bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationally Designed Double‐Shell Dodecahedral Microreactors with Efficient Photoelectron Transfer: N‐Doped‐C‐Encapsulated Ultrafine In2O3 Nanoparticles
Authors: Sun Liming , Li Rong , Zhan Wenwen , Wang Fan , Zhuang Yuan , Wang Xiaojun , Han Xiguang
Published: December 2018

It is desirable but challenging to design efficient micro‐/nanoreactors for chemical reactions. In this study, we have fabricated mesoporous double‐shelled hollow microreactors composed of N‐doped‐C‐coated ultrafine In2O3 nanoparticles [N‐C/In2O3 HD (hollow dodecahedron)] by the thermolysis of a dodecahedral In‐based framework in Ar atmosphere. The obtained N‐C/In2O3 HD exhibited excellent activity in the photocatalytic oxidative hydroxylation of a series of arylboronic acid substrates. This property can be attributed to its enhanced optical absorption and efficient separation of photo‐generated electron–hole pairs, imparted by the unique structure and uniformly coated N‐doped C layers. Furthermore, we found O2.− to be the critical active species in the process of photocatalytic oxidative hydroxylation of arylboronic acids, and the formation mechanism of this radical is also proposed. Theoretical calculations further confirmed that the N‐doped C layer serves as an electron acceptor and revealed the microscopic charge‐carrier migration path through the In2O3/N‐doped graphite interfaces. Thus, photo‐generated electrons from hybrid states of In2O3, composed of In 5s and 2p orbitals, are transferred into the hybrid states of N‐doped graphite, composed of C 2p and N 2p orbitals. The present study may be helpful for understanding and designing carbon‐based micro‐/nanoreactors for photocatalytic reactions, and may also be useful for investigating related micro‐/nanoreactors.
A peri‐Xanthenoxanthene Centered Columnar‐Stacking Organic Semiconductor for Efficient, Photothermally Stable Perovskite Solar Cells
Authors: Xu Niansheng , Li Yang , Wu Ruihan , Zhu Rui , Zhang Jidong , Zakeeruddin Shaik M. , Li Hanying , Li Ze‐Sheng , Grätzel Michael , Wang Peng
Published: December 2018

Modulating the structure and property of hole‐transporting organic semiconductors is of paramount importance for high‐efficiency and stable perovskite solar cells (PSCs). This work reports a low‐cost peri‐xanthenoxanthene based small‐molecule P1, which is prepared at a total yield of 82 % using a three‐step synthetic route from the low‐cost starting material 2‐naphthol. P1 molecules stack in one‐dimensional columnar arrangement characteristic of strong intermolecular π–π interactions, contributing to the formation of a solution‐processed, semicrystalline thin‐film exhibiting one order of magnitude higher hole mobility than the amorphous one based on the state‐of‐the art hole‐transporter, 2,2‐7,7‐tetrakis(N,N′‐di‐paramethoxy‐phenylamine 9,9′‐spirobifluorene (spiro‐OMeTAD). PSCs employing P1 as the hole‐transporting layer attain a high efficiency of 19.8 % at the standard AM 1.5 G conditions, and good long‐term stability under continuous full sunlight exposure at 40 °C.
Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1n−3 DPA
Authors: Tungen Jørn Eivind , Gerstmann Lisa , Vik Anders , De Matteis Roberta , Colas Romain Alexandre , Dalli Jesmond , Chiang Nan , Serhan Charles Nicholas , Kalesse Markus , Hansen Trond Vidar
Published: December 2018

New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro‐resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro‐resolving mediator RvD1n−3 DPA has been achieved using the underutilized sp3–sp3 Negishi cross coupling reaction and an alkyne hydrosilylation–protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro‐resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents.
Aerobic exercise reduces triglycerides by targeting apolipoprotein C3 in patients with coronary heart disease
Authors: Wang Yating , Shen Li , Xu Danyan
Published: December 2018

Background

Aerobic exercise, which has been shown to have beneficial effects on plasma lipids, has been recommended as an effective measure to improve the prognosis of individuals with coronary heart disease (CHD). Apolipoprotein C3 (apoC3) is associated with hypertriglyceridemia and is therefore closely related to CHD.

Hypothesis

We measured apoC3 concentration change in patients with CHD before and after long‐term aerobic exercise.

Methods

Thirty‐eight patients with coronary heart disease were randomly assigned to a non‐exercise group (19 patients) or exercise group (19 patients). Both groups received essential drugs for CHD. The non‐exercise group was kept sedentary while the exercise group performed moderate‐intensive aerobic exercise for 8 weeks. Lipid levels and apoC3 levels were measured on the first day and 8 weeks later.

Results

Exercise for 8 weeks led to a significant decrease in concentration of triglyceride and apoC3 compared with the baseline. Triglyceride concentration changes were positively associated with apoC3 level changes.

Conclusions

Aerobic exercise can improve the lipid profile. It is effective in decreasing triglycerides by targeting apoC3 levels in patients with coronary heart disease.
On high‐risk, low‐grade glioma: What distinguishes high from low?
Authors: Geurts Marjolein , van den Bent Martin J.
Published: December 2018

The distinction between high‐risk and low‐risk patients with low‐grade glioma is far from clear. yet this criterion is used to select patients for immediate postsurgery radiotherapy and chemotherapy.
Osimertinib in patients with T790M mutation‐positive, advanced non–small cell lung cancer: Long‐term follow‐up from a pooled analysis of 2 phase 2 studies
Authors: Ahn Myung‐Ju , Tsai Chun‐Ming , Shepherd Frances A. , Bazhenova Lyudmila , Sequist Lecia V. , Hida Toyoaki , Yang James C. H. , Ramalingam Suresh S. , Mitsudomi Tetsuya , Jänne Pasi A. , Mann Helen , Cantarini Mireille , Goss Glenwood
Published: December 2018

Background

Osimertinib is a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR‐TKI–sensitizing and T790M (threonine‐to‐methionine substitution at codon 790)‐resistance mutations. The authors present long‐term follow‐up data from a preplanned, pooled analysis of phase 2 studies, the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial (clincialtrials.gov identifier NCT01802632) and the AURA2 trial (NCT02094261).

