bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Copy Number Alterations by Shallow Whole-Genome Sequencing of Formalin-Fixed, Paraffin-Embedded Tumor Tissue
Authors: Van der Linden Malaïka , Raman Lennart , Vander Trappen Ansel , Dheedene Annelies , De Smet Matthias , Sante Tom , Creytens David , Lievens Yolande , Menten Björn , Van Dorpe Jo , Van Roy Nadine
Published: December 2019

Context.—

In routine clinical practice, tumor tissue is stored in formalin-fixed, paraffin-embedded blocks. However, the use of formalin-fixed, paraffin-embedded tissue for genome analysis is challenged by poorer DNA quality and quantity. Although several studies have reported genome-wide massive parallel sequencing applied on formalin-fixed, paraffin-embedded samples for mutation analysis, copy number analysis is not yet commonly performed.

Objective.—

To evaluate the use of formalin-fixed, paraffin-embedded tissue for copy number alteration detection using shallow whole-genome sequencing, more generally referred to as copy number variation sequencing.

Design.—

We selected samples from 21 patients, covering a range of different tumor entities. The performance of copy number detection was compared across 3 setups: array comparative genomic hybridization in combination with fresh material; copy number variation sequencing on fresh material; and copy number variation sequencing on formalin-fixed, paraffin-embedded material.

Results.—

Very similar copy number profiles between paired samples were obtained. Although formalin-fixed, paraffin-embedded profiles often displayed more noise, detected copy numbers seemed equally reliable if the tumor fraction was at least 20%.

Conclusions.—

Copy number variation sequencing of formalin-fixed, paraffin-embedded material represents a trustworthy method. It is very likely that copy number variation sequencing of routinely obtained biopsy material will become important for individual patient care and research. Moreover, the basic technology needed for copy number variation sequencing is present in most molecular diagnostics laboratories.
Impact of Solid Waste Dumpsite on Groundwater Quality in the Neighbouring Communities
Authors: Ajibade O. V. , Ogungbile P. O. , Sridhar M. K. C. , Coker A. O.
Published: December 2019

Leachate seepages into groundwater aquifer from solid waste dumpsites is likely to release toxic pollutants in groundwater which are hazardous to human health and local ecosystem. A study was conducted on the Physico-chemical parameters of dumpsite leachate and surrounding groundwater from Awotan Solid Waste Dumpsite, in Ibadan, Oyo State. The study was aimed at assessing the impact of the leachate from the dumpsite. The physicochemical analyses of the water samples were carried by standard analytical methods. The results obtained were compared with the WHO (World Health Organization) permissible limit of those parameters in drinking water. The Physico-chemical values obtained for the dumpsite leachate were generally higher than those of groundwater samples, suggesting that a source of contamination could be from the dumpsite leachate. The pH of groundwater samples ranged between 5.03 to 6.94, indicating that the groundwater was acidic. Results of Physico-chemical parameters of dumpsite leachate for Cl-, NO3, TH, Alk, BOD, COD exceeded the WHO limits for drinking water. The BOD and COD of dumpsite leachate and groundwater samples exceeded the WHO limits and hence not safe for drinking. The concentration of Cl- and TH in the groundwater closer to the dumpsite were higher than WHO permissible limits for drinking water. Also, concentrations of the analyzed parameters decreased with increasing distance from the dumpsite, thus implicating leachate seepage from the dumpsite into the groundwater. It is therefore recommended that dumpsites be located away from the human settlements to avoid drinking water contamination and local ecosystem & biodiversity degradation.
Antifungal Activity of Copper, Zinc and Potassium Compounds on Mycelial Growth and Conidial Germination of Fusarium solani f. sp. piperis
Authors: Dos Santos Renata Aparecida Ahnert , D’Addazio Verônica , Silva João Vitor Garcia , Falqueto Antelmo Ralph , Barreto da Silva Marcelo , Schmildt Edilson Romais , Fernandes Adriano Alves
Published: December 2019

Fusariosis is a disease that causes economic damage to black pepper (Piper nigrum L.) producers. Despite being a major disease, there is no record of efficient chemical control. Thus, the objective was to evaluate the antifungal activity of copper, zinc and potassium compounds in mycelial growth and conidial germination of Fusarium solani f. sp. piperis in vitro. For inoculation in PDA (Potato Dextrose Agar) medium, 7 mm discs from the pure culture were transferred to Petri dishes. The plates were incubated at 25ºC in a biochemical oxygen demand (BOD) chamber, with photoperiod of 12 h, for 15 days. Micronutrients were supplied as sulfates, CuSO4 (copper sulfate) and ZnSO4 (zinc sulfate), at concentrations of 1, 5, 10, 15 and 20 mmol/L. Potassium macronutrient (K) was supplied as KCl (potassium chloride) at concentrations of 30, 60, 90,120 and 150 mmol/L. The experiment was performed using a completely randomized design with 6 treatments and ten replications. CuSO4 showed fungicidal effect at concentrations of 10, 15 and 20 mmol/L. For ZnSO4 mycelial growth was completely inhibited at concentrations of 15 and 20 mmol/L. There was no inhibition or reduction of fungal growth in the presence of K. Copper and zinc at minimal concentrations were efficient in controlling mycelial growth and inhibition of spore germination of F. solani f. sp. piperis. In contrast, potassium did not exert fungicidal or fungistatic effect on the fungus.
Incorporating Cannibalization into Pricing Optimization Using Choice Data: An Application to the Pricing of Mobile Broadband Services
Authors: Pratikto Fransiscus Rian
Published: December 2019

