bluuebunny/crossref_metadata_2025 huggingface dataset:
Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules
Authors: Kourounakis Angeliki P. , Xanthopoulos Dimitrios , Tzara Ariadni
Published: September 2019

Morpholine is a heterocycle featured in numerous approved and experimental drugs as well as bioactive molecules. It is often employed in the field of medicinal chemistry for its advantageous physicochemical, biological, and metabolic properties, as well as its facile synthetic routes. The morpholine ring is a versatile and readily accessible synthetic building block, it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies. This versatile scaffold, appropriately substituted, possesses a wide range of biological activities. There are many examples of molecular targets of morpholine bioactive in which the significant contribution of the morpholine moiety has been demonstrated; it is an integral component of the pharmacophore for certain enzyme active‐site inhibitors whereas it bestows selective affinity for a wide range of receptors. A large body of in vivo studies has demonstrated morpholine's potential to not only increase potency but also provide compounds with desirable drug‐like properties and improved pharamacokinetics. In this review we describe the medicinal chemistry/pharmacological activity of morpholine derivatives on various therapeutically related molecular targets, attempting to highlight the importance of the morpholine ring in drug design and development as well as to justify its classification as a privileged structure.
High expression of PRKDC promotes breast cancer cell growth via p38 MAPK signaling and is associated with poor survival
Authors: Zhang Yan , Yang Wei‐kang , Wen Guo‐ming , Tang Hongping , Wu Chuan‐an , Wu Yan‐xia , Jing Zhi‐liang , Tang Min‐shan , Liu Guang‐long , Li Da‐zhou , Li Yan‐hua , Deng Yong‐Jian
Published: September 2019

Background

DNA‐Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression.

Methods

Here we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer.

Results

Our results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients’ data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF‐7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients.

Conclusion

Together, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients.
Rett and Rett‐like syndrome: Expanding the genetic spectrum to KIF1A and GRIN1 gene
Authors: Wang Jiaping , Zhang Qingping , Chen Yan , Yu Shujie , Wu Xiru , Bao Xinhua
Published: September 2019

Background

This study aimed to investigate the new genetic etiologies of Rett syndrome (RTT) or Rett‐like phenotypes.

Methods

Targeted next‐generation sequencing (NGS) was performed on 44 Chinese patients with RTT or Rett‐like phenotypes, in whom genetic analysis of MECP2, CDKL5, and FOXG1 was negative.

Results

The detection rate was 31.8% (14/44). A de novo pathogenic variant (c.275_276ins AA, p. Cys92*) of KIF1A was identified in a girl with all core features of typical RTT. A patient with atypical RTT was detected having de novo GRIN1 pathogenic variant (c.2337C > A, p. Val793Phe). Additionally, compound heterozygous pathogenic variants of PPT1 gene were detected in a girl, who initially displayed typical RTT features, but progressed into neuronal ceroid lipofuscinoses (NCL) afterwards. Pathogenic variants in KCNQ2, MEF2C, WDR45, TCF4, IQSEC2, and SDHA were also found in our cohort.

Conclusions

It is the first time that pathogenic variants of GRIN1 and KIF1A were linked to RTT and Rett‐like profiles. Our findings expanded the genetic heterogeneity of Chinese RTT or Rett‐like patients, and also suggest that some patients with genetic metabolic disease such as NCL, might displayed Rett features initially, and clinical follow‐up is essential for the diagnosis.
Current status of simulation and training models in microsurgery: A systematic review
Authors: Javid Pernia , Aydın Abdullatif , Mohanna Pari‐Naz , Dasgupta Prokar , Ahmed Kamran
Published: September 2019

With the prolific uptake of simulation‐based training courses, this systematic review aims to identify the available microsurgical simulation and training models, their status of validation, associated studies, and levels of evidence (LoE) for each training model, thereby establishing a level of recommendation (LoR). MEDLINE, Embase, and the Cochrane Library databases were searched for English language articles, describing microsurgery simulators and/or validation studies. All studies were assessed for LoE, and each model was subsequently awarded a LoR using a modified Oxford Centre for Evidence‐Based Medicine classification, adapted for education, with 1 being the highest and 4 the lowest score. A total of 86 studies were identified describing 64 models and simulators ranging from bench models, cadaveric animal tissue, cadaveric human tissue, live animal models, virtual reality simulators, and training curricula. Of these, 49 simulators had at least one validation study. Models were assessed for face (n= 42), content (n= 31), construct (n= 25), transfer (n= 10), and concurrent validity (n= 1) by these studies. The most commonly identified modality was bench models (n= 28) followed by cadaveric animal tissue (n= 24). The cryopreserved rat aorta model received the highest LoR followed by chicken wing, chicken thigh and practice cardboard models. Microsurgery simulation is a growing field and increasing numbers of models are being produced. However, there are still only a few validation studies with a high LoE. It is therefore imperative that training models and/or programs are evaluated for validity and efficacy in order to allow utilization in microsurgical skills acquisition.
Diffusion maps‐based surrogate modeling: An alternative machine learning approach
Authors: Kalogeris I. , Papadopoulos V.
Published: September 2019

