocene) from Santa Cruz Province in Argentina. The skull includes most of the rostrum, skull roof, and mandible and is compared with material from other members of the Phorusrhacinae. The new data from the skull and vertebra provide morphological features of this clade that benefit future taxonomic and phylogenetic analyses of this iconic group of birds.
MULTIPLE CHOICES IMPLY THE INGLETON AND KREIN–MILMAN AXIOMS
Authors: MORILLON MARIANNE
Published: July 2019

In set theory without the Axiom of Choice, we consider Ingleton’s axiom which is the ultrametric counterpart of the Hahn–Banach axiom. We show that in ZFA, i.e., in the set theory without the Axiom of Choice weakened to allow “atoms,” Ingleton’s axiom does not imply the Axiom of Choice (this solves in ZFA a question raised by van Rooij, [27]). We also prove that in ZFA, the “multiple choice” axiom implies the Krein–Milman axiom. We deduce that, in ZFA, the conjunction of the Hahn–Banach, Ingleton and Krein–Milman axioms does not imply the Axiom of Choice.
Regional to global correlation of Eocene–Oligocene boundary transition successions using biostratigraphic, geophysical and geochemical methods
Authors: Ellwood Brooks B. , Febo Lawrence , Anderson Laurie , Hackworth Rebecca T. , Means Guy H. , Bryan Jonathon A. , Tomkin Jonathan , Rowe Harry , Jovane Luigi
Published: July 2019

Regional to global high-resolution correlation and timing is critical when attempting to answer important geological questions, such as the greenhouse to icehouse transition that occurred during the Eocene–Oligocene boundary transition. Timing of these events on a global scale can only be answered using correlation among many sections, and multiple correlation proxies, including biostratigraphy, lithostratigraphy, geochemistry and geophysical methods. Here we present litho- and biostratigraphy for five successions located in the southeastern USA. To broaden the scope of correlation, we also employ carbon and oxygen stable isotope and magnetic susceptibility (χ) data to interpret these sections regionally, and correlate to the Global Boundary Stratotype Section and Point (GSSP) near Massignano in central Italy. Our results indicate that approaching the Eocene–Oligocene boundary, climate warmed slightly, but then δ18O data exhibit an abruptc.+5 ‰ positive shift towards cooling that reached a maximumc.1 m below the boundary at St Stephens Quarry, Alabama. This shift was accompanied by ac.−3 ‰ negative shift in δ13C interpreted to indicate environmental changes associated with the onset of the Eocene–Oligocene boundary planktonic foraminiferal extinction event. The observed cold pulse may be responsible for the final extinction of Hantkeninidae, used to define the beginning of the Rupelian Stage. Immediately preceding the boundary, Hantkeninidae species dropped significantly in abundance and size (pre-extinction dwarfing occurring before the final Eocene–Oligocene extinctions), and these changes may be the reason for inconsistencies in past Eocene–Oligocene boundary placement in the southeastern USA.
Collisional shock waves induced by laser radiation pressure
Authors: Henis Zohar , Eliezer Shalom , Raicher Erez
Published: July 2019

The formation of a collisional shock wave by the light pressure of a short-laser pulse at intensities in the range of 1018–1023 W/cm2 is considered. In this regime the thermodynamic parameters of the equilibrium states, before and after the shock transition, are related to the relativistic Rankine–Hugoniot equations. The electron and ion temperatures associated with these shock waves are calculated. It is shown that if the time scale of energy dissipation is shorter than the laser pulse duration a collisional shock is formed. The electrons and the ions in the shock-heated layer may have equal or different temperatures, depending on the laser pulse duration, the material density and the laser intensity. This shock wave may serve as a heating mechanism in a fast ignition scheme.
Tight closure of powers of ideals and tight hilbert polynomials
Authors: GOEL KRITI , VERMA J. K. , MUKUNDAN VIVEK
Published: July 2019