Price differentiation may not be as effective in increasing profitability due to imperfect segmentation, arbitrage, and, cannibalization. Cannibalization takes place when customer with higher willingness-to-pay buys lower-priced product. This research proposes an approach to incorporating cannibalization into pricing optimization using choice data. From choice data, individual level utilities are estimated using hierarchical Bayes and individual choice is predicted using randomized first choice simulation. Individual choices are then aggregated to obtain the demand function. The novelty of this research is in the way cannibalization is incorporated into the pricing optimization. Instead of integrating cannibalization into the demand function or representing it as a separate component in the optimization formulation, in this research, cannibalizing products are incorporated into the simulation scenario as competing products, based on which the demand functions used in the optimization are derived. This approach is more direct and realistic than those in the previous research. The approach was implemented in a case study of mobile broadband services in Indonesian price-sensitive market. The result shows that two-fare-class price differentiation incoporated with product differentiation increases total contribution of about 60% compared to single-fare-class policy. Furthermore, it is also shown from our case study that starting from a three-fare-class policy, through iterations, our approach suggests that policy with two-fare-class results in a not significantly different total contribution.
Synchronous 3D Bioprinting of Large‐Scale Cell‐Laden Constructs with Nutrient Networks
Authors: Shao Lei , Gao Qing , Xie Chaoqi , Fu Jianzhong , Xiang Meixiang , He Yong
Published: December 2019

Maintaining an adequate supply of nutrients/oxygen is a major challenge in the biofabrication of large tissue constructs. However, building preformed nutrient networks may be an effective strategy for engineering thick tissues. Here, a novel way for bioprinting large‐scale tissue constructs with intentional nutrient networks is presented. A special nozzle is developed which can print bioink and sacrificial ink half and half synchronously in a single filament. Nutrient networks of these bioprinted constructs are formed by subsequently dissolving away gelatin, which allows for effective oxygen, nutrient, and waste diffusion, facilitating the cell activity and the generation of functional tissues. Due to the cell‐laden bioink and sacrificial ink working together and promoting each other's printability to support themselves, complex soft cell‐laden constructs with nutrient networks can easily be printed. Furthermore, two different cell types (osteoblast, human umbilical vein endothelial cells) encapsulated in the bioprinted large‐scale constructs (≥1 cm) with nutrient networks show enhanced cell viability and spreading within a period of culture. It is envisioned that the advanced bioprinting technology may have significant potentials in facilitating the engineering of complex structures for tissue‐specific needs, and bioprinting large‐scale tissue constructs with nutrient networks toward applications in organ transplantation and repair.
S‐(Diethyl phosphonodifluoromethyl)Benzenesulfonothioate: A New Reagent for the Synthesis of SCF2PO(OEt)2‐containing Molecules
Authors: Petit‐Cancelier Fabien , François Benjamin , Pannecoucke Xavier , Couve‐Bonnaire Samuel , Besset Tatiana
Published: December 2019

In this manuscript, the synthesis of an original SCF2PO(OEt)2‐containing reagent was depicted. Thanks to the unique properties of this newly‐designed source, an unprecedented transformation with aldehydes was conducted under radical conditions, offering an access to value‐added fluoroalkylthio compounds. Preliminary mechanistic studies were conducted and supported a radical reaction mechanism. Remarkably, thiol and disulfide derivatives turned out to be suitable coupling partners in a transition metal free transformation towards the synthesis of difficult‐to‐synthesize unsymmetrical disulfides. Finally, the difunctionalization of 4‐phenyl‐butene was investigated using this reagent.

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Substrate‐Induced Dimerization Assembly of Chiral Macrocycle Catalysts toward Cooperative Asymmetric Catalysis
Authors: Guo Hao , Zhang Lie‐Wei , Zhou Hao , Meng Wei , Ao Yu‐Fei , Wang De‐Xian , Wang Qi‐Qiang
Published: December 2019

An artificial system of substrate‐induced dimerization assembly of chiral macrocycle catalysts enables a highly cooperative hydrogen‐bonding activation network for efficient enantioselective transformation. These macrocycles contain two thiourea and two chiral diamine moieties and dimerize with sulfate to form a sandwich‐like assembly. The macrocycles then adopt an extended conformation and reciprocally complement the hydrogen‐bonding interaction sites. Inspired by the guest‐induced dynamic assembly, these macrocycles catalyze the decarboxylative Mannich reaction of cyclic aldimines containing a sulfamate heading group. The imine substrate can be activated toward nucleophilic attack of β‐ketoacid by a cooperative hydrogen‐bonding network enabled by sulfamate‐induced dimerization assembly of the macrocycle catalysts. Highly efficient (>95 % yield in most cases) and enantioselective (up to 97.5:2.5 er) transformation of a variety of substrates using only 5 mol % macrocycle was achieved.
Near perfect thin film flexible broadband optical absorber with high thermal/electrical conductivity
Authors: Ghai Viney , Singh Harpreet , Agnihotri Prabhat K.
Published: December 2019