In this work, an alternative machine learning methodology is proposed, which utilizes nonlinear manifold learning techniques in the frame of surrogate modeling. Under the assumption that the solutions of a parametrized physical system lie on a low‐dimensional manifold embedded in a high‐dimensional Euclidean space, the goal is to unveil the manifold's intrinsic dimensionality and use it for the construction of a surrogate model, which will be used as a cost‐efficient emulator of the high‐dimensional physical system. To this purpose, a computational framework based on the diffusion maps algorithm is put forth herein, where a set of system solutions is used to identify the geometry of a low‐dimensional space called the diffusion maps space. This space is completely described by a low‐dimensional basis, which is constructed from the eigenvectors and eigenvalues of a diffusion operator on the data. The proposed approach exploits the diffusion maps space's reduced dimensionality for the construction of locally clustered interpolation schemes between the parameter space, the diffusion maps space, and the solution space, which are cheap to evaluate and highly accurate. This way, the need to formulate and solve the governing equations of the system is eliminated. In addition, a sampling methodology is proposed based on the metric of the diffusion maps space to efficiently sample the parameter space, thus ensuring the quality of the surrogate model. Even though it is exploited herein in the premises of uncertainty quantification, this methodology is applicable to any other problem type that depends on some parametric space (ie, optimization, sensitivity analysis, etc). In the numerical examples, it is shown that the proposed surrogate model is capable of high levels of accuracy, as well as significant computational gains.
Role of municipal councillors in the implementation of social protection schemes for children—A case of Ahmedabad, India
Authors: Agarwalla Astha , Sarin Ankur , Gupta Ishu
Published: September 2019

The 74th constitutional amendment paved the path for strengthening of local governments in India, by devolution of functional and financial powers. The elected local representatives (municipal councillors), as the closest link of the Government to the citizenry, are expected to be the bearers of information regarding the needs and priorities of the people they represent. They can become the champions for effective implementation of service delivery schemes designed locally or at higher levels of governance. This study examines the designated and perceived roles of municipal councillors in the context of the implementation of social protection schemes for children in the city of Ahmedabad. Based on the information collected through personal interviews with a sample of 18 municipal councillors over 4 months, the study brings out the stark absence of designated roles for councillors and the limited perceived role in information dissemination. Councillors’ political ambition, experience, and access to the executive machinery come out to be the most critical determinants of the effectiveness of limited mediation role played by councillors to ensure faster delivery of benefits or inclusion of beneficiaries. The need for institutional strengthening and capacity building at the local level also gets substantiated by the analysis.
Multi‐Relaxation Test to Characterize PE Pipe Performance
Authors: Tan Na , Jar P‐Y Ben
Published: September 2019

A new concept is proposed, which uses results from a multi‐relaxation test to characterize transition of deformation mechanisms in polyethylene (PE) pipes, for plastic deformation from the amorphous phase only to the involvement of the crystalline phase. The former mechanism is believed to lead to brittle fracture, while the latter to ductile fracture. This phenomenon is believed to be related to the transition from ductile to brittle (DB) fracture that has been observed in creep tests of PE pipes by reducing the applied stress below a critical level. This paper presents results from 6 PE pipes of different density and molecular weight distribution. The results suggest that high‐density PE pipes require a higher deformation level for the DB transition than the medium‐density PE pipes. The results also suggest that the trend of change in the critical stress level for the DB transition is close to the trend of change in the hydrostatic design base, but the former takes less than two weeks to complete, while the latter more than 1 year. Therefore, the multi‐relaxation test can be used as an alternative method to characterize PE pipe performance, as a means for preliminary screening or in‐service monitoring of pipe performance.
Peramivir for Influenza A and B Viral Infections: A Pharmacokinetic Case Series
Authors: Cies Jeffrey J. , Moore Wayne S. , Enache Adela , Chopra Arun
Published: September 2019

Objective

To describe the peramivir (PRV) pharmacokinetics in critically ill children treated for influenza A or B viral infections.

Design

Retrospective electronic medical record review of prospectively collected data from critically ill children receiving peramivir for influenza A or B viral infections in the pediatric intensive care unit (PICU).

Setting

A 189‐bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA.

Patients

Critically ill children admitted to the PICU who were infected with influenza between January 1, 2016 and March 31, 2018.

Interventions

None.

Results

Eleven patients, two females (18%) and nine males (82%), accounted for 24 peramivir samples for therapeutic drug management. The median age was 5 years (interquartile range 1.5–6.5 yrs) with a median weight of 16.4 kg (interquartile range 14–24 kg). Ten (91%) patients demonstrated a larger volume of distribution, 11 (100%) patients demonstrated an increase in clearance, and 11 (100%) patients demonstrated a shorter half‐life estimate as compared with the package insert and previous pediatric trial data for peramivir. Eight (73%) patients tested positive for a strain of influenza A and 3 (27%) patients tested positive for influenza B; 4 of 11 (36%) patients tested positive for multiple viruses. All patients had adjustments made to their dosing interval to a more frequent interval. Ten (91%) patients were adjusted to an every‐12‐hour regimen and 1 (9%) patient was adjusted to an every‐8‐hour regimen. No adverse events were associated with peramivir treatment.

