bluuebunny/crossref_metadata_2025 huggingface dataset:
A 1‐bit full adder using CNFET based dual chirality high speed domino logic
Authors: Garg Sandeep , Gupta Tarun K. , Pandey Amit K.
Published: December 2019

CNFET devices are preferred over CMOS devices for designing high‐speed digital circuits. This paper introduces a new technique Dual Chirality High‐speed Domino Logic (DCHSDL) for implementing low power and high‐speed domino circuits in CNFET technology. Simulations are carried out for 32 nm Stanford CNFET model in HSPICE for 2, 4, 8 and 16 input domino OR gates at a clock frequency of 200 MHz on a DC supply voltage of 0.9 V. The proposed domino technique shows maximum power reduction of 82.55% and maximum delay reduction of 57.97% compared to CPVT technique in CNFET technology at a frequency of 200 MHz. The proposed circuit shows maximum power reduction of 97.90% compared to its analogous circuit in CMOS technology for a 2‐input domino OR gate. The proposed technique shows maximum improvement of 1.05× to 1.63× in unity noise gain (UNG) compared to various existing techniques in CNFET technology at a frequency of 200 MHz. The 1‐bit Full Adder designed using the proposed technique shows a power reduction of 16.91% and a delay reduction of 23.64% compared to standard FDL 1‐bit Full Adder.
Full flexible performance characterization of a feedback applied transistor with LNA applications
Authors: Güneş Filiz , Yurttakal Oktay
Published: December 2019

In this paper, the full flexible performance characterization of a transistor with series inductive/parallel capacitive feedback is carried out in terms of LNA applications. For this purpose, the input VSWR Vin–maximum available gain GTmax variations are constructed for a high technology low‐noise transistor that is subject to the required noise figure Freq(f) ≥ Fmin(f) along the device's operation band depending on the feedback. These Vin–GTmax variations result in the application of a design chart that indicates which value of feedback can be applied within which region of the operation band with the improvable trade‐off between the Vin and output VSWR Vout for the Freq(f) ≥ Fmin(f). Following this, the optimum trade‐off between Vin and Vout is made for the necessary operation frequency regions using the load impedance ZL as an instrument with the predetermined source impedance ZS. Finally, the LNA applications of a series inductive/parallel capacitive feedback applied transistor with the optimum Vin, Vout, and GT subject to Freq(f) ≥ Fmin(f) ≥ are also presented as distributed across the entire bandwidth in the different operation bands. It can be concluded that this rigorous work will enable a designer to utilize the entire operation frequency band of transistor through using only a single series inductive/parallel capacitive feedback for the LNA designs of Freq(f) ≥ Fmin(f) with the optimum trade‐offs among its performance measures.
Thermal dynamics in the flux‐coordinate independent turbulence code GRILLIX
Authors: Zholobenko W. , Stegmeir A. , Body T. , Ross A. , Manz P. , Maj O. , Coster D. , Jenko F. , Francisquez M. , Zhu B. , Rogers B.N.
Published: December 2019

GRILLIX employs the flux‐coordinate independent approach (FCI), which allows us to study boundary plasma turbulence in realistic diverted configurations. Recently, the physical model in GRILLIX has been extended to a global drift‐reduced Braginskii model, without any separation between background and fluctuations. It includes electromagnetic and thermal dynamics with hot ions, relaxation of the Boussinesq approximation and non‐linear parametric dependencies. This contribution presents solutions to associated issues, that is, the ion diamagnetic polarization and the stiff parallel heat conduction. Simulations based on parameters characteristic for the Alcator C‐Mod tokamak were carried out. In circular geometry, the self‐consistent electric field contains zonal flows and geodesic acoustic modes in the confined region. In the scrape‐off layer, the electron parallel heat conduction and its boundary condition determine the temperature and electric field, leading to sheared flows at the last closed flux surface.
Binge eating and purging in first‐year college students: Prevalence, psychiatric comorbidity, and academic performance
Authors: Serra Riccardo , Kiekens Glenn , Vanderlinden Johan , Vrieze Elske , Auerbach Randy P , Benjet Corina , Claes Laurence , Cuijpers Pim , Demyttenaere Koen , Ebert David D , Tarsitani Lorenzo , Green Jennifer Greif , Kessler Ronald C , Nock Matthew K , Mortier Phillippe , Bruffaerts Ronny
Published: December 2019

Background

Binge eating and purging behaviors (BPB) are common among college students, but evidence is scant on prevalence and associations of BPB with mental health problems and objective academic performance. This study aims to investigate: (a) 12‐month prevalence of BPB among college first‐year students, (b) comorbidity patterns of BPB with various mental health problems, and (c) the association of BPB with objective academic functioning.

Methods

Using data from the Leuven College Surveys (Belgium), as part of the World Mental Health Surveys International College Student initiative, we cross‐sectionally assessed 12‐month BPB and mental health problems among college first‐year students (n = 4,889; response rate = 73.2%) at the beginning of the academic year. Objective measures of academic functioning (final grades, expressed in academic year percentage “AYP” [0–100%] and academic failure) were obtained from administrative records at the end of the academic year.