Flexible ultra‐black absorber with high thermal/electrical conductivity finds huge applications in the field of stray light attenuation, solar collectors, flexible electronics, and electronic thermal management systems. In this work, we report the fabrication of ultrablack absorber consists of vertically aligned carbon nanotubes (VACNT) in Polydimethylsiloxane (PDMS) having an absorption capacity of more than 98% in UV–Vis wavelength and more than 94% in NIR wavelength range. It is observed that the PDMS‐VACNT composite shows ultra‐high absorption capacity due to enhanced impedance matching and multiple scattering. In addition to this, the PDMS‐VACNT composite shows an emissivity of 0.94 along with a 118% increase in thermal conductivity. Moreover, with the infiltration of VACNT in PDMS, the sheet resistance decrease drastically to 0.08 KΩ/sq, which signify the possible use of ultrablack absorber in electronic skin and flexible sensors etc. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48855.
Local metric with parameterized evolution
Authors: Land Martin
Published: December 2019

We present a canonical Hamiltonian formulation of general relativity in which τ, the parameter of system evolution, is external to spacetime, playing a role similar to what we call time in nonrelativistic mechanics. This approach, known as Stueckelberg–Horwitz–Piron (SHP) theory, inherits the full computational power of classical analytical mechanics while maintaining manifest covariance throughout and eliminating possible conflict with general diffeomorphism invariance. In particular, SHP theory simplifies the initial value problem with potential applications in highly dynamical interactions, such as black hole collisions. By allowing the energy–momentum tensor and metric to depend explicitly on τ, we may describe particle motion in geodesic form with respect to a dynamically evolving background metric. As a toy model, we consider a τ‐dependent mass M(τ), first as a perturbation in the Newtonian approximation and then for a Schwarzschild‐like metric. As expected, the extended Einstein equations imply a nonzero energy–momentum tensor, proportional to dM/dτ, representing a flow of mass and energy into spacetime that corresponds to the changing source mass. In τ‐equilibrium, this system becomes a generalized Schwarzschild solution for which the extended Ricci tensor and energy–momentum tensor vanish.
Process design and evaluations for producing pyrolytic jet fuel
Authors: Liu Yu‐Cheng , Wang Wei‐Cheng
Published: December 2019

In this study, process simulation and techno‐economic analysis (TEA) were conducted to evaluate the production of renewable jet fuel (RJF) through the pyrolysis‐to‐RJF process. The process model was developed based on experimental results for the renewable jet fuel production process using the fast pyrolysis of rice husk, hydro‐processing of pyrolytic oil, and hydro‐cracking / isomerization of hydro‐processed oil. The mass and energy flows were input into the TEA model, which was established based on local conditions in Taiwan. The study included three parts: (1) the mass, energy and carbon balances – the major product, RJF, gave an energy yield of 26.8%, a mass yield of 9%, and a carbon yield of 21%; (2) an economic analysis – the MJSP of RJF for the pyrolysis‐to‐RJF process was $3.21/L, based on the plant capacity of 600 tonnes per day; (3) a sensitivity analysis: the impacts of the feedstock cost, catalyst life, co‐product selling price, catalyst cost, hydrogen cost, and plant capacity were discussed. This study demonstrated the economic potential of locally developing a pyrolysis‐to‐RJF process to produce RJF from solid biomass. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
The Activation of Glycerol Dehydrogenase from Escherichia coli by ppGpp
Authors: Hoang Huyen Nga , Tran Thanh Tuyen , Jung Che‐Hun
Published: December 2019

Glycerol dehydrogenase (GldA) from Escherichia coli is a Zn2+‐containing alcohol dehydrogenase which catalyzes the NAD+‐dependent oxidation of glycerol to dihydroxyacetone. In this study, GldA has been cloned, over‐expressed, and isolated by an affinity and an ion‐exchange chromatography. GldA shows a strong intrinsic fluorescence at 320 nm, when excited at 280 nm. The fluorescence intensity decreases in the presence of NAD+, NADH, and dihydroxyacetone, the substrate and products for GldA, which allows us to determine the dissociation constants for those molecules as 110.6 ± 5.0 μM, 9,1 ± 0.6 μM, 33.3 ± 2.3 mM, respectively. The dissociation constant for NAD+ was similar to the kinetic constant, KM. Guanosine‐5′‐diphosphate 3′‐diphosphate (ppGpp), accumulated in E. coli when starved for amino acids, nutrients, and phosphate, serves as a global regulator in replication, transcription, and translation. In this study, the fluorescence intensity of GldA also decreases in the presence of ppGpp and the dissociation constant for ppGpp is calculated as 108.9 ± 8.6 μM. ppGpp increases GldA activity with the half maximal activation at 33.1 ± 3.1 μM. On the contrary, GTP and GDP inhibit GldA, with the inhibition constants of 16.1 ± 1.1 mM and 10.6 ± 0.3 mM, respectively. Tris(hydroxymethyl)aminomethane serves as a competitive inhibitor against glycerol. GTP and GDP also bind to GldA with the dissociation constants of 60.0 ± 0.8 and 61.0 ± 1.3 μM, respectively. These results suggest that GTP and GDP bind to GldA as strongly as ppGpp but only ppGpp activates GldA. This study shows that ppGpp binds to GldA and activates its activity for the first time. It is also suggested that the strong intrinsic fluorescence of enzymes and their changes in the presence of various ligands can be utilized to measure the binding affinities for those ligands. The method described here is especially effective for bindings with the relatively lower affinities.
Big Data – How to Realize the Promise
Authors: Cave Alison , Brun Nikolai C. , Sweeney Fergus , Rasi Guido , Senderovitz Thomas ,   the HMA‐EMA Joint Big Data Taskforce
Published: December 2019