Let (R, ) be an analytically unramified local ring of positive prime characteristic p. For an ideal I, let I* denote its tight closure. We introduce the tight Hilbert function $$H_I^*\left( n \right) = \Im \left( {R/\left( {{I^n}} \right)*} \right)$$ and the corresponding tight Hilbert polynomial $$P_I^*\left( n \right)$$, where I is an m-primary ideal. It is proved that F-rationality can be detected by the vanishing of the first coefficient of $$P_I^*\left( n \right)$$. We find the tight Hilbert polynomial of certain parameter ideals in hypersurface rings and Stanley-Reisner rings of simplicial complexes.
(Re)Reading Pop Personae: A Transmedial Approach to Studying the Multiple Construction of Artist Identities
Authors: HANSEN KAI ARNE
Published: July 2019

This article engages with a wide range of existing literature relevant to understanding the artist persona in popular music, and advocates a view of personae as multiply constructed through sound recordings, music videos, live performances, interviews, social media posts, and a variety of other means. In an initial effort to theorize pop personae as transmedial phenomena, I merge a critical musicological understanding of the performative potential of aesthetics with perspectives from celebrity studies and media studies to produce new insights into how personae are articulated across a variety of disparate but intersecting spaces. Through a case study of Sam Smith, I demonstrate how the signs and symbols scattered across numerous platforms are aggregated in the pop persona, and elucidate the interpretive possibilities afforded by different points of contact between artist and audience. I conclude that the task of reading pop personae amounts to an assessment of the conglomerate of texts and contexts that shape both the production and the reception of pop expressions.
Anarchy, ordering principles and the constitutive regime of the international system
Authors: HELAL MOHAMED S
Published: July 2019

Anarchy is the conceptual cornerstone of international relations theory and international law scholarship. Anarchy is described as the ordering principle of the international system, it is used as a variable that explains state behaviour, and the international legal order is depicted as anarchic and decentralised. This article questions this privileged status of anarchy. It challenges the designation of anarchy as the ‘ordering principle’ of the international system, and proposes an alternative theoretical construct – the Constitutive Regime of the International System – that performs the functions of the ‘ordering principles’ of the international system. This Constitutive Regime consists of three components. The first is a principle of differentiation that identifies the constituent units of the international system. The second is a theory of world order that prescribes policies and principles that are necessary to maintain order within the system, and the third are the secondary rules of international law that generate the international law-making and law-enforcement processes. In short, the Constitutive Regime provides a novel theoretical vernacular to understand and conceptualise the normative foundations of the international system.
Gulf Dead Zone Looms Large in 2019
Authors: Morton Mary
Published: July 2019

A new forecast predicts widespread hypoxia after a wet Midwest spring.
Scientists Who Selfie from the Field
Authors: Cartier Kimberly
Published: July 2019

How did the research trip go? Better check the selfies—I mean, field log.
Revisiting Recent Elevation‐Dependent Warming on the Tibetan Plateau Using Satellite‐Based Data Sets
Authors: Guo Donglin , Sun Jianqi , Yang Kun , Pepin Nick , Xu Yongming
Published: July 2019

Satellite data, characterized by extensive regional coverage and relatively high spatial resolution, have a distinct advantage for examining elevation‐dependent warming (EDW) across rugged topography in mountain regions where there are sparse in situ observations. Based on recent (2001–2015) comprehensive satellite‐based data sets (2 m air temperature, land surface temperature, snow cover, and daytime and nighttime cloud), this study finds that annual mean 2 m  air temperature warming rates show rapid decrease above 4,500 m despite increasing from 2,000 to 4,500 m. This indicates a reversal in EDW at the highest elevations on the Tibetan Plateau, which is somehow different from the EDW derived from short‐term land surface temperature presented in earlier research. The decrease of warming rate above 4,500 m coincides with the elevation at which most of the current solid water resources reside. Thus, their decline may be less rapid than previously thought. Trends in nighttime cloud and snow cover are both correlated with patterns of EDW on the Tibetan Plateau, but the leading factor varies on an annual and seasonal basis. These results provide important evidence for understanding EDW and its controlling mechanisms in an extreme high‐elevation context.
EGFR TKIs impair lysosome-dependent degradation of SQSTM1 to compromise the effectiveness in lung cancer
Authors: Yang Lixian , Ying Shilong , Hu Shiman , Zhao Xiangtong , Li Muchun , Chen Miaoqin , Zhu Yiran , Song Ping , Zhu Liyuan , Jiang Tingting , An Huimin , Yousafzai Neelum Aziz , Xu Wenxia , Zhang Zhiguo , Wang Xian , Feng Lifeng , Jin Hongchuan
Published: July 2019

Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR TKIs) greatly improved clinical outcomes of patients with non-small cell lung cancer (NSCLC). Unfortunately, primary and acquired resistance limits their clinical benefits. To overcome such resistance, new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR. However, much less effort has been put into alternative strategies, such as targeting the intrinsic protective responses to EGFR TKIs. In this study, we found that EGFR TKIs, including gefitinib and AZD9291, impaired lysosome-dependent degradation of SQSTM1, thus compromising their anti-cancer efficiency. By accumulating in the lysosome lumen, gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity. As a result, SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance. Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo. Furthermore, a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells. Therefore, targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy.
Loss of Bcl-G, a Bcl-2 family member, augments the development of inflammation-associated colorectal cancer
Authors: Nguyen Paul M. , Dagley Laura F. , Preaudet Adele , Lam Nga , Giam Maybelline , Fung Ka Yee , Aizel Kaheina , van Duijneveldt Gemma , Tan Chin Wee , Hirokawa Yumiko , Yip Hon Yan K. , Love Christopher G. , Poh Ashleigh R. , Cruz Akshay D’ , Burstroem Charlotte , Feltham Rebecca , Abdirahman Suad M. , Meiselbach Kristy , Low Ronnie Ren Jie , Palmieri Michelle , Ernst Matthias , Webb Andrew I. , Burgess Tony , Sieber Oliver M. , Bouillet Philippe , Putoczki Tracy L.
Published: July 2019

Gastrointestinal epithelial cells provide a selective barrier that segregates the host immune system from luminal microorganisms, thereby contributing directly to the regulation of homeostasis. We have shown that from early embryonic development Bcl-G, a Bcl-2 protein family member with unknown function, was highly expressed in gastrointestinal epithelial cells. While Bcl-G was dispensable for normal growth and development in mice, the loss of Bcl-G resulted in accelerated progression of colitis-associated cancer. A label-free quantitative proteomics approach revealed that Bcl-G may contribute to the stability of a mucin network, which when disrupted, is linked to colon tumorigenesis. Consistent with this, we observed a significant reduction in Bcl-G expression in human colorectal tumors. Our study identifies an unappreciated role for Bcl-G in colon cancer.
Soluble Wood Smoke Extract Promotes Barrier Dysfunction in Alveolar Epithelial Cells through a MAPK Signaling Pathway
Authors: Zeglinski Matthew R. , Turner Christopher T. , Zeng Rui , Schwartz Carley , Santacruz Stephanie , Pawluk Megan A. , Zhao Hongyan , Chan Arthur W. H. , Carlsten Christopher , Granville David J.
Published: July 2019

Wildfire smoke induces acute pulmonary distress and is of particular concern to risk groups such as the sick and elderly. Wood smoke (WS) contains many of the same toxic compounds as those found in cigarette smoke (CS) including polycyclic aromatic hydrocarbons, carbon monoxide, and free radicals. CS is a well-established risk factor for respiratory diseases such as asthma and COPD. Limited studies investigating the biological effects of WS on the airway epithelium have been performed. Using a cell culture-based model, we assessed the effects of a WS-infused solution on alveolar epithelial barrier function, cell migration, and survival. The average geometric mean of particles in the WS was 178 nm. GC/MS analysis of the WS solution identified phenolic and cellulosic compounds. WS exposure resulted in a significant reduction in barrier function, which peaked after 24 hours of continuous exposure. The junctional protein E-cadherin showed a prominent reduction in response to increasing concentrations of WS. Furthermore, WS significantly repressed cell migration following injury to the cell monolayer. There was no difference in cell viability following WS exposure. Mechanistically, WS exposure induced activation of the p44/42, but not p38, MAPK signaling pathway, and inhibition of p44/42 phosphorylation prevented the disruption of barrier function and loss of E-cadherin staining. Thus, WS may contribute to the breakdown of alveolar structure and function through a p44/42 MAPK-dependent pathway and may lead to the development and/or exacerbation of respiratory pathologies with chronic exposure.
The β2-adrenergic receptor antagonist ICI-118,551 blocks the constitutively activated HIF signalling in hemangioblastomas from von Hippel-Lindau disease
Authors: Cuesta A. M. , Albiñana V. , Gallardo-Vara E. , Recio-Poveda L. , de Rojas-P I. , de Las Heras K. Villar Gómez , Aguirre D. T. , Botella L. M.
Published: July 2019

