bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Synapses Based on Multiterminal Memtransistors for Neuromorphic Application
Authors: Wang Lin , Liao Wugang , Wong Swee Liang , Yu Zhi Gen , Li Sifan , Lim Yee‐Fun , Feng Xuewei , Tan Wee Chong , Huang Xin , Chen Li , Liu Liang , Chen Jingsheng , Gong Xiao , Zhu Chunxiang , Liu Xinke , Zhang Yong‐Wei , Chi Dongzhi , Ang Kah‐Wee
Published: April 2019

Neuromorphic computing, which emulates the biological neural systems could overcome the high‐power consumption issue of conventional von‐Neumann computing. State‐of‐the‐art artificial synapses made of two‐terminal memristors, however, show variability in filament formation and limited capacity due to their inherent single presynaptic input design. Here, a memtransistor‐based artiﬁcial synapse is realized by integrating a memristor and selector transistor into a multiterminal device using monolayer polycrys‐talline‐MoS2 grown by a scalable chemical vapor deposition (CVD) process. Notably, the memtransistor offers both drain‐ and gate‐tunable nonvolatile memory functions, which efficiently emulates the long‐term potentiation/depression, spike‐amplitude, and spike‐timing‐dependent plasticity of biological synapses. Moreover, the gate tunability function that is not achievable in two‐terminal memristors, enables significant bipolar resistive states switching up to four orders‐of‐magnitude and high cycling endurance. First‐principles calculations reveal a new resistive switching mechanism driven by the diffusion of double sulfur vacancy perpendicular to the MoS2 grain boundary, leading to a conducting switching path without the need for a filament forming process. The seamless integration of multiterminal memtransistors may offer another degree‐of‐freedom to tune the synaptic plasticity by a third gate terminal for enabling complex neuromorphic learning.
High‐Performance Hierarchical Black‐Phosphorous‐Based Soft Electrochemical Actuators in Bioinspired Applications
Authors: Wu Guan , Wu Xingjiang , Xu Yijun , Cheng Hengyang , Meng Jinku , Yu Qiang , Shi Xinyiao , Zhang Kai , Chen Wei , Chen Su
Published: April 2019

Bioinspired methods allowing artificial actuators to perform controllably are potentially important for various principles and may offer fundamental insight into chemistry and engineering. To date, the main challenges persist regarding the achievement of large deformation in fast response‐time and potential‐engineering applications in which electrode materials and structures limit ion diffusion and accumulation processes. Herein, a novel electrochemical actuator is developed that presents both higher electromechanical performances and biomimetic applications based on hierachically structured covalently bridged black phosphorous/carbon nanotubes. The new actuator demonstrates astonishing actuation properties, including low power consumption/strain (0.04 W cm−2 %−1), a large peak‐to‐peak strain (1.67%), a controlled frequency response (0.1–20 Hz), faster strain and stress rates (11.57% s−1; 28.48 MPa s−1), high power (29.11 kW m−3), and energy (8.48 kJ m−3) densities, and excellent cycling stability (500 000 cycles). More importantly, bioinspired applications such as artificial‐claw, wings‐vibrating, bionic‐flower, and hand actuators have been realized. The key to high performances stems from hierachically structured materials with an ordered lamellar structure, large redox activity, and electrochemical capacitance (321.4 F g−1) for ions with smooth diffusion and flooding accommodation, which will guide substantial progress of next‐generation electrochemical actuators.
Light‐Triggered In Situ Gelation to Enable Robust Photodynamic‐Immunotherapy by Repeated Stimulations
Authors: Meng Zhouqi , Zhou Xuanfang , Xu Jun , Han Xiao , Dong Ziliang , Wang Hairong , Zhang Yaojia , She Jialin , Xu Ligeng , Wang Chao , Liu Zhuang
Published: April 2019

Photodynamic therapy (PDT) has shown the potential of triggering systemic antitumor immune responses. However, while the oxygen‐deficient hypoxic tumor microenvironment is a factor that limits the PDT efficacy, the immune responses after conventional PDT usually are not strong enough to eliminate metastatic tumors. Herein, a light‐triggered in situ gelation system containing photosensitizer‐modified catalase together with poly(ethylene glycol) double acrylate (PEGDA) as the polymeric matrix is designed. Immune adjuvant nanoparticles are further introduced into this system to trigger robust antitumor immune responses after PDT. Following local injection of the mixed precursor solution into tumors and the subsequent light exposure, polymerization of PEGDA can be initiated to induce in situ gelation. Such hybrid hydrogel with long‐term tumor retention of various agents and the ability to enable persistent tumor hypoxia relief can enable multiple rounds of PDT, which results in significantly enhanced immune responses by multiround stimulation. Further combination of such gel‐based multiround PDT with anticytotoxic T‐lymphocyte antigen‐4 checkpoint blockade offers not only the abscopal effect to inhibit growth of distant tumors but also effective long‐term immune memory protection from rechallenged tumors. Therefore, such a light‐triggered in situ gelation system by a single‐dose injection can enable greatly enhanced photoimmunotherapy by means of repeated stimulations.
Chemical, Structural, and Electronic Aspects of Formation and Degradation Behavior on Different Length Scales of Ni‐Rich NCM and Li‐Rich HE‐NCM Cathode Materials in Li‐Ion Batteries
Authors: de Biasi Lea , Schwarz Björn , Brezesinski Torsten , Hartmann Pascal , Janek Jürgen , Ehrenberg Helmut
Published: April 2019

