bluuebunny/crossref_metadata_2025 huggingface dataset:
Coherent Land Policy and Land Value
Authors: Krajewska Małgorzata , Pawłowski Krzysztof
Published: December 2019

The present article is an attempt at to prove the thesis that the accurate selection of land use in a local spatial development plan carries over to the behaviours of investors and has a positive influence on the value of land affected by noise nuisance neighbouring an airport – i.e. it does not depreciate it. To this aim, a case study of transaction prices of non-developed land located near the Bydgoszcz airport – Szwederowo was carried out. In its region, two study areas were selected: I – with a noise level of 55–60 dB and II – with a noise level not exceeding 55 dB, and next, the market of land zoned for services-related and services-technical development, parking lots, depots, and warehouses in these areas was diagnosed. Resources of the strategic noise map (SNM) were used in the research. The research period covered years 2016–2018. The studies show that the location of a real property in an impact area of airport noise was not an obstacle and did not limit market turnover of real property which remained under the unfavourable influence of this factor. The reason behind the demand is the shrewd introduction of functions in the local plan in the area of increased noise levels as an expression of coherent land use planning. The article addresses the need for the real estate market for help in planning, decision-making and implementation activities in the field of spatial and real estate management.
Regulation of zebrafish melanocyte development by ligand-dependent BMP signaling
Authors: Gramann Alec K , Venkatesan Arvind M , Guerin Melissa , Ceol Craig J
Published: December 2019

Preventing terminal differentiation is important in the development and progression of many cancers including melanoma. Recent identification of the BMP ligand GDF6 as a novel melanoma oncogene showed GDF6-activated BMP signaling suppresses differentiation of melanoma cells. Previous studies have identified roles for GDF6 orthologs during early embryonic and neural crest development, but have not identified direct regulation of melanocyte development by GDF6. Here, we investigate the BMP ligand gdf6a, a zebrafish ortholog of human GDF6, during the development of melanocytes from the neural crest. We establish that the loss of gdf6a or inhibition of BMP signaling during neural crest development disrupts normal pigment cell development, leading to an increase in the number of melanocytes and a corresponding decrease in iridophores, another neural crest-derived pigment cell type in zebrafish. This shift occurs as pigment cells arise from the neural crest and depends on mitfa, an ortholog of MITF, a key regulator of melanocyte development that is also targeted by oncogenic BMP signaling. Together, these results indicate that the oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.
From single neurons to behavior in the jellyfish Aurelia aurita
Authors: Pallasdies Fabian , Goedeke Sven , Braun Wilhelm , Memmesheimer Raoul-Martin
Published: December 2019

Jellyfish nerve nets provide insight into the origins of nervous systems, as both their taxonomic position and their evolutionary age imply that jellyfish resemble some of the earliest neuron-bearing, actively-swimming animals. Here, we develop the first neuronal network model for the nerve nets of jellyfish. Specifically, we focus on the moon jelly Aurelia aurita and the control of its energy-efficient swimming motion. The proposed single neuron model disentangles the contributions of different currents to a spike. The network model identifies factors ensuring non-pathological activity and suggests an optimization for the transmission of signals. After modeling the jellyfish’s muscle system and its bell in a hydrodynamic environment, we explore the swimming elicited by neural activity. We find that different delays between nerve net activations lead to well-controlled, differently directed movements. Our model bridges the scales from single neurons to behavior, allowing for a comprehensive understanding of jellyfish neural control of locomotion.
Activation of a nucleotide-dependent RCK domain requires binding of a cation cofactor to a conserved site
Authors: Teixeira-Duarte Celso M , Fonseca Fátima , Morais-Cabral João H
Published: December 2019

RCK domains regulate the activity of K+ channels and transporters in eukaryotic and prokaryotic organisms by responding to ions or nucleotides. The mechanisms of RCK activation by Ca2+ in the eukaryotic BK and bacterial MthK K+ channels are well understood. However, the molecular details of activation in nucleotide-dependent RCK domains are not clear. Through a functional and structural analysis of the mechanism of ATP activation in KtrA, a RCK domain from the B. subtilis KtrAB cation channel, we have found that activation by nucleotide requires binding of cations to an intra-dimer interface site in the RCK dimer. In particular, divalent cations are coordinated by the γ-phosphates of bound-ATP, tethering the two subunits and stabilizing the active state conformation. Strikingly, the binding site residues are highly conserved in many different nucleotide-dependent RCK domains, indicating that divalent cations are a general cofactor in the regulatory mechanism of many nucleotide-dependent RCK domains.
Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth
Authors: Palomo-Guerrero Marta , Fadó Rut , Casas Maria , Pérez-Montero Marta , Baena Miguel , Helmer Patrick O , Domínguez José Luis , Roig Aina , Serra Dolors , Hayen Heiko , Stenmark Harald , Raiborg Camilla , Casals Núria
Published: December 2019

