bluuebunny/crossref_metadata_2025 huggingface dataset:
Precultures Grown under Fed‐Batch Conditions Increase the Reliability and Reproducibility of High‐Throughput Screening Results
Authors: Keil Timm , Landenberger Markus , Dittrich Barbara , Selzer Sebastian , Büchs Jochen
Published: July 2019

One essential task in bioprocess development is strain selection. A common screening procedure consists of three steps: first, the picking of colonies; second, the execution of a batch preculture and main culture, e.g., in microtiter plates (MTPs); and third, the evaluation of product formation. Especially during the picking step, unintended variations occur due to undefined amounts and varying viability of transferred cells. The aim of this study is to demonstrate that the application of polymer‐based controlled‐release fed‐batch MTPs during preculture eliminates these variations. The concept of equalizing growth through fed‐batch conditions during preculture is theoretically discussed and then tested in a model system, namely, a cellulase‐producing Escherichia coli clone bank containing 32 strains. Preculture is conducted once in the batch mode and once in the fed‐batch mode. By applying the fed‐batch mode, equalized growth is observed in the subsequent main culture. Furthermore, the standard deviation of cellulase activity is reduced compared to that observed in the conventional approach. Compared with the strains in the batch preculture process, the first‐ranked strain in the fed‐batch preculture process is the superior cellulase producer. These findings recommend the application of the fed‐batch MTPs during preculture in high‐throughput screening processes to achieve accurate and reliable results.
Engineering high‐gravity fermentations for ethanol production at elevated temperature with Saccharomyces cerevisiae
Authors: Caspeta Luis , Coronel Jesús , Montes de Oca Arturo , Abarca Eduardo , González Lidia , Martínez Alfredo
Published: July 2019

Thermal damage, high osmolarity, and ethanol toxicity in the yeast Saccharomyces cerevisiae limit titer and productivity in fermentation to produce ethanol. We show that long‐term adaptive laboratory evolution at 39.5°C generates thermotolerant yeast strains, which increased ethanol yield and productivity by 10% and 70%, in 2% glucose fermentations. From these strains, which also tolerate elevated‐osmolarity, we selected a stable one, namely a strain lacking chromosomal duplications. This strain (TTY23) showed reduced mitochondrial metabolism and high proton efflux, and therefore lower ethanol tolerance. This maladaptation was bolstered by reestablishing proton homeostasis through increasing fermentation pH from 5 to 6 and/or adding potassium to the media. This change allowed the TTY23 strain to produce 1.3–1.6 times more ethanol than the parental strain in fermentations at 40°C with glucose concentrations ~300 g/L. Furthermore, ethanol titers and productivities up to 93.1 and 3.87 g·L
−1·hr
−1 were obtained from fermentations with 200 g/L glucose in potassium‐containing media at 40°C. Albeit the complexity of cellular responses to heat, ethanol, and high osmolarity, in this study we overcome such limitations by an inverse metabolic engineering approach.
Heparan sulfate proteoglycan, integrin, and syndecan‐4 are mechanosensors mediating cyclic strain‐modulated endothelial gene expression in mouse embryonic stem cell‐derived endothelial cells
Authors: Nikmanesh Maria , Cancel Limary M. , Shi Zhong‐Dong , Tarbell John M.
Published: July 2019

It is widely believed that the differentiation of embryonic stem cells (ESCs) into viable endothelial cells (ECs) for use in vascular tissue engineering can be enhanced by mechanical forces. In our previous work, we reported that shear stress enhanced important EC functional genes on a CD31+/CD45− cell population derived from mouse ESC committed to the EC lineage. In the present study, in contrast to the effects of shear stress on this cell population, we observed that cyclic strain significantly reduced the expression of EC‐specific marker genes (vWF, VE‐cadherin, and PECAM‐1), tight junction protein genes (ZO‐1, OCLD, and CLD5), and vasoactive genes (eNOS and ET1), while it did not alter the expression of COX2. Taken together, these studies indicate that only shear stress, not cyclic strain, is a useful mechanical stimulus for enhancing the properties of CD31+/CD45− cells for use as EC in vascular tissue engineering. To begin examining the mechanisms controlling cyclic strain‐induced suppression of gene expression in CD31+/CD45− cells, we depleted the heparan sulfate (HS) component of the glycocalyx, blocked integrins, and silenced the HS proteoglycan syndecan‐4 in separate experiments. All of these treatments resulted in the reversal of cyclic strain‐induced gene suppression. The current study and our previous work provide a deeper understanding of the mechanisms that balance the influence of cyclic strain and shear stress in endothelial cells.
Potentiation of concurrent expression of lipogenic genes by novel strong promoters in the oleaginous microalga Phaeodactylum tricornutum
Authors: Zou Li‐Gong , Balamurugan Srinivasan , Zhou Tian‐Bao , Chen Jia‐Wen , Li Da‐Wei , Yang Wei‐Dong , Liu Jie‐Sheng , Li Hong‐Ye
Published: July 2019

There has been growing interest in using microalgae as production hosts for a wide range of value‐added compounds. However, microalgal genetic improvement is impeded by lack of genetic tools to concurrently control multiple genes. Here, we identified two novel strong promoters, designated Pt202 and Pt667, and delineated their potential role on simultaneously driving the expression of key lipogenic genes in Phaeodactylum tricornutum. In silico analyses of the identified promoter sequences predicted the presence of essential core cis elements such as TATA and CAAT boxes. Regulatory role of the promoters was preliminarily assessed by using GUS reporter which demonstrated strong GUS expression. Thereafter, two key lipogenic genes including malic enzyme (PtME) and 5‐desaturase (PtD5b), were overexpressed by the two promoters Pt202 and Pt667, respectively, in P. tricornutum. Combinatorial gene overexpression did not impair general physiological performance, meanwhile neutral lipid content was remarkably increased by 2.4‐fold. GC‐MS analysis of fatty acid methyl esters revealed that eicosapentaenoic acid (EPA; C20:5) was increased significantly. The findings augment a crucial kit to microalgal genetic tools that could facilitate the multiple‐gene expression driven by various promoters, and promote microalgae for industrial bioproduction.
One‐Pot Synthesis of Highly Monodisperse Poly(lactic‐co‐glycolic Acid) Particles with Controlled Porosity as Efficient Drug Delivery Vehicles
Authors: Kim Yoon Hyuck , Byun Junhyoung , Kim Byoungjae , Lee Kijeong , Lee Jae‐Seung , Kim Tae Hoon
Published: July 2019