Conclusion

The pharmacokinetics of PRV demonstrated in this PICU cohort differs in comparison to healthy pediatric and adult patients, and alterations to dosing regimens may be needed in PICU patients to achieve pharmacodynamic exposures. Additional investigations in the PICU population are needed to confirm these findings.
Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations
Authors: Leader Lauren D. , O'Connell Megan , VandenBerg Amy
Published: September 2019

Our aim was to review the efficacy, safety, and pharmacology of brexanolone (Zulresso), a new antidepressant with a novel mechanism of action, in the treatment of postpartum depression (PPD). Pertinent data and information were obtained via PubMed (1993 to August 2018). Articles published in English that evaluated the safety and efficacy of brexanolone and other off‐label PPD treatments were included. Literature regarding epidemiology and pathophysiology of PPD was also selected. Brexanolone, administered as an intravenous infusion over 60 hours, produced a statistically significant and clinically meaningful reduction in Hamilton Depression Rating Scale (HAM‐D) scores compared with placebo at both 60 and 90 μg/kg/hour in patients with moderate to severe PPD. Brexanolone groups had higher response and remission rates compared with placebo. Common adverse effects were somnolence, dizziness, and headache. A small percentage (4%) of patients required cessation of therapy due to excessive sedation or loss of consciousness. Although the evidence for brexanolone as a novel treatment for PPD looks promising, a Risk Evaluation and Mitigation Strategies (REMS) program requirement and the logistics of prolonged infusions serve as barriers to treatment. A discussion of these obstacles as well as pharmacokinetics, monitoring, and dosing is provided. Brexanolone is a novel antidepressant indicated for the treatment of PPD. Clinical trials demonstrated that brexanolone significantly reduces depression scores in women with moderate to severe PPD. Due to risk of oversedation and loss of consciousness, a REMS program will be put in place to mitigate the risk of adverse events.
Al2O3 Thin Films Prepared by a Combined Thermal‐Plasma Atomic Layer Deposition Process at Low Temperature for Encapsulation Applications
Authors: Zhu Zhen , Merdes Saoussen , Ylivaara Oili M. E. , Mizohata Kenichiro , Heikkilä Mikko J. , Savin Hele
Published: September 2019

In this article, a combined H2O thermal atomic layer deposition of Al2O3 with in situ N2 plasma treatment process at 90 °C for encapsulation applications is reported. The effect of process parameters on the growth behavior and properties of Al2O3 thin films, such as elemental composition, residual stress, moisture permeation barrier ability, density, and roughness, is investigated. Optimization of plasma exposure time gives films with a low impurity (≈3.8 at% for hydrogen, ≈0.17 at% for carbon, and ≈0.51 at% for nitrogen), a high mass density (≈3.1 g cm−3), and a low tensile residual stress (≈160 MPa). A water vapor transmission rate of 2.9 × 10−3 g m−2 day−1 is obtained for polyethylene naphthalate substrates coated with 4‐nm‐thick Al2O3 films.
1,7‐Bis(4‐hydroxyphenyl)‐4‐hepten‐3‐one from Betula platyphylla induces apoptosis by suppressing autophagy flux and activating the p38 pathway in lung cancer cells
Authors: Jung Hyun Jin , Song Kyung‐Sik , Son Youn Kyoung , Seong Je Kyung , Kim Sun Yeou , Oh Seung Hyun
Published: September 2019

Betula platyphylla (BP) is frequently administered in the treatment of various human diseases, including cancers. This study was undertaken to investigate the pharmacological function of the active components in BP and the underlying mechanism of its chemotherapeutic effects in human lung cancer cells. We observed that BP extracts and 1,7‐bis(4‐hydroxyphenyl)‐4‐hepten‐3‐one (BE1), one of the components of BP, effectively decreased the cell viability of several lung cancer cell lines. BE1‐treated cells exhibited apoptosis induction and cell cycle arrest at the G2/M phase. Further examination demonstrated that BE1 treatment resulted in suppression of autophagy, as evidenced by increased protein expression levels of both LC3 II and p62/SQSTM1. Interestingly, the pharmacological induction of autophagy with rapamycin remarkably reduced the BE1‐induced apoptosis, indicating that apoptosis induced by BE1 was associated with autophagy inhibition. Our data also demonstrated that BE1 exposure activated the p38 pathway resulting in regulation of the pro‐apoptotic activity. Taken together, we believe that BE1 is a potential anticancer agent for human lung cancer, which exerts its effect by enhancing apoptosis via regulating autophagy and the p38 pathway.
A model study of the effect of clustering on the last stage of drizzle formation
Authors: Madival Deepak G.
Published: September 2019