Anterograde transport of late endosomes or lysosomes (LE/Lys) is crucial for proper axon growth. However, the role of energetic nutrients has been poorly explored. Malonyl-CoA is a precursor of fatty acids, and its intracellular levels highly fluctuate depending on glucose availability or the energy sensor AMP-activated protein kinase (AMPK). We demonstrate in HeLa cells that carnitine palmitoyltransferase 1C (CPT1C) senses malonyl-CoA and enhances LE/Lys anterograde transport by interacting with the endoplasmic reticulum protein protrudin and facilitating the transfer of Kinesin-1 from protrudin to LE/Lys. In cultured mouse cortical neurons, glucose deprivation, pharmacological activation of AMPK or inhibition of malonyl-CoA synthesis decreases LE/Lys abundance at the axon terminal, and shortens axon length in a CPT1C-dependent manner. These results identify CPT1C as a new regulator of anterograde LE/Lys transport in response to malonyl-CoA changes, and give insight into how axon growth is controlled by nutrients.
Robust cullin-RING ligase function is established by a multiplicity of poly-ubiquitylation pathways
Authors: Hill Spencer , Reichermeier Kurt , Scott Daniel C , Samentar Lorena , Coulombe-Huntington Jasmin , Izzi Luisa , Tang Xiaojing , Ibarra Rebeca , Bertomeu Thierry , Moradian Annie , Sweredoski Michael J , Caberoy Nora , Schulman Brenda A , Sicheri Frank , Tyers Mike , Kleiger Gary
Published: December 2019

The cullin-RING ligases (CRLs) form the major family of E3 ubiquitin ligases. The prototypic CRLs in yeast, called SCF enzymes, employ a single E2 enzyme, Cdc34, to build poly-ubiquitin chains required for degradation. In contrast, six different human E2 and E3 enzyme activities, including Cdc34 orthologs UBE2R1 and UBE2R2, appear to mediate SCF-catalyzed substrate polyubiquitylation in vitro. The combinatorial interplay of these enzymes raises questions about genetic buffering of SCFs in human cells and challenges the dogma that E3s alone determine substrate specificity. To enable the quantitative comparisons of SCF-dependent ubiquitylation reactions with physiological enzyme concentrations, mass spectrometry was employed to estimate E2 and E3 levels in cells. In combination with UBE2R1/2, the E2 UBE2D3 and the E3 ARIH1 both promoted SCF-mediated polyubiquitylation in a substrate-specific fashion. Unexpectedly, UBE2R2 alone had negligible ubiquitylation activity at physiological concentrations and the ablation of UBE2R1/2 had no effect on the stability of SCF substrates in cells. A genome-wide CRISPR screen revealed that an additional E2 enzyme, UBE2G1, buffers against the loss of UBE2R1/2. UBE2G1 had robust in vitro chain extension activity with SCF, and UBE2G1 knockdown in cells lacking UBE2R1/2 resulted in stabilization of the SCF substrates p27 and CYCLIN E as well as the CUL2-RING ligase substrate HIF1α. The results demonstrate the human SCF enzyme system is diversified by association with multiple catalytic enzyme partners.
Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks
Authors: Branchereau Pascal , Martin Elodie , Allain Anne-Emilie , Cazenave William , Supiot Laura , Hodeib Fara , Laupénie Amandine , Dalvi Urvashi , Zhu Hongmei , Cattaert Daniel
Published: December 2019

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons (MNs) during late adulthood. Here, with the aim of identifying early changes underpinning ALS neurodegeneration, we analyzed the GABAergic/glycinergic inputs to E17.5 fetal MNs from SOD1G93A (SOD) mice in parallel with chloride homeostasis. Our results show that IPSCs are less frequent in SOD animals in accordance with a reduction of synaptic VIAAT-positive terminals. SOD MNs exhibited an EGABAAR 10 mV more depolarized than in WT MNs associated with a KCC2 reduction. Interestingly, SOD GABAergic/glycinergic IPSCs and evoked GABAAR-currents exhibited a slower decay correlated to elevated [Cl-]i. Computer simulations revealed that a slower relaxation of synaptic inhibitory events acts as compensatory mechanism to strengthen GABA/glycine inhibition when EGABAAR is more depolarized. How such mechanisms evolve during pathophysiological processes remain to be determined, but our data indicate that at least SOD1 familial ALS may be considered as a neurodevelopmental disease.
MeCP2 nuclear dynamics in live neurons results from low and high affinity chromatin interactions
Authors: Piccolo Francesco M , Liu Zhe , Dong Peng , Hsu Ching-Lung , Stoyanova Elitsa I , Rao Anjana , Tjian Robert , Heintz Nathaniel
Published: December 2019

Methyl-CpG-binding-Protein 2 (MeCP2) is an abundant nuclear protein highly enriched in neurons. Here we report live-cell single-molecule imaging studies of the kinetic features of mouse MeCP2 at high spatial-temporal resolution. MeCP2 displays dynamic features that are distinct from both highly mobile transcription factors and immobile histones. Stable binding of MeCP2 in living neurons requires its methyl-binding domain and is sensitive to DNA modification levels. Diffusion of unbound MeCP2 is strongly constrained by weak, transient interactions mediated primarily by its AT-hook domains, and varies with the level of chromatin compaction and cell type. These findings extend previous studies of the role of the MeCP2 MBD in high affinity DNA binding to living neurons, and identify a new role for its AT-hooks domains as critical determinants of its kinetic behavior. They suggest that limited nuclear diffusion of MeCP2 in live neurons contributes to its local impact on chromatin structure and gene expression.
Indirect sexual selection drives rapid sperm protein evolution in abalone
Authors: Wilburn Damien Beau , Tuttle Lisa M , Klevit Rachel E , Swanson Willie J
Published: December 2019