In order to satisfy the energy demands of the electromobility market, both Ni‐rich and Li‐rich layered oxides of NCM type are receiving much attention as high‐energy‐density cathode materials for application in Li‐ion batteries. However, due to different stability issues, their longevity is limited. During formation and continuous cycling, especially the electronic and crystal structure suffers from various changes, eventually leading to fatigue and mechanical degradation. In recent years, comprehensive battery research has been conducted at Karlsruhe Institute of Technology, mainly aiming at better understanding the primary degradation processes occurring in these layered transition metal oxides. The characteristic process of formation and mechanisms of fatigue are fundamentally characterized and the effect of chemical composition on cell chemistry, electrochemistry, and cycling stability is addressed on different length scales by use of state‐of‐the‐art analytical techniques, ranging from “standard” characterization tools to combinations of advanced in situ and operando methods. Here, the results are presented and discussed within a broader scientific context.
POEMS Syndrome: 2019 Update on diagnosis, risk‐stratification, and management
Authors: Dispenzieri Angela
Published: April 2019

Disease Overview

Polyneuropathy, organomegaly, endocrinopathy, M‐protein, skin changes (POEMS) syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome.

Diagnosis

The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal PCD, and at least one of the minor criteria.

Risk Stratification

Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR.

Risk‐Adapted Therapy

For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.
A novel missense mutation in TFAP2B associated with Char syndrome and central diabetes insipidus
Authors: Edward Heather L. , D'Gama Alissa M. , Wojcik Monica H. , Brownstein Catherine A. , Kenna Margaret A. , Grant P. Ellen , Majzoub Joseph A. , Agrawal Pankaj B.
Published: April 2019

Char syndrome is characterized by persistent patent ductus arteriosus (PDA) associated with hand‐skeletal abnormalities and distinctive facial dysmorphism. Pathogenic variants in the transcription factor gene TFAP2B have been shown to cause Char syndrome; however, there is significant phenotypic variability linked to variant location. Here, we report a pediatric patient with a novel de novo variant in the fifth exon of TFAP2B, c.917C > T (p.Thr306Met), who presented with PDA, patent foramen ovale, postaxial polydactyly of the left fifth toe and clinodactyly of the left fourth toe, sensorineural hearing loss, scoliosis, dental anomalies, and central diabetes insipidus (CDI). CDI, scoliosis, and hearing loss have not previously been reported in a patient with Char syndrome, and while the association may be coincidental, this report expands the genotypes and potentially phenotypes associated with this syndrome.
In situ erzeugte Goldnanopartikel auf Aktivkohle als wiederverwendbare hocheffiziente Katalysatoren für eine C‐C‐Stille‐Kupplung
Authors: Holz Julia , Pfeffer Camilla , Zuo Hualiang , Beierlein Dennis , Richter Gunther , Klemm Elias , Peters René
Published: April 2019

Goldnanopartikel sind für viele industrielle Prozesse wichtige Katalysatoren. In traditionellen C‐C‐Kreuzkupplungen wurden sie jedoch selten eingesetzt, da Pd‐Katalysatoren in der Regel überlegen sind. Hier beschreiben wir in situ gebildete Goldmetallnanopartikel als hochaktive Katalysatoren für die Kreuzkupplung von Allylstannanen und aktivierten Alkylbromiden zur Bildung von C‐C‐Bindungen. In Gegenwart von Aktivkohle als Trägermaterial, was eine einfache Katalysatorrückgewinnung und ‐wiederverwendung ermöglichte, konnten Umsatzzahlen von bis zu 29.000 erreicht werden. Die vorliegende Studie ist ein seltenes Beispiel für eine Kreuzkupplungsreaktion eines organischen Halogenids mit einem metallorganischen Reagens, bei der ein Goldmetallkatalysator Pd‐Katalysatoren überlegen ist.
The Role of Organic Synthesis in the Emergence and Development of Antibody–Drug Conjugates as Targeted Cancer Therapies
Authors: Nicolaou K. C. , Rigol Stephan
Published: April 2019

With a number of antibody–drug conjugates (ADCs) approved for clinical use as targeted cancer therapies and numerous candidates in clinical trials, the field of ADCs is emerging as one of the frontiers in biomedical research, particularly in the area of cancer treatment. Chemists, biologists and clinicians, among other scientists, are partnering their expertise to improve their design, synthesis, efficacy and precision as they strive to advance this paradigm of personalized and targeted medicine to treat cancer patients more effectively and to expand its scope to other indications. Just as Alexander Fleming's penicillin, and the myriad other bioactive natural products that followed its discovery and success in the clinic, ignited a revolution in medicine after the Second World War, so did calicheamicin γ1I, and other highly potent naturally occurring antitumor agents, play a pivotal role in enabling the advent of this new paradigm of “biological‐small molecule hybrid” medical intervention. Today there are four clinically approved drugs from the ADC paradigm, Mylotarg, Adcetris, Kadcyla and Besponsa, in order of approval, the first and the last of which carry the same calicheamicin γ1I‐derived payload. Covering oncological applications, and after a brief history of the emergence of the field of antibody–drug conjugates triggered more than a century ago by Paul Ehrlich's “magic bullet” concept, this Review is primarily focusing on the chemical synthesis aspects of the ADCs multidisciplinary research enterprise.
In situ green synthesis of Cu‐Ni bimetallic nanoparticles supported on reduced graphene oxide as an effective and recyclable catalyst for the synthesis of N‐benzyl‐N‐aryl‐5‐amino‐1H‐tetrazoles
Authors: Nasrollahzadeh Mahmoud , Sajjadi Mohaddeseh , Komber Hartmut , Khonakdar Hossein Ali , Sajadi S. Mohammad
Published: April 2019