One of the major consequences of the lack of a functional VHL protein in von Hippel-Lindau disease, a rare cancer, is the constitutive activation of the HIF pathway. This activation ends up in the generation of Central Nervous System (CNS) Hemangioblastomas among other tumours along the lifespan of the patient. Nowadays, only surgery has been proven efficient as therapy since the systemic attempts have failed. Propranolol, a non-specific β1-and β2-adrenergic receptor antagonist, was recently designated as the first therapeutic (orphan) drug for VHL disease. Nevertheless, its β1 affinity provokes the decrease in blood pressure, being not recommended for low or regular blood pressure VHL patients. In order to overcome the β1-drawback, the properties of a high specific β2-adrenergic receptor blocker named ICI-118,551 have been studied. ICI-118,551 was able to decrease Hemangioblastomas cell viability in a specific manner, by triggering apoptosis. Moreover, ICI-118,551 also impaired the nuclear internalization of HIF-1α in Hemangioblastomas and hypoxic primary endothelial cells, reducing significantly the activation of HIF-target genes and halting the tumour-related angiogenic processes. In this work, we demonstrate the therapeutical properties of ICI-118,551 in VHL-derived CNS-Hemangioblastoma primary cultures, becoming a promising drug for VHL disease and other HIF-related diseases.
Real-time Particle Size Analysis Using the Focused Beam Reflectance Measurement Probe for In Situ Fabrication of Polyacrylamide–Filler Composite Materials
Authors: Sankaranarayanan Sivashunmugam , Likozar Blaž , Navia Rodrigo
Published: July 2019

Real-time particle size analysis, using an engineered focused beam reflectance measurement (FBRM), was studied for the fabrication of chemical composite materials, applying various (inorganic/organic/biological) filler powders with polyacrylamide via the in situ polymerization production process at 80 °C for 24 h. The measured diameter dimensions, differential distribution functions and growth during reactive compound manufacturing technology were monitored by determining quantitative chord length, this being the altering scale use of FBRM technique. Materials characterizations such as formulation part-, scanning electron microscopy-, substance elemental- and complex Fourier-transform infrared spectroscopy analyses, supported well the successful structural preparation of differing-property constituent compositions. In addition, it was also observed that operations such as granulation, coating and filling, were involved in the design of stronger polymer–reinforcement components. A comparison of the surface area variation of montmorillonite (245 m2/g), alumina (236 m2/g) and residual biomass (0.8 m2/g) with their corresponding formed composites (112, 84 and 0.1 m2/g, respectively) revealed that the presence of thermoset plastic matrix results in a drop in interface due to a defined multiple step formation processing. Furthermore, thermal characterization of alumina and the developed nanocomposite materials confirmed, as expected, the interaction of the nanocomposite precursors.
Nanoscale modification of silicon and germanium surfaces exposed to low-energy helium plasma
Authors: Thompson Matt , Magyar Luke , Corr Cormac
Published: July 2019

Complex surface nanostructures were observed in germanium and silicon samples exposed to low energy (24 or 36 eV ion kinetic energy) helium plasma. Pyramidal growth is observed in germanium across the temperature range studied (185 °C to 336 °C), while significant modification in silicon was only observed at 630 °C. Nano-wire growth was observed in both germanium and silicon, and appears to be linked to the strength of the electric field, which in turn determines the implantation energy of the helium ions. Nanostructure formation is proposed to be driven by surface adatom migration which is strongly influenced by an Ehrlich-Schwoebel-type surface instability. The role of helium in this model is to drive germanium interstitial formation by ejecting germanium atoms from lattice sites, leading to germanium interstitial diffusion towards the sample surface and subsequent adatom and surface nanostructure formation.
Design Factors Important for Antibody–Drug Conjugate (ADC) Payloads
Authors: Lambert John M.
Published: July 2019