Sexual selection can explain the rapid evolution of fertilization proteins, yet sperm proteins evolve rapidly even if not directly involved in fertilization. In the marine mollusk abalone, sperm secrete enormous quantities of two rapidly evolving proteins, lysin and sp18, that are stored at nearly molar concentrations. We demonstrate that this extraordinary packaging is achieved by associating into Fuzzy Interacting Transient Zwitterion (FITZ) complexes upon binding the intrinsically disordered FITZ Anionic Partner (FITZAP). FITZ complexes form at intracellular ionic strengths and, upon exocytosis into seawater, lysin and sp18 are dispersed to drive fertilization. NMR analyses revealed that lysin uses a common molecular interface to bind both FITZAP and its egg receptor VERL. As sexual selection alters the lysin-VERL interface, FITZAP coevolves rapidly to maintain lysin binding. FITZAP-lysin interactions exhibit a similar species-specificity as lysin-VERL interactions. Thus, tethered molecular arms races driven by sexual selection can generally explain rapid sperm protein evolution.
Thermodynamics
Authors: Sandler Stanley I.
Published: December 2019

Thermodynamics is a discipline with broad applications based on three basic principles: conservation of mass, conservation of energy (first law), and that isolated systems evolve toward an equilibrium, time‐invariant state in which temperature and pressure are spatially uniform, and in composition is uniform in each phase (ie, vapor, liquid, or solid). It is shown here how these principles lead to a broad range of applications. These include the analysis of heat engines, heat pumps (refrigerators), turbines, fuel cells, and understanding and predicting phase transitions among the solid, liquid, and vapor phases in both pure fluids and mixtures and chemical equilibria.
Provision of aquatic ecosystem services as a consequence of societal changes: The case of the Baltic Sea
Authors: Hyytiäinen Kari , Bauer Barbara , Bly Joyce Kerstin , Ehrnsten Eva , Eilola Kari , Gustafsson Bo G. , Meier H. E. Markus , Norkko Alf , Saraiva Sofia , Tomczak Maciej , Zandersen Marianne
Published: December 2019

Aquatic ecosystem services are important for human wellbeing, but they are much less studied than terrestrial ecosystem services. The objectives of this study are to broaden, itemize and exemplify the human‐nature interactions in modeling the future provision of aquatic ecosystem services. We include shared socioeconomic and representative concentration pathways, used extensively in climate research, as drivers of change for the future development of the Baltic Sea. Then we use biogeochemical and ecosystem models to demonstrate the future development of exemplary supporting, provisioning and cultural ecosystem services for two distinct combinations of regionally downscaled global climate and socioeconomic futures. According to the model simulations, the two global futures (“Sustainable well‐being” vs. “Fossil‐fuelled development”) studied lead to clearly deviating trajectories in the provision of marine ecosystem services. Under the “Sustainable well‐being”‐scenario primary production decreases by 20%, catches of demersal fish increases and the recreation opportunities increase significantly by the end of the ongoing century. Under the “fossil‐fuelled development”‐scenario primary production doubles, fisheries focus on less valued pelagic fish and the recreation possibilities will decrease. Long‐term projections of aquatic ecosystem services prepared for alternative global socioeconomic futures can be used by policy makers and managers to adaptively and iteratively adjust mitigation and adaptation effort with plausible future changes in the drivers of water pollution.
Lexical Borrowing
Authors: Daulton Frank E.
Published: December 2019

Virtually every language has enriched its vocabulary by borrowing from others. Lexical borrowing is the adoption of individual or sets of words from another language or dialect. It can include roots and affixes, sounds, collocations, and grammatical processes. In this entry examples of lexical borrowing are provided and factors prompting lexical borrowing are identified. The linguistic processes that take place when a borrowed word becomes nativized include both structural and semantic changes. Language users react to lexical borrowing in a variety of ways and lexical borrowing has profound implications for various aspects of applied linguistics, which include foreign and second language learning.
Intercultural Interaction
Authors: Spencer‐Oatey Helen , Franklin Peter
Published: December 2019

“Intercultural interaction” refers to the behavior (including, but not limited to, verbal and nonverbal communication) that occurs when members of different cultural groups engage in joint activity. Such a definition raises a number of questions, including how to distinguish different cultural groups and what interaction entails. Traditionally, nationality or ethnicity has been taken as the criterion for distinguishing cultural groups, but in fact the situation is much more complex than this. We are all members of multiple different cultural groups (e.g., professional, organizational, religious), each of which can be said to have its own culture in terms of values, norms, and patterns of behavior. So what then counts as “intercultural” interaction? There is no definitive answer to this question, but Spencer‐Oatey and Franklin suggest that an interaction becomes intercultural (rather than intracultural) when the cultural difference between the participants is significant enough for one or more of them to notice its impact. Analysts of intercultural interaction are thus chiefly concerned with the impact of culture on the dynamics of engagement with others. Numerous different approaches can be taken, and in this entry we focus on three issues that are often of concern to the interactants: achieving understanding, managing relations, and analyzing identity and personal growth.
Metal–CO2 Batteries at the Crossroad to Practical Energy Storage and CO2 Recycle
Authors: Xie Jiafang , Zhou Zhen , Wang Yaobing
Published: December 2019