Results

Twelve‐month prevalence of BPB was 7.6% (7.3%binge eating and 1.0%purging), with higher rates among females than males. Bivariate models showed an association between BPB and numerous mental health problems (ORs = 3.4–18.4). Multivariate models showed associations with non‐suicidal self‐injury, post‐traumatic stress, internalizing/externalizing problems and suicidal ideation. After controlling for sociodemographic characteristics and comorbid mental health problems, BPB were still associated with lower AYP (−4.1 to −11.2% range) and elevated odds of academic year failure (ORs = 1.4–4.2).

Conclusions

BPB (especially binge eating) are relatively common and associated with mental health problems, comparatively low academic performance, and higher risk of academic failure among college first‐year students. Further study is needed to examine the causal dynamics underlying these associations.
Overfishing and the ecological impacts of extirpating large parrotfish from Caribbean coral reefs
Authors: Shantz Andrew A. , Ladd Mark C. , Burkepile Deron E.
Published: December 2019

The unique traits of large animals often allow them to fulfill functional roles in ecosystems that small animals cannot. However, large animals are also at greater risk from human activities. Thus, it is critical to understand how losing large animals impacts ecosystem function. In the oceans, selective fishing for large animals alters the demographics and size structure of numerous species. While the community‐wide impacts of losing large animals are a major theme in terrestrial research, the ecological consequences of removing large animals from marine ecosystems remain understudied. Here, we combine survey data from 282 sites across the Caribbean with a field experiment to investigate how altering the size structure of parrotfish populations impacts coral reef communities. We show that Caribbean‐wide, parrotfish populations are skewed toward smaller individuals, with fishes <11 cm in length comprising nearly 70% of the population in the most heavily fished locations vs. ~25% at minimally fished sites. Despite these differences in size structure, sites had similar overall parrotfish biomass. As a result, algal cover was unrelated to parrotfish biomass and instead, was negatively correlated with the density of large parrotfishes. To mechanistically explore how large parrotfishes shape benthic communities, we manipulated fishes’ access to the benthos to create three distinct fish communities with different size structure. We found that excluding large or large and medium‐sized parrotfishes did not alter overall parrotfish grazing rates but caused respective 4‐ and 10‐fold increases in algal biomass. Unexpectedly, branching corals benefited from excluding large parrotfishes whereas the growth of mounding coral species was impaired. Similarly, removing large parrotfishes led to unexpected increases in coral recruitment that were absent when both large and medium bodied fishes were excluded. Our data highlight the unique roles of large parrotfishes in driving benthic dynamics on coral reefs and suggests that diversity of size is an important component of how herbivore diversity impacts ecosystem function on reefs. This study adds to a growing body of literature revealing the ecological ramifications of removing large animals from ecosystems and sheds new light on how fishing down the size structure of parrotfish populations alters functional diversity to reshape benthic reef communities.
Validity of heart failure diagnoses made in 2000–2012 in western Sweden
Authors: Schaufelberger Maria , Ekestubbe Sofia , Hultgren Simon , Persson Hans , Reimstad Ann , Schaufelberger Mattias , Rosengren Annika
Published: December 2019

Aims

The aim of this study is to validate a diagnosis of heart failure (HF) according to the European Society of Cardiology (ESC) guidelines among patients hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, between 2000 and 2012.

Methods and results

In Sweden, it is mandatory to report all hospital discharge diagnoses to the Swedish national inpatient register. In total, 27 517 patients were diagnosed with HF at the Sahlgrenska University hospital between 2000 and 2012. Altogether, 1100 records with a primary (n = 550) or contributory (n = 550) diagnosis of HF were randomly selected. The diagnosis was validated according to the ESC guidelines from 1995, 2001, 2005, and 2008, and cases were divided into three groups: definite, probable, and miscoded. In total, 965 cases were validated, while 135 records were excluded for various reasons. Of the 965 records, the diagnosis was validated as definite in 601 (62.3%) and as probable in 310 (32.1%); only 54 (5.6%) of cases had been miscoded. Echocardiography, as an objective evidence of cardiac dysfunction, had been performed in 581 (96.7%) of the definite, 106 (34.2%) of the probable, and 31 (57.4%) of the miscoded cases. Among the probable cases, the main reason they had not been classified as a definitive diagnosis of HF was lack of examination by echocardiography (63.8%).

Conclusions

The overall validity of HF diagnosis at Sahlgrenska University Hospital is high. This may reflect a high diagnostic validity at the time of diagnosis in the national Swedish patient register, supporting the continued use of this register in epidemiological research.
Direct Arylations of Heteroarenes with Benzenesulfonyl Chlorides Using Pd/C Catalyst
Authors: Mao Shuxin , Shi Xinzhe , Soulé Jean‐François , Doucet Henri
Published: December 2019

The reactivity of heteroaromatics in direct arylation with benzenesulfonyl chlorides using 10 % Pd/C as catalyst was explored. With (benzo)thiophenes, (benzo)furans, pyrroles and selenophenes, high yields in arylated heteroarenes were obtained. These arylations were performed using only 5 mol‐% Pd/C and Li2CO3 as inexpensive base. The regioselectivities are similar to those observed with homogeneous palladium catalysts. Better yields were obtained with electron‐deficient benzenesulfonyl chlorides than with the electron‐rich ones. Notably, useful substituents such as bromo or iodo on the benzenesulfonyl chloride were tolerated, as no cleavage of the C–Br or C–I bonds was observed under these conditions. The use of Pd/C presents several advantages compared to the previously employed homogeneous palladium catalysts, as it can be easily removed by filtration at the end of the reaction. The major side‐products of the reaction are HBr associated to Li2CO3. Therefore, this new protocol affords a very attractive synthetic scheme in terms of cost, simplicity and low environmental impact for the access to arylated heteroaromatics.
Single Cell Electrochemiluminescence Analysis of Cholesterol in Plasma Membrane during Testosterone Treatment
Authors: Li Linyu , Liu Kang , Fang Danjun
Published: December 2019