In the present work, for the first time we have designed a novel approach for the synthesis of N‐benzyl‐N‐aryl‐5‐amino‐1H‐tetrazoles using reduced graphene oxide (rGO) decorated with Cu‐Ni bimetallic nanoparticles (NPs). In situ synthesis of Cu/Ni/rGO nanocomposite was performed by a cost efficient, surfactant‐free and environmentally benign method using Crataegus azarolus var. aronia L. leaf extract as a stabilizing and reducing agent. Phytochemicals present in the extract can be used to reduce Cu2+ and Ni2+ ions and GO to Cu NPs, Ni NPs and rGO, respectively. Analyses by means of FT‐IR, UV–Vis, EDS, TEM, FESEM, XRD and elemental mapping confirmed the Cu/Ni/rGO formation and also FT‐IR, NMR, and mass spectroscopy as well as elemental analysis were used to characterize the tetrazoles. The Cu/Ni/rGO nanocomposite showed the superior catalytic activity for the synthesis of N‐benzyl‐N‐aryl‐5‐amino‐1H‐tetrazoles within a short reaction time and high yields. Furthermore, this protocol eliminates the need to handle HN3.
Antileismanial activity, mechanism of action study and molecular docking of 1,4‐bis(substituted benzalhydrazino)phthalazines
Authors: Romero Angel H. , Rodríguez Noris , Oviedo Henry , Lopez Simón E.
Published: April 2019

To identify new agents for the treatment of American cutaneous leishmaniasis, a series of eight 1,4‐bis(substituted benzalhydrazino)phthalazines was evaluated against Leishmania braziliensis and Leishmania mexicana parasites. These compounds represent a disubstituted version of the 1‐chloro‐4‐(monoaryl/heteroarylhydranizyl)phthalazine that exhibited a significant response against L. braziliensis according to our previous findings. Two disubstituted phthalazines 3b and 3f were identified as potential antileishmanial agents against L. braziliensis parasites, exhibiting a submicromolar IC50 response of 2.37 and 7.90 µM on the promastigote form, and of 1.82 and 4.56 µM against intracellular amastigotes, respectively. In particular, compound 3b showed interesting responses against amastigote isolates from reference, glucantime‐resistant and clinical human strains, which were by far superior to the biological response found for the glucantime drug. With regard to the toxicity results, both 3b and 3f exhibited moderate LD50 values against murine macrophages (BMDM), with good selectivity indexes on promastigotes and intracellular amastigotes of L. braziliensis. A comparison of biological response was established between the monosubstituted and disubstituted versions of these benzalhydrazino‐phthalazines. Easy synthetic procedure and significant response against amastigote strains including against resistant lines made compound 3b a potential candidate for further pharmacokinetic and in vivo experiments as antileishmanial agent, and as a platform for further structural optimization. Mechanism‐of‐action studies and molecular docking simulations discarded to inhibition of superoxide dismutase as possible mode of action.
Long‐term in vitro treatment with telomerase inhibitor MST‐312 induces resistance by selecting long telomeres cells
Authors: Morais Karollyne da Silva , Arcanjo Daniel da Silva , de Faria Lopes Giselle Pinto , da Silva Guilherme Guimarães , da Mota Tales Henrique Andrade , Gabriel Thiago Rodrigues , Rabello Ramos Doralina do Amaral , Silva Fábio Pittella , de Oliveira Diêgo Madureira
Published: April 2019

Telomerase is a good target for new anticancer drug development because it is present in over 85% of human tumours. However, despite chronic therapy is a condition for anti‐telomerase approach, the effects of long‐term treatment with telomerase inhibitors remain not well understood. In this work, it was evaluated the effects of long‐term treatment of human MDA‐MB‐231 breast cancer cells with the telomerase inhibitor MST‐312. Cells were treated for 72 hours or 140 days, and it was accessed their viability, proliferation rate, morphology, telomeric DNA content, and resistance mechanism. The drug had a clear short‐term effect, including chemosensitizing cells for docetaxel and irinotecan, but the chronic exposition led to selection of long telomeres clones, changing characteristics of original cell line. This effect was confirmed in a clonal culture with homogenous karyotype. MRP‐1 expression and alternative lengthening of telomeres (ALT) were discarded as additional mechanisms of resistance. This data suggest that, considering the intra‐tumour heterogeneity (ITH), what is already a big challenge for treatment of cancer, chronic exposition to telomerase inhibitors can promote tumour adaptations with potential clinical repercussion, drawing attention to ongoing clinical trials and pointing important considerations most times neglected on studies about use of these inhibitors on cancer therapy.