Metal–CO2 batteries show great promise in meeting the growing energy, chemical, and environmental demands of daily life and industry, because of their advantages of high flexibility and efficiency in both energy storage and CO2 recycle applications. It has been a trend that Li/Na‐CO2 and Zn/Al‐CO2 systems show different developments to achieve practical energy storage (e.g., high electricity supply) and CO2 recycling (e.g., flexible chemical production), respectively, which is often neglected. This inhibits the application of metal–CO2 batteries in maximizing energy supply and value‐added CO2 conversion. This progress report presents a critically selected overview of the individual developments of metal–CO2 batteries with emphasis on diverse fundamental origins, performance advantages, and the future of these two systems. Furthermore, the reaction pathways, particularly for catalytic materials, for the Li/Na‐CO2 and Zn/Al‐CO2 systems are discussed. Finally, the challenges of these two systems along with a hybrid Li/Na‐CO2 battery design that may simultaneously provide high operating voltages and flexible chemicals are outlined.
On the History of Reactive Mesogens: Interview with Dirk J. Broer
Authors: Broer Dirk J.
Published: December 2019

Prof. Dirk Broer is among the pioneers and most active researchers in the field of stimuli‐responsive liquid crystal (LC) networks. He is the inventor of reactive mesogens, a class of materials with far‐reaching implications in liquid‐crystal photonics and in the triumph of LC‐based shape‐shifting polymers. Together with his team, Prof. Broer continuously produces innovative solutions for controlling and programming new functions into soft responsive materials. Through this Interview, it is our great pleasure to gain insights into his personal views on both the past and the future, and to learn about the historical turns that led to the development of reactive mesogens as well as his vision on where the field is heading.
Bridging the van der Waals Interface for Advanced Optoelectronic Devices
Authors: Wen Yao , He Peng , Yao Yuyu , Zhang Yu , Cheng Ruiqing , Yin Lei , Li Ningning , Li Jie , Wang Junjun , Wang Zhenxing , Liu Chuansheng , Fang Xuan , Jiang Chao , Wei Zhipeng , He Jun
Published: December 2019

Van der Waals (vdW) heterostructures exhibit excellent optoelectronic properties and novel functionalities. However, their applicability is impeded due to the common issue of the tunneling barrier, which arises from the vdW gap; this significantly increases the injection resistance of the photoexcited carriers. Herein, a generic strategy is demonstrated to eliminate the vdW gap in a broad class of heterostructures. It is observed that the vdW gap in the interface is bridged via strong orbital hybridization between the interface dangling bonds of nonlayered chalcogenide semiconductors and the artificially induced vacancies of transition metal chalcogenides (TMDCs). The photoresponse times of bridged PbS/ReS2, PbS/MoSe2, and PbS/MoS2 are ≈30, 51, and 43 µs, respectively. The photon‐triggered on/off ratio of the bridged PbS/MoS2, ZnSe/MoS2, and ZnTe/MoS2 heterostructures exceed 106, 105, and 105, respectively. These are several orders of magnitude higher than common vdW heterostructures. The findings obtained in this study present a versatile strategy for overcoming the performance limitations of vdW heterostructures.
Flexible Quasi‐2D Perovskite/IGZO Phototransistors for Ultrasensitive and Broadband Photodetection
Authors: Wei Shali , Wang Fang , Zou Xuming , Wang Liming , Liu Chang , Liu Xingqiang , Hu Weida , Fan Zhiyong , Ho Johnny C. , Liao Lei
Published: December 2019

Organic–inorganic hybrid perovskites (PVKs) have recently emerged as attractive materials for photodetectors. However, the poor stability and low electrical conductivity still restrict their practical utilization. Owing to the quantum‐well feature of two‐dimensional (2D) Ruddlesden–Popper PVKs (2D PVKs), a promising quasi‐2D PVK/indium gallium zinc oxide (IGZO) heterostructure phototransistor can be designed. By using a simple ligand‐exchange spin‐coating method, quasi‐2D PVK fabricated on flexible substrates exhibits a desirable type‐II energy band alignment, which facilitates effective spatial separation of photoexcited carriers. The device exhibits excellent photoresponsivity values of >105 A W−1 at 457 nm, and broadband photoresponse (457–1064 nm). By operating the device in the depletion regime, the specific detectivity is found to be 5.1 × 1016 Jones, which is the record high value among all PVK‐based photodetectors reported to date. Due to the resistive hopping barrier in the quasi‐2D PVK, the device can also work as an optoelectronic memory for near‐infrared information storage. More importantly, the easy manufacturing process is highly beneficial, enabling large‐scale and uniform quasi‐2D PVK/IGZO hybrid films for detector arrays with outstanding ambient and operation stabilities. All these findings demonstrate the device architecture here provides a rational avenue to the design of next‐generation flexible photodetectors with unprecedented sensitivity.
Terahertz Electrodynamics in Transition Metal Oxides
Authors: Kumar Kadakuntla Santhosh , Prajapati Gulloo Lal , Dagar Rahul , Vagadia Megha , Rana Dhanvir Singh , Tonouchi Masayoshi
Published: December 2019