Creating antibody–drug conjugates (ADCs) by attaching cytotoxic effector molecules to antibodies that can selectively bind to targets on the surface of cancer cells is an approach for the selective delivery of cytotoxic agents to cancer cells while minimizing toxicity toward normal cells that lack the cell-surface target of the antibody. The successful application of this concept should yield ADCs that have a wider therapeutic index than that of small-molecule cytotoxic compounds (i.e. “classical” chemotherapy). Since the approvals of brentuximab vedotin in 2011 and ado-trastuzumab emtansine in 2013, two ADCs that contain potent tubulin-binding agents as their payloads, there has been an explosion of research in the field, with more than 65 ADC compounds in clinical evaluation at the end of 2017. In the last few years, medicinal chemists have generated a wide variety of cytotoxic compounds that kill cells by a variety of mechanisms, and that could serve as payloads for ADCs. The purpose of this chapter is to review the factors important for the design of ADCs, factors that medicinal chemists need to take into account when creating payloads and their linkers and when designing the payload-release mechanisms, all of which can influence the therapeutic effectiveness of ADCs in treating patients with cancer.
Use of Molecular Modelling Techniques in Antibody–Drug Conjugate (ADC) Payload Discovery and Development
Authors: Jackson Paul J. M. , Thurston David E.
Published: July 2019

In silico techniques are frequently adopted in drug discovery in order to assist with ligand design. Although relevant software and technologies are readily available, there are few examples in the literature of the use of molecular modelling techniques in the development of antibody–drug conjugate (ADC) payloads. This chapter summarises the in silico studies that have been carried out on the tubulin-binding monomethyl auristatin E and F (MMAE/MMAF) and DNA-interactive pyrrolobenzodiazepine (PBD) dimer payloads, the two best-known examples of the application of this approach. The PBD dimers are possibly the only example of a payload family where molecular modelling approaches have been extensively used for their discovery and development. Therefore, the main focus of the discussion is on how computational methods have led to a set of “rules” for the interaction of PBD dimers with DNA which can be used as a tool for the design of next-generation DNA-binding payloads.
Maytansinoid Payloads for Antibody–Drug Conjugates (ADCs)
Authors: Widdison Wayne C.
Published: July 2019

The maytansinoids are highly cytotoxic benzoansamacrolides that suppress microtubule dynamics to preferentially kill dividing versus quiescent cells, typically with concentrations that give 50% inhibition (IC50 values) in the sub-nanomolar range. Here, methods are described for preparing maytansinoids for incorporation into antibody–drug conjugates (ADCs) via coupling to antibodies that selectively target antigens on the surface of cancer cells. Maytansinoid ADCs kill antigen-positive cancer cells and, in some instances, release metabolites that can also kill other tumour cells, a mechanism termed “bystander killing”. In vitro and in vivo models comparing maytansinoid ADCs with different linker stabilities as well as those releasing metabolites that induce different degrees of bystander killing are presented. In vivo, non-specific cellular uptake and premature metabolite release are discussed as potential mechanisms leading to ADC systemic toxicity. In addition, the relative tolerance of slowly dividing cells to maytansinoids is presented as a potential tolerability advantage for this payload class compared with payloads that kill cells less discriminately.
Cleavable linkers in antibody–drug conjugates
Authors: Bargh Jonathan D. , Isidro-Llobet Albert , Parker Jeremy S. , Spring David R.
Published: July 2019

This tutorial review summarises the advances in the field of cleavable linker technologies for antibody–drug conjugates (ADCs).
ZnO decorated laser-induced graphene produced by direct laser scribing
Authors: Rodrigues Joana , Zanoni Julia , Gaspar Guilherme , Fernandes António J. S. , Carvalho Alexandre F. , Santos Nuno F. , Monteiro Teresa , Costa Florinda M.
Published: July 2019