Poly(lactic‐co‐glycolic acid) (PLGA) particles are one of the most widely used biocompatible and biodegradable materials, and have been extensively investigated as drug delivery vehicles. While a number of different types of additives have been used during and after the synthesis of the PLGA particles for the enhancement of their functions, the shape control of the particles and observations of their shape‐dependent properties have been rarely reported to date. To overcome the limitations of conventional PLGA particles, including the slow degradation of PLGA and the resultant slow drug release, we synthesized porous PLGA particles with much higher surface area than in previous works. Unlike in previous studies, the porous PLGA particles in this work exhibit distinctive advantages such as a simpler synthetic scheme, improved size monodispersity, and controllable pore size distribution (approximately 1 μm in diameter). Polyethylenimine (PEI) was chosen as a pore‐generating material, which simplified the synthesis process significantly. The performance of the porous PLGA particles was evaluated using doxorubicin (DOX) and the A549 cell line as a drug and target cells of a model system, respectively. Based on the observation of the cell viability, the DOX‐loaded porous PLGA particles were determined to be five times more efficient than molecular DOX.
Solid‐State Photochemical [2+2] Cycloaddition Reaction of MnII Complexes
Authors: Yadava Khushboo , Vittal Jagadese J.
Published: July 2019

Three MnII complexes have been synthesized under similar experimental conditions. Of these [Mn2(benzoate)4(L)2] (where L=4‐styrylpyridine or 4spy, 1 and 2‐fluoro‐4′‐styrylpyridine or 2F‐4spy, 3) are paddlewheel complexes, but crystallized in different space groups. Whereas [Mn2(benzoate)4(3F‐4spy)4] (3F‐4spy=3‐fluoro‐4′‐styrylpyridine), 4 is a dinuclear complex having different stoichiometry from 1 and 3 with two pairs of 3F‐4spy ligands aligned in face‐to‐face manner. An irreversible phase transition occurs from the space group P21/c to C2/c when 1 was heated up to 125 °C to 2 in a single‐crystal‐to‐single‐crystal fashion or when ground 1 to powder. 2 is isomorphous and isostructural to 3. Complimentary π–π interactions in head‐to‐tail alignment of the styrylpyridine ligands furnishes 1D aggregates in 1–3 which are congenial to undergo [2+2] cycloaddition reaction under UV light. Whereas, face‐to‐face alignment of the 4spy pairs in 4 is expected to provide a head‐to‐head photoproduct. All the MnII complexes are indeed found to be photoreactive. To our surprise, contrary to their ZnII analogues, 2 and 3 were not found to be photosalient. The percentage volume expansion during the photoreaction as determined from the density measurements, was found to be too low (3.2 and 4.6 % respectively for 2 and 3) to have this behavior.
The Shape of the Archetypical Oxocarbon Squaric Acid and Its Water Clusters
Authors: Sanz‐Novo Miguel , Alonso Elena R. , León Iker , Alonso J. L.
Published: July 2019

Herein, a full structural description is presented for the archetypical supramolecular synthone squaric acid (3,4‐dihydroxy‐3‐cyclobutene‐1,2‐dione), placed in the gas phase by laser ablation and characterized by chirped pulse Fourier transform microwave technique. Free from natural environmental disturbances, two different anti‐anti and syn‐anti planar forms and the corresponding water clusters have been revealed in a supersonic expansion. The substitution structure of the most stable anti‐anti conformer has also been extracted from the analysis of the rotational spectra of the 13C and 18O isotopic species in their natural abundance. The interplay between inter‐ and intramolecular interactions involving hydroxy and carbonyl groups has been analyzed by QTAIM (quantum theory of atoms in molecules) methods for squaric acid and its water clusters to understand their chemical behavior and further rationalize their role in the stabilization of these molecular systems.
Recent Advances in Aggregation‐Induced Electrochemiluminescence
Authors: Wei Xing , Zhu Meng‐Jiao , Yan Hong , Lu Changsheng , Xu Jing‐Juan
Published: July 2019

The emergence of the rising alliance between aggregation‐induced emission (AIE) and electrochemiluminescence (ECL) is defined as aggregation‐induced electrochemiluminescence (AIECL). The booming science of AIE has proved to be not only distinguished in luminescent materials but could also inject new possibility into ECL analysis. Especially in the aqueous phase and solid state for hydrophobic materials, AIE helps ECL circumvent the dilemma between substantial emission intensity and biocompatible media. The wide range of analytes makes ECL an overwhelmingly interesting analytical technique. Therefore, AIECL has gained potential in clinical diagnostics, environmental assays, and biomarker detections. This review will focus on introduction of the novel concept of AIECL, current applied luminophores, and related applications developed in recent years.
Treatment of Silylene–Phosphinidene with Chalcogens Resulted Exclusively in the Formation of Silicon‐Bonded Chalcogens
Authors: Sinhababu Soumen , Siddiqui Mujahuddin M. , Sarkar Samir Kumar , Münch Annika , Herbst‐Irmer Regine , George Anjana , Parameswaran Pattiyil , Stalke Dietmar , Roesky Herbert W.
Published: July 2019