Transition metal oxides (TMOs) are among the most contemporary topics in condensed matter research. For over the past three decades, the most astounding discoveries of high temperature superconductivity, colossal magnetoresistance, multiferroics, topological matter, and several other novel electronic and magnetic phases have been realized and hosted in the TMOs. Almost simultaneously and specifically during the past 5 years, the implementation of terahertz (THz) spectroscopy to unveil the complexity of such materials has delivered unprecedented success. THz spectroscopy extracts material parameters such as dynamic conductivity, dielectric constant, and magnetic permeability in spectral range of 1–20 meV. This imparts the capability to probe a variety of quasiparticles emerging from the electrodynamics of collective, bound and free charge carriers, and complex spin orders, which is the key to decode the complex phases of TMOs class of quantum matter. Herein, the THz spectroscopic investigations of quasiparticle electrodynamics of correlated TMOs are reviewed. Several long‐standing issues are resolved and there is enormous potential for a lot more to offer, emphasizing the growing indispensability of THz technology in condensed matter.
Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease—A New Navigated Focal Brain Therapy
Authors: Beisteiner Roland , Matt Eva , Fan Christina , Baldysiak Heike , Schönfeld Marleen , Philippi Novak Tabea , Amini Ahmad , Aslan Tuna , Reinecke Raphael , Lehrner Johann , Weber Alexandra , Reime Ulrike , Goldenstedt Cédric , Marlinghaus Ernst , Hallett Mark , Lohse‐Busch Henning
Published: December 2019

Ultrasound‐based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical study using ultrasound brain stimulation and first observations of long term effects are presented. Comprehensive feasibility, safety, and efficacy data are provided. They consist of simulation data, laboratory measurements with rat and human skulls and brains, in vivo modulations of somatosensory evoked potentials (SEP) in healthy subjects (sham controlled) and clinical pilot data in 35 patients with Alzheimer's disease acquired in a multicenter setting (including neuropsychological scores and functional magnetic resonance imaging (fMRI)). Preclinical results show large safety margins and dose dependent neuromodulation. Patient investigations reveal high treatment tolerability and no major side effects. Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to three months and correlates with an upregulation of the memory network (fMRI data). The results encourage broad neuroscientific application and translation of the method to clinical therapy and randomized sham‐controlled clinical studies.
Nickel Hollow Spheres Concatenated by Nitrogen‐Doped Carbon Fibers for Enhancing Electrochemical Kinetics of Sodium–Sulfur Batteries
Authors: Guo Bingshu , Du Wenyan , Yang Tingting , Deng Jianhua , Liu Dingyu , Qi Yuruo , Jiang Jian , Bao Shu‐Juan , Xu Maowen
Published: December 2019

The high energy density of room temperature (RT) sodium–sulfur batteries (Na‐S) usually rely on the efficient conversion of polysulfide to sodium sulfide during discharging and sulfur recovery during charging, which is the rate‐determining step in the electrochemical reaction process of Na‐S batteries. In this work, a 3D network (Ni‐NCFs) host composed by nitrogen‐doped carbon fibers (NCFs) and Ni hollow spheres is synthesized by electrospinning. In this novel design, each Ni hollow unit not only can buffer the volume fluctuation of S during cycling, but also can improve the conductivity of the cathode along the carbon fibers. Meanwhile, the result reveals that a small amount of Ni is polarized during the sulfur‐loading process forming a polar NiS bond. Furthermore, combining with the nitrogen‐doped carbon fibers, the Ni‐NCFs composite can effectively adsorb soluble polysulfide intermediate, which further facilitates the catalysis of the Ni unit for the redox of sodium polysulfide. In addition, the in situ Raman is employed to supervise the variation of polysulfide during the charging and discharging process. As expected, the freestanding S@Ni‐NCFs cathode exhibits outstanding rate capability and excellent cycle performance.
Long‐term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2‐year follow‐up of the CHRONOS‐1 study
Authors: Dreyling Martin , Santoro Armando , Mollica Luigina , Leppä Sirpa , Follows George , Lenz Georg , Kim Won Seog , Nagler Arnon , Dimou Maria , Demeter Judit , Özcan Muhit , Kosinova Marina , Bouabdallah Krimo , Morschhauser Franck , Stevens Don A. , Trevarthen David , Munoz Javier , Rodrigues Liana , Hiemeyer Florian , Miriyala Ashok , Garcia‐Vargas Jose , Childs Barrett H. , Zinzani Pier Luigi
Published: December 2019

Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2‐year follow‐up of the CHRONOS‐1 study. A total of 142 patients with histologically confirmed indolent B‐cell lymphoma who had relapsed after or were refractory to ≥2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28‐day cycle). The primary efficacy endpoint was objective response rate (ORR) after ≥4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression‐free survival, and overall survival were 14.1 months (median follow‐up, 16.1 months), 12.5 months (median follow‐up, 14.0 months), and 42.6 months (median follow‐up, 31.5 months), respectively. Median safety follow‐up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment‐emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long‐term follow‐up of patients with relapsed/refractory indolent B‐cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors.
Platelets from Calreticulin mutated essential thrombocythemia patients are less reactive than JAK2 V617F mutated platelets
Authors: Hauschner Hagit , Bokstad Horev Melanie , Misgav Modi , Nagar Meital , Seligsohn Uri , Rosenberg Nurit , Koren‐Michowitz Maya
Published: December 2019