A scalable laser scribing approach to produce ZnO decorated laser-induced graphene in a unique laser-processing step was developed. The produced composites reveal promising optical and electrochemical properties to be applied in sensing devices.
Development and validation of an instrument to measure undergraduate chemistry students’ critical thinking skills
Authors: Danczak Stephen M. , Thompson Christopher D. , Overton Tina L.
Published: July 2019

The importance of developing and assessing student critical thinking at university can be seen through its inclusion as a graduate attribute for universities and from research highlighting the value employers, educators and students place on demonstrating critical thinking skills. Critical thinking skills are seldom explicitly assessed at universities. Commercial critical thinking assessments, which are often generic in context, are available. However, literature suggests that assessments that use a context relevant to the students more accurately reflect their critical thinking skills. This paper describes the development and evaluation of a chemistry critical thinking test (the Danczak–Overton–Thompson Chemistry Critical Thinking Test or DOT test), set in a chemistry context, and designed to be administered to undergraduate chemistry students at any level of study. Development and evaluation occurred over three versions of the DOT test through a variety of quantitative and qualitative reliability and validity testing phases. The studies suggest that the final version of the DOT test has good internal reliability, strong test–retest reliability, moderate convergent validity relative to a commercially available test and is independent of previous academic achievement and university of study. Criterion validity testing revealed that third year students performed statistically significantly better on the DOT test relative to first year students, and postgraduates and academics performed statistically significantly better than third year students. The statistical and qualitative analysis indicates that the DOT test is a suitable instrument for the chemistry education community to use to measure the development of undergraduate chemistry students’ critical thinking skills.
Optimization of an enzyme linked DNA aptamer assay for cardiac troponin I detection: synchronous multiple sample analysis on an integrated microfluidic platform
Authors: Gopinathan Priya , Sinha Anirban , Chung Yi-Da , Shiesh Shu-Chu , Lee Gwo-Bin
Published: July 2019

In this study, an enzyme linked DNA aptamer based assay was optimized for human cardiac troponin I (cTnI) detection which is a prominent biomarker for acute myocardial infarction (AMI), on an integrated microfluidic platform.
A Co8 metallacycle stabilized by double anion–π interactions
Authors: Alexandropoulos Dimitris I. , Dolinar Brian S. , Xie Haomiao , Vignesh Kuduva R. , Dunbar Kim R.
Published: July 2019

The syntheses, crystal structures and magnetic studies of two new CoII 2,2′-bipyrimidine bridged complexes stabilized by hydrogen bonding versus anion–π interactions are reported.
An anti-inflammatory nanoagent for tumor-targeted photothermal therapy
Authors: Pan Wei , Zhang Xinhao , Gao Peng , Li Na , Tang Bo
Published: July 2019

An anti-inflammatory nanoagent based on polydopamine nanospheres was developed to achieve highly efficient photothermal therapy, which can effectively kill cancer cells and simultaneously eliminate photothermal therapy-induced inflammation.
A novel hydrosoluble near-infrared fluorescent probe for specifically monitoring tyrosinase and application in a mouse model
Authors: Zhang Jiahang , Li Zhao , Tian Xinwei , Ding Ning
Published: July 2019

A novel hydrosoluble near-infrared fluorescent probe is applied to imaging and detection of endogenous tyrosinase in living cells, zebrafish and a mouse model.
Effect of the length of anodically grown titania nanotubes on the efficiency of a moisture-stable hole transport material (HTM)-free perovskite solar cell
Authors: Tenkyong Tenzin , Praveen B. , Pugazhendhi K. , Sharmila D. J. , Shyla J. Merline
Published: July 2019

A simple and facile means of developing a cost-efficient, easily reproducible perovskite solar cell (PSC) is presented in this report.
An experimental study on polymorph control and continuous heterogeneous crystallization of carbamazepine
Authors: Hu Chuntian , Testa Christopher J. , Shores Brianna T. , Wu Wei , Shvedova Khrystyna , Born Stephen C. , Chattopadhyay Saptarshi , Takizawa Bayan , Mascia Salvatore
Published: July 2019