The fluctuation of cholesterol in plasma membrane at single cells during testosterone treatment was evaluated using luminol electrochemiluminescence at the first time. Testosterone over the human physiological concentration induced more membrane cholesterol that was associated with upregulated cholesterol synthesis inside the cells. However, the evaluation at single cell level revealed some individual cells with similar membrane cholesterol, while the other individual cells with more membrane cholesterol after the treatment. The observation of non‐responsive cells to testosterone treatment exhibited the heterogeneous cellular function during this process, which should provide more information to understand the side effects of testosterone replacement therapy.
Chlorpromazine Electro‐oxidation at BDD Electrode Modified with nZVI Nanoparticles Impregnated NiAl LDH
Authors: Djebbi Mohamed Amine , Boubakri Saber , Braiek Mohamed , Jaffrezic‐Renault Nicole , Namour Philippe , Amara Abdesslem Ben Haj
Published: December 2019

Nanocomposite of nanoscale zero‐valent iron (nZVI) and layered double hydroxide (LDH) was used as modifier for boron‐doped diamond electrode in determination of anti‐psychotic drug chlorpromazine (CPZ). nZVI nanoparticles were prepared by liquid phase reduction of ferric chloride with sodium borohydride on the surface of NiAl LDH matrix owing to the strong exchange and confinement efficiency of LDH. The structure, binding and surface properties of the nZVI@LDH nanocomposite were monitored using powder X‐ray diffractometry, FT‐IR spectroscopy, scanning and transmission microscopy and BET techniques. The electrochemical properties of the modified electrode were investigated by CV and EIS, performed in a phosphate buffer containing ferro/ferricyanide as redox probe. The modified electrode exhibited excellent electrochemical performance compared with unmodified electrode. As regard potential application of the nanocomposite surface to the CPZ detection, square‐wave voltammetric signals showed a good linear correlation over CPZ concentrations in a broad range from 0.1 to 8.0 μM with low detection limit of 0.005 μM. Nevertheless, these results suggest that the proposed nanocomposite modifier surface provides exceptional synergy and significant enhancement effect to the voltammetric response of CPZ and thus could be applied as highly efficient and stable platform of sensors in clinical analysis.
EPOWT: A denoising technique of the electrocardiography signal transmission via 5G wireless communications
Authors: Bhuyar Devendra Laxman , Kureshi Abdul Kadir
Published: December 2019

This article provides a thorough review of 5G wireless electrocardiography (ECG) communication for actual cardiac signal using both technical and clinical features for the purpose of recommending real‐time observation. Major issue regarding this frame work is the distortion and smoothness of ECG signal for the cardiologist advice also it needs correct diagnosis at the proper time. Extensive 5G wireless simulated scenarios are used to supervise the compressed ECG signal on reception. An efficient ECG transmission protocol is a modern and consistent ECG transmission protocol which is used to retransmit the noise signals. Thus, we are filtering the ECG signals to improve the quality which may directly affects the medical diagnosis. Because, time and frequency indicators can be obtained by the wavelet analysis but majority of the error functions cannot be flexible to various signals because of the static transition curve of threshold. Hence, we proposed a new emperor penguin optimization (EPO) together with wavelet thresholding (EPOWT) method. Here, the EPOWT is estimated through the means of real‐time ECG records. The outcomes of filtering process shows that the proposed EPOWT approach can achieve smooth threshold transition and soft thresholding bring the wavelet coefficient. EPOEPO algorithm is used to improve its flexibility to different signals. The EPOWT can generate an essential noise‐free signal by balancing the smoothness and signal distortion filtering for transmission. The proposed method can attains 2.9 seconds delay during simulation. Thus, the 5G wireless channel parameter's functioning zone is simple to acquire.
Antipyretic and hepatoprotective potential of Tinospora crispa and investigation of possible lead compounds through in silico approaches
Authors: Rakib Ahmed , Ahmed Shahriar , Islam Md. Ashiqul , Haye Abdul , Uddin S. M. Naim , Uddin Mir Muhammad Nasir , Hossain Mohammed Kamrul , Paul Arkajyoti , Emran Talha Bin
Published: December 2019

This research describes an investigation of the antipyretic and hepatoprotective properties of both a crude organic extract and various subfractions of the ethnomedicinal plant Tinospora crispa, using appropriate animal models. In an attempt to identify potential lead hepatoprotective compounds, in silico experiments were utilized. Antipyretic activity was assessed via the Brewer's yeast‐induced pyrexia method, while hepatoprotective effects were evaluated in a carbon tetrachloride (CCl4)‐induced animal model. A computer‐aided prediction of activity spectra for substances (PASS) model was applied to a selection of documented phytoconstituents, with the aim of identifying those compounds with most promising hepatoprotective effects. Results were analyzed using Molinspiration software. Our results showed that both the methanol extract (METC) and various subfractions (pet ether, PEFTC; n‐hexane, NHFTC; and chloroform, CFTC) significantly (p < .05) reduced pyrexia in a dose‐dependent manner. In CCl4‐induced hepatotoxicity studies, METC ameliorated elevated hepatic markers including serum alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), and total bilirubin. Malondialdehyde (MDA) levels were significantly reduced, while superoxide dismutase (SOD) levels were significantly increased. Among a selection of metabolites of T. crispa, genkwanin was found to be the most potent hepatoprotective constituent using PASS predictive models. These results demonstrate that both the methanolic extract of T. crispa and those fractions containing genkwanin may offer promise in reducing pyrexia and as a source of potential hepatoprotective agents.
Sedimentary characteristics, dispersal patterns, and pathway formation in Liaoxi Sag, Liaodong Bay Depression, North China: Evolution of source‐to‐sink systems in strike‐slip tectonics belt
Authors: Fu Chao , Li Shengli , Li Shunli , Fan Xue , Xu Jianyong
Published: December 2019