Both JAK2V617F and calreticulin (CALR) mutated essential thrombocythemia (ET) patients have different clinical characteristics, with lower thrombosis risk in patients with CALR mutations. To elucidate the mechanism for this lower risk we studied platelet function in ET patients with either JAK2V617F or a CALR mutation. Platelet activation state was similar in ET and healthy controls at baseline using P‐selectin and PAC1 flow cytometry analysis. However, CALR mutated platelets were significantly less activated following ADP stimulation, compared to control or JAK2 mutated platelets (P < .001). In live‐cell imaging of platelet attachment to immobilized fibrinogen by Interference Reflection Microscopy (IRM), the number of attached CALR mutated platelets was lower compared to control and JAK2 mutated platelets, with lower fractions of platelets achieving the fully spread state (90%, 78% and 54% of adherent cells for control, JAK2 and CALR mutated subjects, respectively). Compared to controls, ET patients, regardless of the mutation type, had increased numbers of immature platelets (IP) and leukocyte platelet aggregates (LPA), as well as plasma sP‐selectin. These were all correlated with the platelet count and not to the state of platelet activation. We also found that intracellular free Ca2+ was increased in resting ET compared to control platelets. Note, CALR had a more dispersed localization in activated ET platelets compared to healthy controls, and mutated CALR interact physically with TpoR in CALR mutated platelets. We hypothesize that defects in platelet activation and spreading in CALR mutated patients can explain, at least in part, the lower thrombotic tendency in CALR mutated ET patients.
Predictive methods for efficacy of house dust mite subcutaneous immunotherapy in allergic rhinitis patients: a prospective study in a Chinese population
Authors: Liu Zhuofu , Lu Hanyu , Feng Xian , Hu Li , Wang Jingjing , Yu Hongmeng
Published: December 2019

Background

Allergen‐specific immunotherapy (AIT) is the only available treatment that can induce specific immune tolerance to allergens. However, the treatment course lasts >3 years, and there is no reliable method to predict treatment response. Therefore, in this study we aimed to establish a method that can predict treatment response to AIT in the second year.

Methods

This prospective study enrolled 119 patients who had undergone 2‐years of standard‐quality house dust mite subcutaneous immunotherapy. Clinical characteristics, skin‐prick test response, and treatment response were evaluated at months 4, 6, 12, and 18. Effective AIT was defined as a 25% reduction in average adjusted symptom score (AAdSS) from baseline at the end of the second year of immunotherapy.

Results

The overall efficacy rate at the end of year 2 of the AIT was 67.4%. Age, sex, asthma, body mass index, smoking history, and aeroallergen categories were not associated with efficacy of AIT. Meanwhile, efficacy data at month 4 (odds ratio [OR], 4.250; p = 0.004), month 6 (OR, 10.476; p < 0.000), month 12 (OR, 18.000; p < 0.000), and month 18 (OR, 9.716; p < 0.000) were associated with month 24 efficacy. The area under the curve for improvement at 4, 6, 12, and 18 months was 0.805, 0.834, 0.837, and 0.854, respectively.

Conclusion

Efficacy of AIT at months 4, 6, 12, and 18 is strongly associated with efficacy at month 24. Efficacy as early as month 4 can predict efficacy at the second year, and this may help to determine the need for long‐term treatment. Our findings may be useful for identifying novel treatment strategies for AIT.
Melanin Biopolymers: Tailoring Chemical Complexity for Materials Design
Authors: d'Ischia Marco , Napolitano Alessandra , Pezzella Alessandro , Meredith Paul , Buehler Markus
Published: December 2019

Melanins, a group of dark insoluble pigments found widespread in nature, have become the focus of growing interest in materials science for various biomedical and technological applications, including opto‐bioelectronics, nanomedicine and mussel‐inspired surface coating. Recent progress in the understanding of melanin optical, paramagnetic redox, and conductivity properties, including photoconductivity, would point to a revision of the traditional concept of structural disorder in terms of more sophisticated and interrelated levels of chemical complexity which however have never been defined and codified. Herein, we bring to focus the various levels of structural disorder that emerged from spectral and chemical signatures over the past decade. A revised approach to structure–property relationships in terms of intermolecular interactions is also provided that may pave the way towards the rational design of next‐generation melanin‐based functional materials.
Three Reactions, One Catalyst: A Multi‐Purpose Platinum(IV) Complex and its Silica‐Supported Homologue for Environmentally Friendly Processes
Authors: Racles Carmen , Zaltariov Mirela‐Fernanda , Damoc Madalin , Macsim Ana‐Maria , Iacob Mihail , Sacarescu Liviu
Published: December 2019