In the final stage of growth, settling cloud drops become drizzle by collision and coalescence with the smaller droplets in their path. We study the impact of droplet clustering on the growth of settling collector drops by modelling it as an exponentially decaying correlation. Enhancement in collector drop growth is measured by the reduction in time needed for drizzle formation in the last stage. The effect of clustering is characterized by two dimensionless parameters C = δλL and K = (λ0L)−1, where δλ is the enhancement in the collision rate inside the clusters, L is the cluster size perceived by the settling collector drop and λ0 is the initial collision rate. Increasing C or K reduces the time needed for drizzle formation compared to the unclustered case. We find that for K ≥ 5, C ≤ 2 even a small increase in droplet concentration inside clusters can cause a significant enhancement in the collector drop growth. Further even for low turbulence intensities (low K) significant reduction in the time for drizzle formation is achieved for moderate values of C. These findings are relevant to the debate on the intensity of clustering needed to explain rapid drizzle formation.
Toward Arbitrary Control of Lattice Interactions in Nonequilibrium Condensates
Authors: Kalinin Kirill P. , Berloff Natalia G.
Published: September 2019

There is a growing interest in investigating new states of matter using out‐of‐equilibrium lattice spin models in two dimensions. However, a control of pairwise interactions in such systems has been elusive as due to their nonequilibrium nature they maintain nontrivial particle fluxes even at the steady state. Here it is suggested how to overcome this problem and formulate a method for engineering reconfigurable networks of nonequilibrium condensates with control of individual pairwise interactions. Representing spin by condensate phase, the effective two spin interactions are created with nonresonant pumping, are directed with dissipative channels, and are further controlled with dissipative gates. The dissipative barriers are used to block unwanted interactions between condensates. Together, spatial anisotropy of dissipation and pump profiles allow an effective control of sign and intensity of the coupling strength between any two neighbouring sites independent of the rest of the spins, which is demonstrated with a 2D square lattice of polariton condensates. Experimental realization of such fully controllable networks offers great potential for reservoir computing, modelling of the systems of coupled oscillators, simulation of the new state of matters, studying the phase transitions in large‐scale systems, and optimization.
Ten years later: The progress and future of integrating sustainable principles, practices, and metrics into remediation projects
Authors: Favara Paul , Raymond Dick , Ambrusch Matthew , Libera Arianna , Wolf Gerlinde , Simon John A. , Maco Barbara , Collins Elizabeth R. , Harclerode Melissa A. , McNally Amanda D. , Ridsdale Reanne , Smith Maile , Howard Lyndsey
Published: September 2019

In 2009, the Sustainable Remediation Forum released a white paper entitled “Integrating sustainable principles, practices, and metrics into remediation projects” (Ellis & Hadley, 2009, Remediation, 19, pp. 5–114). Sustainable remediation was a relatively new concept, and the white paper explored a range of approaches on how sustainability could be integrated into traditional remediation projects. This paper revisits the 2009 white paper, providing an overview of the early days of the evolving sustainable remediation practice and an assessment of the progress of sustainable remediation over the last 10 years with a primary focus on the United States. The current state of the sustainable remediation practice includes published literature, current practices and resources, applications, room for improvement, international progress, the virtuous cycle that applying sustainable remediation creates, and the status of the objectives cited in the 2009 white paper. Over the last decade, several sustainable remediation frontiers have emerged that will likely be a focus in advancing the practice. These frontiers include climate change and resiliency, weighting and valuation to help better consolidate different sustainable remediation metrics, programmatic implementation, and better integration of the societal impacts of sustainable remediation. Finally, as was the case for the 2009 white paper, this paper explores how sustainable remediation may evolve over the next 10 years and focuses on the events and drivers that can be significant in the pace of further development of the practice. The events and drivers include transformation impacts, societal influences, and the continued development of new technologies, approaches, and tools by remediation practitioners. The remediation industry has made significant progress in developing the practice of sustainable remediation and has implemented it successfully into hundreds of projects. While progress has been significant, an opportunity exists to implement the tenets of sustainable remediation on many more projects and explore new frontiers to help improve the communication, integration, and derived benefits from implementing sustainable remediation into future remediation projects.
Practical considerations for kriging groundwater surfaces
Authors: Uetrecht Rachel M. , Elmore Andrew C. , Guggenberger Joe D. , Helwig Zane D.
Published: September 2019

