bluuebunny/crossref_metadata_2025 huggingface dataset:
Internodular functional connectivity in heterotopia‐related epilepsy
Authors: Khoo Hui Ming , von Ellenrieder Nicolás , Zazubovits Natalja , Hall Jeffery A. , Dubeau François , Gotman Jean
Published: May 2019

Objective

A vast network involving the nodules and overlying cortices is believed to be responsible for the epileptogenicity in gray matter heterotopia with multiple nodules, which often associated with difficult‐to‐treat epilepsy. We sought to determine if functional magnetic resonance imaging (fMRI) could detect internodular functional connectivity (FC), and if this connectivity reflects an actual synchronized neuronal activity and partakes in epileptogenicity.

Methods

We studied 16 epilepsy patients with multiple heterotopic nodules; eight underwent subsequent intracerebral EEG. We examined the internodular FC using fMRI and its correspondence with internodular synchrony of intracerebral interictal activity. We then compared the spreading speed of ictal activity between connected and unconnected nodules; and the FC among possible combinations of nodule pairs in terms of their involvement at seizure onset.

Results

Seventy nodules were studied: 83% have significant connection to at least one other nodule. Among the 49 pairs studied with intracerebral EEG, (1) synchronized interictal activity is more prevalent in fMRI‐connected pairs (P < 0.05), (2) ictal activity spreads faster between connected pairs (P < 0.0001), and (3) stronger FC was observed between pairs in which both nodules were involved at seizure onset (P < 0.01).

Interpretation

fMRI could reliably and noninvasively detect the FC between heterotopic nodules. These functional connections correspond to the synchrony of interictal epileptic activity between the nodules and to the ability of nodules to generate synchronous seizure onsets or rapid seizure spread. These findings may help in understanding the complexity of the epileptogenic network in multiple heterotopic nodules and better targeting the likely epileptogenic nodules.
Information leakage in the Response Time‐Based Concealed Information Test
Authors: Lukács Gáspár , Ansorge Ulrich
Published: May 2019

The Response Time‐Based Concealed Information Test (RT‐CIT) can reveal when a person recognizes a relevant (probe) item among other, irrelevant items, based on comparatively slow responses to the probe item. For example, if a person is concealing his or her true identity, one can use the suspected identity details as probes, and other, random details as irrelevants. However, in our study, we show that even when participants are merely informed about such probes (i.e., the relevant identity details) before performing the RT‐CIT, their responses will also be slower to these details. Hence, it is more difficult to distinguish such innocent but pre‐informed persons from actually guilty persons. At the same time, we introduce a CIT version with familiarity‐related inducer stimuli, but with no targets, that elicits probe‐minus‐irrelevant RT differences only among guilty participants but not among informed innocent participants. Implications for the theory and the application of CITs are discussed.
Stable, High‐Sensitivity and Fast‐Response Photodetectors Based on Lead‐Free Cs2AgBiBr6 Double Perovskite Films
Authors: Yang Jie , Bao Chunxiong , Ning Weihua , Wu Bo , Ji Fuxiang , Yan Zhibo , Tao Youtian , Liu Jun‐Ming , Sum Tze Chien , Bai Sai , Wang Jianpu , Huang Wei , Zhang Wenjing , Gao Feng
Published: May 2019

Solution‐processed metal halide perovskites (MHPs) have demonstrated great advances on achieving high‐performance photodetectors. However, the intrinsic material instability and the toxicity of lead still hinder the practical applications of MHPs‐based photodetectors. In this work, the first highly sensitive and fast‐response lead‐free perovskite photodetectors based on Cs2AgBiBr6 double perovskite films are demonstrated. A convenient solution method is developed to deposit high‐quality Cs2AgBiBr6 film with large grain sizes, low trap densities, and long charge carrier lifetimes. Incorporated within a photodiode device architecture comprised of optimized hole‐ and electron‐transporting layers, lead‐free perovskite photodetectors are achieved exhibiting a high detectivity of 3.29 × 1012 Jones, a large linear dynamic range of 193 dB, and a fast response time of ≈17 ns. All the key figures of merit of the devices are comparable with the reported best‐performing photodetectors based on lead halide perovskites. In addition, the resulting devices exhibit excellent thermal and environmental stability. The nonencapsulated devices show negligible degradation after thermal stressing at 150 °C and less than 5% degradation in the photoresponsivity after storage in ambient air for ≈2300 h. The results demonstrate the great potential of the lead‐free Cs2AgBiBr6 double perovskite in applications for environmentally friendly and high‐performance photodetectors.
Strategy for Controlling the Electrical Conductivity of Indium Tin Oxide (ITO) Nanobranches
Authors: Lee Dong Kyu , Choi Kyoung Soon , Lee Jaeyeong , Kim Youngho , Oh Sein , Shin Hojun , Jeon Cheolho , Yu Hak Ki
Published: May 2019

The electronic properties of indium tin oxide (ITO) nanobranches fabricated by electron beam evaporation are controlled using the following two methods: i) The growth direction of the rods and branches is controlled by an epitaxial relationship with a yttria‐stabilized zirconia substrate. The aligned growth of ITO nanobranches causes low sheet resistance because of the high density and good connectivity of the branches. ii) Heterojunction metal‐oxide nanoparticles are coated on the surface of the nanobranches to form a depletion region in the near surface for band bending. The morphology of the metal oxide also affects the electronic properties of the nanobranches. The sheet resistance of Fe2O3‐coated nanobranches (Fe2O3: film shape) increases linearly with the number of coatings. In the case of Mn2O3 (Mn2O3: nanoparticle shape), the sheet resistance is dramatically increased and saturated with the increase in the number of coatings.
Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal, intermediate, and premutation alleles
Authors: Nolin Sarah L. , Glicksman Anne , Tortora Nicole , Allen Emily , Macpherson James , Mila Montserrat , Vianna‐Morgante Angela M. , Sherman Stephanie L. , Dobkin Carl , Latham Gary J. , Hadd Andrew G.
Published: May 2019