Liaodong Bay Depression is a strike‐slip basin with complex tectonic movement that lead the source‐to‐sink (S2S) systems evolution vary greatly in temporal and spatial characteristics. This study explored the sedimentary characteristics, dispersal patterns, and pathway formation in Liaodong Bay Depression, as well as their controlling factors. We selected more than 10 pathways with north‐west and north‐east directions in Liaoxi Sag in the western part of Liaodong Bay Depression, a typical strike‐slip bet controlled graben, to investigate their S2S system distribution. By combining seismic data, we divided the strike‐slip fault bends into three stress setting parts, namely, a central restraining bend, which is the fault translation part, and two releasing bends in the southern and northern of fault terminals. As the heavy mineral assemblage and clay content in the west side of Liaoxi Sag differs from that in the east side, we put forward an S2S index to show the sediment transport distance according to the data we have obtained. Using this index, we recovered the dispersal pattern and pathway development and speculated on the sedimentary provenance. In the restraining bend, we recognized that the pathways mainly show a symmetrical “V” or “W” shape with unclear erosion boundaries and were dominated by filling processes. Considering the heavy mineral assemblage data, we also found that the sediment provenance area decreased and the sediment provided direction transferred from the two‐side provenance to one. Combining the fast sedimentary rate calculated with clay content data, the S2S systems in this area were steep–wide–deep systems and a wide and shallow system. In the releasing bend, the pathways show an asymmetrical “V” or “W” shape and a clear erosional boundary. As shown by the heavy mineral assemblage data, the sediments from these areas mainly have a west side provenance and were deposited in the proximal area. Thus, the S2S system in this area is a kind of steep–deep system. Then, the investigation by integrated of tectonic movement and S2S geomorphic statistical parameters revealed that the elevation height of the S2S is a key factor in control pattern development. The various evolution patterns within the two different stress settings provide insights into the formation process of the S2S developed in a strike‐slip tectonic belt.
A molecularly distinct subset of glioblastoma requires serum‐containing media to establish sustainable bona fide glioblastoma stem cell cultures
Authors: Maturi Naga Prathyusha , Tan E‐Jean , Xie Yuan , Sundström Anders , Bergström Tobias , Jiang Yiwen , Uhrbom Lene
Published: December 2019

Glioblastoma (GBM) is the most frequent and deadly primary malignant brain tumor. Hallmarks are extensive intra‐tumor and inter‐tumor heterogeneity and highly invasive growth, which provide great challenges for treatment. Efficient therapy is lacking and the majority of patients survive less than 1 year from diagnosis. GBM progression and recurrence is caused by treatment‐resistant glioblastoma stem cells (GSCs). GSC cultures are considered important models in target identification and drug screening studies. The current state‐of‐the‐art method, to isolate and maintain GSC cultures that faithfully mimic the primary tumor, is to use serum‐free (SF) media conditions developed for neural stem cells (NSCs). Here we have investigated the outcome of explanting 218 consecutively collected GBM patient samples under both SF and standard, serum‐containing media conditions. The frequency of maintainable SF cultures (SFCs) was most successful, but for a subgroup of GBM specimens, a viable culture could only be established in serum‐containing media, called exclusive serum culture (ESC). ESCs expressed nestin and SOX2, and displayed all functional characteristics of a GSC, that is, extended proliferation, sustained self‐renewal and orthotopic tumor initiation. Once adapted to the in vitro milieu they were also sustainable in SF media. Molecular analyses showed that ESCs formed a discrete group that was most related to the mesenchymal GBM subtype. This distinct subgroup of GBM that would have evaded modeling in SF conditions only provide unique cell models of GBM inter‐tumor heterogeneity.
Caprin‐1 Promotes Cellular Uptake of Nucleic Acids with Backbone and Sequence Discrimination
Authors: Galli Valentina , Sadhu Kalyan K. , Masi Daniela , Saarbach Jacques , Roux Aurélien , Winssinger Nicolas
Published: December 2019

The cellular delivery of oligonucleotides has been a major obstacle in the development of therapeutic antisense agents. PNAs (Peptide Nucleic Acid) are unique in providing a modular peptidic backbone that is amenable to structural and charge modulation. While cationic PNAs have been shown to be taken up by cells more efficiently than neutral PNAs, the generality of uptake across different nucleobase sequences has never been tested. Herein, we quantified the relative uptake of PNAs across a library of 10 000 sequences for two different PNA backbones (cationic and neutral) and identified sequences with high uptake and low uptake. We used the high uptake sequence as a bait for target identification, leading to the discovery that a protein, caprin‐1, binds to PNA with backbone and sequence discrimination. We further showed that purified caprin‐1 added to cell cultures enhanced the cellular uptake of PNA as well as DNA and RNA.
A resistance to change perspective on nonusers of telecenters
Authors: Gollakota Kamala , Pick James B.
Published: December 2019