Kriging is an accepted method of characterizing the groundwater elevation surface at sites where the water level data are available but where there may be insufficient additional data necessary for groundwater flow modeling. Groundwater surface interpolation via kriging is readily performed using commercial, state of the practice software, but some practitioners may not be able to justify such efforts because the process is not validated within studies documented in the peer‐reviewed literature. This paper describes the available kriging software and literature studies and then uses a case study to compare practical groundwater surface modeling to the studies available in the scientific literature. The literature review shows that the state of the practice as represented by the commercial software approach is consistent with the literature. Specifically, cokriging with groundwater elevation as the primary variable with trend removal and ground‐surface elevation as the secondary variable is an appropriate point of departure in practice. The literature review‐based summary of variogram model parameters (model type, nugget, sill, range, and trend model) was not useful as a quality‐control step to assess the reasonableness of variogram parameters identified by the standard practice of software‐assisted iteration when applied to the case‐study data set. The literature review indicated that groundwater elevation kriging has been performed using as few as 10 data points but a comparison of the case‐study simulated groundwater elevations and groundwater gradient magnitudes and directions indicated that the 30‐well threshold more commonly found in the literature was an appropriate minimum at the study site.
Perfluoroalkyl and polyfluoroalkyl substances thermal desorption evaluation
Authors: Crownover Emily , Oberle Daniel , Kluger Mark , Heron Gorm
Published: September 2019

Per‐ and polyfluoroalkyl substances (PFAS) are highly resistant to biotic and abiotic degradation and can withstand very high temperatures before breaking down. The storage of PFAS‐impacted water and sediments in a holding pond or stockpiled investigation or remedial action‐derived waste is occurring on an increasing number of sites. The most common PFAS water treatment options include granular‐activated carbon and resins and the most common soil treatment options have been primarily limited to excavation, offsite incineration, and, in some cases, soil stabilization. An increasing number of states across the United States are establishing part per trillion PFAS guidance levels for drinking water. Removing PFAS from soils removes PFAS source impacts to groundwater. In this study, volatilization of PFAS from soil treated using in situ thermal heating is evaluated as a treatment method to achieve a high degree of PFAS removal from soils. The evaluation of temperatures needed to achieve removal is described. To minimize vapor treatment required for PFAS thermal remediation, a scrubber was incorporated into the treatment train to transfer PFAS to the liquid phase in a concentrated, low‐volume solution. Vapor‐liquid equilibrium behavior and the extent of PFAS volatilization from impacted soil over a range of temperatures were evaluated. Results showed that heating soil to 350°C and 400°C reduces PFAS soil concentrations by 99.91% and 99.998%, respectively. It was also confirmed that sulfonate‐based PFAS generally required higher temperatures for volatilization to occur than carboxylate‐based PFAS.
Static output feedback control for discrete‐time hidden Markov jump systems against deception attacks
Authors: Su Lei , Ye Dan
Published: September 2019

This paper investigates the static output feedback control problem for Markov jump systems subject to asynchronous mode information and deception attacks. A hidden Markov model is employed to observe the unmeasurable system mode. In this case, the asynchronous phenomenon between the controller and the original system is depicted. By using the mode‐dependent Lyapunov function, a sufficient condition is established such that the resulting closed‐loop system is stochastically mean square exponentially ultimately bounded under randomly occurring deception attacks and external disturbance. Based on this condition, the asynchronous static output feedback controller is designed in view of linear matrix inequalities. Finally, the effectiveness and superiority of the presented method are elaborated via a numerical example and a practical example.
SO3Cu‐Carbon: A Novel Heterogeneous Catalyst for the Synthesis of β‐Hydroxy 1,2,3‐Triazoles by One Pot Cycloaddition Reaction
Authors: Rani G. Sandhya , Vijay Manneganti , Prabhavathi Devi Bethala L. A.
Published: September 2019

A novel heterogeneous carbon‐based sulfonated copper (SO3Cu‐carbon) catalyst was developed for the first time and investigated its catalytic activity for the regioselective synthesis of β‐hydroxy 1,2,3‐triazoles by azide–alkyne cycloaddition in aqueous medium. The SO3Cu‐carbon catalyst was prepared by the modification of the glycerol‐based SO3H‐carbon catalyst on treatment with 10% aqueous CuCl2 solution under controlled conditions. Based on its physico‐chemical characteristics the structure of the catalyst is proposed as a polycyclic aromatic carbon attached with ‐SO3Cu, ‐COOCu and –OCu functionalities. The catalytic activity of the SO3Cu‐carbon catalyst was demonstrated for the one pot ‘click’ reaction of epoxide, sodium azide and terminal alkyne in water at 60 °C for the synthesis of β‐hydroxy 1,2,3‐triazoles in excellent yields (89‐94%) without any additives. The formation of the product proceeds in one pot through a mechanism that involves in situ generation of organic azide intermediate followed by rapid ring closure with alkynes. The catalyst was easily recovered by simple filtration and reused for 5 cycles without any leaching and deactivation thus exhibiting its excellent stability and reusability. Moreover, the cascade reaction was best performed in water at moderate temperature, rendering all the processes truly green.
Planar Anchoring of C70 Liquid Crystals Using a Covalent Organic Framework Template
Authors: Cui Daling , MacLeod Jennifer M. , Rosei Federico
Published: September 2019