Chalcogen‐bonded silicon phosphinidenes LSi(E)−P−MecAAC (E=S (1); Se (2); Te (3); L=PhC(NtBu)2; MecAAC=C(CH2)(CMe2)2N‐2,6‐iPr2C6H3)) were synthesized from the reactions of silylene–phosphinidene LSi−P−MecAAC (A) with elemental chalcogens. All the compounds reported herein have been characterized by multinuclear NMR, elemental analyses, LIFDI‐MS, and single‐crystal X‐ray diffraction techniques. Furthermore, the regeneration of silylene–phosphinidene (A) was achieved from the reactions of 2–3 with L′Al (L′=HC{(CMe)(2,6‐iPr2C6H3N)}2). Theoretical studies on chalcogen‐bonded silicon phosphinidenes indicate that the Si−E (E=S, Se, Te) bond can be best represented as charge‐separated electron‐sharing σ‐bonding interaction between [LSi−P−MecAAC]+ and E−. The partial double‐bond character of Si−E is attributed to significant hyperconjugative donation from the lone pair on E− to the Si−N and Si−P σ*‐molecular orbitals.
Ratiometric DNA Walking Machine for Accurate and Amplified Bioassay
Authors: Wang Chaoqun , Liu Rui , Hu Jianyu , Lv Yi
Published: July 2019

DNA walking machines opened new avenues for the biosensing and demonstrated great success in the past few years. Since DNA machines are mainly nonequilibrium systems driven by dynamic interactions, the matrix effects on DNA machines is a bottleneck and more intricate than common DNA‐mediated assays, especially for complicated physiological samples. Herein, to realize an accurate and reliable quantitative machine, a ratiometric DNA walking machine was developed in human serums and cell lysates based on the elemental isotope ratio measurement. The target DNA‐triggered walking machine converted and amplified biological signals into mass spectrometric signal ratios (197Au/115In) via a burnt‐bridge mechanism. Under the optimized conditions, the limit of detection (LOD, 3σ) was 8 fM for target DNA, with a dynamic linear range of 0.05–0.7 pM. The ratiometric DNA walking machine was directly applied in human serum samples with satisfactory recoveries of 94 to 105 %, demonstrating an excellent stability and a high accuracy. Combining the aptamer‐based specific recognition, the proposed DNA machine is expected to be a versatile platform for other targets, such as small biomolecules and proteins.
Water Reuse Fit for Purpose by a Sustainable Industrial Wastewater Management Concept
Authors: Bauer Sonja , Behnisch Justus , Dell Anna , Gahr Achim , Leinhos Michael , Linke Hans Joachim , Shen Weimin , Tolksdorf Johanna , Wagner Martin
Published: July 2019

Water shortage is often a challenge for industrial park developments. To ensure a more sustainable water supply, the Industrial Wastewater Management Concept with a focus on Reuse (IW2MC→R) provides a strategy to meet the challenges. Main requirements to achieve water reuse fit for purpose are optimized wastewater treatment, an optimized sewer and pipe system, and an innovative water quality monitoring concept. To evaluate water‐reuse concepts, a reuse factor is calculated, which relates to all wastewater inflows to the central wastewater treatment plant and all reuse‐water flows.
Theoretical estimation of the apparent rate constants for ozone decomposition in gas and aqueous phases using ab initio calculations
Authors: Parchei Esfahani Mehrshad , Wu Chongchong , De Visscher Alex
Published: July 2019

An ab initio study, using the coupled cluster calculations (CCSD) method was conducted to investigate the kinetics of the ozone degradation in gas and aqueous phases considering the reaction of ozone with the hydroperoxyl radical. Two potential transition state paths, oxygen and hydrogen transfer, are studied and compared. It was revealed by the ab initio quantum chemical calculations that the calculated overall rate constant in the gas phase differs by approximately an order of magnitude from measured values. However, the calculated selectivity (branching fraction), which was measured directly with isotope studies of hydrogen atom transfer, is almost exactly equal to the experimental value at 298.15 K. The sensitivity analysis showed that adding the reaction between ozone and hydroperoxyl radical to the kinetic model accelerates the decomposition process by more than four times in the aqueous phase (pH = 7–8.5), and for an order of magnitude change in the rate constant of this reaction, the decomposition half‐life changes by 20–45 %. This result might affect our understanding of atmospheric ozone chemistry.
Influence of a fully magnetically levitated left ventricular assist device on functional interrogation of implantable cardioverter defibrillators
Authors: Schukro Christoph , Schlöglhofer Thomas , Khazen Cesar , Röhrich Michael , Laufer Günther , Zimpfer Daniel , Wiedemann Dominik
Published: July 2019

Background

Electromagnetic interference between left ventricular assist devices (LVAD) and the telemetry wand of implantable cardioverter‐defibrillators (ICD) with impairment of ICD interrogation has previously been described in HVAD and HeartMate II devices. This is the first study showing the potential influence of the LVAD model HeartMate 3 (with the unique feature of fully magnetically levitated rotor with consistent wide blood‐flow gaps) on functional interrogation of different ICD models.

Methods and Results

Among 51 patients treated with a HeartMate 3 LVAD, 34 patients (66.7%) already had an ICD implanted prior to LVAD therapy. In this cohort, impairment of ICD interrogation was observed in five patients (14.7%) with five different device models. In patients with Biotronik ICD, stretching of the ipsilateral arm to increase the distance between both devices >10 cm was sufficient in one patients, whereas surgical contralateral repositioning was necessary in two patients; in one further patient no action could be taken, as he died early from embolic stroke. In the only patient with a MicroPort ICD, this issue was resolved by using a wireless telemetry. The distances between both devices showed no statistical significant correlation with an impaired interrogation, neither in the overall collective nor within the groups with the same manufacturer.