Significance of the study

Antitumour action of telomerase inhibitors is well known, but it depends on a long‐term exposition because cells will undergo telomere erosion only after many duplication cycles. Recently, the frustrating results of clinical trials with these inhibitors aroused the interest of the scientific community to understand the mechanisms of resistance to anti‐telomerase therapy. In this study, we conducted an 18‐week experiment to show that telomerase inhibition can lead to cell adaptations and selection of long‐telomeres clones, leading to acquisition of resistance. However, we also showed that this inhibitor can sensitize cells to the chemotherapeutic drugs docetaxel and irinotecan.
Biocatalytic Reversal of Advanced Glycation End Product Modification
Authors: Kim Nam Y. , Goddard Tyler N. , Sohn Seungjung , Spiegel David A. , Crawford Jason M.
Published: April 2019

Advanced glycation end products (AGEs) are a heterogeneous group of molecules that emerge from the condensation of sugars and proteins through the Maillard reaction. Despite a significant number of studies showing strong associations between AGEs and the pathologies of aging‐related illnesses, it has been a challenge to establish AGEs as causal agents primarily due to the lack of tools in reversing AGE modifications at the molecular level. Herein, we show that MnmC, an enzyme involved in a bacterial tRNA‐modification pathway, is capable of reversing the AGEs carboxyethyl‐lysine (CEL) and carboxymethyl‐lysine (CML) back to their native lysine structure. Combining structural homology analysis, site‐directed mutagenesis, and protein domain dissection studies, we generated a variant of MnmC with improved catalytic properties against CEL in its free amino acid form. We show that this enzyme variant is also active on a CEL‐modified peptidomimetic and an AGE‐containing peptide that has been established as an authentic ligand of the receptor for AGEs (RAGE). Our data demonstrate that MnmC variants are promising lead catalysts toward the development of AGE‐reversal tools and a better understanding of AGE biology.
Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV‐1 Fusion Inhibitors
Authors: Kobayakawa Takuya , Ebihara Kento , Honda Yuzuna , Fujino Masayuki , Nomura Wataru , Yamamoto Naoki , Murakami Tsutomu , Tamamura Hirokazu
Published: April 2019

C34, a 34‐mer fragment peptide, is contained in the HIV‐1 envelope protein gp41. A dimeric derivative of C34 linked through a disulfide bridge at its C terminus was synthesized and found to display potent anti‐HIV activity, comparable with that of a previously reported PEGylated dimer of C34REG. The reduction in the size of the linker moiety for dimerization was thus successful, and this result might shed some light on the mechanism of the suppression of six‐helix bundle formation by these C34 dimeric derivatives. Addition of a Gly‐Cys(CH2CONH2)‐Gly‐Gly motif at the N‐terminal position of a C34 monomeric derivative significantly increased the anti‐HIV‐1 activity. This moiety functions as a new pharmacophore, and this might provide a useful insight into the design of potent HIV‐1 fusion inhibitors.
Physicochemical Characterization of Polymer‐Stabilized Coacervate Protocells
Authors: Yewdall N. Amy , Buddingh Bastiaan C. , Altenburg Wiggert J. , Timmermans Suzanne B. P. E. , Vervoort Daan F. M. , Abdelmohsen Loai K. E. A. , Mason Alexander F. , van Hest Jan C. M.
Published: April 2019

The bottom‐up construction of cell mimics has produced a range of membrane‐bound protocells that have been endowed with functionality and biochemical processes reminiscent of living systems. The contents of these compartments, however, experience semidilute conditions, whereas macromolecules in the cytosol exist in protein‐rich, crowded environments that affect their physicochemical properties, such as diffusion and catalytic activity. Recently, complex coacervates have emerged as attractive protocellular models because their condensed interiors would be expected to mimic this crowding better. Here we explore some relevant physicochemical properties of a recently developed polymer‐stabilized coacervate system, such as the diffusion of macromolecules in the condensed coacervate phase, relative to in dilute solutions, the buffering capacity of the core, the molecular organization of the polymer membrane, the permeability characteristics of this membrane towards a wide range of compounds, and the behavior of a simple enzymatic reaction. In addition, either the coacervate charge or the cargo charge is engineered to allow the selective loading of protein cargo into the coacervate protocells. Our in‐depth characterization has revealed that these polymer‐stabilized coacervate protocells have many desirable properties, thus making them attractive candidates for the investigation of biochemical processes in stable, controlled, tunable, and increasingly cell‐like environments.
Spatial‐spectral analysis method using texture features combined with PCA for information extraction in hyperspectral images
Authors: Xu Jun‐Li , Gowen Aoife A.
Published: April 2019

This work proposes a new method to treat spatial and spectral information interactively. The method extracts spatial features, ie, variogram, gray‐level co‐occurrence matrix (GLCM), histograms of oriented gradients (HOG), and local binary pattern (LBP) features, from each wavelength image of hypercube and principal component analysis (PCA) is applied on this spatial feature matrix to identify wavelength‐dependent variation in spatial patterns. Resultant image is obtained by projecting the score values to the original data. Three datasets, including a synthetic hyperspectral image (Dataset 1), a set of real hyperspectral images of salmon fillets (Dataset 2), and remote‐sensing images (Dataset 3), were utilized to evaluate the performance of the proposed method. Results from Dataset 1 showed that the spatial‐spectral methods had the potential of reducing baseline offset noise. Dataset 2 revealed that spatial‐spectral methods can alleviate noisy pixels with strong signal and reduce shadow effects. In addition, substantial improvements were obtained in case of classification between white stripe and red muscle pixels by using the HOG‐based approach with correct classification rate (CCR) of 0.97 compared with the models directly built from raw and standard normal variate (SNV) preprocessed spectra (CCR = 0.94). Samson image of Dataset 3 suggested the flexibility and effectiveness of the proposed method by improving CCR of 0.96 using conventional PCA on SNV pretreated spectra to 0.98 using GLCM‐based approach on SNV preprocessed spectra. Overall, experimental results demonstrated that the spatial‐spectral methods can improve the results found by using the spectral information alone because of the spatial information provided.
A General One‐Pot Methodology for the Preparation of Mono‐ and Bimetallic Nanoparticles Supported on Carbon Nanotubes: Application in the Semi‐hydrogenation of Alkynes and Acetylene
Authors: Lomelí‐Rosales Diego A. , Delgado Jorge A. , Díaz de los Bernardos Miriam , Pérez‐Rodríguez Sara , Gual Aitor , Claver Carmen , Godard Cyril
Published: April 2019