The increasing volume and complexity of data now being captured across multiple settings and devices offers the opportunity to deliver a better characterization of diseases, treatments, and the performance of medicinal products in individual healthcare systems. Such data sources, commonly labeled as big data, are generally large, accumulating rapidly, and incorporate multiple data types and forms. Determining the acceptability of these data to support regulatory decisions demands an understanding of data provenance and quality in addition to confirming the validity of new approaches and methods for processing and analyzing these data. The Heads of Agencies and the European Medicines Agency Joint Big Data Taskforce was established to consider these issues from the regulatory perspective. This review reflects the thinking from its first phase and describes the big data landscape from a regulatory perspective and the challenges to be addressed in order that regulators can know when and how to have confidence in the evidence generated from big datasets.
Develop strategies now to protect faculty from targeted harassment
Authors: Pavlik Amelia
Published: December 2019

A ride through the “right‐wing echo chamber” — this is what C. Kyle Rudick knew was in store as soon as he was contacted by a columnist from Campus Reform, a conservative news site.
Reflect upon life for self‐improvement
Authors: Hodges Dawn Z.
Published: December 2019

It's no coincidence that this column is entitled “The Reflective Leader.” If you're a regular reader, you know that I spend a lot of time considering, pondering, wondering, thinking, and reflecting. I know that introspection is not everyone's thing, but anyone can benefit from a bit of soul‐searching every now and then.
How to use clinical signs and symptoms to estimate the probability of limb ischaemia in patients with a diabetic foot ulcer
Authors: Boyko Edward J.
Published: December 2019

Assessment of ischaemia and interventions to improve perfusion are key elements in the management of the diabetic foot ulcer to achieve wound healing. This article will review, analyse and interpret the value of clinical information in determining the likelihood of limb ischaemia and thereby the need for referral to a vascular specialist. I conducted an historical review of the genesis of several currently recommended clinical signs and their diagnostic properties in the assessment of limb ischaemia. Changes in limb ischaemia probability based on such results were calculated using Bayes theorem, and the use of such probabilities is discussed in the context of the threshold approach to clinical decision making. Some clinical signs have negligible value in altering probability of limb ischaemia, possibly because they were advocated by Buerger for the diagnosis of thromboangiitis obliterans, an occlusive vascular disease of a different pathophysiology than atherosclerosis. Pedal pulse palpation, the most widely studied clinical sign, will marginally change a pre‐test probability of ischaemia of 50% to 76% if positive (abnormal pulses) and to 36% if negative (normal pulses). Higher or lower pre‐test probabilities of ischaemia will change the post‐test probabilities such that these are too low or high to rule in or rule out ischaemia, respectively. Individual clinical signs convey little information regarding the presence of limb ischaemia but may have some value in combination or with pre‐test probability near 50% in the assessment of ischaemia and the decision to refer for a vascular consultation.
A systems thinking perspective on the barriers to treatment access for people with eating disorders
Authors: Lane Ben R. , Read Gemma J. M. , Cook Lesley , Salmon Paul M.
Published: December 2019

Treatment access remains low for people with eating disorders. In addressing the complexity inherent in this challenge, this article introduces systems thinking and argues that it could provide new insights. Systems thinking views behavior as an emergent property of a system and considers the relationships between technical, organizational, and social components. Several methods used in safety science incorporate this thinking. For example, AcciMap draws focus to the influence of decisions and actions made across hierarchical levels of a system, including those by government, regulatory bodies, management, services, and individuals. By examining the findings of the existing literature on barriers to eating disorder treatment access according to these levels, it is evident that most identified barriers relate to individuals and that further research is needed to consider the influence of high‐level stakeholders. Research using systems thinking should consider the causal networks of influence from government, regulatory, and organizational decisions and actions through to outcomes for clinicians and individuals. The understanding of how barriers operate within specific healthcare systems also warrants investigation. Systems thinking is yet to be formally applied in the area of eating disorders and thus represents an opportunity to inform the development and implementation of more effective, system wide interventions.
Arc temperature measurement with microsecond spectroscopic measurement
Authors: Kano Ryota , Nemoto Yusuke , Maeda Yoshifumi , Yamamoto Shinji , Iwao Toru
Published: December 2019

The quality of electric power caused by frequency fluctuation and voltage rise will be degraded because of the lightning surge and the mass introduction of distributed power. Thus, it is necessary to improve the performance of gas circuit breaker in order to maintain the stable supply of electric power. It has been reported that the arc conductance is calculated as the index of the current interruption in numerical analysis. However, few report have the measured value in the current interruption. This is because that the current interruption is the steep phenomenon of micro seconds range. Thus, it is necessary to establish the time‐high precision and noncontact measurement method. In this paper, the arc temperature is measured near current zero using the microsecond spectroscopic measurement. As a result, the microsecond spectroscopic measurement which combines the conventional spectroscope and the high speed video camera is 200 times faster than the measurement of conventional spectroscope. For this reason, the microsecond spectroscopic measurement is possible with the high speed video camera. Therefore, it is possible to measure the arc temperature with decreasing the current using the microsecond spectroscope.
Highly Sensitive Electrochemiluminescent Insecticide Sensor Based on ZnO Nanocrystals Anchored Nickel Foam for Determination of Imidacloprid in Real Samples
Authors: Kamyabi Mohammad Ali , Moharramnezhad Mohsen
Published: December 2019