Although platinum nanoparticles and complexes ‐especially of Pt(0) and Pt(II)‐ are well known catalysts, siloxane‐based platinum complexes are rarely reported. Herein, a Platinum(IV) complex of 4‐aminopyridinium‐modified disiloxane was prepared and characterized by medium and far infrared spectroscopy, NMR and EDX. The formation of the complex was monitored by UV–Vis spectroscopy, which showed the high affinity and selectivity of this ligand for Pt, with a stability constant of 7.53·103 M−1. The catalytic activity of the siloxane‐based complex was tested in three types of reactions: reduction of p‐nitrophenol, oxidation of glucose and starch, and hydrosilylation. The hydrophobic behavior of the permethylated disiloxane moiety ensures good hydrolytic stability, while the N‐donor ligand stabilizes thein‐situformed Pt nanoparticles. The generation of Pt nanoparticles during p‐nitrophenol reduction was confirmed by TEM and SEM. Contrary to most reports, the aerobic oxidation of mono‐ and polysaccharides occurred without oxidation agents or mediators added, in mild conditions, at room temperature and pH ~9. The same metal complex was found active in hydrosilylation of vinyl‐siloxanes with temperature‐modulated rate, thus being useful in silicone cross‐linking systems without the need of inhibitors. The method was adapted to one‐pot synthesis of silica‐supported Pt(IV) complex, which acted as efficient and reusable heterogeneous hydrosilylation catalyst, limiting the contamination of the product with Pt. This approach is promising for superior valorization of scarcely available and expensive platinum metal. By the same method, multifunctional soluble complexes and mesoporous silica may be obtained, with tunable catalytic performance.
Sugarcane biomass conversion influenced by lignin
Authors: Schmatz Alison A. , Tyhoda Luvuyo , Brienzo Michel
Published: December 2019

Plant biomass residues are renewable sources for the production of biofuels and high‐value macromolecules. Sugarcane bagasse is one such plant biomass residue that is available from the sugar‐processing industry. It is used as a raw material for biobased ethanol production. However, some of its properties and its behavior during processing have a major inhibitory effect on its successful conversion. Chief among these inhibitory properties are the lignin content, its distribution in plant tissues, and its chemical properties. These make the materials naturally resistant to bioconversion processes. Further, lignin and carbohydrate degradation products can be formed during acid pretreatment, which is one of the major steps during biomass conversion to bioethanol. These products negatively affect the liberation of fermentable sugars and the yield of ethanol during the fermentation stage of the conversion process. Other factors that also have an influence on the production of fermentable sugar are related to the different structural arrangement of plant tissues (cane fractions of the node, internode, and external fraction), as well as biomass variety. Biomass varieties with low lignin content result in an improved yield of fermentable sugars, which in turn contributes to improved viability of the second‐generation bioethanol production processes. By selecting sugarcane varieties with the best properties, ethanol production can be increased without increasing the total area under cultivation. Efforts have been dedicated to reducing biomass recalcitrance by classical and precision breeding. Genetic modification of sugarcane alters the genes responsible for the encoding enzymes for lignin biosynthesis, generating sugarcane with low recalcitrance. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
Hydrogen Production from Makgeolli Wastewater Using a Single‐Chamber Microbial Electrolysis Cell
Authors: Kim Jun Hyun , Kim Changhoon , Jeon Yongwon , Kim Sunghyun
Published: December 2019

Domestic and industrial wastewaters are subject to the biological treatment process before discharged to environment. In that process, organic substances contained in the wastewater are degraded by microorganisms. Microbial electrolysis cells (MECs) are suitable technology for wastewater treatment, simultaneously producing hydrogen. In most case, however, a significant amount of methane instead of hydrogen is produced when the wastewater is used for MECs. Here we show that hydrogen is the main product when Makgeolli wastewater (MW) is used as a substrate in a single‐chamber MEC which was operated using acetate and MW. Although current generation profiles vary according to the substrate type and the applied voltage, hydrogen portions were maintained over 90% at −0.6 V and −0.8 V with production rates of 0.95 and 1.55 m3H2/m3/d, respectively. This result shows a possibility of implementing MECs in the real wastewater treatment and hydrogen production.
Long‐term stability and characteristics of behavioral, biochemical, and molecular markers of three different rodent models for depression
Authors: Zhu Han , Tao Yanlin , Wang Tingting , Zhou Jin , Yang Yingwen , Cheng Lin , Zhu Huirong , Zhang Weiqi , Huang Fei , Wu Xiaojun
Published: December 2019

Objective

The present study was designed to explore the long‐term differences between three mouse models for depression.

Method

In the present study, the unpredictable chronic mild stress (UCMS) model, the glucocorticoid/corticosterone model, and the olfactory bulbectomy model were compared at two, three, and five weeks after model induction. Behavioral testing performed included forced‐swimming, tail suspension, open‐field and elevated plus‐maze tests. In addition, 5‐hydroxytryptamine (5‐HT) and dopamine levels, and mRNA and protein expressions related to 5‐HT synthesis, transport, and signaling were analyzed in the hippocampus of tested animals.

Results

Our results revealed that each model demonstrated a specific profile of markers, whereas the stability of them differed over testing time.

