bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosing congenital syphilis using Hutchinson's method: Differentiating between syphilitic, mercurial, and syphilitic‐mercurial dental defects
Authors: Ioannou Stella , Sassani Sadaf , Henneberg Maciej , Henneberg Renata J.
Published: December 2015

Objectives

This study focuses on the dental abnormalities observed by Sir Jonathan Hutchinson, Henry Moon and Alfred Fournier in patients with congenital syphilis and in those treated with mercury, in order to define alterations in dental morphology attributable to each of these causes. These definitions are applied to reported paleopathological cases, exploring various etiologies behind the defects, in order to aid in the diagnosis of congenital syphilis.

Methods

Original works were examined for descriptions of dental abnormalities in congenital syphilis and in mercurial treatments. These descriptions were compared with dentitions of paleopathological cases (n = 4) demonstrating abnormalities attributed to congenital syphilis.

Results

Distinct morphological differences were recognized between congenital syphilitic teeth and teeth affected by mercury. Mercury produces a pronounced deficiency in enamel of incisors, canines and first permanent molars that become rugged and pitted, and of dirty grey honeycombed appearance. Mercury‐induced dental changes are evident in three out of four cases studied here. In one case, only syphilitic changes were present.

Discussion

Dental changes in congenital syphilis range from no visible signs to those beyond the classical models of Hutchinson, Moon and Fournier. Treatment of neonates and infants with mercury produces additional changes. Signs of disease and treatment with mercury on teeth may occur together; permanent incisors, first molars and canines, are typically affected, premolars and second/third molars are usually spared. Signs of treatment with mercury might be the only evidence of the occurrence of the disease as mercury was rarely used to treat other diseases. Am J Phys Anthropol 159:617–629, 2016. © 2015 Wiley Periodicals, Inc.
Ringmethylierung kontrolliert die Wasserstoffbrücken‐Andockstelle bei Anisol
Authors: Gottschalk Hannes C. , Altnöder Jonas , Heger Matthias , Suhm Martin A.
Published: December 2015

Ein Methanolmolekül kann mit seiner OH‐Gruppe entweder über einen OH⋅⋅⋅O‐ oder einen OH⋅⋅⋅π‐Kontakt an ein Anisolmolekül binden. Wie durch FTIR‐Absorptionsspektroskopie nachgewiesen wird, lässt sich das Verhältnis der Häufigkeiten dieser beiden Motive in Überschallexpansionen um eine Größenordnung verändern, indem Anisol am aromatischen Ring ein‐ bis dreifach methyliert oder mit einer tert‐Butylgruppe substituiert wird. Diese starke Abhängigkeit vom Methylierungsgrad liefert einen auf kJ mol−1 genauen Maßstab für die Vorhersagequalität quantenchemischer Methoden und kann zu einem besseren Verständnis von induktiven, mesomeren und dispersionsgesteuerten Effekten beitragen. Auf B3LYP‐D3/aVTZ‐Niveau mit Schwingungsnullpunktkorrektur gelingt eine ausgewogene Beschreibung der beiden Wasserstoffbrückenmotive, wie auch mit einem Wellenfunktions‐basierten Protokoll, das auf Einzelpunktrechnungen auf MP2‐ und CCSD(T)‐Niveau an den optimierten Strukturen basiert. Dagegen überschätzt das M06‐2X‐Funktional systematisch die Stabilität des OH⋅⋅⋅π‐Motivs.
[Cu(NHC)]‐Catalyzed C−H Allylation and Alkenylation of both Electron‐Deficient and Electron‐Rich (Hetero)arenes with Allyl Halides
Authors: Xie Weilong , Chang Sukbok
Published: December 2015

New reactivity of a [Cu(NHC)] (NHC=N‐heterocyclic carbene) catalyst is disclosed for the efficient C−H allylation of polyfluoroarenes using allyl halides in benzene at room temperature. The same catalyst system also promotes an isomerization‐induced alkenylation of initially the generated allyl arenes when the reaction is run in tetrahydrofuran. Significantly, not only electron‐deficient but also electron‐rich (hetero)arenes undergo this double‐bond migration process, thus leading to alkenylated products. The present system features mild reaction conditions, broad scope with respect to the arene substrates and allyl halide reactants, good functional‐group tolerance, and high stereoselectivity.
Quantitative Packaging of Active Enzymes into a Protein Cage
Authors: Azuma Yusuke , Zschoche Reinhard , Tinzl Matthias , Hilvert Donald
Published: December 2015

Genetic fusion of cargo proteins to a positively supercharged variant of green fluorescent protein enables their quantitative encapsulation by engineered lumazine synthase capsids possessing a negatively charged lumenal surface. This simple tagging system provides a robust and versatile means of creating hierarchically ordered protein assemblies for use as nanoreactors. The generality of the encapsulation strategy and its effect on enzyme function were investigated with eight structurally and mechanistically distinct catalysts.
Control over the Hydrogen‐Bond Docking Site in Anisole by Ring Methylation
Authors: Gottschalk Hannes C. , Altnöder Jonas , Heger Matthias , Suhm Martin A.
Published: December 2015