A facile and straightforward methodology for the preparation of monometallic (copper and palladium) and bimetallic nanocatalysts (NiCu and PdCu) stabilized by a N‐heterocyclic carbene ligand is reported. Both colloidal and supported nanoparticles (NPs) on carbon nanotubes (CNTs) were prepared in a one‐pot synthesis with outstanding control on their size, morphology and composition. These catalysts were evaluated in the selective hydrogenation of alkynes and alkynols. PdCu/CNTs revealed an efficient catalytic system providing high selectivity in the hydrogenation of terminal and internal alkynes. Moreover, this catalyst was tested in the semi‐hydrogenation of acetylene in industrially relevant acetylene/ethylene‐rich model gas feeds and showed excellent stability even after 40 h of reaction.
Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum
Authors: Kiefer Alexander , Bader Chantal D. , Held Jana , Esser Anna , Rybniker Jan , Empting Martin , Müller Rolf , Kazmaier Uli
Published: April 2019

Cyclomarins are highly potent antimycobacterial and antiplasmodial cyclopeptides isolated from a marine bacterium (Streptomyces sp.). Previous studies have identified the target proteins and elucidated a novel mode of action, however there are currently only a few studies examining the structure–activity relationship (SAR) for both pathogens. Herein, we report the synthesis and biological evaluation of 17 novel desoxycyclomarin‐inspired analogues. Optimization via side chain modifications of the non‐canonical amino acids led to potent lead structures for each pathogen.
Auslegung von Blasensäulen mithilfe von Compartmentmodellen
Authors: Rieth Iris , Grünewald Marcus
Published: April 2019

In Blasensäulen sind die Phänomene des Stoff‐ und Wärmetransportes sowie der Reaktion eng mit der komplexen Fluiddynamik verknüpft. Die Compartmentmodellierung mehrphasiger Reaktoren bietet in diesem Zusammenhang einen Lösungsansatz, der zum einen die o. g. Einzelphänomene integriert und zum anderen bei vertretbarem Rechenaufwand neben der axialen auch eine radiale Auflösung der Modellparameter innerhalb des Reaktors bietet. Im Rahmen dieses Beitrags werden Methoden zur Generierung eines Compartmentmodells aufgezeigt, das dann der Optimierung einer Produktionsblasensäule dienen kann.
Phase 1/2 study of fractionated dose lutetium‐177–labeled anti–prostate‐specific membrane antigen monoclonal antibody J591 (177Lu‐J591) for metastatic castration‐resistant prostate cancer
Authors: Tagawa Scott T. , Vallabhajosula Shankar , Christos Paul J. , Jhanwar Yuliya S. , Batra Jaspreet S. , Lam Linda , Osborne Joseph , Beltran Himisha , Molina Ana M. , Goldsmith Stanley J. , Bander Neil H. , Nanus David M.
Published: April 2019

Background

Prostate cancer is radiosensitive. Prostate‐specific membrane antigen (PSMA) is selectively overexpressed on advanced, castration‐resistant tumors. Lutetium‐177–labeled anti‐PSMA monoclonal antibody J591 (177Lu‐J591) targets prostate cancer with efficacy and dose‐response/toxicity data when delivered as a single dose. Dose fractionation may allow higher doses to be administered safely.

Method

Men with metastatic castration‐resistant prostate cancer refractory to or refusing standard treatment options with normal neutrophil and platelet counts were enrolled in initial phase 1b dose‐escalation cohorts followed by phase 2a cohorts treated at recommended phase 2 doses (RP2Ds) comprising 2 fractionated doses of 177Lu‐J591 2 weeks apart. 177Lu‐J591 imaging was performed after treatment, but no selection for PSMA expression was performed before enrollment. Phase 2 patients had circulating tumor cell (CTC) counts assessed before and after treatment.

Results

Forty‐nine men received fractionated doses of 177Lu‐J591 ranging from 20 to 45 mCi/m2 ×2 two weeks apart. The dose‐limiting toxicity in phase 1 was neutropenia. The RP2Ds were 40 mCi/m2 and 45 mCi/m2 ×2. At the highest RP2D (45 mCi/m2 ×2), 35.3% of patients had reversible grade 4 neutropenia, and 58.8% of patients had thrombocytopenia. This dose showed a greater decrease in prostate‐specific antigen (PSA) levels and longer survival (87.5% with any PSA decrease, 58.8% with >30% decrease, 29.4% with >50% decrease; median survival, 42.3 months [95% confidence interval, 19.9‐64.7]). Fourteen of 17 (82%) patients with detectable CTCs experienced a decrease in CTC count. Overall, 79.6% of patients had positive PSMA imaging; those with less intense PSMA imaging tended to have poorer responses.

Conclusion

Fractionated administration of 177Lu‐J591 allowed higher cumulative radiation dosing. The frequency and depth of PSA decrease, overall survival, and toxicity (dose‐limiting myelosuppression) increased with higher doses.
Trends in pediatric thyroid cancer incidence in the United States, 1998‐2013
Authors: Bernier Marie‐Odile , Withrow Diana R. , Berrington de Gonzalez Amy , Lam Clara J. K. , Linet Martha S. , Kitahara Cari M. , Shiels Meredith S.
Published: April 2019

Background

Pediatric differentiated thyroid cancer (DTC) rates have increased over time in the United States and worldwide. Improvements in imaging for the diagnosis of DTC have been hypothesized as a potential driver of these increases. This study stratifies temporal trends in pediatric DTC by stage and tumor size to assess whether rates of large, late‐stage cancers, which are likely to be clinically meaningful, are increasing over time.