Conclusions

In patients with impaired ICD interrogation caused by electromagnetic interference between a HeartMate 3 LVAD and the ICD, the actions mentioned above have to be taken, to resolve this technical issue. Especially, a sufficient distance of at least 10 cm between both devices was crucial for avoiding this problem.
Optimization of LpxC Inhibitors for Antibacterial Activity and Cardiovascular Safety
Authors: Cohen Frederick , Aggen James B. , Andrews Logan D. , Assar Zahra , Boggs Jen , Choi Taylor , Dozzo Paola , Easterday Ashton N. , Haglund Cat M. , Hildebrandt Darin J. , Holt Melissa C. , Joly Kristin , Jubb Adrian , Kamal Zeeshan , Kane Timothy R. , Konradi Andrei W. , Krause Kevin M. , Linsell Martin S. , Machajewski Timothy D. , Miroshnikova Olga , Moser Heinz E. , Nieto Vincent , Phan Thu , Plato Craig , Serio Alisa W. , Seroogy Julie , Shakhmin Anton , Stein Adam J. , Sun Alex D. , Sviridov Serguei , Wang Zhan , Wlasichuk Kenneth , Yang Wen , Zhou Xiaoming , Zhu Hai , Cirz Ryan T.
Published: July 2019

UDP‐3‐O‐(R‐3‐hydroxymyristoyl)‐N‐acetylglucosamine deacetylase (LpxC) is a Zn2+ deacetylase that is essential for the survival of most pathogenic Gram‐negative bacteria. ACHN‐975 (N‐((S)‐3‐amino‐1‐(hydroxyamino)‐3‐methyl‐1‐oxobutan‐2‐yl)‐4‐(((1R,2R)‐2‐(hydroxymethyl)cyclopropyl)buta‐1,3‐diyn‐1‐yl)benzamide) was the first LpxC inhibitor to reach human clinical testing and was discovered to have a dose‐limiting cardiovascular toxicity of transient hypotension without compensatory tachycardia. Herein we report the effort beyond ACHN‐975 to discover LpxC inhibitors optimized for enzyme potency, antibacterial activity, pharmacokinetics, and cardiovascular safety. Based on its overall profile, compound 26 (LPXC‐516, (S)‐N‐(2‐(hydroxyamino)‐1‐(3‐methoxy‐1,1‐dioxidothietan‐3‐yl)‐2‐oxoethyl)‐4‐(6‐hydroxyhexa‐1,3‐diyn‐1‐yl)benzamide) was chosen for further development. A phosphate prodrug of 26 was developed that provided a solubility of >30 mg mL−1 for parenteral administration and conversion into the active drug with a t1/2 of approximately two minutes. Unexpectedly, and despite our optimization efforts, the prodrug of 26 still possesses a therapeutic window insufficient to support further clinical development.
Synthesis, Spectral, Electrochemical and Photovoltaic Studies of A3B Porphyrinic Dyes having Peripheral Donors
Authors: Prakash Kamal , Alsaleh Ajyal Z. , Neeraj  , Rathi Pinki , Sharma Ankit , Sankar Muniappan , D'Souza Francis
Published: July 2019

Three new ‘push‐pull’ A3B Zn(II)porphyrin dyes having meso‐pyrenyl, carbazolyl and phenothiazine as electron donors (A) and phenylcarboxylic acid as acceptor/anchor (B) were synthesized and utilized for DSSC application. The spectral and electrochemical redox properties of these new dyes were studied and compared with trans‐A2BC Zn(II) porphyrin dyes under similar experimental conditions. Red‐shifted, broadened absorption peaks, lower fluorescence quantum yields, and shortened lifetimes were observed for the A3B dyes as compared to zinc tetraphenylporphyrin control, ZnTPP. DFT optimized structures suggested effective charge separation related to enhanced charge injection efficiency. Driving force for electron injection (ΔGinj) and dye regeneration (ΔGreg) calculated from the spectral and electrochemical studies predicted facile electron injection from excited dye into semiconductor TiO2 in the constructed solar cells. Phenothiazine appended dye (KP‐TriPTZ‐Zn) showed the highest η value of 7.3 % for PCE with greater Jsc and Voc values due to its better light harvesting ability and reduced dye aggregation as compared to other dyes. Our studies demonstrate that the dyes having multiple electron‐donating groups exhibit higher photon‐to‐current conversion efficiency.
Novel Perovskite Materials for Thermal Water Splitting at Moderate Temperature
Authors: Azcondo M. Teresa , Orfila María , Marugán Javier , Sanz Raúl , Muñoz‐Noval Alvaro , Salas‐Colera Eduardo , Ritter Clemens , García‐Alvarado Flaviano , Amador Ulises
Published: July 2019

Materials with the formula Sr2CoNb1−xTixO6−δ (x=1.00, 0.70; δ=number of oxygen vacancies) present a cubic perovskite‐like structure. They are easily and reversibly reduced in N2 or Ar and re‐oxidized in air upon heating. Oxidation by water (wet N2), involving splitting of water at a temperature as low as 700 °C, produces hydrogen. Both compounds displayed outstanding H2 production in the first thermochemical cycle, the Sr2CoNb0.30Ti0.70O6−δ material retaining its outstanding performance upon cycling, whereas the hydrogen yield of the x=1 oxide showed a continuous decay. The retention of the materials’ ability to promote water splitting correlated with their structural, chemical, and redox reversibility upon cycling. On reduction/oxidation, Co ions reversibly changed their oxidation state to compensate the release/recovery of oxygen in both compounds. However, in Sr2CoTiO6−δ, two phases with different oxygen contents segregated, whereas in Sr2CoNb0.30Ti0.70O6−δ this effect was not evident. Therefore, this latter material displayed a hydrogen production as high as 410 μmol
 g−1perovskite after eight thermochemical cycles at 700 °C, which is among the highest ever reported, making this perovskite a promising candidate for thermosolar water splitting in real devices.
Classification of esophageal and bolus movements for evaluation of swallowing function by ultrasound video processing using optical flow and stable extremal region method
Authors: Suzuki Yutaka , Hatsushika Kyosuke , Masuyama Keisuke , Sakata Osamu , Tanimoto Morimasa , Morisawa Masayuki
Published: July 2019