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55–200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45–54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes. For normal alleles, instability was more frequent in paternal transmissions and in alleles with long 3′ uninterrupted repeat lengths. For premutation alleles, contractions also occurred more often in paternal than maternal transmissions and the frequency of paternal contractions increased linearly with repeat size. All paternal premutation allele contractions were transmitted as premutation alleles, but maternal premutation allele contractions were transmitted as premutation, intermediate, or normal alleles. The eight losses of AGG interruptions in the FMR1 repeat occurred exclusively in contractions of maternal premutation alleles. We propose a refined model of FMR1 repeat progression from normal to premutation size and suggest that most normal alleles without AGG interruptions are derived from contractions of maternal premutation alleles.
Isotopic equifinality and rethinking the diet of Australopithecus anamensis
Authors: Quinn Rhonda L.
Published: May 2019

Objectives

Australopithecus anamensis has comparable δ13Cenamel values to Ardipithecus ramidus, and both have been characterized as C3 feeders in open woodland habitats similar to “savanna” chimps. Unlike Ar. ramidus and “savanna” chimps, A. anamensis shows a derived dentognathic morphology for tough foods and a dental microwear pattern similar to the C3–C4‐mixed‐feeding A. afarensis. Here I test the hypothesis that changing the variables (ε*enamel‐diet, δ13CC3, δ13CC4 values) used to calculate the percentage of dietary C4 foods (%C4 diet) by 1–2‰ does not make a substantial difference for hominin diet reconstructions [van der Merwe, Masao, & Bamford, 2008, South African Journal of Science 104:153–155].

Materials and Methods

I estimate vegetation structures for A. anamensis with pedogenic carbonate and faunal enamel δ13C values from the Pliocene Omo‐Turkana Basin (4.2–3.9 Ma). I recalculate A. anamensis' %C4 diet based on new body size‐dependent estimates of the ε*enamel‐diet value and alternative δ13CC3 and δ13CC4 values.

Results

The Pliocene Omo‐Turkana Basin shows evidence for dietary resources with a wide range of δ13C values including canopy‐driven 13C depleted ground C3 foods. Alternative equation variables changed by 1–2‰ yield higher C4 estimates for A. anamensis (15–31%) than previously thought (0–10%). The choice of δ13CC3 and δ13CC4 values for estimating %C4 is not a perfunctory task and potentially explains the δ13C isotopic equifinality of A. anamensis and “savanna” chimps.

Discussion

My integrative diet model reconciles the carbon isotopic data with the dentognathic and microwear evidence of A. anamensis' diet and suggests that “savanna” chimps are not proper dietary analogs of A. anamensis. A foraging strategy across heterogeneous habitats of the Pliocene Omo‐Turkana Basin incorporating an array of 13C‐depleted and 13C‐enriched C3 foods and a portion of C4 resources may have served as one of the selective pressures for A. anamensis, the earliest habitual biped [van der Merwe et al., 2008, South African Journal of Science 104:153–155].
Those who died very young—Inferences from δ15N and δ13C in bone collagen and the absence of a neonatal line in enamel related to the possible onset of breastfeeding
Authors: Siebke Inga , Moghaddam Negahnaz , Cunningham Craig A. , Witzel Carsten , Lösch Sandra
Published: May 2019

Objectives

Stable isotope analysis has often been used in neonatal remains from archeological contexts to investigate the presence of a signal of breastfeeding and weaning in past populations. Tooth histology on the other hand might be used as an indicator of birth survival. This pilot study aimed to investigate the feasibility of using stable nitrogen (δ15N) and carbon (δ13C) isotope values from neonatal bone collagen to elucidate if values deviating from the adult female average could indicate breastfeeding and co‐occur with the presence of a neonatal line (NNL). The combination of these independent indicators might be useful in clarifying the fate of individuals who died around birth.

Materials and Methods

Bone collagen from 21 archeological human and animal specimens was extracted and analyzed via mass‐spectrometry for δ15N and δ13C. A verification of the stable isotope results was undertaken using tooth histology on three individuals who were investigated for the presence of a NNL as an indicator of live birth and short survival.

Results

The biological age of the human samples varied between 8.5 lunar months (Lm) and 2 postnatal months (Pm) of age. All except one individual exhibited elevated δ15N values compared to the female average. The histological analyses revealed no NNL for this and two further individuals (n = 3).

Discussion

The results indicate that elevated nitrogen values of very young infants relative to a female average in archeological contexts are not necessarily associated with a breastfeeding onset signal, and therefore cannot be used exclusively as a proxy of birth survival. The elevation might be possible due to various reasons; one could be nutritional, in particular maternal stress during pregnancy or a metabolic disorder of mother and/or her child. In those cases, the evaluation of a NNL might reveal a false breastfeeding signal as seen for two individuals in our sample who have elevated nitrogen values despite the fact no NNL could be observed. Overall, our data support the growing awareness that bone collagen δ15N values of neonates/infants should not be used as a proxy for breastfeeding or birth survival on its own.
Age at death estimation by cementochronology: Too precise to be true or too precise to be accurate?
Authors: Bertrand Benoit , Cunha Eugenia , Bécart Anne , Gosset Didier , Hédouin Valery
Published: May 2019

Objectives

Cementochronology based on annual deposition of acellular cementum is acknowledged for its superior performance for estimating age‐at‐death but is also disregarded because of its suspicious effectiveness. This article aims to provide a standardized framework for the validation of the technique and to define and test cementochronology's performance and limitations.