Methods

Age‐standardized incidence rates (ASRs) of DTC and annual percent changes (APCs) in primary DTC rates were estimated for 0‐ to 19‐year‐olds with data from 39 US cancer registries during 1998‐2013.

Results

During 1998‐2013, 7296 cases of DTC were diagnosed (6652 papillary cases and 644 follicular cases). APCs of pediatric DTCs significantly increased by 4.43%/y [95% CI, 3.74%/y‐5.13%/y], primarily because of increases in papillary histologies. Increasing trends were observed for children aged 10 to 19 years for both sexes and for non‐Hispanic whites, non‐Hispanic blacks, and Hispanics. Rates increased significantly over the time period for all tumor stages (APClocalized, +4.06%/y [95% CI, 2.84%/y‐5.29%/y]; APCregional, +5.68%/y [95% CI, 4.64%/y‐6.73%/y]; APCdistant, +8.55%/y [95% CI, 5.03%/y‐12.19%/y]) and across tumor sizes (APC<1 cm, +9.46%/y [95% CI, 6.13%/y‐12.90%/y]; APC1‐2 cm, +6.92%/y [95% CI, 4.31%/y‐9.60%/y]; APC>2 cm, +4.69%/y [95% CI, 2.75%/y‐6.67%/y]).

Conclusions

Significantly increasing rates of DTC over time among 10‐ to 19‐year‐olds in the United States are unlikely to be entirely explained by increases in medical surveillance during childhood because rates of large and late‐stage DTC are increasing over time. Future studies should examine environmental and other factors that may be contributing to rising DTC rates.
A phase 1 trial of the oral DNA methyltransferase inhibitor CC‐486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors
Authors: Gaillard Stéphanie L. , Zahurak Marianna , Sharma Anup , Durham Jennifer N. , Reiss Kim A. , Sartorius‐Mergenthaler Susan , Downs Melinda , Anders Nicole M. , Ahuja Nita , Rudek Michelle A. , Azad Nilofer
Published: April 2019

Background

Epigenetic abnormalities are manifold in all solid tumors and include changes in chromatin configuration and DNA methylation. The authors designed a phase 1 study to evaluate the oral DNA methyltransferase inhibitor CC‐486 combined with the histone deacetylase inhibitor romidepsin in advanced solid tumors with dose expansion to further evaluate pharmacodynamics and possible clinical benefit of the recommended phase 2 dose (RP2D).

Methods

This was a phase 1 study with a 3 + 3 dose‐escalation design and an expansion phase for patients with virally mediated cancers. The disease control rate (DCR) was the primary outcome for the expansion cohort. Correlative studies included long interspersed nucleotide element 1 (LINE‐1) methylation and drug exposure in blood samples (clinicaltrials.gov identifier NCT01537744).

Results

Fourteen patients were enrolled in the dose‐escalation portion at 3 dose levels. Three patients experienced dose‐limiting toxicities; the RP2D was oral CC‐486 300 mg daily on days 1 through 14 and romidepsin 8 mg/m2 on days 8 and 15. Because of slow accrual into the expansion phase, the trial was closed after 4 patients enrolled. Common toxicities of the combination included nausea (83.3%), anorexia (72.2%), fatigue (61.1%), and constipation (55.6%). There were 12 patients evaluable for response, 5 with stable disease, of whom 2 received >4 cycles; there were no responses. Exposure to CC‐486 and romidepsin was consistent with prior data. LINE‐1 methylation on C1D8 was significantly reduced (mean, −6.23; 95% CI, −12.23, −0.24; P = .04).

Conclusions

Although, at the RP2D, the combination of CC‐486 and romidepsin was tolerable, no significant anticancer activity was observed. Significant demethylation in post‐treatment circulating tumor DNA and biopsies provided proof of target acquisition.
Maintenance of physical activity and sedentary behavior change, and physical activity and sedentary behavior change after an abridged intervention: Secondary outcomes from the ACTIVATE Trial
Authors: Lynch Brigid M. , Nguyen Nga H. , Moore Melissa M. , Reeves Marina M. , Rosenberg Dori E. , Boyle Terry , Milton Shakira , Friedenreich Christine M. , Vallance Jeff K. , English Dallas R.
Published: April 2019

Background

This brief report examines the maintenance of moderate to vigorous physical activity (MVPA) and sedentary behavior changes approximately 12 weeks after the delivery of the ACTIVATE Trial primary intervention (use of the Garmin Vivofit 2 activity tracker coupled with a behavioral feedback and goal‐setting session and 5 telephone‐delivered health coaching sessions). We also examine the efficacy of an abridged intervention (use of the Garmin Vivofit 2 only) in the waitlist control group.

Methods

A pre‐post design was employed to examine the secondary aims of the ACTIVATE Trial (n = 80; mean age = 62 years). MVPA and sedentary behavior were measured using Actigraph and activPAL accelerometers after delivery of the primary intervention (T2), and again 12 weeks later (T3). Linear mixed models with random effects were used to examine within‐group changes in MVPA and sitting time variables.