In this work, a novel electrochemiluminescent (ECL) pesticide sensor based on zinc oxide nanocrystals decorated nickel foam is proposed for determination of imidacloprid for the first time. The silica film was used as a morphology‐controlling factor for modification of the electrode with zinc oxide nanocrystals. Zinc oxide was selected as luminescent material due to its cheapness, non‐toxicity, high thermal stability and excellent luminescence properties which truly adhered on the surface of nickel foam. The K2S2O8 was used as strong co‐reactant for this purpose. The silica template plays an important role in controlling the size of ZnO nanocrystals. The Physical morphology of the ZnO/Ni‐foam electrode was performed by electrochemical impedance spectroscopy, Brunauer‐Emmett‐Teller (BET), X‐Ray diffraction analysis, field emission scanning electron microscopy, and energy‐dispersive X‐ray analysis. The ultra‐sensitive electrochemiluminescence method was successfully used for ultra‐trace determination of imidacloprid. The linear dynamic range and low detection limit were obtained 3×10−14 −8×10−8 M and 4.4×10−15 M, respectively. Also, the relative standard deviation for 15 repetitive optical signals was calculated 1.09 %.The present ECL sensor exhibited superior performance toward the accurate determination of imidacloprid with good reproducibility and stability.
The Longitudinal Development of Grammatical Complexity at the Phrasal and Clausal Levels in Spoken and Written Responses to the TOEFL iBT® Test
Authors: Gray Bethany , Geluso Joe , Nguyen Phuong
Published: December 2019

In the present study, we take a longitudinal, corpus‐based perspective to investigate short‐term (over 9 months) linguistic change in the language produced for the spoken and written sections of the TOEFL iBT® test by a group of English‐as‐a‐foreign‐language (EFL) learners in China. The goal of the study is to identify patterns that characterize the trajectory that language learners move through in terms of their use of phrasal and clausal grammatical complexity, as mediated by mode (spoken and written) and task type (independent and integrated). Results of a multidimensional analysis reveal that in many cases, learners developed in expected ways: discourse styles at Time 1 were not always aligned with mode‐ and task type‐specific discourse patterns but developed over time, with discourse styles at Time 2 better approximating expected norms and exhibiting increased task differentiation. These changes were particularly noteworthy for Dimension 1, which is related to phrasal and clausal complexity. Results of a developmental complexity analysis revealed more mixed results, seeming to indicate that the relatively low‐proficiency learners represented by the longitudinal corpus may just be beginning on the hypothesized paths of development. The most important developments occurred for independent writing, in which students exhibited increases in the frequency of phrasal features, as well as functional expansion in the use of a range of complexity features.
Safety evaluation of arabinase (arabinan endo‐1,5‐α‐L‐arabinanase) from Aspergillus tubingensis
Authors: Okado Nobuo , Sugi Mai , Kasamoto Sawako , Mizuhashi Fukutaro , Roberts Ashley , Danielewska‐Nikiel Barbara , Sulaiman Christina , Pham Sa
Published: December 2019

Arabinase is an enzyme recognized for its ability to degrade arabinan, a plant cell wall constituent. It has been applied in the food industry most commonly for juice processing. One commercial source of arabinase is Aspergillus tubingensis (A. tubingensis), a black Aspergillus species. Given the intended use in food for human consumption, and noting its potential presence at trace levels in finished products, a series of safety studies including in vitro Ames and chromosome aberration assays, in vivo mammalian erythrocyte micronucleus and alkaline comet assays, and a 90‐day rat oral toxicity study were conducted. No test article‐related mutagenic activity was observed in the Ames assay. Although positive activity was observed in the chromosome aberration assay, this was not replicated in the in vivo genotoxicity assays including in preabsorptive cells. In the subchronic toxicity study, no test article‐related adverse effects were observed following oral administration of arabinase at doses of 15.3, 153, or 1,530 mg total organic solids (TOS)/kg body weight/day to Sprague Dawley rats. The no‐observed‐adverse‐effect level was considered to be the highest dose tested (1,530 mg TOS/kg body weight/day). The results of the genotoxicity studies and the subchronic toxicity study support the safe use of arabinase from A. tubingensis in food production.
Physiochemical properties of short‐term frying oil for chicken wing and its oxidative stability in an oil‐in‐water emulsion
Authors: Jiang He , Chen Wenwei , Jia Zhenbao , Tao Fei
Published: December 2019