Materials and methods

To determine the boundaries of the cementum aging technique, we applied a certified protocol on a sample of 200 healthy canines from individuals of known age, sex, postmortem, and inhumation intervals from anthropological and anatomical collections. We scored readability and preservation of cementum and measured the agreement between estimates, i.e., the precision, and assessed the quality of the accordance between estimates and chronological age, i.e., the accuracy. To investigate the applicability on ancient material, 200 additional canines extracted from archeological assemblages were included. Accuracy and precision were analyzed for each age group in considering postmortem intervals and taphonomical conditions.

Results

A strong correlation was found between chronological age and estimates (r = .927; p = .000) but results reveal an association between readability of incremental lines and chronological age (p < .05) and a notable difference in both precision and accuracy between individuals under and over 50 years. Results also demonstrate that taphonomy can be a serious obstacle increasing imprecision by a factor of three.

Discussion

Improperly adopted, cementochronology can lead to precise but inaccurate estimations. If methodological, physiological, and taphonomical factors are taken into account, then, and only then, cementochronology will serve as a versatile and powerful tool for age‐at‐death estimation.
The Effect of Intrathecal Baclofen in Dyskinetic Cerebral Palsy: The IDYS Trial
Authors: Bonouvrié Laura A. , Becher Jules G. , Vles Johan S. H. , Vermeulen R. Jeroen , Buizer Annemieke I. ,   on behalf of the IDYS Study Group
Published: May 2019

Objective

Intrathecal baclofen treatment is used for the treatment of dystonia in patients with severe dyskinetic cerebral palsy; however, the current level of evidence for the effect is low. The primary aim of this study was to provide evidence for the effect of intrathecal baclofen treatment on individual goals in patients with severe dyskinetic cerebral palsy.

Methods

This multicenter, randomized, double‐blind, placebo‐controlled trial was performed at 2 university medical centers in the Netherlands. Patients with severe dyskinetic cerebral palsy (Gross Motor Functioning Classification System level IV–V) aged 4 to 24 years who were eligible for intrathecal baclofen were included. Patients were assigned by block randomization (2:2) for treatment with intrathecal baclofen or placebo for 3 months via an implanted microinfusion pump. The primary outcome was goal attainment scaling of individual treatment goals (GAS T score). A linear regression model was used for statistical analysis with study site as a covariate. Safety analyses were done for number and type of (serious) adverse events.

Results

Thirty‐six patients were recruited from January 1, 2013, to March 31, 2018. Data for final analysis were available for 17 patients in the intrathecal baclofen group and 16 in the placebo group. Mean (standard deviation) GAS T score at 3 months was 38.9 (13.2) for intrathecal baclofen and 21.0 (4.6) for placebo (regression coefficient = 17.8, 95% confidence interval = 10.4‐25.0, p < 0.001). Number and types of (serious) adverse events were similar between groups.

Interpretation

Intrathecal baclofen treatment is superior to placebo in achieving treatment goals in patients with severe dyskinetic cerebral palsy. ANN NEUROL 2019
Impact of Oxidation State on Reactivity and Selectivity Differences between Nickel(III) and Nickel(IV) Alkyl Complexes
Authors: Roberts Courtney C. , Camasso Nicole M. , Bowes Eric G. , Sanford Melanie S.
Published: May 2019

Described is a systematic comparison of factors impacting the relative rates and selectivities of C(sp3)−C and C(sp3)−O bond‐forming reactions at high‐valent Ni as a function of oxidation state. Two Ni complexes are compared: a cationic octahedral NiIV complex ligated by tris(pyrazolyl)borate and a cationic octahedral NiIII complex ligated by tris(pyrazolyl)methane. Key features of reactivity/selectivity are revealed: 1) C(sp3)−C(sp2) bond‐forming reductive elimination occurs from both centers, but the NiIII complex reacts up to 300‐fold faster than the NiIV, depending on the reaction conditions. The relative reactivity is proposed to derive from ligand dissociation kinetics, which vary as a function of oxidation state and the presence/absence of visible light. 2) Upon the addition of acetate (AcO−), the NiIV complex exclusively undergoes C(sp3)−OAc bond formation, while the NiIII analogue forms the C(sp3)−C(sp2) coupled product selectively. This difference is rationalized based on the electrophilicity of the respective M−C(sp3) bonds, and thus their relative reactivity towards outer‐sphere SN2‐type bond‐forming reactions.
meta‐Selective C−H Activation of Arenes at Room Temperature Using Visible Light: Dual‐Function Ruthenium Catalysis
Authors: Sagadevan Arunachalam , Greaney Michael F.
Published: May 2019

Ruthenium‐catalyzed meta‐C−H activation of arenes at room temperature is reported to proceed under blue‐light irradiation. A variety of heteroarenes are compatible with this photochemical process, which leads to the corresponding meta C−C coupling products in good to very good yields. Initial mechanistic studies suggest a single‐electron transfer process occurs between a photoexcited RuII‐cyclometalated complex and alkyl halides, enabling meta‐C−H functionalization reaction via carbon‐centered radicals.
Optimizing the Size of Platinum Nanoparticles for Enhanced Mass Activity in the Electrochemical Oxygen Reduction Reaction
Authors: Garlyyev Batyr , Kratzl Kathrin , Rück Marlon , Michalička Jan , Fichtner Johannes , Macak Jan M. , Kratky Tim , Günther Sebastian , Cokoja Mirza , Bandarenka Aliaksandr S. , Gagliardi Alessio , Fischer Roland A.
Published: May 2019