Methods

Patients with centrally confirmed, T790M mutation‐positive, advanced non‐small cell lung cancer received osimertinib 80 mg once daily until disease progression or study discontinuation. Response was assessed by a blinded, independent, central review using Response Evaluation Criteria in Solid Tumors, version 1.1. The primary endpoint was the objective response rate.

Results

In total, 411 patients received osimertinib (second line, 129 patients; third line or later, 282 patients). At the data cutoff date of November 1, 2016, the median treatment exposure was 16.4 months (range, 0‐29.7 months), the objective response rate was 66% (95% confidence interval [CI], 61%‐70%), the median response duration was 12.3 months (95% CI, 11.1‐13.8 months), and the median progression‐free survival was 9.9 months (95% CI, 9.5‐12.3 months). At the data cutoff date of May 1, 2018, 271 patients (66%) had died, and 140 patients (34%) had discontinued before death. The median overall survival was 26.8 months (95% CI, 24.0‐29.1 months); and the 12‐month, 24‐month, and 36‐month survival rates were 80%, 55%, and 37%, respectively. Grade ≥3 possibly causally related (investigator assessed) adverse events were reported in 65 patients (16%), and the most common were rash (grouped terms; 42%; grade ≥3, 1%) and diarrhea (39%; <1%).

Conclusions

This pooled analysis represents the most mature clinical trial data for osimertinib in patients with pretreated, T790M‐positive, advanced non‐small cell lung cancer, further establishing osimertinib as a standard of care for this patient population.
Post‐Imprinting‐Modified Molecularly Imprinted Nanocavities with Two Synergetic, Orthogonal, Glycoprotein‐Binding Sites to Transduce Binding Events into Fluorescence Changes
Authors: Morishige Takahiro , Takano Eri , Sunayama Hirobumi , Kitayama Yukiya , Takeuchi Toshifumi
Published: December 2018

We developed sensitive and selective polymeric nanocavities for glycoprotein detection using a novel molecular imprinting technique involving post‐imprinting modification (PIM). It allowed the introduction of two different interaction sites and a fluorescent reporter within each nanocavity. The hepatocellular carcinoma biomarker α‐fetoprotein (AFP) was used as a model glycoprotein. For PIM‐based molecular imprinting, AFP conjugated with polymerizable groups by disulfide bonding was prepared and immobilized on a 4‐carboxy‐3‐fluorophenylboronic acid‐immobilized substrate by cyclic diester formation between AFP glycans in an oriented immobilization manner, facilitating the creation of homogeneous AFP‐imprinted nanocavities. Surface‐initiated controlled/living radical polymerization was performed with a functional monomer, co‐monomer, and crosslinker. The disulfide bonds and cyclic diesters were cleaved to create AFP‐imprinted nanocavities, generating free thiol groups present inside the nanocavities only. A thiol‐reactive fluorescent dye was added to the nanocavities by in‐cavity PIM, yielding signaling AFP‐imprinted nanocavities capable of transducing AFP‐binding events into fluorescence changes. Reference proteins showed little response, while the limit of detection of AFP was 0.27 ng/mL (ca. 3.9 pM) in diluted human serum. Thus, the proposed in‐cavity PIM‐based molecular imprinting technique is effective for ELISA‐relevant, antibody‐free sensing systems for glycoproteins.
ADD: Accelerator Design and Deploy ‐ A tool for FPGA high‐performance dataflow computing
Authors: C. Penha Jeronimo , B. Silva Lucas , M. Silva Jansen , Coelho Kristtopher K. , P. Baranda Hector , M. Nacif José Augusto , S. Ferreira Ricardo
Published: December 2018