The surface‐induced anchoring effect is a well‐developed technique to control the growth of liquid crystals (LCs). Nevertheless, a defined nanometer‐scale template has never been used to induce the anchored growth of LCs with molecular building units. Scanning tunneling microscopy results at the solid/liquid interface reveal that a 2D covalent organic framework (COF‐1) can offer an anchoring effect to template C70 molecules into forming several LC mesophases, which cannot be obtained under other conditions. Through comparison with the C60 system, a stepwise breakdown in ordering of C70 LC is observed. The process is described in terms of the effects of molecular anisotropy on the epitaxial growth of molecular crystals. The results suggest that using a surface‐confined template to anchor the initial layer of LC molecules can be a modular and potentially broadly applicable approach for organizing molecular mesogens into LCs.
Surface Plasmon Resonance–Enhanced Photoacoustic Imaging and Photothermal Therapy of Endogenous H2S‐Triggered Au@Cu2O
Authors: Tao Cheng , An Lu , Lin Jiaomin , Tian Qiwei , Yang Shiping
Published: September 2019

Smart theranostics agents triggered by endogenous H2S with combined activated photoacoustic imaging and photothermal therapy can improve the diagnosis and treatment of colon cancer. However, the low theranostic performance of the current smart theranostics agents after the triggering step has limited their further application. In this work, the theranostic performance of endogenous H2S‐triggered Au@Cu2O for the diagnosis and treatment of colon cancer, which is generated from the localized surface plasmon resonance coupling effect between a noble metal (Au) and a semiconductor (Cu2O), is investigated. Compared with Cu2O, the prepared H2S‐triggered Au@Cu2O shows a significantly stronger absorption at the near‐infrared region, such as a ≈2.1 times change at 808 nm, giving a photothermal conversion efficiency increase of ≈1.2 times. More importantly, Au@Cu2O still exhibits good photoacoustic imaging contrast and photothermal properties for treatment of colon cancer in vivo even at very low injection doses. This work not only investigates an endogenous H2S‐triggered Au@Cu2O theranostic agent with enhanced theranostic performance for colon cancer but also provides a novel strategy for designing high‐performance theranostic agents.
Defect‐Enriched Nitrogen Doped–Graphene Quantum Dots Engineered NiCo2S4 Nanoarray as High‐Efficiency Bifunctional Catalyst for Flexible Zn‐Air Battery
Authors: Liu Wenwen , Ren Bohua , Zhang Wenyao , Zhang Maiwen , Li Gaoran , Xiao Meiling , Zhu Jianbing , Yu Aiping , Ricardez‐Sandoval Luis , Chen Zhongwei
Published: September 2019

Flexible Zn‐air batteries have recently emerged as one of the key energy storage systems of wearable/portable electronic devices, drawing enormous attention due to the high theoretical energy density, flat working voltage, low cost, and excellent safety. However, the majority of the previously reported flexible Zn‐air batteries encounter problems such as sluggish oxygen reaction kinetics, inferior long‐term durability, and poor flexibility induced by the rigid nature of the air cathode, all of which severely hinder their practical applications. Herein, a defect‐enriched nitrogen doped–graphene quantum dots (N‐GQDs) engineered 3D NiCo2S4 nanoarray is developed by a facile chemical sulfuration and subsequent electrophoretic deposition process. The as‐fabricated N‐GQDs/NiCo2S4 nanoarray grown on carbon cloth as a flexible air cathode exhibits superior electrocatalytic activities toward both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), outstanding cycle stability (200 h at 20 mA cm−2), and excellent mechanical flexibility (without observable decay under various bending angles). These impressive enhancements in electrocatalytic performance are mainly attributed to bifunctional active sites within the N‐GQDs/NiCo2S4 catalyst and synergistic coupling effects between N‐GQDs and NiCo2S4. Density functional theory analysis further reveals that stronger OOH* dissociation adsorption at the interface between N‐GQDs and NiCo2S4 lowers the overpotential of both ORR and OER.
Creation of Nonspherical Microparticles through Osmosis‐Driven Arrested Coalescence of Microfluidic Emulsions
Authors: Feng Kai , Gao Ning , Zhang Wanlin , Zhou Kang , Dong Hao , Wang Peng , Tian Li , He Guokang , Li Guangtao
Published: September 2019

Droplet‐based microfluidics enable the production of emulsions and microparticles with spherical shapes, but the high‐throughput fabrication of nonspherical emulsions and microparticles still remains challenging because interfacial tension plays a dominant role during preparation. Herein, ionic liquids (ILs) containing salts, which possess sufficient osmotic pressure to realize water transport and phase separation, are introduced as inner cores of oil‐in‐oil‐in‐water double emulsions and it is shown that nonspherical emulsions can be constructed by osmosis‐driven arrested coalescence of inner cores. Subsequently, ultraviolet polymerization of the nonspherical emulsions leads to nonspherical microparticles. By tailoring the number, composition, and size of inner cores as well as coalescence time, a variety of nonspherical shapes such as dumbbell, rod, spindle, snowman, tumbler, three‐pointed star, triangle, and scalene triangle are created. Importantly, benefitting from excellent solvency of ILs, this system can serve as a general platform to produce nonspherical microparticles made from different materials. Moreover, by controlling the osmotic pressure, programmed coalescence of inner cores in double emulsions is realizable, which indicates the potential to build microreactors. Thus, a simple and high‐throughput strategy to create nonspherical microparticles with arrested coalescence shapes is developed for the first time and can be further used to construct novel materials and microreactors.
Effects of Multiple Nonnative Fish on an Imperiled Cyprinid, Hornyhead Chub
Authors: Hickerson Brian T. , Maitland Bryan M. , Walters Annika W.
Published: September 2019