High oxygen reduction (ORR) activity has been for many years considered as the key to many energy applications. Herein, by combining theory and experiment we prepare Pt nanoparticles with optimal size for the efficient ORR in proton‐exchange‐membrane fuel cells. Optimal nanoparticle sizes are predicted near 1, 2, and 3 nm by computational screening. To corroborate our computational results, we have addressed the challenge of approximately 1 nm sized Pt nanoparticle synthesis with a metal–organic framework (MOF) template approach. The electrocatalyst was characterized by HR‐TEM, XPS, and its ORR activity was measured using a rotating disk electrode setup. The observed mass activities (0.87±0.14 A mgPt−1) are close to the computational prediction (0.99 A mgPt−1). We report the highest to date mass activity among pure Pt catalysts for the ORR within similar size range. The specific and mass activities are twice as high as the Tanaka commercial Pt/C catalysis.
Decreasing student behavior problems and fostering academic engagement through function‐based support and fading of token reinforcement
Authors: Petursdottir Anna‐Lind , Ragnarsdottir Gudrun Björg
Published: May 2019

This study examined the effects of function‐based behavior support plans (BSPs) on the persistent behavior problems and lack of academic engagement of three, 7‐ to 8‐year‐old, male students from two public schools in Iceland. Based on the results of functional behavioral assessments, BSPs were created for each participant. Each plan included a token system. The goal for all students was to foster independent functioning. A multiple baseline across participants showed that disruptive behavior decreased by 85% on average and academic engagement increased by 78% on average. Statistical analyses suggest significant positive effects were obtained. Findings suggest that persistent behavior problems can be reduced and independent academic engagement fostered in inclusive school settings through function‐based BSPs with gradual fading of token reinforcement.
Screening potential antagonists of epidermal growth factor receptor from Marsdenia tenacissima via cell membrane chromatography model assisted by HPLC–ESI–IT–TOF–MS
Authors: Lv Yanni , Shi Xianpeng , Fu Jia , Jia Qianqian , Lin Yuanyuan , Wang Hongying , Yang Xin , Han Shengli
Published: May 2019

Marsdenia tenacissima, or Tongguanteng in Chinese, is a traditional Chinese herb and has a broad application in clinical practice for its pharmacological effects of treating asthma, pneumonia, tonsillitis, pharyngitis tumors, etc. However, few studies have reported the screening of the active components of this medicine for tumor therapy. In this work, a two‐dimensional analytical system was developed to screen antagonists of epidermal growth factor receptor (EGFR) from M. tenacissima. A fraction was retained on the EGFR cell membrane chromatography (CMC) column, separated and identified as tenacissoside G (TG), tenacissoside H (TH) and tenacissoside I (TI) by two‐dimensional HPLC–IT–TOF–MS. Molecular docking and 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay were carried out to assess the activity of TS (including TG, TH and TI). Molecular docking results showed that the binding mode of TS on EGFR is similar to that of gefitinib. The MTT assay demonstrated that gefitinib and TS (especially TI) could inhibit the growth of EGFR highly expressed cell lines in a dose‐dependent manner in the range of 5–50 μmol/L. In conclusion, the two‐dimensional EGFR/CMC–HPLC–IT–TOF–MS system could be a useful approach in drug discovery from traditional Chinese medicines for searching for potential antitumor candidates.
A reliable LC–MS/MS method for the quantification of five bioactive saponins of crude and processed Bupleurum scorzonerifolium in rat plasma and its application to a pharmacokinetic study
Authors: Tao Yi , Huang Surun , Yan Jizhong , Cai Baochang
Published: May 2019

A simple and reliable liquid chromatography–mass spectrometry (LC–MS) method was developed for simultaneous determination of saikosaponin A, saikosaponin B1, saikosaponin C, saikosaponin D and saikosaponin F in rat plasma using glycyrrhetinic acid as an internal standard (IS). The separation was operated on a Waters BEH C18 column. The mobile phases of gradient elution consisted of acetonitrile (A) and 0.1% aqueous acetic acid (B). The mass spectrometric detection was accomplished in multiple reaction monitoring mode. The five saponins displayed good linearity (r2 > 0.9996). The lower limits of quantitation of saikosaponin A, saikosaponin B1, saikosaponin C, saikosaponin D and saikosaponin F were determined to be 2.9, 2.3, 3.5, 2.9 and 3.1 ng/mL, respectively. Moreover, the intra‐ and inter‐day precisions of the five saponins showed an RSD within 2.96%, whereas the accuracy (RE) ranged from −2.28 to 2.78%. Finally, the developed method was fully validated and applied to a comparative pharmacokinetic study of the five bioactive saponins in rats following oral administration of crude and vinegar‐processed Bupleurum scorzonerifolium.
Green technology innovation: Anatomy of exploration processes from a learning perspective
Authors: Wicki Samuel , Hansen Erik G.
Published: May 2019