We contend that nonuse is different from low use and explore reasons for nonuse of telecenters by small and marginal farmers in rural India. We take a resistance to change perspective to understand reasons for nonuse. Based on an exploratory empirical study of small and marginal farmers, we show that there are important differences between users and nonusers. In addition to demographic differences, nonusers were more satisfied with current sources of information, had lower awareness of the potential of telecenters, and were less concerned about the factors that influenced low use, such as quality of information, cost, and location. These differences have important implications for providers and policy makers who need to have different strategies toward nonusers and users.
Computations of Colorings 7D‐Hypercube's Hyperplanes for All Irreducible Representations
Authors: Balasubramanian Krishnan
Published: December 2019

In the present study, we compute and enumerate the colorings of 7D‐hypercube for all of its hyperplanes (q = 1–7) for all 110 irreducible representations (IRs) of the seventh‐dimensional hyperoctahedral group consisting of 645,120 symmetry operations. The computations of colorings of the 7D‐hypercube are motivated by a number of chemical and biological applications such as the 7D‐hypercube representation of the periodic table, hypercube representations of water heptamer clusters, genetic regulatory networks, isomerization graphs, massively large data representations, and so forth. We have employed the Möbius inversion technique combined with generalized character cycle indices for 110 IRs to compute the generating functions for colorings of seven different types of hyperplanes of the 7D‐hypercube varying from the vertices (q = 7) to hexeracts (q = 1) of the 7D‐hypercube. Explicit computed tables are provided for 110 IRs from q = 1 to q = 7 for the 7D‐hypercube. © 2019 Wiley Periodicals, Inc.
Clay as support for copper catalysts for the hydrogenation of furfural and phenolics
Authors: Tian Hongli , Shao Yuewen , Zhang Lijun , Jia Peng , Zhang Zhanming , Liu Qianhe , Zhang Shu , Liu Qing , Wang Yi , Hu Xun
Published: December 2019

BACKGROUND

Ordinary clay is an abundantly available and widely distributed material, the use of which as supporting material can minimize the cost in manufacturing catalysts. This study investigated the potential for the direct use of ordinary clay and treated clay as supports of copper (Cu)‐based catalysts for hydrogenation of furfural and some phenolic compounds.

RESULTS

The catalyst treated with alkali showed better activity at 100 °C whereas the activity of other catalysts was negligible, and when the temperature was raised, the activity of all the catalysts was obviously improved. In addition, the catalysts treated with sodium hydroxide (NaOH) showed fair activity for 5‐hydroxyl methyl furfural, vanillin and benzaldehyde, and the stability of the catalyst also was good: after four cycles of experiments, the yield of furfuryl alcohol could still reach >95%.

CONCLUSIONS

Activation of clay with NaOH effectively enhanced not only the surface area and porous structures, but also the alkalinity of the catalyst, suppressing side reactions such as acetalization between furfural and ethanol, and facilitated hydrogenation of furfural. Comparing with clay washed with sulfuric acid or calcined at various temperatures, the clay activated with NaOH showed superior hydrogenation of not only furfural, but also 5‐hydroxyl methyl furfural, vanillin and benzaldehyde, as a result of the presence of abundant mesopores and alkaline sites. The ordinary clay‐supported Cu catalyst also showed acceptable activity for hydrogenation reactions at a higher reaction temperature, which has particular importance for practical applications because the clay can be used directly as supporting material. © 2019 Society of Chemical Industry
Synthesis of 1,2,3 triazole‐linked pyrimidines catalyzed by mg‐Al‐LDH‐immobilized‐CuI as a heterogeneous catalyst
Authors: Rezaeimanesh Fatemeh , Bakherad Mohammad , Nasr‐Isfahani Hossein , Bahramian Bahram , Naderi Soheila
Published: December 2019

A useful and efficient procedure was obtained for the synthesis of 1,2,3‐triazole‐linked pyrimidines via click reaction of propynylated pyrimidine and aromatic azides in the presence of Mg‐Al‐LDH‐immobilized‐CuI with high‐to‐excellent yields. Moreover, the prepared catalyst was characterized by the FT‐IR spectroscopy, XRD, BET, SEM, and ICP techniques. The developed synthetic technique offers numerous advantages such as a clean reaction, easy workup, high reaction yields, and short reaction time.
Synthesis and biological evaluation of 4,5,6,7‐tetrahydrothieno[2,3‐c]pyridine–based β‐aminonitriles and their derivatives: β‐amino carboxamides, (thio)ureas, and tetracycles
Authors: Madácsi Ramóna , Traj Péter , Hackler László , Nagy Lajos I. , Kari Beáta , Puskás László G. , Kanizsai Iván
Published: December 2019

The preparation and cytotoxic characterization of 4,5,6,7‐tetrahydrothieno[2,3‐c]pyridine–based β‐aminonitriles, β‐amino carboxamides, and their (thio)urea and annulated derivatives were accomplished. Following a synthetic route involving Gewald three‐component reactions (G‐3CR) and a Lewis acid–catalyzed iso (thio)cyanate coupling, 30 compounds were prepared for antitumor evaluation. For derivatizations, a catalytic amount of CuOAc2 (20 mol%) was essential for improving the reactivity of either the C‐2 amino function of thiophene or isocyanates. The synthesized analogues demonstrated a weak to moderate antitumor activity in a low micromolar range against A549 and K562 cancer cell lines.
Towards an understanding of Angelman syndrome in mice studies
Authors: Yang Xin
Published: December 2019