Dataflow‐based FPGA accelerators have become a promising alternative to deliver energy‐efficient high‐performance computing. However, FPGA programming is still a challenge. This paper presents Accelerator Design and Deploy (ADD), a high‐level framework to specify, to simulate, and to implement dataflow accelerators for streaming applications. The framework includes an open dataflow operator library, and templates are provided to easily design new operators. The framework also provides a high‐level and an accurate simulation at circuit level with short execution times. Moreover, ADD provides software and hardware APIs to simplify the integration process, extending the benefits of portability from low‐cost FPGA boards to high performance datacenter FPGA platforms. Our framework supports coupling with high‐level programming languages, and it has been validated on two FPGA platforms: the Intel high‐performance CPU‐FPGA heterogeneous computing platform and an educational FPGA kit. We show that our simple approach presents competitive performance, both in time and energy, when compared to multi‐core and GPU accelerators.
Effect of CYP4F2,VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single‐Patient Data Meta‐Analysis in More Than 15,000 Individuals
Authors: Danese Elisa , Raimondi Sara , Montagnana Martina , Tagetti Angela , Langaee Taimour , Borgiani Paola , Ciccacci Cinzia , Carcas Antonio J. , Borobia Alberto M. , Tong Hoi Y. , Dávila‐Fajardo Cristina , Rodrigues Botton Mariana , Bourgeois Stephane , Deloukas Panos , Caldwell Michael D. , Burmester Jim K. , Berg Richard L. , Cavallari Larisa H. , Drozda Katarzyna , Huang Min , Zhao Li‐Zi , Cen Han‐Jing , Gonzalez‐Conejero Rocio , Roldan Vanessa , Nakamura Yusuke , Mushiroda Taisei , Gong Inna Y. , Kim Richard B. , Hirai Keita , Itoh Kunihiko , Isaza Carlos , Beltrán Leonardo , Jiménez‐Varo Enrique , Cañadas‐Garre Marisa , Giontella Alice , Kringen Marianne K. , Haug Kari Bente Foss , Gwak Hye Sun , Lee Kyung Eun , Minuz Pietro , Lee Ming Ta Michael , Lubitz Steven A. , Scott Stuart , Mazzaccara Cristina , Sacchetti Lucia , Genç Ece , Özer Mahmut , Pathare Anil , Krishnamoorthy Rajagopal , Paldi Andras , Siguret Virginie , Loriot Marie‐Anne , Kutala Vijay Kumar , Suarez‐Kurtz Guilherme , Perini Jamila , Denny Josh C. , Ramirez Andrea H. , Mittal Balraj , Rathore Saurabh Singh , Sagreiya Hersh , Altman Russ , Shahin Mohamed Hossam A. , Khalifa Sherief I. , Limdi Nita A. , Rivers Charles , Shendre Aditi , Dillon Chrisly , Suriapranata Ivet M. , Zhou Hong‐Hao , Tan Sheng‐Lan , Tatarunas Vacis , Lesauskaite Vaiva , Zhang Yumao , Maitland‐van der Zee Anke H. , Verhoef Talitha I. , de Boer Anthonius , Taljaard Monica , Zambon Carlo Federico , Pengo Vittorio , Zhang Jieying Eunice , Pirmohamed Munir , Johnson Julie A. , Fava Cristiano
Published: December 2018

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta‐analysis at the individual patients level to capture the possible effect of ethnicity, gene—gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta‐analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients’ data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7–10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived.
Lewis Acid Modulation of meso‐Pyridyl BODIPY Chromophores
Authors: Sun Choung Ku , Teets Thomas S.
Published: December 2018

Two pyridyl‐substituted boron dipyrromethene (BODIPY) compounds are shown to interact with the strong Lewis acid B(C6F5)3. The borane adducts are characterized by multinuclear NMR and in one case by X‐ray crystallography. The titration of pyridyl‐substituted BODIPYs with B(C6F5)3 results in a bathochromic shift of the UV/Vis absorption and emission spectra, with the magnitude of the shift depending on the distance of the bound borane from the BODIPY core. In meso‐4‐pyridyl‐BODIPY, binding of B(C6F5)3 induces a small circa 230 cm−1 red shift in the UV/Vis absorption maximum, with a much larger 1950 cm−1 shift in the photoluminescence maximum. In meso‐4‐pyridylphenyl‐BODIPY, where the pyridine Lewis base is separated from the BODIPY core by a phenyl spacer, smaller shifts of circa 120 cm−1 in UV/Vis absorption and 330 cm−1 in photoluminescence are observed. This work shows that these organic chromophores can interact with Lewis acids as a means of systematically perturbing the electronic structure and excited‐state properties.
Restorative practices in residence halls at Victoria University of Wellington, New Zealand
Authors: Pointer Lindsey
Published: December 2018

This article charts Victoria University of Wellington's progress in implementing restorative practices, including restorative justice as a response to conflicts and rule violations, and proactive measures, including circles as a way to build a positive culture rooted in restorative principles. Survey results indicate positive outcomes including better communication, increased accountability, and a greater emphasis on relationships. Areas for further growth are also identified, including the need for a wider spread understanding of restorative approaches among staff, faculty, and students, the importance of full‐university implementation, and the need for learners to experience a restorative process to understand the impact.
DMSO‐Triggered Complete Oxygen Transfer Leading to Accelerated Aqueous Hydrolysis of Organohalides under Mild Conditions
Authors: Liu Haicheng , Liu Jianping , Cheng Xiaokai , Jia Xiaojuan , Yu Lei , Xu Qing
Published: December 2018

Addition of DMSO is found to greatly accelerate the aqueous hydrolysis of organohalides to alcohols, providing a neutral, more efficient, milder and more economic process. Mechanistic studies using 18O‐DMSO and 18O‐H2O showed that, contrary to the opinion that DMSO works as a dipolar solvent to enhance water's nucleophilicity, the accelerating effect comes from a complete oxygen transfer from DMSO to organohalides through generation of ROS+Me2⋅X− salts through C−O bond formation, followed by O−S bond disassociative hydrolysis of ROS+Me2⋅X− with water. This method is applicable to a wide range of organohalides and thus may have potential for practical industrial application, owing to easy recovery of DMSO from the H2O/DMSO mixture by regular vacuum rectification.
Direct Conversion of Activated 5‐Hydroxymethylfurfural into δ‐Lactone‐Fused Cyclopentenones
Authors: Gomes Rafael F. A. , Coelho Jaime A. S. , Afonso Carlos A. M.
Published: December 2018