Video endoscopy (VE) and video fluorography (VF) are the classic inspection methods used for evaluating the function of swallowing, but are disadvantageous as they are invasive. Therefore, we have proposed a noninvasive method that uses pharyngeal ultrasound videos to estimate the internal flow characteristics of foods and evaluates the swallowing function level quantitatively. We are proposing a new method that combines optical flow with Maximally Stable Extremal Regions (MSERs) to extract the movement velocity and position of esophagus and bolus. The results showed that the movement velocity could be used as an indicator to quantify the internal flow characteristics of foods. The displacement of the esophagus indicates the esophageal opening; this could be used as an indicator to evaluate the swallowing. In this study, we confirmed that a classification of esophageal and bolus movements should be performed automatically by the developed method to decrease the evaluation time.
Tristriazolotriazines with Azobenzene Arms ‐ Acidochromic Dyes and Discotic Liquid Crystals
Authors: Sperner Marcel , Tober Natalie , Detert Heiner
Published: July 2019

Tristriazolotriazines with azobenzene substitution and peripheral alkoxy‐ or alkylamino chains were prepared from the corresponding aryltetrazoles and cyanuric chloride. These star‐shaped dyes are highly acidochromic. Alkoxy‐substitution allows reversible trans‐cis photoswitching. Compounds with a 3,4‐dialkoxy substitution are discotic liquid crystals that form broad and stable thermotropic mesophases. The thermal behavior was studied by DSC and polarizing optical microscopy.
Objective and quantifiable measuring mechanism for assessing flap pliability: Our experience with 92 patients
Authors: Elia Jhonatan , Hassidim Ayal , Billig Allan , Chapchay Katya , Wu Chieh‐Tsai , Hung Shao‐Yu , Cheong David Chon‐Fok , Tsao Chung‐Kan
Published: July 2019

Background

Pliability describes a flaps' ability to bend under spatial limitations, yet a quantifiable measurement for this flexibility does not exist.

Methods

Between January 2015 and January 2017, we applied a novel measuring mechanism to two free flaps for head and neck reconstruction. We allocated a flap pliability score (FPS) to these flaps and observed correlations to common variables.

Results

Forty profunda artery perforator (PAP) and 52 anterolateral thigh (ALT) flaps were allotted a score depending on how pliable they performed on our test. Proximal PAP and distal ALT were more pliable than their respective opposite ends. Other interesting conclusions regarding these flaps were also made.

Conclusions

With our technique, pliability of the proximal and distal ends of PAP and ALT flaps was ascertained. Herein, we describe an innovative measuring mechanism via which we can allocate a FPS to any flap and thus obtain information regarding how suitable they are for a given recipient site.
Overcoming liabilities of origin: Human resource management localization of Chinese multinational corporations in developed markets
Authors: Ouyang Can , Liu Mingwei , Chen Yan , Li Ji , Qin Weiping
Published: July 2019

Despite the rapid growth of Chinese outward foreign direct investment in developed markets, many Chinese multinational corporations (MNCs) suffer from liabilities of origin (LOR)—capability‐ and legitimacy‐based disadvantages associated with the country of origin. This study identifies localization as a strategic mechanism through which Chinese MNCs overcome their LOR. With a specific focus on human resource management (HRM), we examine how factors associated with firms' perceived LOR, including springboard intent, local competition, and host country regulatory pressures, affect Chinese MNCs' adoption of local HRM practices in developed markets. We differentiate HRM practices that managers intend to adopt from those that are actually implemented and explore how state ownership affects the intention–implementation gap. Based on a sample of Chinese MNCs in the United States, we find that springboard intent, local competition, and host country regulatory pressures are positively associated with intended, but not implemented, HRM localization. Further examination demonstrates that springboard intent and local competition have significant effects on implemented HRM localization among private businesses but not in state‐owned enterprises (SOEs). The managerial constraints and resource endowment of Chinese SOEs may hinder their overseas subsidiaries from implementing local HRM practices to address LOR.
Resorting the function of the colorectal cancer gatekeeper adenomatous polyposis coli
Authors: Kariv Revital , Caspi Michal , Fliss‐Isakov Naomi , Shorer Yamit , Shor Yarden , Rosner Guy , Brazowski Eli , Beer Gil , Cohen Shlomi , Rosin‐Arbesfeld Rina
Published: July 2019

As a large number of cancers are caused by nonsense mutations in key genes, read‐through of these mutations to restore full‐length protein expression is a potential therapeutic strategy. Mutations in the adenomatous polyposis coli (APC) gene initiate the majority of both sporadic and hereditary colorectal cancers (CRC) and around 30% of these mutations are nonsense mutations. Our goal was to test the feasibility and effectiveness of APC nonsense mutation read‐through as a potential chemo‐preventive therapy in Familial Adenomatous Polyposis (FAP), an inherited CRC syndrome patients. Ten FAP patients harboring APC nonsense mutations were treated with the read‐through inducing antibiotic erythromycin for 4 months. Endoscopic assessment of the adenomas was performed at baseline, after 4 and after 12 months. Adenoma burden was documented in terms of adenoma number, maximal polyp size and cumulative polyp size per procedure. Tissue samples were collected and subjected to molecular and genetic analyses. Our results show that in the majority of patients the treatment led to a decrease in cumulative adenoma burden, median reduction in cumulative adenoma size and median reduction in adenoma number. Molecular and genetic analyses of the adenomas revealed that the treatment led to a reduced number of somatic APC mutations, reduced cellular proliferation and restoration of APC tumor‐suppressing activity. Together, our findings show that induced read‐through of APC nonsense mutations leads to promising clinical results and should be further investigated to establish its therapeutic potential in FAP and sporadic CRCs harboring nonsense APC mutations.
A comparison of response interruption and redirection and competing items on vocal stereotypy and appropriate vocalizations
Authors: Shawler Lesley A. , Dianda Mia , Miguel Caio F.
Published: July 2019