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe mental retardation, absence of speech, abnormal motor coordination, abnormal EEG, and spontaneous seizure. AS is caused by a deficiency in the ubiquitin ligase E3A (Ube3a) gene product, known to play a dual role as both ubiquitin ligase and transcription coactivator. In AS animal models, multiple Ube3a substrates are accumulated in neurons. So far, studies in mouse models have either aimed at re‐expressing Ube3a or manipulating downstream signaling pathways. Reintroducing Ube3a in AS mice showed promising results but may have two caveats. First, it may cause an overdosage in the Ube3a expression, which in turn is known to contribute to autism spectrum disorders. Second, in mutation cases, the exogenous Ube3a may have to compete with the mutated endogenous form. Such two caveats left spaces for developing therapies or interventions directed to targets downstream Ube3a. Notably, Ube3a expression is dynamically regulated by neuronal activity and plays a crucial role in synaptic plasticity. The abnormal synaptic plasticity uncovered in AS mice has been frequently rescued, but circuits symptoms like seizure are resistant to treatment. Future investigations are needed to further clarify the function (s) of Ube3a during development. Here I reviewed the recently identified major Ube3a substrates and signaling pathways involved in AS pathology, the Ube3a expression, imprinting and evolution, the AS mouse models that have been generated and inspired therapeutic potentials, and finally proposed some future explorations to better understand the AS pathology.
Quantitative imaging of anterior cruciate ligament (ACL) graft demonstrates longitudinal compositional changes and relationships with clinical outcomes at 2 years after ACL reconstruction
Authors: Lansdown Drew A. , Xiao Weiyuan , Zhang Alan L. , Allen Christina R. , Feeley Brian T. , Li Xiaojuan , Majumdar Sharmila , Ma C. Benjamin
Published: December 2019

T1ρ and T2 magnetic resonance imaging (MRI) may allow for a noninvasive assessment of ligamentization after anterior cruciate ligament (ACL) reconstruction. We hypothesized that ACL graft T1ρ and T2 relaxation times would decrease over time, that T1ρ and T2 relaxation times would be inversely correlated with Knee Osteoarthritis Outcome Scores (KOOS), and that T1ρ and T2 values would be lower for autograft relative to allograft reconstruction. Thirty‐nine patients (age: 30.5 ± 8.2 years) were followed prospectively after ACL reconstruction with hamstring autograft (N = 27) or soft‐tissue allograft (N = 12). Magnetic resonance (MR) imaging and KOOS surveys were completed at 6, 12, 24, and 36 months after surgery. ACL graft was segmented to define T1ρ and T2 relaxation times. Relaxation times were compared between time points with ANOVA tests. Log‐transformed autograft and allograft relaxation times were compared with the Student t tests. The relationship between KOOS and relaxation times at 24 months was investigated with Spearman's rank correlation. ACL graft T1ρ relaxation times were significantly higher at 6 months relative to 12 months (P = .042), 24 months (P < .001), and 36 months (P < .001). ACL graft T2 relaxation times were significantly higher at 6 months relative to 12 months (P = .036), 24 months (P < .001), and 36 months (P < .001). T1ρ and T2 relaxation times were significantly lower for autograft reconstruction vs allograft reconstruction at 24 months postreconstruction. Two‐year KOOS Sports, Pain, and Symptoms were significantly inversely correlated with T1ρ and T2 relaxation times. T1ρ and T2 sequences may offer a noninvasive method for monitoring ACL graft maturation that correlates with patient‐reported knee function after ACL reconstruction.
A catalogue of major and trace element data for Icelandic Holocene silicic tephra layers
Authors: Meara RH. H. , Thordarson TH. , Pearce N. J. G. , Hayward C. , Larsen G.
Published: December 2019

Tephra layers with Icelandic provenance have been identified across the North Atlantic region in terrestrial, lacustrine, marine and glacial environments. These tephra layers are used as marker horizons in tephrochronology including climate studies, archaeology and environmental change. The major element chemistries of 19 proximally deposited Holocene Icelandic silicic tephra layers confirm that individual volcanic systems have unique geochemical signatures and that eruptions from the same system can often be distinguished. In addition, glass trace element chemistry highlights subtle geochemical variations between tephra layers which appear to have identical major element chemistry and thus allows for the identification of some, if not all, tephra layers previously considered identical in composition. This paper catalogues the compositional variation between the widespread Holocene Icelandic silicic tephra deposits.
Prognostic and therapeutic implications of NHERF1 expression and regulation in colorectal cancer
Authors: Leiphrakpam Premila D. , Lazenby Audrey J. , Chowdhury Sanjib , Smith Lynette M. , Mathiesen Michelle , Brattain Michael G. , Wang Jing , Black Jennifer D. , Are Chandrakanth
Published: December 2019

Background

Na+/H+ exchanger regulatory factor 1 (NHERF1) has been implicated in the tumorigenesis of several cancer types and is a potential therapeutic target. The current study evaluated the relationship between NHERF1 expression and clinical outcome in colorectal cancer (CRC).