In this study, the physiochemical properties of corn oil and its oxidative stability in an O/W emulsion were studied following short‐term (120 min) deep‐frying of chicken wing. The results showed that the levels of polyunsaturated fatty acids in corn oil decreased after frying. Furthermore, total polar compound content in frying oil was significantly increased to 11.3%. Fourier transform infrared spectra (FTIR) indicated that hydrolysis and oxidation reactions involving triglycerides occurred after frying. Additionally, the increased a* and b* values demonstrated that deep‐frying greatly enhanced the intensity of the red and yellow colors of corn oil. Frying reduced the oxidative stability of corn oil in an O/W emulsion as determined by the peroxide value and acid value. These findings indicated that short‐term deep‐frying of chicken wing deteriorated the quality of corn oil and decreased its oxidative stability in an O/W emulsion. Consumers should consider the potential hazards of food containing short‐term deep‐frying oil.
How ‘Green’ Is Green—An Overview of Carbon Emissions From Clean Energy Resources
Authors: Currey Brad R.
Published: December 2019

The development and use of renewable energy resources in response to climate change has received significant public attention due to recent climate activism, as well as various proposals put forth by politicians and elected officials. Clearly, there is increasing interest and desire among many, including the clean energy sector, the general public, environmentalists, and public officials, to name a few, to expand and increase the use of clean energy resources to reduce carbon dioxide and other greenhouse gas (GHG) emissions associated with the use of fossil fuels. Consider the politicizing of climate change and clean energy by the Democratic presidential candidates. Some have gone as far as to call for a renewable/net‐zero carbon emissions economy in their energy plans. These goals, though laudable, raise two issues worthy of discussion—the reality of achieving a fossil‐free future from where we currently are in 2019, and determining how truly “green” we can be with our current technologies in terms of large‐scale adoption of renewable technologies in order to reduce carbon emissions.
The relative risk of noncervical high‐risk human papillomavirus‐related (pre)malignancies after recurrent cervical intraepithelial neoplasia grade 3: A population‐based study
Authors: Loopik Diede L. , Ebisch Renée M. , IntHout Joanna , Melchers Willem J. , Massuger Leon F. , Bekkers Ruud L. , Siebers Albert G.
Published: December 2019

Women with cervical intraepithelial neoplasia grade 3 (CIN3) have a long‐lasting increased risk for noncervical high‐risk human papillomavirus (hrHPV)‐related (pre)malignancies. The aim of our study was to estimate this risk in women with recurrent CIN3 compared to women without a history of CIN3 and women with a single episode of CIN3. Women with a CIN3 diagnosis between 1990 and 2010 were obtained from the Dutch Pathology Registry (PALGA) and matched with a control group of women without CIN3. Analysis has been conducted in a subset of women with recurrent CIN3, defined as reoccurrence minimally 2 years post‐treatment. Cases of noncervical hrHPV‐related (pre)malignancies of the anus, vulva, vagina and oropharynx were identified until 2015 and incidence rate ratios (IRRs) were estimated. Then, 1,797 women with recurrent CIN3 were included with a median age of 34 years (range 18–76) and 31,594 person‐years of follow‐up. Women with recurrent CIN3 had an increased risk of developing noncervical hrHPV‐related (pre)malignancies compared to women without CIN3 with an IRR of 25.96 (95%CI 6.32–106.58). The IRR was 2.48 (95% CI 1.87–3.30) compared to women with a single episode of CIN3. Studies on posttreatment follow‐up and prophylactic hrHPV vaccination are warranted.
Adenosine receptor 2B activity promotes autonomous growth, migration as well as vascularization of head and neck squamous cell carcinoma cells
Authors: Wilkat Max , Bast Hanna , Drees Robert , Dünser Johannes , Mahr Amelie , Azoitei Ninel , Marienfeld Ralf , Frank Felicia , Brhel Magnus , Ushmorov Alexey , Greve Jens , Goldberg‐Bockhorn Eva , Theodoraki Marie‐Nicole , Doescher Johannes , Laban Simon , Schuler Patrick J. , Hoffmann Thomas K. , Brunner Cornelia
Published: December 2019

Adenosine is a signaling molecule that exerts dual effects on tumor growth: while it inhibits immune cell function and thereby prevents surveillance by the immune system, it influences tumorigenesis directly via activation of adenosine receptors on tumor cells at the same time. However, the adenosine‐mediated mechanisms affecting oncogenic processes particularly in head and neck squamous cell carcinomas (HNSCC) are not fully understood. Here, we investigated the role of adenosine receptor activity on HNSCC‐derived cell lines. Targeting the adenosine receptor A2B (ADORA2B) on these cells with the inverse agonist/antagonist PSB‐603 leads to inhibition of cell proliferation, transmigration as well as VEGFA secretion in vitro. At the molecular level, these effects were associated with cell cycle arrest as well as the induction of the apoptotic pathway. In addition, shRNA‐mediated downmodulation of ADORA2B expression caused decreased proliferation. Moreover, in in vivo xenograft experiments, chemical and genetic abrogation of ADORA2B activity impaired tumor growth associated with decreased tumor vascularization. Together, our findings characterize ADORA2B as a crucial player in the maintenance of HNSCC and, therefore, as a potential therapeutic target for HNSCC treatment.
Transcriptomic effect marker patterns of genotoxins – a comparative study with literature data
Authors: Kreuzer Katrin , Frenzel Falko , Lampen Alfonso , Braeuning Albert , Böhmert Linda
Published: December 2019