Influences of superstaturation, stirring, anti-solvent, and polymer type on polymorph are investigated.
Toward a new type of proton conductor based on imidazole and aromatic acids
Authors: Zięba Sylwia , Dubis Alina T. , Gzella Andrzej K. , Ławniczak Paweł , Pogorzelec-Glaser Katarzyna , Łapiński Andrzej
Published: July 2019

The substitution pattern of the counterions affects electrical conductivity and thermal properties of the new proton conducting imidazolium salts.
Dispersion-controlled docking preference: multi-spectroscopic study on complexes of dibenzofuran with alcohols and water
Authors: Bernhard D. , Fatima M. , Poblotzki A. , Steber A. L. , Pérez C. , Suhm M. A. , Schnell M. , Gerhards M.
Published: July 2019

The planarity and rigidity of dibenzofuran inverts the docking preference for increasingly bulky R-OH solvent molecules, compared to the closely related diphenyl ether. Now, London dispersion favors OH⋯π hydrogen bonding.
A hierarchically-assembled Fe–MoS2/Ni3S2/nickel foam electrocatalyst for efficient water splitting
Authors: Xue Jiang-Yan , Li Fei-Long , Zhao Zhong-Yin , Li Cong , Ni Chun-Yan , Gu Hong-Wei , Braunstein Pierre , Huang Xiao-Qing , Lang Jian-Ping
Published: July 2019

Hierarchically-assembled Fe–MoS2/Ni3S2/NF demonstrates excellent HER, OER and full water splitting catalytic performances in an alkaline electrolyte.
Facile fabrication of oxygen and carbon co-doped carbon nitride nanosheets for efficient visible light photocatalytic H2 evolution and CO2 reduction
Authors: Wan Shipeng , Ou Man , Wang Xinming , Wang Yanan , Zeng Yiqing , Ding Jie , Zhang Shule , Zhong Qin
Published: July 2019

C3N4 nanosheets with oxygen and carbon co-doping were successfully designed for H2 evolution and CO2 reduction. A mechanistic study was also performed.
Synthesis and reactivity of boryl substituted silaimines
Authors: Yuvaraj K. , Jones Cameron
Published: July 2019

Two bulky N-boryl substituted silaimines have been prepared and their reactivity toward a number of small molecule substrates examined (e.g. see picture, Dip = 2,6-diisopropylphenyl).
Sustainable hydrogenation of aliphatic acyclic primary amides to primary amines with recyclable heterogeneous ruthenium–tungsten catalysts
Authors: Coeck Robin , Berden Sarah , De Vos Dirk E.
Published: July 2019

Hydrogenation of primary aliphatic amides was achieved in CPME with a novel RuWOx/MgAl2O4catalyst with yields up to 83%.
One-pot synthesis of tetrahydro-pyrrolobenzodiazepines and tetrahydro-pyrrolobenzodiazepinones through sequential 1,3-dipolar cycloaddition/N-alkylation (N-acylation)/Staudinger/aza-Wittig reactions
Authors: Ma Xiaoming , Zhang Xiaofeng , Awad John Mark , Xie Guoshu , Qiu Weiqi , Zhang Wei
Published: July 2019

A new diastereoselective synthesis of benzodiazepines and diazepinones is developed. This one-pot and three-step synthesis of four components gave two different heterocyclic scaffolds. Green chemistry metrics analysis of the reaction processes provided favorable results.
Synthesis of 2-substituted indoles through cyclization and demethylation of 2-alkynyldimethylanilines by ethanol
Authors: Zhao Guangkuan , Roudaut Christelle , Gandon Vincent , Alami Mouad , Provot Olivier
Published: July 2019

EtOH is an ideal reagent for transforming 2-alkynyldimethylanilines into 2-substituted indoles with high yields without the need for metal catalysts or additives.
The production of reactive oxygen species enhanced with the reduction of menadione by active thioredoxin reductase
Authors: Li Jing , Zuo Xin , Cheng Ping , Ren Xiaoyuan , Sun Shibo , Xu Jianqiang , Holmgren Arne , Lu Jun
Published: July 2019