Methods

NHERF1 expression was evaluated by immunohistochemistry in 167 patients with CRC primary tumors, 37 patients with no disease, and 27 patients with metastatic CRC (mCRC); and in the orthotopically implanted tumors in mice. NHERF1 expression was manipulated in CRC cells using inducible short hairpin RNAs to determine its biological functions.

Results

High expression of NHERF1 correlated with CRC progression and metastasis, as well as significantly worse overall survival, recurrence‐free survival, and disease‐specific survival. Orthotopic implantation studies demonstrated increased NHERF1 expression in liver metastases. Treatment of CRC xenografts with insulin‐like growth factor 1 receptor (IGF1R) inhibitors downregulated NHERF1 expression, indicating NHERF1 is downstream of IGF1R signaling. Knockdown of NHERF1 increased apoptosis and reduced X‐linked inhibitor of apoptosis protein (XIAP) and survivin expression, indicating NHERF1 is critical for CRC cell survival.

Conclusion

NHERF1 expression levels correlated with worse prognosis in patients with CRC and plays a critical role in CRC cell survival. Together, our findings establish NHERF1 as a novel potential marker for increased risk of CRC‐specific mortality and identify NHERF1 as an attractive therapeutic target for mCRC treatment.
Clinical features of sarcomatoid change in patients with intrahepatic cholangiocarcinoma and prognosis after surgical liver resection: A Propensity Score Matching analysis
Authors: Wang Tao , Kong Junjie , Yang Xianwei , Shen Shu , Zhang Menglan , Wang Wentao
Published: December 2019

Background

Intrahepatic cholangiocarcinoma with sarcomatoid change (iCCA‐SC) is a rare histological subtype of iCCA, the clinical features and outcomes after surgical resection on the prognosis is still unknown.

Methods

We retrospectively reviewed the clinical data of patients with histologically proven iCCA who underwent curative liver resection at our hospital between January 2008 and December 2018. Propensity score matching analysis was used to match patients with and without sarcomatoid change at a ratio of 1:4. The nomogram integrating all significant independent factors for overall survival (OS) and recurrence‐free survival (RFS) was constructed to predict prognosis for iCCA. The predictive accuracy ability of the nomogram was determined by Harrell's index (C‐index).

Results

A total of 40 iCCA‐SC and 160 ordinary iCCA patients were included in this study. RFS and OS in the iCCA‐SC group were significantly lower than those in the ordinary iCCA group (P<.001 and P = .002, respectively). The calibration curve for the probability of survival showed good agreement between the nomogram prediction and actual observation.

Conclusion

The histological sarcomatoid subtype is an independent predictor of tumor recurrence and shorter OS in iCCA patients. The nomogram we established could provide more accurate prognostic prediction for iCCA patients.
Assessing the Performance of Morphologic and Echogenic Features in Median Nerve Ultrasound for Carpal Tunnel Syndrome Diagnosis
Authors: Byra Michal , Hentzen Eric , Du Jiang , Andre Michael , Chang Eric Y. , Shah Sameer
Published: December 2019

Objectives

To assess the feasibility of using ultrasound (US) image features related to the median nerve echogenicity and shape for carpal tunnel syndrome (CTS) diagnosis.

Methods

In 31 participants (21 healthy participants and 10 patients with CTS), US images were collected with a 30‐MHz transducer from median nerves at the wrist crease in 2 configurations: a neutral position and with wrist extension. Various morphologic features, including the cross‐sectional area (CSA), were calculated to assess the nerve shape. Carpal tunnel syndrome commonly results in loss of visualization of the nerve fascicular pattern on US images. To assess this phenomenon, we developed a nerve‐tissue contrast index (NTI) method. The NTI is a ratio of average brightness levels of surrounding tissue and the median nerve, both calculated on the basis of a US image. The area under the curve (AUC) from a receiver operating characteristic curve analysis and t test were used to assess the usefulness of the features for differentiation of patients with CTS from control participants.

Results

We obtained significant differences in the CSA and NTI parameters between the patients with CTS and control participants (P < .01), with the corresponding highest AUC values equal to 0.885 and 0.938, respectively. For the remaining investigated morphologic features, the AUC values were less than 0.685, and the differences in means between the patients and control participants were not statistically significant (P > .10). The wrist configuration had no impact on differences in average parameter values (P > .09).

Conclusions

Patients with CTS can be differentiated from healthy individuals on the basis of the median nerve CSA and echogenicity. Carpal tunnel syndrome is not manifested in a change of the median nerve shape that could be related to circularity or contour variability.
Contemporary techniques in human otopathology and promise for the future
Authors: Nadol Joseph B.
Published: December 2019

Contemporary histopathology of the ear is based on an evolution of equipment and histological techniques over the last 500 years, including the invention of the light microscope and protocols for fixation, embedment, sectioning, and staining of tissue samples, and visual documentation of findings. Several recent techniques which can be utilized in otopathology hold promise for significant improvement in methods and a better understanding of pathologic processes in diseases of the ear.
Inhibition of Calcineurin and Glycogen Synthase Kinase‐3β by Ricinoleic Acid Derived from Castor Oil
Authors: Yoshida Jun , Okawa Yusuke , Oyama Takuya , Shimoda Nozomu , Uesugi Shota , Takagi Hiroshi , Ito Yoshiaki , Kimura Ken‐ichi
Published: December 2019