Nonnative fish can have substantial negative effects on the abundance and distribution of native fishes through predation and competition. Nonnative predators are of particular interest because they represent novel threats to native prey species that are not adapted to their presence. Prey species with limited distributions or population sizes may be particularly vulnerable to the effects of nonnative predators. In the Laramie River, four nonnative predators—Brown TroutSalmo trutta, Rainbow TroutOncorhynchus mykiss, Brook TroutSalvelinus fontinalis,and Smallmouth BassMicropterus dolomieuare present along with a state‐imperiled population of Hornyhead ChubNocomis biguttatus. The abundance of Hornyhead Chub has declined with increasing abundance of nonnative predators, with the probability of occurrence of Hornyhead Chub dropping drastically when Smallmouth Bass were present. All four nonnative species preyed on native cyprinids, but Smallmouth Bass relied most heavily on fish as a prey item. Isotopic niche overlap occurred between Hornyhead Chub and all of the nonnative predator species. Our results demonstrate that nonnative predators have the potential to negatively affect the abundance and distribution of Hornyhead Chub through the mechanisms of predation and competition, and predator identity is important in determining the extent of effects. Smallmouth Bass are a greater concern than nonnative salmonids because of their more piscivorous behavior, and their recent upstream expansion may be limiting the downstream distribution of Hornyhead Chub in the Laramie River.
Survey methodology for detecting eastern massasauga rattlesnakes in southern Michigan
Authors: Shaffer Stephanie A. , Roloff Gary J. , Campa Henry
Published: September 2019

The U.S. Fish and Wildlife Service listed the eastern massasauga rattlesnake (Sistrurus catenatus catenatus) as threatened in 2016 under the 1973 Endangered Species Act. We tested a visual‐encounter survey method during 2016 to aid researchers and managers in successfully detecting massasaugas in occupied habitat in southern Michigan, USA. We conducted 54 surveys (paired, independent searchers) in 2‐ha areas occupied by telemetered massasaugas. Our detection process parameters included environmental conditions (air temperature, humidity, solar radiation, surface temperature, precipitation) and searcher characteristics (e.g., experience, time spent searching). We detected massasaugas on 11 of 54 surveys. Detection probability from the null model was 0.31; however, we found that time spent searching and minimum air temperature improved detection probability. Detection probability approached 1.00 as time searched by an individual exceeded 90 minutes and approached 0.80 on cooler mornings (12.8° C). Our findings provide survey protocol guidance to increase massasauga detections during visual encounter surveys, which offer useful information to help guide habitat management decisions. © 2019 The Wildlife Society.
Separation of variables and scalar products at any rank
Authors: Cavaglià Andrea , Gromov Nikolay , Levkovich-Maslyuk Fedor
Published: September 2019

Abstract

Separation of variables (SoV) is a special property of integrable models which ensures that the wavefunction has a very simple factorised form in a specially designed basis. Even though the factorisation of the wavefunction was recently established for higher rank models by two of the authors and G. Sizov, the measure for the scalar product was not known beyond the case of rank one symmetry. In this paper we show how this measure can be found, bypassing an explicit SoV construction. A key new observation is that the measure for spin chains in a highest-weight infinite dimensional representation of 𝔰𝔩(N) couples Q-functions at different nesting levels in a non-symmetric fashion. We also managed to express a large number of form factors as ratios of determinants in our new approach. We expect our method to be applicable in a much wider setup including the problem of computing correlators in integrable CFTs such as the fishnet theory,

$$ \mathcal{N} $$

N

= 4 SYM and the ABJM model.
Dijets at Tevatron cannot constrain SMEFT four-quark operators
Authors: Keilmann Eduard , Shepherd William
Published: September 2019

Abstract

We explore the sensitivity of Tevatron data to heavy new physics effects in differential dijet production rates using the SMEFT in light of the fact that consistent and conservative constraints from the LHC cannot cover relatively low cutoff scales in the EFT. In contrast to the results quoted by the experimental collaborations and other groups, we find that, once consistency of the perturbation expansion is enforced and reasonable estimates of theoretical errors induced by the SMEFT series in

$$ \frac{E}{\Lambda} $$

E
Λ

are included, there is no potential to constrain four-quark contact interactions using Tevatron data. This shows the general difficulty of constraining physics model-independently using fairly imprecise measurements, limited by low luminosity and/or systematic errors inherent to the precision of the detectors.
Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes
Authors: Joshi Kriti , Elso Colleen , Motazedian Ali , Labonne Tanya , Schiesser Jacqueline V. , Cameron Fergus , Mannering Stuart I. , Elefanty Andrew G. , Stanley Edouard G.
Published: September 2019

Aims/hypothesis

Type 1 diabetes is an autoimmune disorder characterised by loss of insulin-producing beta cells of the pancreas. Progress in understanding the cellular and molecular mechanisms underlying the human disease has been hampered by a dearth of appropriate human experimental models. We previously reported the characterisation of islet-infiltrating CD4+ T cells from a deceased organ donor who had type 1 diabetes.