Valorization of biomass derived feedstock (e.g., 5‐hydroxymethylfurfural platform) is a very active field of chemical research. In this study, 5‐hydroxymethylfurfural is converted into cyclopenten‐2‐ones by virtue of furfural's activation and Meldrum's acid's tendency to undergo decomposition/esterification. Experimental and computational studies suggest a domino rearrangement–lactonization reaction involving BINOL‐catalyzed lactonization as the rate‐determining step. The novel lactone‐fused cyclopenten‐2‐ones, which bear a quaternary carbon and resemble a didemnenone natural product structure, are converted into several derivatives with potential interest for the fields of synthetic and medicinal chemistry.
Spontaneous mutations conferring antibiotic resistance to antitubercular drugs at a range of concentrations in Mycobacterium smegmatis
Authors: Nyinoh Iveren Winifred
Published: December 2018

Mycobacteria populations can undergo mutations in their DNA sequence during replication, which if not repaired would be transferred to future generations. Earlier studies have tackled the estimation of mutation rate in mycobacteria at fixed concentrations. However, in this study, in vitro spontaneous mutations in Mycobacterium smegmatis (Msm) mc2155 (Msm) that confers resistance to some of the most important antitubercular drugs; isoniazid (INHr), rifampicin (RIFr), kanamycin (KANr) and streptomycin (STRr) were first determined at several highly lethal concentrations, a few of which have not been previously investigated, in a fluctuation assay. Thereafter, mutation rate was estimated using the most commonly adopted Po method, and estimates were then compared concurrently with the Lea‐Coulson method of the median and Ma‐Sandri‐Sarkar Maximum Likelihood Estimator method available on the Fluctuation AnaLysis CalculatOR (FALCOR). The mutation rates of RIFr ranged from 9.24 × 10−8 to 2.18 × 10−10, INHr 1.2 × 10−7‑1.20 × 10−9, STRr 2.77 × 10−8‑5.31 × 10−8 and KANr 1.7 × 10−8 mutations per cell division. Data obtained in this study provide mutation rate estimates to key antitubercular drugs at a range of concentrations while also validating a number of the frequent approaches for estimating mutation rates.
Evaluation of selected commercial pharmacotherapeutic drugs as potential pancreatic lipase inhibitors and antiproliferative compounds
Authors: Mamdooh Noor , Kasabri Violet , Al‐Hiari Yusuf , Almasri Ihab , Al‐Alawi Sundus , Bustanji Yasser
Published: December 2018

In this study, 15 commercial acidic drugs have been evaluated for pancreatic lipase (PL) inhibitory activity using an in vitro spectrophotometric method. The acidity was the basis of selection, since most PL inhibitors exhibit acidic groups and high lipophilicity. Orlistat was the robust reference agent for potency and efficacy determinations. In comparison to the cisplatin, the evaluation of the antineoplastic activities of selected drugs in a panel of colorectal cancer cell lines (HT‐29, HCT‐116, SW620, CACO‐2, and SW480) and normal periodontal ligament fibroblasts for safety examination was performed by using a sulforhodamine procuring ascorbic acid as a reference in diphenyl‐2‐picryl‐hydrazyl assay of radical scavenging properties was performed. This research revealed three highly acidic pharmacological classes with reasonable PL inhibitory activity in comparison to orlistat out of 15 selected drugs, namely sulfonylureas, fluoroquinolones, and proton pump inhibitors. Docking studies supported the hypothesis of a selection based on acidity, since it showed that the sulfonamide acid group (glyburide) is a remarkably potent interacting group with the enzyme. Failing to fulfill other structure‐activity relationship requirements (lipophilicity) led to weak activity. Since the drugs are of different chemical classes with unknown mechanisms, they showed diverse antiproliferative activity. Some drugs such as atorvastatin and gemifloxacin showed higher antiproliferative activity than cisplatin with high‐safety profiles against SW620 and SW480 cell lines, respectively, whereas lansoprazole and clopidogrel revealed comparable activity to cisplatin against HCT‐116 and SW480, respectively. Unfortunately, selected tested drugs exhibited negligible radical scavenging activity versus ascorbic acid.

Hit, Lead & Candidate Discovery
Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model
Authors: Xiao Hongtao , Shi Tingting , Han Lizhu , Tong Rongsheng , Liao Zhi
Published: December 2018

Primary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Different doses of PHC were administrated intraperitoneally following estradiol benzoate administration. Writhing scores were assessed, and pathological changes of the uterus were observed via hematoxylin and eosin staining. Western blot and real‐time PCR were used to evaluate the expression level of the M3 receptor, both TLR3 and TLR4 in uterine tissue, and the level of Ca2+ was measured in uterine tissues. Writhing scores significantly decreased in the PHC treatment group compared to model, and PHC alleviated the occurrence of edema or necrosis in the uteri compared to model group. PHC can decrease the M3 receptor, TLR3, TLR4 expression, and the Ca2+ level compared to the model group. PHC is a potential candidate for the future treatment of primary dysmenorrhea due to its ability to attenuate muscarinic receptors and TLRs.