Conclusions

Each model provided a unique set of advantages that can be considered depending on the context and aims of each study. Among the three models, the UCMS model was mostly stable and appeared to the best model for testing long‐term depression‐like state.
A structural equation model to evaluate students’ learning and satisfaction
Authors: Turhangil Erenler Hale H.
Published: December 2019

Due to the shift from traditional face‐to‐face to online learning, challenges in learning environments are on the rise. The aim of this study was to assess students’ satisfaction with a service course conducted online at a funded university in Europe using a structural equation model. The construction and validation of five scales for measuring students’ learning and satisfaction is also presented. One thousand one hundred and sixteen students were given an online questionnaire in January, 2019. The scales were found to be sufficiently valid and reliable. The interaction, instructor behaviors, advantages/flexibility, and perceived learning/course quality were influential in students’ satisfaction. Success in e‐learning can be achieved with the help of these findings via improving e‐learning strategies. Further studies can be conducted on students’ learning and satisfaction while participating in other online courses using the same scales.
In Vivo Expression of Genetic Information from Phosphoramidate–DNA
Authors: Nguyen Hoai , Abramov Mikhail , Eremeeva Elena , Herdewijn Piet
Published: December 2019

Chemically modified genes and genomes with customized properties will become a valuable tool in numerous fields, including synthetic biology, biotechnology, and medicine. These genetic materials are meant to store and exchange information with DNA and RNA while tuning their functionality. Herein, we outline the development of an alternative genetic system carrying phosphoramidate linkages that successfully propagates genetic information in bacteria and at the same time is labile to acidic conditions. The P3′→N5′ phosphoramidate‐containing DNA (PN‐DNA) was enzymatically synthesized by using 5′‐amino‐2′,5′‐deoxycytidine 5′‐N‐triphosphates (NH‐dCTPs) as substrates for DNA polymerases and employed to encode antibiotic resistance in Escherichia coli. The resulting PN‐DNA can be efficiently destroyed by mild acidic conditions, whereas an unmodified counterpart remains intact. A cloning strategy was proposed for assembling modified fragments into a genome. This method can be of interest to scientists working in the field of orthogonal nucleic acid genes and genomes.
Impact of the residual SYNTAX score on clinical outcomes after percutaneous coronary intervention for patients with chronic renal insufficiency
Authors: Yan Liqiu , Li Peiyao , Wang Yabin , Han Dong , Li Sulei , Zhang Jibin , Jiang Min , Fan Li , Han Yaling , Cao Feng
Published: December 2019

Objectives

This study demonstrated the prognostic value of the residual SYNTAX score (rSS) for patients with chronic renal insufficiency (CRI).

Background

The rSS has been proposed as a useful tool for quantifying and stratifying the degree and complexity of residual stenosis and predicting long‐term clinical outcomes following percutaneous coronary intervention (PCI). However, it has never been validated for patients with CRI.

Methods

A total of 2,468 consecutive patients with an estimated glomerular filtration rate <90 ml/min/1.73 m2 who underwent PCI were retrospectively enrolled. Patients with rSS >0 were defined as having incomplete revascularization and were stratified into the reasonable incomplete revascularization (RICR; 0 < rSS ≤ 8) group or the incomplete revascularization (ICR; rSS >8) group. Their outcomes were compared to those of the complete revascularization (CR) group.

Results

During follow‐up (median, 3 years; range, 1.5–5 years), the ICR group had the highest incidence of all‐cause death, cardiac death, myocardial infarction (MI), unplanned revascularization, stroke, and major adverse cardiovascular and cerebrovascular events (MACCE). Despite having higher rates of unplanned revascularization and MACCE, RICR group had comparable all‐cause mortality, cardiac mortality, MI, and stroke with CR group. A multivariable Cox analysis indicated that rSS was an independent predictor of cardiac death, MI, unplanned revascularization, stroke, and MACCE. Furthermore, compared with baseline SYNTAX score, rSS had stronger prognostic accuracy when predicting the risk of unplanned revascularization, stroke, and MACCE at the 3‐year follow‐up.

Conclusions

The rSS is a powerful indicator of clinical outcomes and may help determine reasonable levels of revascularization for patients with CRI following PCI.
A randomized controlled trial on the effectiveness of a portable patient education video prior to coronary angiography and angioplasty
Authors: Yap Jonathan , Teo Tse Y. , Foong Priscilla , Binte Hussin Norwati , Wang Hannah , Shen Tong , Yeo Khung K.
Published: December 2019

Introduction

Time limitations in busy clinical settings may impede adequate explanation of coronary angiography/angioplasty. We aim to evaluate the effectiveness of a portable patient education video in improving knowledge and allaying patient's anxiety.

Methods

Consecutive patients undergoing coronary angiography/angioplasty were prospectively recruited over 1 year from a tertiary cardiac institution. A 3‐min animated patient education video on the procedure was developed to be shown on a tablet. Patients were randomized 3:1 into an intervention group (video plus routine care) versus a control group (routine care). Before the procedure, a self‐administered questionnaire was conducted in both groups. The questionnaire was repeated post‐video in the intervention group.

Results

A total of 332 patients (252 intervention groups, 80 controls) were recruited. At baseline, the intervention group had lower knowledge scores (p = .022) and similar anxiety scores (p = .323) compared with the control group. After the video, the intervention group had significantly higher knowledge scores (p ≤ .001) and lower anxiety scores (p ≤ .001). Within the intervention group, there was a significant increase in knowledge scores (p ≤ .001) and reduction in anxiety scores (p ≤ .001) before versus after watching the video. In the subset of patients who had previously undergone a similar procedure (n = 131), there was also significant improvement in knowledge scores and reduction in anxiety scores (p < .001). The video is accessible at https://youtu.be/R8AdaIbNq7Y.

Conclusion

The video improved knowledge and reduced anxiety in patients undergoing coronary angiography and angioplasty. This is a useful adjunct to incorporate into existing workflows to improve patient care.