This paper examines how established firms use their core competences to diversify their business by exploring and ultimately developing green technologies. In contrast to start‐ups dedicated to a green mission, diversifying into green markets by developing new products based on existing core competences has proven to be challenging. This is because the exploration processes to find a match between green technology opportunities and internal competences is complex and new to most established firms. This paper gains insights into exploration processes for green technologies and the learning modes and outcomes linked to these processes. We examined exploration processes at the microlevel in an embedded case study of an engineering firm using a combination of the “fireworks” innovation process model and organizational learning theory. First, we found that developing green technologies involves a long‐term exploratory process without guarantee of (quick) success and likely involves many exploration failures. Second, as exploration unfolds along multiple technology trajectories, learning occurs in individual exploration paths (on‐path), when new paths are pursued (path‐initiation), and when knowledge from one path is spilled over to subsequent paths (across‐paths). Third, to increase their chances for success, firms can increase the efficiency of exploration by fostering a failure‐friendly organizational culture, deliberately experimenting, and purposefully learning from failures.
Silver‐gold alloy nanoparticles biofabricated by fungal xylanases exhibited potent biomedical and catalytic activities
Authors: Elegbede Joseph A. , Lateef Agbaje , Azeez Musibau A. , Asafa Tesleem B. , Yekeen Taofeek A. , Oladipo Iyabo C. , Hakeem Abbas S. , Beukes Lorika S. , Gueguim‐Kana Evariste B.
Published: May 2019

The search for biocompatible nanoparticles with vast applicability has impacted on exploration of various biomaterials for the synthesis of mono and bimetallic nanoparticles. Xylanase is widely regarded as an industrially important enzyme but its potentials in nanotechnological applications are yet to be fully explored. The current study investigates the exploit of xylanases of Aspergillus niger L3 (NE) and Trichoderma longibrachiatum L2 (TE) produced through valorization of corn‐cob, to synthesize silver‐gold alloy nanoparticles (Ag‐AuNPs). Characterization of the Ag‐AuNPs involved UV–vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy and transmission electron microscopy, while their prospective use as antimicrobial, antioxidant, catalytic, anticoagulant, and thrombolytic agents were studied. The biosynthesized Ag‐AuNPs were ruby red and light purple with surface plasmon resonance at 520 and 534 nm for NEAg‐AuNPs and TEAg‐AuNPs, respectively; while FTIR showed that protein molecules capped and stabilized the nanoparticles. The Ag‐AuNPs were anisotropic with spherical, oval, and irregular shapes having sizes ranging from 6.98 to 52.51 nm. The nanoparticles appreciably inhibited the growth of tested clinical bacteria (23.40–90.70%) and fungi (70.10–89.05%), and also scavenged 2,2‐diphenyl‐1‐picrylhydrazyl (48.51–53.79%) and hydrogen peroxide (80.5–95.50%). Furthermore, the Ag‐AuNPs degraded malachite green (91.39%) and methylene blue (47.10%). Moreover, the Ag‐AuNPs displayed outstanding anticoagulant and thrombolytic activities using human blood. This study further emphasizes the significance of xylanases in nanobiotechnology as it has established the potential of xylanases to synthesize Ag‐AuNPs, which is being reported for the first time.
Development of an alternating tangential flow (ATF) perfusion‐based transient gene expression (TGE) bioprocess for universal influenza vaccine
Authors: Hong Jinsung , Demirji Jacob , Blackstock Daniel , Lee James , Dinh Tracey , Goh Alvenne , Arnold Frank , Horwitz Joe
Published: May 2019

An alternating tangential flow (ATF) perfusion‐based transient gene expression (TGE) bioprocess has been developed using human embryonic kidney (HEK) 293 cells to produce H1‐ss‐np, a promising candidate for a universal influenza vaccine. Two major adjustments were taken to improve the process: (1) eliminate the interference of microbubbles during gene transfection; and (2) utilize an ATF perfusion system for a prolonged culture period. As a result, a closed‐operation 9‐days ATF perfusion‐based TGE bioprocess was developed. The TGE bioprocess showed continuous cell growth with high cell viability and prolonged cellular productivity that achieved recombinant product level of ~270 mg/L which was more than two times that of 4‐days base‐line TGE bioprocess. In addition, the consumables cost per milligram for ATF perfusion‐based TGE bioprocess was ~70% lower than that of the base‐line TGE bioprocess suggesting high cost savings potential in vaccine manufacturing. Based on the lower contamination risk, higher productivity, and cost efficiency, the ATF perfusion‐based TGE bioprocess can likely provide potential benefits to many future applications in vaccine and drug manufacturing.
A novel scale‐down mimic of perfusion cell culture using sedimentation in an automated microbioreactor (SAM)
Authors: Kreye Steffen , Stahn Rainer , Nawrath Karina , Goralczyk Vicky , Zoro Barney , Goletz Steffen
Published: May 2019

Continuous upstream processing in mammalian cell culture for recombinant protein production holds promise to increase product yield and quality. To facilitate the design and optimization of large‐scale perfusion cultures, suitable scale‐down mimics are needed which allow high‐throughput experiments to be performed with minimal raw material requirements. Automated microbioreactors are available that mimic batch and fed‐batch processes effectively but these have not yet been adapted for perfusion cell culture. This article describes how an automated microbioreactor system (ambr15) can be used to scale‐down perfusion cell cultures using cell sedimentation as the method for cell retention. The approach accurately predicts the viable cell concentration, in the range of about 1 × 107 cells/mL for a human cell line, and cell viability of larger scale cultures using a hollow fiber based cell retention system. While it was found to underpredict cell line productivity, the method accurately predicts product quality attributes, including glycosylation profiles, from cultures performed in bioreactors with working volumes between 1 L and 1,000 L. The spent media exchange method using the ambr15 was found to predict the influence of different media formulations on large‐scale perfusion cultures in contrast to batch and chemostat experiments performed in the microbioreactor system. The described experimental setup in the microbioreactor allowed an 80‐fold reduction in cell culture media requirements, half the daily operator time, which can translate into a cost reduction of approximately 2.5‐fold compared to a similar experimental setup at bench scale.
Marco antonio della torre and leonardo da vinci
Authors: Picardi Edgardo Enrico Edoardo , Macchi Veronica , Porzionato Andrea , Boscolo‐Berto Rafael , Loukas Marios , Tubbs R. Shane , De Caro Raffaele
Published: May 2019