Ricinoleic acid (RA) is the main fatty acid component of castor oil and was found to inhibit Ca2+‐signal transduction pathway‐mediated cell cycle regulation in a yeast‐based drug screening assay. RA is expected to have antidiabetic, antiallergy, and/or anticancer properties but its target molecule is unknown. To identify a novel pharmacological effect of RA, we investigated its target molecule in the Ca2+‐signal transduction pathway. RA inhibition of calcineurin (CN) was examined in a yeast‐based CN inhibitor screening assay using the rsp5A401E mutant and in a phosphatase assay using recombinant human CN. RA showed growth‐restoration activity at 5 μg/spot in the CN inhibitor screening assay with the rsp5A401E yeast strain. Furthermore, it directly inhibited CN without immunophilins at Ki = 33.7 μM in a substrate‐competitive manner. The effects of RA on CN in mammalian cells were further evaluated by measuring β‐hexosaminidase (β‐HEX) release in RBL‐2H3 cells. RA at 50 μM suppressed the release of β‐HEX from RBL‐2H3 cells. Moreover, this compound was found to inhibit glycogen synthase kinase‐3β (GSK‐3β), as determined by a kinase assay using recombinant human GSK‐3β. RA inhibited GSK‐3β at Ki = 1.43 μM in a peptide substrate‐competitive manner. The inhibition of GSK‐3β by this molecule was further assessed in mammalian cells by measuring the inhibition of glucose production in H4IIE rat hepatoma cells. RA at 25 μM suppressed glucose production in these cells. These findings indicate that RA and/or castor oil could be a useful functional fatty acid to treat allergy or type 2 diabetes.
Climate change effect on water resources in Varanasi district, India
Authors: Nistor Mărgărit‐Mircea , Rai Praveen K. , Dugesar Vikas , Mishra Varun N. , Singh Prafull , Arora Aman , Kumra Virendra Kumar , Carebia Iulius‐Andrei
Published: December 2019

Evapotranspiration and water availability are driven by changing climate and land cover parameters. In the present study, climatological records and land cover data were analysed simultaneously to accomplish the spatial distributions of climate change effects on water resources in Varanasi district, north India. Humidity–aridity was assessed by Lang's rain factor and De Martonne's aridity index, based on mean monthly rainfall and air temperature from seven meteorological stations. The climate change effect on water resources was evaluated using a 5 × 5 matrix that includes water availability and the aridity index by considering two time periods: 1941–1970 (1950s) and 1971–2000 (1980s). The methodology is based on seasonal crop evapotranspiration (ETc) (initial, mid‐season, end season and cold season) and annual water availability calculations. The high values (≤ 1,045 mm) of ETc were identified during the mid‐season stage. Water availability indicates decreases in the maximums from 718 to 636 mm during the two analysed periods, with a negative impact at the spatial scale. Lang's rain factor (< 40) indicates an arid climate in the northwest, west, east and central parts of the district and a humid climate (Lang's rain factor > 40) in the south. De Martonne's aridity index indicates rapid aridization from south to north (28.3 in the 1950s and 25.6 in the 1980s). The high and very high climate effects on water resources in Varanasi district were found mainly in the crop lands, while in the urban areas the climate effect is low. The much affected area by climate change and land cover was depicted during the recent period (1980s). This statement was proved also by the Mann and Kendall test, which indicates a negative trend for annual precipitation at all stations (for the period 1941–2000), while the mean annual temperature had a positive trend for four stations. These findings suggest that climate change had a negative effect on water resources during the last 60 years in the study area.
Improving the weighted mean temperature model: A case study using nine year (2007–2015) radiosonde and COSMIC data in Hong Kong
Authors: Xia Pengfei , Ye Shirong , Chen Biyan , Chen Dezhong , Xu Keke
Published: December 2019

The important role of a humidity conversion factor in mapping the zenith wet delay (ZWD) onto precipitable water vapour (PWV) makes it a vital parameter in Global Navigation Satellite System (GNSS) meteorology. The accuracy of the humidity conversion factor depends mainly on the quality of the atmospheric weighted mean temperature (Tm) calculation. Several effective models have been developed to calculate Tm with parameters such as the station's location, date of measurement and surface temperature. However, the drawbacks of these models, including low accuracy in some areas and complex model functions, cannot be ignored because they prevent further application in atmosphere analysis. Therefore, a new discrete integral formula for highly accurate calculation of Tm is proposed. Moreover, the linear relationships between time, surface temperature (Ts), height (H) and Tm are well studied based on radiosonde and Constellation Observation System for Meteorology Ionosphere and Climate (COSMIC) historical data (2007–2015). A new regional Tm model was investigated on the basis of parameters time, Ts and H in Hong Kong, China. The evaluation results indicate that the improvement of Tm derived from the new integral is > 4.6 K based on radiosonde data. In addition, the statistical results of Tm with different sampling based on radiosonde data and a COSMIC “wetPrf” profile show that the improvement of Tm derived from the new integral are > 2.10 and 2.75 K, respectively. Finally, wetPrf profiles collocated with Hong Kong and the 45,004 radiosonde station collected from January 1 to October 31, 2016, are used to evaluate the accuracy of the new Tm model. Compared with the Bevis model, the statistical results indicate that the Tm accuracy is improved by 34.75%. Therefore, the model for Ts and time is suggested to estimate the Tm in Hong Kong.