Results

After the 12‐week follow‐up period, women in the primary intervention group had maintained their higher levels of MVPA (change from T2 to T3 = 14 min/wk; 95% CI = −18 to 46; P = .37). However, their sitting time increased slightly, by 7 min/d (95% CI = −20 to 34; P = .58), but it did not return to its preintervention level. After receiving the Garmin Vivofit 2, the waitlist control group increased their MVPA by 33 min/wk (95% CI = 3‐64; P = .03) and reduced their sitting time by 38 min/d (95% CI = −69 to −7; P = .02) over the same 12‐week period.

Conclusion

The secondary outcomes from the ACTIVATE Trial suggest that wearable technology may generate sustainable changes in MVPA and sitting time. Wearable technology alone may be sufficient to change behavior, at least in the short term.
A randomized controlled trial of a wearable technology‐based intervention for increasing moderate to vigorous physical activity and reducing sedentary behavior in breast cancer survivors: The ACTIVATE Trial
Authors: Lynch Brigid M. , Nguyen Nga H. , Moore Melissa M. , Reeves Marina M. , Rosenberg Dori E. , Boyle Terry , Vallance Jeff K. , Milton Shakira , Friedenreich Christine M. , English Dallas R.
Published: April 2019

Background

The benefits of an active lifestyle after a breast cancer diagnosis are well recognized, but the majority of survivors are insufficiently active. The ACTIVATE Trial examined the efficacy of an intervention (use of the Garmin Vivofit 2 activity monitor coupled with a behavioral feedback and goal‐setting session and 5 telephone‐delivered health coaching sessions) to increase moderate to vigorous physical activity (MVPA) and reduce sedentary behavior in breast cancer survivors.

Methods

This randomized controlled trial recruited 83 inactive, postmenopausal women diagnosed with stage I‐III breast cancer who had completed primary treatment. Participants were randomly assigned to the intervention group or to the control group, and the intervention was delivered over a 12‐week period. MVPA and sedentary behavior were measured with Actigraph and activPAL accelerometers at baseline (T1) and at the end of the intervention (T2).

Results

Retention in the trial was high, with 80 (96%) of participants completing T2 data collection. At T2, there was a significant between‐group difference in MVPA (69 min/wk; 95% CI = 22‐116) favoring the intervention group. The trial resulted in a statistically significant decrease in both total sitting time and prolonged bouts (≥20 min) of sitting, with between‐group reductions of 37 min/d (95% CI = −72 to −2) and 42 min/d (95% CI = −83 to −2), respectively, favoring the intervention group.

Conclusion

Results from the ACTIVATE Trial suggest that the use of wearable technology presents an inexpensive and scalable opportunity to facilitate more active lifestyles for cancer survivors. Whether or not such wearable technology‐based interventions can create sustainable behavioral change should be the subject of future research.
Cl2 Production by Photocatalytic Oxidation of HCl over TiO2
Authors: Rath Tobias , Uhrich Andrej , Lüken Alexander , Zhao Guixia , Rittermeier André , Muhler Martin
Published: April 2019

We studied the photocatalytic aerobic oxidation of HCl over TiO2 for producing Cl2. Steady‐state Cl2 production rates were determined with a photocatalytic fixed‐bed gas‐phase reactor equipped with UV light‐emitting diodes (LEDs) using iodometric titration as online analytics. We found stable Cl2 production rates of up to 16 mmol h−1 m−2 for commercial anatase TiO2 Hombikat UV100. The rate increased linearly with temperature from 21 to 140 °C, indicating the acceleration of the limiting desorption rate of the coupled product water. Comparing different TiO2 polymorphs revealed that anatase possesses higher activity than rutile. The adsorption of HCl was monitored in situ by IR spectroscopy. The IR spectra indicated that HCl chemisorption chlorinates the surface of TiO2 under the reaction conditions, suggesting it to be the first step of the reaction mechanism. High stability opens up the opportunity of developing a promising photocatalytic process of HCl recycling at lower temperatures suitable for reaching full conversion.
Procedural and declarative learning in dyslexia
Authors: West Gillian , Clayton Francina J. , Shanks David R. , Hulme Charles
Published: April 2019

The procedural deficit hypothesis claims that impaired procedural learning is at least partly responsible for the deficits in learning to read seen in children with developmental dyslexia. This study used a reading ability‐matched design to examine group differences in both procedural and declarative learning. Both children with dyslexia and typically developing children demonstrated procedural learning on a serial reaction time task, although learning in the typically developing group increased at a greater rate towards the end of the task compared with children with dyslexia. However, these results do not provide strong evidence for the procedural deficit hypothesis, because poorer procedural learning in the group with dyslexia may reflect impairments in motor learning, rather than sequence specific procedural learning. In addition, neither group showed a relationship between procedural learning and reading ability.
Habitat edge responses of generalist predators are predicted by prey and structural resources
Authors: Wimp Gina M. , Ries Leslie , Lewis Danny , Murphy Shannon M.
Published: April 2019