Thanks to collaborations with anatomists and the possibility of performing public dissections during the Renaissance period, artists started to represent the human body more accurately and objectively in their drawings. This cultural change provided the basis for subsequent advances in education and learning as well as the institution of an obligatory anatomy course in the Academies of Arts. The encounter in Pavia between the eclectic artist Leonardo Da Vinci (1452–1519) and the physician Marco Antonio Della Torre (1481–1511), Professor of Theoretical Medicine at the University of Padova, who near the end of his short life founded the “Anatomical School” of the University of Pavia, could be considered a perfect example of this collaboration. According to the historian Giorgio Vasari, while Della Torre practiced dissection, Leonardo made a book of drawings with red chalk annotated by pen. All these anatomical drawings by Leonardo, preserved at Windsor Castle as the property of the Queen of England, date from 1513, after the death of Della Torre. During the same period, Leonardo started his own dissections in the crypt of Santa Maria Nuova in Florence with his anatomical knowledge already mature and consolidated. The aim of the present study is to present the life of Della Torre, his intense scientific activity between Padova and Pavia, and his relationship with Leonardo Da Vinci. In particular, we found the only available manuscript of Della Torre in the Marciana library of Venice. Clin. Anat. 32:744–748, 2019. © 2019 Wiley Periodicals, Inc.
Gender stereotypes and contact with gay men and lesbians: The mediational role of sexism and homonegativity
Authors: Salvati Marco , Piumatti Giovanni , Giacomantonio Mauro , Baiocco Roberto
Published: May 2019

This study is grounded in Allport's intergroup contact theory and Herek's sexual prejudice theory. We aimed at (a) investigating the mediational role of sexism and homonegativity on the relation between gender, age, and contact with gay and lesbian people with gender stereotypes about gay men and lesbians; and (b) replicating and corroborating the direct associations found in previous research among these variables. The present research used secondary data from a survey conducted by the Italian National Institute of Statistics and comprehending a representative sample of 5,863 Italian adults. The results from path analysis indicated that both homonegativity and sexism partially mediated the effect of gender and age on gender stereotypes, whereas they totally mediated the effect of contact with gay and lesbian persons. Findings suggest that reducing sexist and homonegative attitudes and increasing contact with gay and lesbian people may reduce stereotypical beliefs about homosexual people.
Unusual Crystal Growth Kinetics of (RS)‐Ibuprofen from Ethanolic Solutions
Authors: Chaisongkram Natchanok , Maosoongnern Somchai , Flood Adrian E.
Published: May 2019

The solubility, secondary nucleation threshold, and growth kinetics of (RS)‐ibuprofen have been studied in an aqueous ethanol solvent. The metastable zone for secondary nucleation is very narrow at lower temperatures in this range, but greatly enlarged at higher temperatures. The crystal growth kinetics not only display significant dispersion of growth rates, but also a dead zone that is dependent on the growth rates of the crystals. Faster growing crystals display almost no dead zone, whereas the smallest crystals have a large dead zone. The size of the dead zone is largely responsible for the dispersion of crystal growth rates, perhaps due to differences in the thermodynamic stability of the different crystals. The mechanism of growth rate dispersion relates to that of the dead zone.
A Spectroscopic and Computationally Minimal Approach to the Analysis of Charge‐Transfer Processes in Conformationally Fluxional Mixed‐Valence and Heterobimetallic Complexes
Authors: Gückel Simon , Gluyas Josef B. G. , Eaves Samantha G. , Safari Parvin , Yufit Dmitry S. , Sobolev Alexandre N. , Kaupp Martin , Low Paul J.
Published: May 2019

Class II mixed‐valence bimetallic complexes {[Cp′(PP)M]C≡C−C≡N[M′(PP)′Cp′]}2+ (M, M′=Ru, Fe; PP=dppe, (PPh3)2; Cp′=Cp*, Cp) exist as conformational ensembles in fluid solution, with a population of structures ranging from cis‐ to trans‐like geometries. Each conformer gives rise to its own series of low‐energy intervalence charge‐transfer (IVCT) and local d–d transitions, which overlap in the NIR region, giving complex band envelopes in the NIR absorption spectrum, which prevent any meaningful attempt at analysis of the band shape. However, DFT and time‐dependent (TD)DFT calculations with dispersion‐corrected global‐hybrid (BLYP35‐D3) or local hybrid (lh‐SsirPW92‐D3) functionals on a small number of optimised structures chosen to sample the ground state potential energy hypersurfaces of each of these complexes has proven sufficient to explain the major features of the electronic spectra. Although modest in terms of computational expense, this approach provides a more accurate description of the underlying molecular electronic structure than would be possible through analysis of the IVCT band by using the static point‐charge model of Marcus–Hush theory and derivatives, or TDDFT calculations from a single (global) minimum energy geometry.
A Simple Central Seven‐Membered BOPYIN: Synthesis, Structural, Spectroscopic Properties, and Cellular Imaging Application
Authors: Zhang Tingting , Yan Jiaying , Hu Yuanyuan , Liu Xiang , Wen Liu , Zheng Kaibo , Zhang Nuonuo
Published: May 2019