The current study compared the reductive effects of response interruption and redirection (RIRD) and competing items (including sound‐producing and nonsound‐producing toys) on the vocal stereotypy exhibited by two children diagnosed with Autism Spectrum Disorder. Sound‐producing toys reduced vocal stereotypy relative to nonsound‐producing toys and RIRD reduced stereotypy and increased rates of appropriate vocalizations to a greater extent than providing competing items. These findings replicate and extend previous literature suggesting that RIRD and sound‐producing competing items are effective methods to treat vocal stereotypy.
The effect of insured liabilities on the demand for external audits: The case of privately‐held United States banks
Authors: Hoelscher Jamie , Reed Brad J. , Sierra Gregory
Published: July 2019

We examine the relationship between government insurance for bank deposits and bank management's voluntary audit choice for a set of privately‐held U.S. banks. Unlikely publicly‐traded banks, U.S. regulations do not require private banks to obtain annual audits. However, all U.S. banks have the feature of insurance on customer deposits that is provided by the Federal Deposit Insurance Corporation—these insured customer deposits comprise a significant portion of the debt of most banks. Consistent with prior research we find that the voluntary choice to be audited is positively related to agency costs as measured by the size of bank assets. Our results show a negative association between a bank's insured deposits and the choice to be audited but (consistent with prior literature) a positive association with uninsured liabilities. In addition, we hypothesize and find that the bank's voluntary audit choice is positively related to the bank's growth rate and related to the bank's primary federal regulator. Taken together, these findings are consistent with the notion that audits create value primarily for uninsured depositors and have implications for bank managers, their customers, and regulators.
Effects of Electronic Structure of Adjacent Carbon on the Strength of C─F⋯H─F Organofluorine Hydrogen Bonds
Authors: Jia Qingqing , Li Hai‐Bei , Luo Mo , Wang Jingjing
Published: July 2019

We investigate the effects of the electronic structure of carbon atom on the organofluorine hydrogen bonds, C─F⋯H─F. Our results show that we can modulate the strength of organofluorine hydrogen bonds by adjusting the volume of fluorine atom in C─F via changing the electronic structure of adjacent carbon atoms. Different with the conventional hydrogen bonds, we found that instead of carbon rehybridization and hyperconjugative effects, the magnitude of fluorine atomic volume plays important roles in determining the strength of the C─F⋯H─F organofluorine hydrogen bonds. The lone pair electrons at both the proximal and the vicinal carbon dramatically reinforce the strength of C─F⋯H─F organofluorine hydrogen bond with its interaction energy in the range of about 15–25 kcal/mol, that is, the carbanion‐mediated organofluorine hydrogen bond could be very strong. Due to the high electronegativity of fluorine atom, it easily attracts the excess electron from the proximal and vicinal carbon, which results in the increase of its volume and negative charge. The enhanced volume of fluorine atom gives rise to the large polarization energy, and its enhanced negative charge favors the large electrostatic interaction, both of which substantially contribute to making the organofluorine hydrogen bonds strong. © 2019 Wiley Periodicals, Inc.
Efficacy, Safety, and Tolerability of ONO‐4474, an Orally Available Pan‐Tropomyosin Receptor Kinase Inhibitor, in Japanese Patients With Moderate to Severe Osteoarthritis of the Knee: A Randomized, Placebo‐Controlled, Double‐Blind, Parallel‐Group Comparative Study
Authors: Ishiguro Naoki , Oyama Shusuke , Higashi Ryunosuke , Yanagida Kunio
Published: July 2019

We examined the efficacy, safety, and tolerability of ONO‐4474 in Japanese patients with osteoarthritis (OA) of the knee. In this multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group comparative study, patients with moderate to severe OA who were refractory to nonsteroidal anti‐inflammatory drugs were orally administered 100 mg of ONO‐4474 twice daily for 28 days. The primary end point was knee pain during walking, assessed by visual analog scale over 24 hours (VAS24). Treatment‐emergent adverse events (TEAEs) and adverse drug reactions were reported for safety. In total, 110 patients were randomized (1:1) to receive placebo or ONO‐4474. The mean (standard deviation) change in VAS24 scores at week 4 was −26.9 (25.0) mm in the ONO‐4474 group and −19.5 (19.6) mm in the placebo group. The difference (ONO‐4474 group − placebo group) in posterior mean change in VAS24 at week 4 was −5.8 (posterior standard deviation, 4.4; 95% confidence interval, −14.3 to 2.8) mm. TEAEs were reported in 41.8% of patients in the ONO‐4474 group and 18.2% of patients in the placebo group. The most common TEAEs in the ONO‐4474 group related to the musculoskeletal system and the peripheral and central nervous systems were myalgia (7.3%), arthralgia (5.5%), dizziness (3.6%), and hypoesthesia (3.6%). Four patients from the ONO‐4474 group and 1 patient from the placebo group discontinued treatment because of AEs; however, none were judged to be serious, and all patients recovered or were recovering after discontinuation. ONO‐4474 is a novel tropomyosin receptor kinase inhibitor that has an analgesic effect in patients with OA.
Ochronotic pigmentation is caused by homogentisic acid and is the key event in alkaptonuria leading to the destructive consequences of the disease—A review
Authors: Ranganath Lakshminarayan R. , Norman Brendan P. , Gallagher James A.
Published: July 2019