Methods

Induced pluripotent stem cell (iPSC) lines derived from the above donor were differentiated into CD14+ macrophages and tested for their capacity to present antigen to T cell receptors (TCRs) derived from islet-infiltrating CD4+ T cells from the same donor.

Results

The iPSC macrophages displayed typical macrophage morphology, surface markers (CD14, CD86, CD16 and CD11b) and were phagocytic. In response to IFNγ treatment, iPSC macrophages upregulated expression of HLA class II, a characteristic that correlated with their capacity to present epitopes derived from proinsulin C-peptide to a T cell line expressing TCRs derived from islet-infiltrating CD4+ T cells of the original donor. T cell activation was specifically blocked by anti-HLA-DQ antibodies but not by antibodies directed against HLA-DR.

Conclusions/interpretation

This study provides a proof of principle for the use of iPSC-derived immune cells for modelling key cellular interactions in human type 1 diabetes.
Adhesive-related warping of thin wooden bi-layers
Authors: Rindler Axel , Vay Oliver , Hansmann Christian , Konnerth Johannes
Published: September 2019

Warping of layered wood-based panels is still a challenging problem in the development of thin engineered wood products. Wood as an anisotropic and hydrophilic material tends to change its volume and mechanical properties with changing moisture content. Besides the wood components, also the mechanical properties of certain adhesives are sensitive to moisture changes. A moisture load onto the adhered wood is resulting in different stress and strain states between the adherends. It is expected that adhesives with different moisture-related properties participate differently to this interaction. To observe an adhesive-related warping, thin spruce/HDF (Picea abies and high-density fibreboard) bi-layers with identical material geometries were manufactured under laboratory conditions, using different wood adhesive systems, which are currently used in furniture and flooring industry [polyurethane (PUR), emulsion polymer isocyanate (EPI), polyvinyl acetate (PVAc), urea formaldehyde (UF) and ultra-low emitting formaldehyde amino adhesive (ULEF)]. The bi-layers were exposed to certain relative humidity conditions, and the resulting deformation was measured with a high-precision laser distance detector. Moisture-dependent warping of the bi-layers was obtained in relation to the used adhesive systems. As a result of the study, it can be shown that initial warping after panel manufacturing strongly depends on the adhesive curing characteristics and, especially, on the amount of water that is released into the wood adherend. For the post-setting panel warping, a differentiation into two adhesive groups became visible: rigid and flexible adhesives. Rigid adhesives (UF and ULEF) showed a higher degree of warping compared to the group of flexible adhesives (PUR, EPI and PVAc).
A prospective phase I multicentre randomized cross-over pharmacokinetic study to determine the effect of food on abiraterone pharmacokinetics
Authors: Lubberman Floor J. E. , Benoist Guillemette E. , Gerritsen Winald , Burger David M. , Mehra Niven , Hamberg Paul , van Oort Inge , van Erp Nielka P.
Published: September 2019

Purpose

Abiraterone acetate is used at a fixed oral dose of 1000 mg once daily (OD) taken fasted. By administering abiraterone acetate with food, a reduced dose can potentially be given while maintaining equivalent abiraterone exposure. Moreover, administering abiraterone acetate with a breakfast is considered more patient friendly. The aim of this study was to establish the bio-equivalent lower dose of abiraterone when taken with a continental breakfast (CB) compared to the standard intake of 1000 mg OD fasted.

Methods

In this phase I, randomized cross-over, multi-center study, abiraterone pharmacokinetics (PK) were evaluated in patients with metastatic castration-resistant prostate cancer who were treated for 14 days with 1000 mg abiraterone acetate taken fasted, followed by 14 days of treatment with 500 mg taken with a CB.

Results

14 patients were enrolled into the study, of whom 12 were eligible for PK analysis. The geometric mean ratio (GMR) (fed/fasted) was 0.88 (90% CI 0.73–1.07) for area-under-the-curve (AUC0–24h), 1.03 (90% CI 0.79–1.34) for Cmax and 0.81 (90% CI 0.60–1.10) for Ctrough, respectively. High inter-patient variability (> 50%) was found for all PK parameters under both intake conditions. Patients seemed to be slightly more satisfied about the intake of 500 mg abiraterone acetate when taken with a CB compared to 1000 mg fasted.

Conclusion

In conclusion, a bioequivalent lower dose of abiraterone taken with food could not be established in our study. Although based on the absence of a exposure–toxicity relationship, the strict bioequivalence margins as defined by the FDA guidelines could be applied more flexible for abiraterone. Information on the effect of food on abiraterone pharmacokinetics as presented in our study can be used for patients with difficulties taken their medication fasted.