A two‐step, one‐flask synthesis of central seven‐membered borondifluoride‐3,3‐dimethyl‐2‐[2‐(2‐pyrrolyl)ethenyl] indole (BOPYIN) ligands has been developed by using the unexplored 3,3‐dimethyl‐2‐[2‐(2‐pyrrolyl)ethenyl] indole. The simple synthetic approach has enabled modification of the electronic structure by changing the substituents on the indole unit. X‐ray analysis indicated that conformations of the seven‐membered BF2 complex including BOPYIN and diazaborepin differ from that of the five‐ and six‐membered organoboron complexes. Interestingly, the bond angle of the N⋅⋅⋅B−N bond increases with the number of atoms in the core ring, based on Baeyer strain theory. These unsymmetric BOPYIN derivatives have excellent photophysical properties, including high fluorescence quantum yields, except for BOPYIN‐4 in the solution state, large Stokes shifts, and good molar absorptivity. The dipole moment of BOPYIN‐3 in the first excited singlet state and ground state was demonstrated by a linear Lippert–Mataga plot. The absorption and emission spectra were not mirror images for BOPYIN‐1–3 and 5, in contradiction to Kasha's rule, as determined by TDDFT. The synthesized BOPYINs have been shown to be biocompatible fluorophores in cell bioimaging.
N‐Ethynylation of Anilides Decreases the Double‐Bond Character of Amide Bond while Retaining trans‐Conformation and Planarity
Authors: Yamasaki Ryu , Morita Kento , Iizumi Hiromi , Ito Ai , Fukuda Kazuo , Okamoto Iwao
Published: May 2019

Activated amide bonds have been attracting intense attention; however, most of the studied moieties have twisted amide character. To add a new strategy to activate amide bonds while maintaining its planarity, we envisioned the introduction of an alkynyl group on the amide nitrogen to disrupt amide resonance by nN→Csp conjugation. In this context, the conformations and properties of N‐ethynyl‐substituted aromatic amides were investigated by DFT calculations, crystallography, and NMR spectroscopic analysis. In contrast to the cis conformational preference of N‐ethyl‐ and vinyl‐substituted acetanilides, N‐ethynyl‐substituted acetanilide favors the trans conformation in the crystal and in solution. It also has a decreased double bond character of the C(O)−N bond, without twisting of the amide. N‐Ethynyl‐substituted acetanilides undergo selective C(O)−N bond or N−C(sp) bond cleavage reactions and have potential applications as activated amides for coupling reactions or easily cleavable tethers.
Die gesamte Anlagendoku in der Hosentasche
Authors: Dubovy Markus
Published: May 2019

Die Dokumentation einer prozesstechnischen Anlage ist permanent im Wandel. Um den as‐built Zustand zu dokumentieren, sind daher digitale Dokumentations‐Lösungen das Mittel der Wahl. Zu Ende gedacht bedeutet das auch, dass man zur Dokumentation keine ortsfesten Bedienstationen nutzen muss, sondern Änderungen mobil vor Ort vornehmen kann. Rösberg hat mit LiveDOK Web deshalb nun eine betriebssystemunabhängige, webbasierte Lösung geschaffen, die sich mobil in der Anlage nutzen lässt.
Widerstandsfähig unter extremen Bedingungen
Authors: Pöhlmann Ulf
Published: May 2019

In Entstaubungsanlagen, die schadstoffhaltige Rauchgase aus Herstellungsprozessen der Stahlindustrie reinigen, können Kompensatoren einer hohen Bewegungsdynamik, hohen Betriebszyklen und extremen Druckwechselbelastungen ausgesetzt sein. Häufig entsteht zudem noch Kondensat. Bei dieser vielschichtigen Problematik veragen klassische Weichstoffkompensatoren oftmals. PTFE‐Verbundkompensatoren von Frenzelit beweisen hingegen unter diesen extremen Bedingungen ihre Widerstandsfähigkeit.
Analysis of crop suitability using clustering technique in Coimbatore region of Tamil Nadu
Authors: Poongodi S. , Rajesh Babu M.
Published: May 2019

Agricultural production is a important thing that should be maintained because need of crop is increasing for the current population. They are affected by various factors of environmental conditions, temperature, soil conditions, etc. Most of the farmers cultivate crops without the knowledge about crop suitability in their location there by reducing the crop productivity and money loss. It tends to cause the economical level of country. Therefore, it is necessary to develop a method to predict the crop productivity. In this work, Coimbatore region is taken for case study to analyze the crop productivity. For this process, new data mining technique is proposed and employed to predict the crop suitability. The proposed method produces the better results in terms of prediction level in region and sub regions of given area.
Evaluating 0–0 Energies with Theoretical Tools: A Short Review
Authors: Loos Pierre‐François , Jacquemin Denis
Published: May 2019