Ochronosis is the process in alkaptonuria (AKU) that causes all the debilitating morbidity. The process involves selective deposition of homogentisic acid (HGA)‐derived pigment in tissues altering the properties of these tissues, leading to their failure. Some tissues like cartilage are more easily affected by ochronosis while others such as the liver and brain are unaffected for reasons that are still not understood. In vitro and mouse models of ochronosis have confirmed the dose relationships between HGA and ochronosis and also their modulation by p‐hydroxyphenylpyruvate dioxygenase inhibition. Ochronosis cannot be fully reversed and is a key factor in influencing treatment decisions. Earlier detection of ochronosis preferably by noninvasive means is desirable. A cause‐effect relationship between HGA and ochronosis is discussed. The similarity in AKU and familial hypercholesterolaemia is explored and lessons learnt. More research is needed to more fully understand the crucial nature of ochronosis.
Molecular analysis of human adenoviruses in hospitalized children <5 years old with acute gastroenteritis in Tehran, Iran
Authors: Arashkia Arash , Bahrami Ferial , Farsi Mahsa , Nejati Behrooz , Jalilvand Somayeh , Nateghian Alireza , Rahbarimanesh Aliakbar , Shoja Zabihollah
Published: July 2019

Human adenoviruses (HAdVs), especially AdV‐40 and 41, are common causes of nonbacterial sporadic and outbreak gastroenteritis in children. The present study aimed to describe the frequency and genetic analysis of HAdVs in hospitalized children <5 years old with acute gastroenteritis. A total of 376 stool samples obtained from June 2015 to December 2017 were investigated for the presence of HAdVs by polymerase chain reaction. The HAdV DNA was detected in 16 (4.3%) out of 376 stool samples. Based on the hexon hypervariable region (HVR), B, C, and F HADV species including five types HAdV‐1, 2, 3, 6, and 41 were identified, among which enteric AdV species F (EAdV‐41) was the most dominant. Moreover, our findings showed the presence of genomic type cluster 1 (GTC1) pattern in Iranian type 41 strains, which was closely similar to the D1 prototype strain (Tak) and D28. In this regard, a recombination was found in AdV‐41 strains presenting the hexon sequence that belonged to GTC1, while fiber sequence clustered with GTC2.
Radiofrequency catheter ablation of accessory pathways at the site of prior valve surgery
Authors: Uhm Jae‐Sun , Kim Jun , Jin Moo‐Nyun , Kim In‐Soo , Cho Min Soo , Yang Pil‐Sung , Yu Hee Tae , Kim Tae‐Hoon , Joung Boyoung , Pak Hui‐Nam , Nam Gi‐Byoung , Choi Kee‐Joon , Kim You‐Ho , Hwang Chun , Lee Moon‐Hyoung
Published: July 2019

Background

Radiofrequency catheter ablation (RFCA) for accessory pathways (APs) at the site of prior valve surgery (VS) remains challenging. We aimed to clarify the factors associated with successful RFCA for such APs.

Methods

Upon reviewing a RFCA registry and previous case reports, we included nine patients who underwent RFCA of APs at the site of prior VS (total‐VS group; age, 34.0 [24.5‐45.0] years; men, 4/9) and 196 patients who underwent RFCA of APs with no history of VS (no‐VS group; age, 40.5 [23.0‐54.0] years; men, 114/196). Electrophysiological features, procedural details, and outcomes were examined.

Results

Accessory pathway exhibited decremental conduction in four of nine patients in the total‐VS group. The number of RFCA attempts was significantly higher in the total‐VS group than in the no‐VS group (10.0 [4.5‐14.5] vs 2.0 [1.0‐3.0];P < 0.001). In four patients who underwent mitral VS, successful RFCA was achieved using the transaortic approach, coronary sinus (CS) approach, or bipolar ablation. In three patients who underwent tricuspid VS, successful RFCA was achieved using the above‐prosthetics or trans‐prosthetics approach. In two patients, RFCA failed. The trans‐prosthetics approach and bipolar ablation technique were effective. The transaortic and CS approaches were occasionally effective. The transseptal approach was ineffective.

Conclusions

Successful RFCA of APs at the site of prior VS can be achieved by detailed mapping of the areas both above and below the prosthetic valve, as well as by ensuring effective radiofrequency energy delivery using various catheter approaches and RFCA techniques.
Characterizing monthly temperature variability states and associated meteorology across southern South America
Authors: Detzer Judah , Loikith Paul C. , Pampuch Luana Albertani , Mechoso C. Roberto , Barkhordarian Armineh , Lee Huikyo
Published: July 2019

Key spatiotemporal patterns of monthly scale temperature variability are characterized over southern South America using k‐means clustering. The resulting clusters reveal patterns of temperature variability, referred to as temperature variability states. Analysis is performed over summer and winter months separately using data covering the period 1980–2015. Results for both seasons show four primary temperature variability states. In both seasons, one state is primarily characterized by warm temperature anomalies across the domain while another is characterized by cold anomalies. The other two patterns tend to be characterized by a warm north–cold south and cold north–warm south feature. This suggests two primary modes of temperature variability over the region. Composites of synoptic‐scale meteorological patterns (wind, geopotential height, and moisture fields) are computed for months assigned to each cluster to diagnose the driving meteorology associated with these variability states. Results suggest that low‐level temperature advection promoted by anomalies in atmospheric circulation patterns is a key process for driving these variability states. Moisture‐related processes also are shown to play a role, especially in summer. The El Niño–Southern Oscillation and the Southern Annular Mode exhibit some relationship with temperature variability state frequency, with some states more common during amplified phases of these two modes than others. However, the climate modes are not a primary driver of the temperature variability states.
A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair
Authors: Cheng Tegan L. , Leblanc Elisabeth , Kalinina Anastassia , Cantrill Laurence C. , Valtchev Peter , Dehghani Fariba , Little David G. , Schindeler Aaron
Published: July 2019