Microarray approaches are frequently used experimental tools which have proven their value for example in the characterization of the molecular mode of action of toxicologically relevant compounds. In a regulatory context, omics techniques are still not routinely used, amongst others due to lacking standardization in experimental setup and data processing, and also due to issues with the definition of adversity. In order to exemplarily determine whether consensus transcript biomarker signatures for a certain toxicological endpoint can be derived from published microarray datasets, we here compared transcriptome data from human HepaRG hepatocarcinoma cells treated with different genotoxins, based on re‐analyzed datasets extracted from the literature. Comparison of the resulting data show that even with similarly‐acting compounds in the same cell line, considerable variation was observed with respect to the numbers and identities of differentially expressed genes. Greater concordance was observed when considering the whole data sets and biological functions associated with the genes affected. The present results highlight difficulties and possibilities in inter‐experiment comparisons of omics data and underpin the need for future efforts towards improved standardization to facilitate the use of omics data in risk assessment. Existing omics datasets may nonetheless prove valuable in establishing biological context information essential for the development of adverse outcome pathways.
Meso‐macroporous crack‐free nanohydroxyapatite coatings templated by C12E10 diblock copolymer on Ti6Al4V implant materials toward human osteoblast‐like cells
Authors: Sharafipour Marjan , Oveisi Hamid , Meshkini Azadeh
Published: December 2019

Meso‐macroporous nanohydroxyapatite coatings (MHACs) were synthesized on Ti6Al4V implant materials calcined at different temperatures using a nonionic diblock copolymer template (C12E10) by sol–gel and dip‐coating methods. To improve the bonding strength between the substrate and coating, a TiO2 intermediate layer was applied on the surface of the substrates. The physicochemical and structural properties of MHAC samples were fully studied by X‐ray diffraction, X‐ray photoelectron spectroscopy, Fourier‐transform infrared spectroscopy, scanning probe microscopy, field‐emission scanning electron microscopy (FESEM), Brunauer–Emmett–Teller method, and contact angle measurements. Based on the data obtained, the hydroxyapatite phase with a flower‐like morphology was formed on the Ti6Al4V substrates in all of the samples. According to confocal optical microscopy and FESEM images, there was no macrocrack and microcrack on the MHACs, whereas they were accompanied by macroporosities and mesoporosities on top of the coatings. By increasing the calcination temperature from 500°C to 650°C, the crystallite sizes increased, while the surface roughness value and hydrophilicity decreased. A reduction in specific surface area and an increase in the pore diameters occurred as the calcination temperature increased. In addition, the assessment of protein adsorption behavior over the samples revealed that the adsorption amounts significantly increased as the substrates were coated with HAP; however, the affinity of surface for protein adsorption was strictly dependent on the surface topography and hydrophilicity. in vitro cellular assay disclosed a great cytocompatibility in terms of adhesion and proliferation in MHAC samples as compared with that in TiO2‐coated and bare substrates. Regarding the physicochemical properties and biological studies, MHAC calcined at 650°C was deemed optimal for bone tissue engineering.
BAND NN: A Deep Learning Framework for Energy Prediction and Geometry Optimization of Organic Small Molecules
Authors: Laghuvarapu Siddhartha , Pathak Yashaswi , Priyakumar U. Deva
Published: December 2019

Recent advances in artificial intelligence along with the development of large data sets of energies calculated using quantum mechanical (QM)/density functional theory (DFT) methods have enabled prediction of accurate molecular energies at reasonably low computational cost. However, machine learning models that have been reported so far require the atomic positions obtained from geometry optimizations using high‐level QM/DFT methods as input in order to predict the energies and do not allow for geometry optimization. In this study, a transferable and molecule size‐independent machine learning model bonds (B), angles (A), nonbonded (N) interactions, and dihedrals (D) neural network (BAND NN) based on a chemically intuitive representation inspired by molecular mechanics force fields is presented. The model predicts the atomization energies of equilibrium and nonequilibrium structures as sum of energy contributions from bonds (B), angles (A), nonbonds (N), and dihedrals (D) at remarkable accuracy. The robustness of the proposed model is further validated by calculations that span over the conformational, configurational, and reaction space. The transferability of this model on systems larger than the ones in the data set is demonstrated by performing calculations on selected large molecules. Importantly, employing the BAND NN model, it is possible to perform geometry optimizations starting from nonequilibrium structures along with predicting their energies. © 2019 Wiley Periodicals, Inc.
A Hydrogel Vitreous Substitute that Releases Antioxidant
Authors: Tram Nguyen K. , Jiang Pengfei , Torres‐Flores Tiara C. , Jacobs Kane M. , Chandler Heather L. , Swindle‐Reilly Katelyn E.
Published: December 2019

Current experimental vitreous substitutes only replace the physical functions of the natural vitreous humor. Removal of the native vitreous disrupts oxygen homeostasis in the eye, causing oxidative damage to the lens that likely results in cataract formation. Neither current clinical treatments nor other experimental vitreous substitutes consider the problem of oxidative stress after vitrectomy. To address this problem, biomimetic hydrogels are prepared by free radical polymerization of poly(ethylene glycol) methacrylate and poly(ethylene glycol) diacrylate. These hydrogels have similar mechanical and optical properties to the vitreous. The hydrogels are injectable through small‐gauge needles and demonstrate in vitro biocompatibility with human retinal and lens epithelial cells. The hydrogels and added vitamin C, an antioxidant, show a synergistic effect in protecting ocular cells against reactive oxygen species, which fulfills a chemical function of the natural vitreous. These hydrogels have the potential to prevent post‐vitrectomy cataract formation and reduce the cost of additional surgeries.
Grain morphology and texture evolution of TC21 titanium alloy during annealing with different time
Authors: Xin L.‐P. , Wang K. , Yan Z.‐B. , Li D.‐R. , Xin R.‐L. , Liu Q.
Published: December 2019