For a given electronic excited state, the 0–0 energy (T0 or T00) is the simplest property allowing straightforward and physically‐sound comparisons between theory and (accurate) experiment. However, the computation of 0–0 energies with ab initio approaches requires determining both the structure and the vibrational frequencies of the excited state, which limits the quality of the theoretical models that can be considered in practice. This explains why only a rather limited, yet constantly increasing, number of works have been devoted to the determination of this property. In this contribution, we review these efforts with a focus on benchmark studies carried out for both gas phase and solvated compounds. Over the years, not only as the size of the molecules increased, but the refinement of the theoretical tools has followed the same trend. Though the results obtained in these benchmarks significantly depend on both the details of the protocol and the nature of the excited states, one can now roughly estimate, in the case of valence transitions, the overall accuracy of theoretical schemes as follows: 1 eV for CIS, 0.2–0.3 eV for CIS(D), 0.2–0.4 eV for TD‐DFT when one employs hybrid functionals, 0.1–0.2 eV for ADC(2) and CC2, and 0.04 eV for CC3, the latter approach being the only one delivering chemical accuracy on a near‐systematic basis.
Identification of embelin, a 3‐undecyl‐1,4‐benzoquinone from Embelia ribes as a multitargeted anti‐Alzheimer agent
Authors: Nuthakki Vijay K. , Sharma Ankita , Kumar Ajay , Bharate Sandip B.
Published: May 2019

Beta‐secreatse (BACE‐1) and cholinesterases are clinically validated targets of Alzheimer's disease (AD), for which natural products have provided immense contribution. The multifaceted nature of AD signifies the need of multitargeted agents to tackle this disease. In the search of new natural products as dual BACE‐1/cholinesterase inhibitors, a library of pure natural products was screened for inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE‐1. The screening efforts have identified 1,4‐benzoquinone “embelin,” a natural product derived from Embelia ribes displaying inhibition of all three enzymes, with IC50 values of 2.5, 5.4, and 2.1 μM, respectively. This screen has also identified isoquinoline alkaloids papaverine and L‐tetrahydropalmatine as AChE inhibitors. Kinetic study has shown that embelin inhibits EeAChE and EqBChE with ki values of 4.59 and 0.57 μM, in an uncompetitive and noncompetitive manner, respectively. The interactions of embelin with allosteric peripheral anionic site of cholinesterases, has further supported the results of kinetic study. Embelin has also enhanced the activity of P‐gp in LS‐180 cells, the efflux pump which is involved in the clearance of amyloid‐β from AD brain. Further, the cell viability study in neuronal cell line has indicated the excellent therapeutic window of embelin. These results are indicative of the fact that embelin is a multitargeted agent playing role in stopping the formation of amyloid‐β oligomers (via inhibition of BACE‐1), improves cholinergic‐transmission (via inhibition of AChE/BChE) and increases amyloid‐β clearance (via P‐gp induction).
Effects of sodium‐glucose cotransporter 2 inhibitors on risk of venous thromboembolism in patients with type 2 diabetes: A systematic review and meta‐analysis
Authors: Wang Aihua , Yang Keming , Wang Tiansheng , Zhang Ning , Tang Huilin , Feng Xin
Published: May 2019

It has been reported that sodium‐glucose cotransporter 2 (SGLT2) inhibitors could increase blood viscosity, which may further increase risk of venous thromboembolism (VTE). Therefore, we conducted this meta‐analysis to evaluate the association between SGLT2 inhibitors and risk of VTE in patients with type 2 diabetes. We systematically searched electronic databases up to April 2019 to identify randomized trials that reported the events of VTE in SGLT2 inhibitors group and control group (placebo or other active antidiabetic drugs). The primary outcome was VTE, and secondary outcomes included deep venous thrombosis (DVT) and pulmonary embolism (PE). A fixed‐effects meta‐analysis was performed to calculate the risk ratio (RR) with 95% CI. In total, 29 randomized trials involving 56 035 patients with type 2 diabetes were included. Incidence of VTE was not significantly different between SGLT2 inhibitors group and control group (128/32 038 vs 92/23 997), yielding an RR of 0.98 (95% CI, 0.75‐1.28). Similarly, null associations were observed in the subgroup analyses. Our cumulative meta‐analysis demonstrated the stability of our overall result over time. There was no significant association between SGLT2 inhibitors and risk of both DVT (17 trials; 31/17 442 vs 15/10 930; RR, 1.06; 95% CI, 0.60‐1.89) and PE (19 trials; 56/26 118 vs 41/19 517; RR, 0.99; 95% CI, 0.67‐1.46). Low statistical heterogeneity and no evidence of publication bias were observed. Current evidence from randomized trials found no association between SGLT2 inhibitors and risk of VTE among patients with type 2 diabetes.
Long‐term impacts of warming drive decomposition and accelerate the turnover of labile, not recalcitrant, carbon
Authors: Stuble Katharine L. , Ma Shuang , Liang Junyi , Luo Yiqi , Classen Aimée T. , Souza Lara
Published: May 2019

Warming is altering the way soils function in ecosystems both directly by changing microbial physiology and indirectly by causing shifts in microbial community composition. Some of these warming‐driven changes are short term, but others may persist over time. Here, we took advantage of a long‐term (14 yr) warming experiment in a tallgrass prairie to tease apart the influence of short‐ and long‐term warming on litter decomposition. We collected soils originating from warmed and control plots and incubated them with a common litter substrate in a reciprocal design under elevated and ambient growth chamber temperatures. Litter decomposition was 40% higher in soils that were warmed in the field for 14 yr (long‐term warming) relative to soils derived from ambient plots. Short‐term warming in the laboratory had less of an impact on decomposition—decomposition increased by 12% under laboratory warming. Using a two‐pool soil carbon model to explore how different carbon pools may be responding, we found that long‐term warming accelerated the turnover of labile, not recalcitrant, carbon in these prairie soils—a result that is likely due to shifts in soil community activity/composition. Taken together, our results offer experimental evidence that warming‐induced changes in the soil community that occur over 14 yr of warming have long‐lasting effects on carbon turnover.