Preclinical Research & Development
Motivational interviewing to improve adherence behaviours for the prevention of diabetic foot ulceration
Authors: Binning Jodi , Woodburn Jim , Bus Sicco A. , Barn Ruth
Published: December 2018

Diabetic foot ulceration is a major complication associated with high morbidity. Little evidence exists on which interventions are effective at preventing ulceration. Participants who are adherent to self‐care behaviours have significantly better outcomes. Motivational interviewing is an intervention that has been used successfully for conditions where adherence is important, such as reduction of obesity and HbA1c levels. A systematic review was conducted to determine whether motivational interviewing is effective at improving adherence for the prevention of Diabetic Foot Ulceration. Electronic searches were run without date or language restrictions in MEDLINE (viaEBSCOhost), CINAHL (viaEBSCOhost), ProQuest (Health and Medical Collection, Nursing and Allied Health Database, PsycINFO, Psychology, PsychArticles), AMED, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, and Web of Science Core Collections. Papers were included if participants had or were at risk of diabetic foot ulceration. Studies required motivational interviewing or a motivational approach as the sole intervention or as a component. Randomised controlled trials and quasi‐experimental studies were included if ulceration and/or at least one behavioural outcome was measured before and after the intervention. Five studies met the inclusion criteria. Heterogeneity prevented the pooling of data. One study used motivational interviewing as the sole intervention. This study found a short‐term positive effect on footwear adherence. The remaining four studies had a motivational component within their interventions. Two of these studies showed the intervention to be effective but both were at a high risk of bias. This review demonstrates an evidence gap. More research is needed.
Can drones count gulls? Minimal disturbance and semiautomated image processing with an unmanned aerial vehicle for colony‐nesting seabirds
Authors: Rush Graham P. , Clarke Lucy E. , Stone Meg , Wood Matt J.
Published: December 2018

Accurate counts of wild populations are essential to monitor change through time, but some techniques demand specialist surveyors and may result in unacceptable disturbance or inaccurate counts. Recent technological developments in unmanned aerial vehicles (UAVs) offer great potential for a range of survey and monitoring approaches. They literally offer a bird's‐eye view, but this increased power of observation presents the challenge of translating large amounts of imagery into accurate survey data. Seabirds, in particular, present the particular challenges of nesting in large, often inaccessible colonies that are difficult to view for ground observers, which are commonly susceptible to disturbance. We develop a protocol for carrying out UAV surveys of a breeding seabird colony (Lesser Black‐backed Gulls, Larus fuscus) and subsequent image processing to provide a semiautomated classification for counting the number of birds. Behavioral analysis of the gull colonies demonstrated that minimal disturbance occurred during UAV survey flights at an altitude of 15 m above ground level, which provided high‐resolution imagery for analysis. A protocol of best practice was developed using the expertise from both a UAV perspective and that of a dedicated observer. A GIS‐based semiautomated classification process successfully counted the gulls, with a mean agreement of 98% and a correlation of 99% with manual counts of imagery. We also propose a method to differentiate between the different gull species captured by our survey. Our UAV survey and analysis approach provide accurate counts (when comparing manual vs. semi‐automated counts taken from the UAV imagery) of a wild seabird population with minimal disturbance, with the potential to expand this to include species differentiation. The continued development of analytical and survey tools whilst minimizing the disturbance to wild populations is both key to unlocking the future of the rapid advances in UAV technology for ecological survey.
Rhodium(III)‐Catalyzed C–H Alkylation/Nucleophilic Addition Domino Reaction
Authors: Tang Mengyao , Li Yunpeng , Han Shengnan , Liu Lei , Ackermann Lutz , Li Jie
Published: December 2018

A C–H alkylation/nucleophilic addition manifold with synthetically useful aryl oximes and pyrazoles was realized by rhodium(III) catalysis under remarkably mild reaction conditions. Valuable β‐acyl substituted arylbutanoates were obtained in moderate to good yields. This strategy is characterized by excellent atom‐ and step‐economy, high chemo‐ and site‐selectivity, a broad substrate scope, and a wide functional group tolerance.
Numerical investigation of the current transition regimes in nanochannels
Authors: Villegas Arturo , Berardi David , Javier Diez Francisco
Published: December 2018

The concentration polarization phenomena and its effects represent one of the main challenges for the optimal operation of many nanofluidic systems. A numerical investigation of the different electric current transition regimes observed during the concentration polarization phenomena in nanochannels is performed. This included a 2D‐axisymmetric simulation of the nanofluidic system (reservoir‐nanochannel‐reservoir). From these simulations, a novel mechanism is discovered that explains that different current transition regimes. This driving mechanism involves the applied electric field penetration while the convective flow mechanism is found to be negligible. This differs with the classical statement that the mixing process with less depleted areas initiated by an electrokinetic vortex instability starts the overlimiting regime. Additionally, the numerical approach allows us to identify new characteristics of the linear‐limiting transition such as source‐like and saddle‐like points of the electric field streamlines. The three voltage–current regimes (linear, limiting and overlimiting) are explained by observing and quantifying changes in electric field, potential, ion concentration and ion concentration gradients within the system.
Electric field assisted multicomponent reaction in a microfluidic reactor for superior conversion and yield
Authors: Maity Surjendu , Chaudhuri Joydip , Mitra Shirsendu , Rarotra Saptak , Bandyopadhyay Dipankar
Published: December 2018

We explore the improvements in yield and conversion of a chemical reaction inside a two‐phase microfluidic reactor when subjected to an externally applied alternating current (AC) electric field. A computational fluid dynamic (CFD) framework has been developed to incorporate the descriptions of the two‐phase flow, multicomponent transport and reaction, and the Maxwell's stresses generated at oil‐water interface owing to the presence of the externally applied electric field. The CFD model ensures that the reactants are flown into a microchannel together with the oil and water phases before the reaction takes place at the interface and products diffuse back to the bulk phases. The study unveils that the variation in the intensity of the AC field helps in converting a two‐phase stratified flow into an oil‐in‐water microemulsion composed of oil slugs, plugs, or droplets. Importantly, the results also suggest that harnessing the vortices inside or outside these flow patterns helps in the improvement in mass transfer across the interface, which can be employed to improve the yield and conversion of a reaction. We have shown an example case of a pseudo‐first order reaction for which the variation in frequency and intensity of AC field is found to form higher surface‐to‐volume‐ratio flow patterns having a higher throughput. The convective recirculation in and around these miniaturized flow morphologies increase the rate of mass transfer, mixing of reactant and products, conversion of reactant, and yield of products. The results reported can be of significance in the design and development of future advanced‐flow rector technologies.
Short‐term forecasts of economic activity: Are fortnightly factors useful?
Authors: Monteforte Libero , Raponi Valentina
Published: December 2018