A homogeneous equiaxed‐structure TC21 titanium alloy is hot rolled and annealed for different time ranging from 1 h to 6 h. The grain morphology and texture evolution of α and β phases during annealing are mainly investigated using the electron back‐scattered diffraction characterization. In the early annealing stage, the α grain mainly maintains the elongated morphology generated in the rolling. With increasing annealing time, more and more elongated α grains become equiaxed due to enhanced static recrystallization and boundary splitting. Differently, the β grain exhibits a fully equiaxed morphology all the time due to the sufficient static recrystallization, and get a coarsening with increasing annealing time. The α phase exhibits a (0001) basal texture in the early annealing stage, and then forms a TD‐split texture with increasing annealing time. The β phase exhibits the {001}<110> texture at every annealing time. Based on the analysis about the texture of different grain sizes, the effects of recrystallization nucleation and oriented growth on texture evolution are discussed. It suggests that TD‐split texture in α phase is originated from both the recrystallization nucleation and oriented growth. The formation of {001}<110> texture in β phase is mainly originated from the oriented growth.
Major weapons procurement: An efficiency‐based approach for the selection of fighter jets
Authors: Lu Wen‐Min , Kweh Qian Long , Nourani Mohammad , Shih Jui‐Min
Published: December 2019

This study applies the epsilon‐based measure method in data envelopment analysis (DEA) to evaluate processes in procuring fighter jets (FJs), which are indicative of the technology and capability of major weapons. Moreover, multidimensional scaling analysis and sensitivity analysis were included to assess the selection of FJs. The DEA analysis indicates that the overall efficiency of the sample of 26 FJs was 0.824 on average. Besides, procurers rely on price and capability to decide which FJ models to purchase. Overall, the evaluation results can be provided to procurement decision makers even in selecting other types of major weapon in a cost‐effective manner.
Tennessee enhances peer program with web‐based video project
Authors: Canady Valerie A.
Published: December 2019

Observing a need to highlight the value peers bring to the behavioral health field is the impetus behind a new web‐based video project series unveiled by the Tennessee Department of Mental Health and Substance Abuse Services (TDMHSAS) earlier this month. In the videos, 14 individuals recount their recovery process and their efforts to inspire hope in others.
On the multidimensional zeta functions associated with theta functions, and the multidimensional Appell polynomials
Authors: Bayad Abdelmejid , Hajli Mounir
Published: December 2019

We define and study the multidimensional Appell polynomials associated with theta functions. For the trivial theta functions, we obtain the various well‐known Appell polynomials. Many other interesting examples are given. To push our study, by Mellin transform, we introduce and investigate the multidimensional zeta functions associated with thetas functions and prove that the multidimensional Appell polynomials are special values at the nonpositive integers of these zeta functions. Using zeta functions techniques, among others, we prove an induction formula for multidimensional Appell polynomials. The last part of this paper is devoted to spectral zeta functions and its generalization associated with Laplacians on compact Riemannian manifolds. From this generalization, we construct new Appell polynomials associated with Riemannan manifolds of finite dimensions.
Combining In Vitro Data and Physiologically Based Kinetic Modeling Facilitates Reverse Dosimetry to Define In Vivo Dose–Response Curves for Bixin‐ and Crocetin‐Induced Activation of PPARγ in Humans
Authors: Suparmi Suparmi , de Haan Laura , Spenkelink Albertus , Louisse Jochem , Beekmann Karsten , Rietjens Ivonne M. C. M.
Published: December 2019

Scope

It is investigated whether at realistic dietary intake bixin and crocetin could induce peroxisome proliferator‐activated receptor γ (PPARγ)‐mediated gene expression in humans using a combined in vitro–in silico approach.

Methods and results

Concentration–response curves obtained from in vitro PPARγ‐reporter gene assays are converted to in vivo dose–response curves using physiologically based kinetic modeling‐facilitated reverse dosimetry, from which the benchmark dose levels resulting in a 50% effect above background level (BMD50) are predicted and subsequently compared to dietary exposure levels. Bixin and crocetin activated PPARγ‐mediated gene transcription in a concentration‐dependent manner with similar potencies. Due to differences in kinetics, the predicted BMD50 values for in vivo PPARγ activation are about 30‐fold different, amounting to 115 and 3505 mg kg bw−1 for crocetin and bixin, respectively. Human dietary and/or supplemental estimated daily intakes may reach these BMD50 values for crocetin but not for bixin, pointing at better possibilities for in vivo PPARγ activation by crocetin.

Conclusion

Based on a combined in vitro–in silico approach, it is estimated whether at realistic dietary intakes plasma concentrations of bixin and crocetin are likely to reach concentrations that activate PPARγ‐mediated gene expression, without the need for a human intervention study.