Cytosolic thioredoxin reductase (TXNRD1) is an important selenoprotein that participates in the reduction of thioredoxin and many other redox-related substrates. The enhancement of ROS production to cause cancer cell death is an effective anticancer strategy. Herein, we found that menadione substantially increased ROS generation via interaction with TXNRD1. To elucidate the mechanism behind this, various TXNRD1 mutant proteins were used to investigate the relationship between ROS production and the reaction between enzymes and menadione. A mutation at the C-terminal active site -GCUG of TXNRD1 to -GSSG or -GC, or the N-terminal active site C59S, C64S, or the deletion of the C-terminal 16 amino acid residues caused the loss of TXNRD1 activity needed for the reduction of menadione and therefore resulted in the loss of the ROS production ability of menadione. In contrast, the mutation of -GCUG to -GCCG resulted in an increase in the TXNRD1 activity towards the reduction of menadione, thus leading to an increase in ROS production. The co-treatment of the TXNRD1 inhibitor aurothioglucose and menadione could significantly alleviate the efficiency of ROS generation in vitro and increase the viability of A549 cells. Moreover, menadione could be reduced by the glutathione system and caused ROS production with less efficiency. These results demonstrate that TXNRD1 can serve as an effective source to generate ROS, which may provide a novel anticancer method based on the use of menadione.
Skin-permeating components of Lonicera japonica flos: a comprehensive study from observations and model computations
Authors: Zhang Keda , Sun Wanyang , Fahr Alfred , Zeng Xiaobin , Ge Lanlan , Chen Ming , Yang Lingzhi , Wu Shipin , Fei Jia , Zhou Boping
Published: July 2019

Flavonoids and essential oils are well absorbed via the skin, while chlorogenic acids, iridoid glycosides and triterpenoids are poorly delivered.
Slow magnetic relaxation in Cu(ii)–Eu(iii) and Cu(ii)–La(iii) complexes
Authors: Dolai Malay , Ali Mahammad , Rajnák Cyril , Titiš Ján , Boča Roman
Published: July 2019

A dinuclear [(H2O)Cu(HLN2O2)Eu(NO3)3] complex exhibits paramagnetic behaviour with S = 1/2 ground state. At low temperature it displays slow magnetic relaxation that is supported by a small external magnetic field.
Click inspired synthesis of hexa and octadecavalent peripheral galactosylated glycodendrimers and their possible therapeutic applications
Authors: Agrahari Anand K. , Singh Anoop S. , Singh Ashish Kumar , Mishra Nidhi , Singh Mala , Prakash Pradyot , Tiwari Vinod K.
Published: July 2019

Click inspired glycodendrimers comprising a rigid hexapropargyloxy benzene core with peripheral β-d-galactopyranosidic units were developed and evaluated for their therapeutic potential.
Atomistic understanding of interfacial interactions between bone morphogenetic protein-7 and graphene with different oxidation degrees
Authors: Hou Jialiang , Liu Binyao , Zhang Yaping , Lu Xiong , Liu Changsheng , Tang Youhong , Wang Menghao , Dong Faqing , Ni Yuxiang , Zhang Hongping
Published: July 2019

Bone morphogenetic protein (BMP) adsorption plays an important role in the osteoinduction properties of graphene (G)-based biomaterials.
Design strategies of n-type conjugated polymers for organic thin-film transistors
Authors: Sui Ying , Deng Yunfeng , Du Tian , Shi Yibo , Geng Yanhou
Published: July 2019

Four molecule design strategies of n-type conjugated polymers for organic thin-film transistors are summarized and discussed.
Atmospheric water triggers supramolecular gel formation of novel low molecular weight maslinic and oleanolic triterpenic derivatives
Authors: Vega-Granados Karina , Ramírez-Rodríguez Gloria Belén , Contreras-Montoya Rafael , Ramírez Francisco J. , Palomo Luis , Parra Andrés , Delgado-López Jose M. , Lopez-Lopez Modesto T. , Álvarez de Cienfuegos Luis
Published: July 2019

Novel maslinic and oleanolic triterpenic derivatives behave as supramolecular gelators. These compounds have the capacity to gelify DMSO and DMF by slowly capturing atmospheric water.