A short‐term mixed‐frequency model is proposed to estimate and forecast Italian economic activity fortnightly. We introduce a dynamic one‐factor model with three frequencies (quarterly, monthly, and fortnightly) by selecting indicators that show significant coincident and leading properties and are representative of both demand and supply. We conduct an out‐of‐sample forecasting exercise and compare the prediction errors of our model with those of alternative models that do not include fortnightly indicators. We find that high‐frequency indicators significantly improve the real‐time forecasts of Italian gross domestic product (GDP); this result suggests that models exploiting the information available at different lags and frequencies provide forecasting gains beyond those based on monthly variables alone. Moreover, the model provides a new fortnightly indicator of GDP, consistent with the official quarterly series.
Predictive likelihood for coherent forecasting of count time series
Authors: Mukhopadhyay Siuli , Sathish Vurukonda
Published: December 2018

A new forecasting method based on the concept of the profile predictive likelihood function is proposed for discrete‐valued processes. In particular, generalized autoregressive moving average (GARMA) models for Poisson distributed data are explored in detail. Highest density regions are used to construct forecasting regions. The proposed forecast estimates and regions are coherent. Large‐sample results are derived for the forecasting distribution. Numerical studies using simulations and two real data sets are used to establish the performance of the proposed forecasting method. Robustness of the proposed method to possible misspecifications in the model is also studied.
Quantitation of 2‐acetyl‐1‐pyrroline in aseptic‐packaged cooked fragrant rice by HS‐SPME/GC‐MS
Authors: Lee Young‐Sang , Oh Yejin , Kim Tae‐Hyung , Cho Yoo‐Hyun
Published: December 2018

Aseptic‐packaged cooked rice (APCR) is a rice‐based food product with a rapidly increasing market size, and APCR made of fragrant rice (FR) has recently appeared on the market. The fragrance of FR is produced by a combination of odoriferous compounds, among which 2‐acetyl‐1‐pyrroline (2AP) has been identified as the most important contributor to overall aroma. This study describes the development of a method to quantify 2AP in FR‐based APCR using headspace solid‐phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC‐MS). The recovery of 2AP spiked into APCR was lower than 10%, which suggests significant matrix effects and inappropriateness of external standard‐based calibration. For standard addition calibration method, up to 1,000 ng of 2AP were spiked into APCR containing 0% to 100% FR. Subsequent regression analyses of recovered peak area (Y) as a function of the amount of 2AP spiked (X) yielded highly linear calibration curves (R2 > 0.9917) with consistent slopes (RSD = 2.7%), regardless of FR composition. Y‐intercepts, however, which represent the amount of 2AP in APCR without spiking, increased linearly (R2 = 0.9898) in proportion to the composition of FR in the APCR. The amount of 2AP in APCR, determined by extrapolating the standard addition calibration curves, also increased linearly (R2 = 0.9963) as a function of FR composition. Practicality of developed method was tested by monitoring 2AP contents in APCR under realistic storage conditions, which successfully demonstrated 38% and 60% 2AP reductions in APCR of 20% FR after 1 and 2 months of storage at 25°C, respectively. The present study demonstrates that a standard addition method, whereby up to 1,000 ng of 2AP standard is spiked into 4 g of APCR containing 5%–100% FR in a 20‐mL headspace vial followed by SPME/GC‐MS, may serve as an effective means of quantitating 2AP in fragrant rice‐based APCR.
Cuprizone‐induced graded oligodendrocyte vulnerability is regulated by the transcription factor DNA damage‐inducible transcript 3
Authors: Fischbach Felix , Nedelcu Julia , Leopold Patrizia , Zhan Jiangshan , Clarner Tim , Nellessen Lara , Beißel Christian , van Heuvel Yasemin , Goswami Anand , Weis Joachim , Denecke Bernd , Schmitz Christoph , Hochstrasser Tanja , Nyamoya Stella , Victor Marion , Beyer Cordian , Kipp Markus
Published: December 2018

Oligodendrocytes are integral to efficient neuronal signaling. Loss of myelinating oligodendrocytes is a central feature of many neurological diseases, including multiple sclerosis (MS). The results of neuropathological studies suggest that oligodendrocytes react with differing sensitivity to toxic insults, with some cells dying early during lesion development and some cells being resistant for weeks. This proposed graded vulnerability has never been demonstrated but provides an attractive window for therapeutic interventions. Furthermore, the biochemical pathways associated with graded oligodendrocyte vulnerability have not been well explored. We used immunohistochemistry and serial block‐face scanning electron microscopy (3D‐SEM) to show that cuprizone‐induced metabolic stress results in an “out of phase” degeneration of oligodendrocytes. Although expression induction of stress response transcription factors in oligodendrocytes occurs within days, subsequent oligodendrocyte apoptosis continues for weeks. In line with the idea of an out of phase degeneration of oligodendrocytes, detailed ultrastructural reconstructions of the axon–myelin unit demonstrate demyelination of single internodes. In parallel, genome wide array analyses revealed an active unfolded protein response early after initiation of the cuprizone intoxication. In addition to the cytoprotective pathways, the pro‐apoptotic transcription factor DNA damage‐inducible transcript 3 (DDIT3) was induced early in oligodendrocytes. In advanced lesions, DDIT3 was as well expressed by activated astrocytes. Toxin‐induced oligodendrocyte apoptosis, demyelination, microgliosis, astrocytosis, and acute axonal damage were less intense in the Ddit3‐null mutants. This study identifies DDIT3 as an important regulator of graded oligodendrocyte vulnerability in a MS animal model. Interference with this stress cascade might offer a promising therapeutic approach for demyelinating disorders.
Dehydrogenative Sn–E (E = S, Se) bond formation catalyzed by an iron complex
Authors: Itazaki Masumi , Ogawa Yudai , Nakamura Wataru , Nakazawa Hiroshi
Published: December 2018