Generalist predators are thought to be less vulnerable to habitat fragmentation because they use diverse resources across larger spatial scales than specialist predators. Thus, it has been suggested that generalist predators may respond positively to habitat edges or demonstrate no edge response, because they can potentially use prey resources equally well on both sides of the habitat edge. However, most predictions about generalist predator responses to the habitat edge are based solely on prey resources, without consideration of other potential drivers. For instance, structural resources are essential for some species to build webs to capture prey or to avoid intraguild predation and cannibalism. In this study, we used both prey and structural resources to predict the response of four predator functional groups (hunting spiders, web‐building spiders, aerial predators, and epigeic predators that feed on the detrital/algal food web) to a habitat edge between two salt‐marsh grasses (Spartina alterniflora and Spartina patens). We found that generalist predators largely demonstrated negative responses to the habitat edge and had distinct habitat associations. Positive edge responses were only observed in one functional group (hunting spiders), and this pattern was driven by the two most abundant species. Negative responses to the habitat edge were more common among taxa and were better explained by structural resources rather than prey resources in the two habitats. Although it is generally acknowledged that specialists decline in fragmented habitats, generalists are thought to be more resilient. However, our research demonstrates that even generalists have habitat structural or food resource requirements that may limit their resilience to habitat loss and fragmentation.
Minisci‐Type C–H Cyanoalkylation of Heteroarenes Through N–O/C–C Bonds Cleavage
Authors: Jian Yong , Chen Ming , Yang Chao , Xia Wu‐jiong
Published: April 2019

A visible‐light‐induced C–H cyanoalkylation of heteroarenes was described, in which cycloketone oximes were readily transformed into carbon‐centered radicals with a terminal cyano‐group via N–O/C–C bonds cleavage in one phtochemical step. This reaction protocol displayed a broad substrate scope of heterocycle compounds, and it provided a promising strategy for the installation of cyanoalkyl groups onto heteroarenes.
Effect of Synthesis Method Using Varying Types of Micropore Level Sulfur Infiltration on Electrochemical Performance in Lithium–Sulfur Batteries
Authors: Dysart Arthur Dence , Cardoza Neal Amadeus , Mitchell Garrett , Ortalan Volkan , Pol Vilas Ganpat
Published: April 2019

The role of physically restrained, noncrystalline sulfur species in rechargeable lithium–sulfur batteries is examined by electrochemical and high‐resolution material characterizations. Carbon–sulfur composites are created by melting and sublimation of sulfur in an isochoric reactor via the autogenic process. These noncrystalline sulfur cathodes demonstrate a high specific capacity of ≈1000 Ah kg−1 after 100 cycles with a gravimetric current of 557 A kg−1. Interestingly, this high‐performance sulfur allotrope lacks a long‐range structural order: high‐resolution X‐ray diffraction, performed at the Advanced Photon Source, indicates the lack of crystalline (i.e., orthorhombic or monoclinic) sulfur in the nanoscale domain. Electrochemical and material characterizations suggest that noncrystalline sulfur is a consequence of synthesis and not necessarily evidence of electrochemical efficacy. Rather, a high rate capacity depends on sulfur distribution, in turn, controlled by synthesis pathway. At higher sulfur content, the performance of carbon–sulfur composites is limited by the available surface area in which crystalline sulfur coincides with reduced gravimetric capacity and greater charge transport impedance, suggesting suboptimal sulfur containment.
Rapid modeling of space structure of rock mass and the method of equivalent assignment
Authors: Luo Zhouquan , Qin Yaguang , Wang Wei , Ma Shaowei , Wen Lei , Zhang Xuyang
Published: April 2019

Accurately grasping the spatial distribution characteristics of fractures is an important basis for computation and analysis of rock engineering. On the basis of field investigation, probability statistics, and numerical simulation, the fast modeling method of fracture with special probability and statistical distribution is proposed. The server connection between COMSOL and MATLAB is established. In the COMSOL with MATLAB programming environment, the fast modeling program of fissure space structure is developed. Aiming at the difficulty of mesh generation due to high fracture aspect ratio, programming language was used to interpolate the material parameters of fissure space structure and construct the equivalent assignment method of fissure space structure. Based on the field fracture investigation in an underground mine, probabilistic data analysis of fracture data is carried out, and the fast modeling and equivalent assignment method is applied to realize the efficient modeling and assignment for the field investigation of fissure spatial structure.
The formation and closure of the Big Breach of Sacalin spit associated with extreme shoreline retreat and shoreface erosion
Authors: Zăinescu Florin Iulian , Vespremeanu‐Stroe Alfred , Tătui Florin
Published: April 2019

We document a case of exceptionally large natural breaching of a sandy spit (Sacalin spit, Danube Delta) using multiannual to seasonal surveys of topography and bathymetry on successive cross‐barrier and shoreface profiles, LiDAR data, satellite imagery, and wind and wave data.

The large breach, which quickly reached 3.4 km in May 2014, is attributed to morphological preconditioning of the narrow (50–150 m) barrier, which was susceptible to breaching even during moderate storm conditions. The event switched the barrier's decadal evolution from low cross‐shore transport to high cross‐shore transport over the barrier, which is an order of magnitude larger than during the non‐breach period. Upper shoreface erosion, as indicated by the extensive erosion down to −4 m, indicates that this zone is a significant source for the rebuilding of the barrier. Barrier recovery and widening trigger a negative feedback which limits the back‐barrier sediment transfer. As a result, back‐barrier deposition decreases whilst the barrier aggradation through overwash becomes more frequent.

The Big Breach (TBB) closed naturally in three years. The very high deposition rate of sediment in the breach is a testimony of the high sediment volumes supplied by the longshore transport and the high sediment released through shoreface retreat, and resulted in widening the barrier to a maximum of 1 km. Since the newly‐formed barrier shoreline retreated 500 m, this reveals that barrier breaching is an important mechanism which significantly accelerates the landward migration of the barrier system and is a proof of the highly non‐linear morphodynamics involved in the barrier island translation. © 2019 John Wiley & Sons, Ltd.