Bone allografts are inferior to autografts for the repair of critical‐sized defects. Prior studies have suggested that bone morphogenetic protein‐2 (BMP‐2) can be combined with allografts to produce superior healing. We created a bioactive coating on bone allografts using polycondensed deoxyribose isobutyrate ester (PDIB) polymer to deliver BMP‐2 ± the bisphosphonate zoledronic acid (ZA) and tested its ability to enhance the functional utility of allografts in preclinical Wistar rat models. One ex vivo and two in vivo proof‐of‐concept studies were performed. First, PDIB was shown to be able to coat bone grafts (BGs). Second, PDIB was used to coat structural allogenic corticocancellous BG with BMP‐2 ± ZA ± hydroxyapatite (HA) microparticles and compared with PDIB‐coated grafts in a rat muscle pouch model. Next, a rat critical defect model was performed with treatment groups including (i) empty defect, (ii) BG, (iii) collagen sponge + BMP‐2, (iv) BG + PDIB/BMP‐2, and (v) BG + PDIB/BMP‐2/ZA. Key outcome measures included detection of fluorescent bone labels, microcomputed tomography (CT) quantification of bone, and radiographic healing. In the muscle pouch study, BMP‐2 did not increase net bone volume measured by microCT, however, fluorescent labeling showed large amounts of new bone. Addition of ZA increased BV by sevenfold (p < 0.01). In the critical defect model, allografts were insufficient to promote reliable union, however, union was achieved in collagen/BMP‐2 and all BG/BMP‐2 groups. Statement of clinical significance: These data support the concept that PDIB is a viable delivery method for BMP‐2 and ZA delivery to enhance the bone forming potential of allografts. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2278–2286, 2019
Trends of INR and Fecal Excretion of Vitamin K During Cholestasis Reversal: Implications in the Treatment of Neonates With Intestinal Failure–Associated Liver Disease
Authors: Dao Duy T. , Anez‐Bustillos Lorenzo , Finkelstein Adam M. , Mitchell Paul D. , O'Loughlin Alison A. , Fell Gillian L. , Baker Meredith A. , Potemkin Alexis K. , Gura Kathleen M. , Puder Mark
Published: July 2019

Background

Vitamin K is a fat‐soluble compound that plays important roles in coagulation. In children with intestinal failure–associated liver disease (IFALD), the disrupted enterohepatic circulation can lead to intestinal loss of vitamin K. Fish oil–based lipid emulsion (FOLE) has proven effective in treating IFALD. As biliary excretion is restored during cholestasis reversal, the accelerated vitamin K loss can pose a risk for deficiency.

Methods

Ten neonates with IFALD and receiving FOLE monotherapy were prospectively enrolled in the study from 2016 to 2018. In addition to weekly measurements of international normalized ratio (INR) and direct bilirubin (DB), ostomy output was collected for determination of fecal concentrations of phylloquinone (PK). Trends of DB, INR, and fecal PK concentrations were summarized with locally estimated scatterplot smoothing.

Results

The median time (interquartile range) from FOLE initiation to cholestasis reversal was 59 (19–78) days. During cholestasis reversal, INR remained relatively unchanged, whereas the mean (95% confidence interval) daily fecal excretion of PK increased from 25.1 (5.0–158.5) ng at the time of FOLE initiation to 158.5 (31.6–1000.0) ng at complete reversal. Examination of individual trends in fecal PK excretion and INR revealed little correlation between the 2 measurements (r = −0.10; P = 0.50).

Conclusion

Children with IFALD are at risk for vitamin K deficiency during cholestasis reversal. Close monitoring and quantified supplementation of vitamin K may be warranted during this period. However, this should not be guided by INR alone, as it is a poor indicator of vitamin K status.
Isolation and identification of zinc‐chelating peptides from sea cucumber (Stichopus japonicus) protein hydrolysate
Authors: Liu Xiaoyang , Wang Zixu , Zhang Jing , Song Liang , Li Deyang , Wu Zixuan , Zhu Beiwei , Nakamura Yoshimasa , Shahidi Fereidoon , Yu Chenxu , Zhou Dayong
Published: July 2019

BACKGROUND

Zinc is known to play an essential role in the biological activities in the human body. In this study, a zinc‐chelating peptide (ZCP) produced by Alcalase‐assisted hydrolysis of the body wall of sea cucumber was isolated and identified. The ZCP was purified stepwise by ultrafiltration, anion‐exchange chromatography, and gel filtration chromatography, in conjunction with ultraviolet–visual (UV–visual) spectrophotometry, which was used to analyze each purified fraction.

RESULTS

Analysis of the purified ZCP revealed that its zinc‐chelating ability was 33.31%. Analysis of isothermal titration calorimetry suggested that the binding of ZCP and zinc (N ≈ 2) was endothermic, with weak binding affinity. Fourier transform infrared spectroscopy spectra (FTIR) indicated that carboxylic and amide groups in ZCP were the primary binding sites of Zn. Sequencing the result by ultra‐performance liquid chromatography‐quadrupole/time of flight mass spectrometry (UPLC‐Q‐TOF‐MS/MS) showed that a representative ZCP had the sequence WLTPTYPE with a molecular weight of 1005.5 Da.

CONCLUSION

These results provide a promising foundation for the production of zinc supplements from sea‐cucumber‐derived ZCPs. © 2019 Society of Chemical Industry