Iron complex‐catalyzed dehydrogenative Sn–E (E = S, Se) bond formation of hydrostannane with thiol and selenol was achieved. All new compounds were fully characterized using 1H, 13C{1H}, 77Se{1H}, and 119Sn{1H} NMR measurements and elemental analyses. The structure of 1,1′‐(1,3‐dithia‐2,2‐dibutylstanyl)‐[3]ferrocenophane was confirmed by single‐crystal X‐ray diffraction.
miR‐4324‐RACGAP1‐STAT3‐ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer
Authors: Ge Qiangqiang , Lu Mengxin , Ju Lingao , Qian Kaiyu , Wang Gang , Wu Chin‐Lee , Liu Xuefeng , Xiao Yu , Wang Xinghuan
Published: December 2018

Considering the importance of microRNAs (miRNAs) in regulating cellular processes, we performed microarray analysis and revealed miR‐4324 as one of the most differentially expressed miRNAs in bladder cancer (BCa). Then, we discovered that miR‐4324 was a negative regulator of Rac GTPase activating protein 1 (RACGAP1) and that RACGAP1 functioned as an oncogenic protein in BCa. Our studies indicated that ectopic overexpression of miR‐4324 in BCa cells significantly suppressed cell proliferation and metastasis and enhanced chemotherapy sensitivity to doxorubicin by repressing RACGAP1 expression. Further studies showed that estrogen receptor 1 (ESR1) increased the expression of miR‐4324 by binding to its promoter, while the downregulation of ESR1 in BCa was caused by hypermethylation of its promoter. p‐STAT3 induced the enrichment of DNMT3B by binding to the ESR1 promoter and then induced methylation of the ESR1 promoter. In turn, RACGAP1 induced STAT3 phosphorylation, increasing p‐STAT3 expression and promoting its translocation to the nucleus. Therefore, the miR‐4324‐RACGAP1‐STAT3‐ESR1 feedback loop could be a critical regulator of BCa progression.
Photochemical Reactions in Supramolecular Assemblies of Gels: Dimerizations and Polymerizations via Pericyclic Reactions
Authors: Dey Avishek , Biradha Kumar
Published: December 2018

Gel state reactions offer new direction for the reactivity of the organic molecules or metal‐organic materials upon photoirradiation with shorter reaction times and high yields compared to solid and solution states. The restricted molecular movement among the molecules in the soft solids control the stereoselectivity of the photoproducts in the gel state reactions. To date, most of the strategies based on self‐assembly have been demonstrated in the solid state, in particular for [2+2] reactions of olefins and polymerization reactions of diacetylenes via 1,4 addition. The soft materials are of emerging materials in recent days given their many applicative day‐to‐day aspects. This review gives a glimpse of recent reports on pericyclic reactions in the gel state that are designed based on the self‐assembly concept. Also it highlights how such reactions accompany the physical changes in the structure of the gels and stereo controlled products with high yields.
Patterns of marijuana use and physical health indicators among Canadian youth
Authors: Ames Megan E. , Leadbeater Bonnie J. , Merrin Gabriel J. , Thompson Kara
Published: December 2018

We examine how trajectories of marijuana use in Canadian youth (ages 15 to 28) are related to physical health indicators in adolescence and young adulthood. Youth were initially recruited in 2003 (N = 662; 48% male; ages 12 to 18) and followed for six waves. Five trajectories of marijuana use (Abstainers‐29%, Occasional users‐27%, Decreasers‐14%, Increasers‐20% and Chronic users‐11%) were identified. Chronic users reported more physical symptoms, poorer physical self‐concept, less physical activity, poorer eating practices, less sleep, and higher number of sexual partners during adolescence than other classes. Decreasers also reported poorer physical self‐concept and poorer eating practices than abstainers. Other trajectory classes showed few significant health problems. Chronic users also reported more acute health problems (i.e. serious injuries, early sexual debut, higher number of sexual partners, greater likelihood of having a STI) in young adulthood than all other classes contributing to costs of healthcare. Youth who engage in early, frequent and continued use of marijuana from adolescence to young adulthood are at‐risk of physical health problems in adolescence and young adulthood.
DNA damage in BV‐2 cells: An important supplement to the neurotoxicity of CdTe quantum dots
Authors: He Keyu , Liang Xue , Wei Tingting , Liu Na , Wang Yan , Zou Linyue , Lu Jie , Yao Ying , Kong Lu , Zhang Ting , Xue Yuying , Wu Tianshu , Tang Meng
Published: December 2018

Microglial cells are resident immune cells in the central nervous system. Activation of microglia as induced by CdTe quantum dots (QDs) can trigger damage to neurons. To quantify the intracellular QDs, we monitored the intracellular Cd concentration in the QD‐exposed mouse microglial cells (BV‐2 cell line). The extent of cell injury at different times correlated with the Cd concentration in cells at that time. In addition to Cd ion detection, we also monitored the intracellular fluorescence of the QDs. More QDs accumulated in the nucleus than in the cytoplasm. Comet assays confirmed that QDs induce DNA damage. However, DNA cannot interact with QDs, so the DNA damage was not caused by CdTe QDs adducts to DNA but by the increase of the Cd ion concentration and the secondary oxidative damage. In addition to DNA damage, biofilm injury and endogenous reduced glutathione depletion were also apparent in QD‐exposed BV‐2 cells. These changes can be prevented or even reversed by exogenous reduced glutathione administration.
Photoacoustic and fluorescent effects in multilayer plasmon‐dye interfaces
Authors: Novoselova Marina V. , Bratashov Daniil N. , Sarimollaoglu Mustafa , Nedosekin Dmitry A. , Harrington Walter , Watts Alex , Han Mikyung , Khlebtsov Boris N. , Galanzha Ekaterina I. , Gorin Dmitry A. , Zharov Vladimir P.
Published: December 2018

Progress in understanding the cell biology and diseases depends on advanced imaging and labeling techniques. Here, we address this demand by exploring novel multilayered nanocomposites (MNCs) with plasmonic nanoparticles and absorbing dyes in thin nonabsorbing shells as supercontrast multimodal photoacoustic (PA) and fluorescent agents in the near‐infrared range. The proof of concept was performed with gold nanorods (GNRs) and indocyanine green (ICG) dispersed in a matrix of biodegradable polymers. We demonstrated synergetic PA effects in MNCs with the gold‐ICG interface that could not be achieved with ICG and GNRs alone. We also observed ultrasharp PA and emission peaks that could be associated with nonlinear PA and spaser effects, respectively. Low‐toxicity multimodal MNCs with unique plasmonic, thermal and acoustic properties have the potential to make a breakthrough in PA flow cytometry and near‐infrared spasers in vivo by using the synergetic interaction of plasmonic modes with a nearby absorbing medium.
Overexpression of KCNJ4 correlates with cancer progression and unfavorable prognosis in lung adenocarcinoma
Authors: Wu Xiao‐Yan , Yu Xue‐Yan
Published: December 2018

KCNJ4 (potassium voltage‐gated channel subfamily J member 4) belongs to the inward rectifier potassium channel family, which is inhibited by novel anticancer agents. However, the biologic significance of KCNJ4 in lung adenocarcinoma (LADC) is largely unknown. Therefore, in this study, we evaluated the expression, clinical correlation, and prognostic value of KCNJ4 in LADC and normal lung tissues according to data from The Cancer Genome Atlas datasets. A small interfering RNA (siRNA)‐mediated technology was used to inhibit the expression level of KCNJ4. Cell counting kit‐8 and plate colony formation assays were used to measure cell proliferation. Wound‐healing and transwell assays were applied to detect cell mobility and metastasis. Quantitative real‐time polymerase chain reaction and western blot analysis were used to examine messenger RNA and protein expressions, respectively. It was found that KCNJ4 was significantly upregulated in LADC tissues and cells. The high level of KCNJ4 predicted shorter overall survival and was identified as an independent prognostic factor in patients with LADC. siRNA‐mediated KCNJ4 silencing impeded LADC cell proliferation, migration, and invasion. Knockdown of KCNJ4 suppressed the expression of phosphorylated mitogen‐activated protein kinase/extracellular signal regulated kinase (p‐MEK) and phosphorylated extracellular signal‐regulated kinase (p‐ERK). Collectively, these results shed some light on the contribution of KCNJ4 functioning as a significant player in LADC, implying that KCNJ4 might be a valuable prognostic biomarker and a potential therapeutic target for LADC treatment.
IL‐6/YAP1/β‐catenin signaling is involved in intervertebral disc degeneration
Authors: Chen Jian , Mei Zhengfeng , Huang Bao , Zhang Xuyang , Liu Junhui , Shan Zhi , Wang Jiasheng , Wang Xianjun , Zhao Fengdong
Published: December 2018

Yes‐associated protein 1 (YAP1) is a transcriptional coactivator and negative regulator of the Hippo pathway. It regulates diverse cellular processes, such as cell proliferation, contact inhibition, and tissue size. However, the role of YAP1 in intervertebral disc degeneration (IDD) remains elusive. Here, we demonstrated that YAP1 was activated by Interleukin 6 (IL‐6) through tyrosine phosphorylation in nucleus pulposus cells (NP cells). Overexpression of YAP1 decreased Sox‐9, Col‐II, aggrecan expression, whereas increased matrix metalloproteinases 13 level. In contrast, knockdown of YAP1 by small interfering RNA (siRNA) showed opposite effects and rescued IL‐6 induced NP cells degeneration. In addition, western blot showed that IL‐6 treatment increased YAP1 and β‐catenin protein level; co‐immunoprecipitation (Co‐IP) and immunofluorescence analysis showed that IL‐6 enhanced YAP1 and β‐catenin interaction and nuclear accumulation. Knockdown of β‐catenin by siRNA blocked IL‐6 treatment or YAP1 overexpression induced degeneration. Moreover, we found that verteporfin, a specific inhibitor of YAP1, effectively alleviated IDD development in rat disks. Taken together, our findings indicated that YAP1 plays an important role in IDD, and β‐catenin is essential for IL‐6/YAP1 signaling.