The supramolecular docking of methanol to anisole may occur via an OH⋅⋅⋅O hydrogen bond or via an OH⋅⋅⋅π contact. The subtle balance between these two structures can be varied in supersonic jets by one order of magnitude through single to triple methylation of the aromatic ring and introduction of a single tert‐butyl substituent, as evidenced by infrared spectroscopy. This steep variation makes it possible to assess the accuracy of relative quantum‐chemical energy predictions on a kJ mol−1 level, promising insights into inductive, mesomeric, and dispersive effects. The zero‐point‐corrected B3LYP‐D3/aVTZ level is shown to provide an accurate relative description of the two very different hydrogen bonds, similar to a wavefunction‐based protocol including CCSD(T) corrections applied to the same structures. M06‐2X alone systematically overestimates the stability of π coordination.
Cyclohexane Rings Reduce Membrane Permeability to Small Ions in Archaea‐Inspired Tetraether Lipids
Authors: Koyanagi Takaoki , Leriche Geoffray , Onofrei David , Holland Gregory P. , Mayer Michael , Yang Jerry
Published: December 2015

Extremophile archaeal organisms overcome problems of membrane permeability by producing lipids with structural elements that putatively improve membrane integrity compared to lipids from other life forms. Herein, we describe a series of lipids that mimic some key structural features of archaeal lipids, such as: 1) single tethering of lipid tails to create fully transmembrane tetraether lipids and 2) the incorporation of small rings into these tethered segments. We found that membranes formed from pure tetraether lipids leaked small ions at a rate that was about two orders of magnitude slower than common bilayer‐forming lipids. Incorporation of cyclopentane rings into the tetraether lipids did not affect membrane leakage, whereas a cyclohexane ring reduced leakage by an additional 40 %. These results show that mimicking certain structural features of natural archaeal lipids results in improved membrane integrity, which may help overcome limitations of many current lipid‐based technologies.
Solid state polymerization in a micro‐reactor: The case of poly(tetramethylene terephthalamide)
Authors: Papaspyrides Constantine D. , Porfyris Athanasios D. , Vouyiouka Stamatina , Rulkens Ruud , Grolman Eric , Poel Geert Vanden
Published: December 2015

The aim of this work was to develop and optimize a direct solid state polymerization (DSSP) process on a micro scale for alkyldiammonium‐terephthalate salts. This was successfully demonstrated for the first time by the case of tetramethylenediammonium‐terepththalate salt (4T salt). The derived polymer (PA4T) presents interesting properties, but the temperature‐favored acid catalyzed cyclization of tetramethylenediamine (TMD) to mono‐functional pyrrolidine and ammonia inhibits a high polymerization conversion. DSSP was performed in a thermogravimetrical analysis (TGA) chamber, and the continuously monitored weight loss was correlated to polymerization conversion via the release of water, excluding any mass and heat transfer limitations. It was found that the conditions under which the DSSP is performed and the morphology of the starting material affect both the reaction rate and the product quality. The effect of the critical process parameters, namely vent size, heating rate to reach SSP temperature, and reaction temperature were quantified by the observed mass loss and by 1H NMR analysis. It was noticed that, besides the water formed by amidation, other volatile compounds were also released during the DSSP reaction, with main component, the TMD. In particular, it was observed that conditions favoring the evaporation of TMD also favored a higher reaction rate. The TMD loss was minimized by optimization of the aforementioned process conditions, leading to a more thermally stable and a higher molecular weight final product. The thermal stability of the PA4T was found to be inversely correlated to the concentration of carboxylic end groups present in the formed polymer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43271.
Maleopimaric acid‐modified two‐component waterborne polyurethane for coating applications
Authors: Si Hongyan , Liu He , Shang Shibin , Song Jie , Liao Shengliang , Wang Dan , Song Zhanqian
Published: December 2015

Maleopimaric acid (MPA), an important rosin derivative, was used to partially substitute isophthalic acid for the preparation of an anionic polyol (MPP) dispersion. The MPP dispersion was then applied to prepare a novel maleopimaric acid‐modified two‐component waterborne polyurethane (MPP‐2K‐WPU). The influences of NCO:OH molar ratio on the thermal properties, water absorption, surface free energy, and application properties of MPP‐2K‐WPU films were investigated. With increasing NCO:OH molar ratio, the thermal stability, pencil hardness, and ethanol resistance of MPP‐2K‐WPU films were improved, but the water resistance was enhanced firstly and then weakened. The surface free energy of MPP‐2K‐WPU films mainly depended on the dispersion interaction which was related to the structure of macromolecules. In addition, compared with the control sample of PP‐2K‐WPU(1.5:1) film, the MPP‐2K‐WPU(1.5:1) film exhibited improved thermal stability, water resistance, gloss, pencil hardness, and ethanol resistance. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43292.
Sustained release of potassium diclofenac from a pH‐responsive hydrogel based on gum arabic conjugates into simulated intestinal fluid
Authors: Reis Adriano V. , Moia Thais A. , Sitta Danielly L. A. , Mauricio Marcos R. , Tenório‐Neto Ernandes T. , Guilherme Marcos R. , Rubira Adley F. , Muniz Edvani C.
Published: December 2015

This work describes the preparation, the swelling properties and the potassium diclofenac (KDF) release profile of hydrogels of gum arabic (GA), N′,N′‐dimethylacrylamide, and methacrylic acid. In order to convert GA into a hydrogel, the polysaccharide was vinyl‐modified with glycidyl methacrylate. The hydrogels showed pH‐responsive swelling changes, which were more expressive in the basic environment. Release data of KDF were adjusted to a diffusion‐based kinetic model that provides an important insight on affinity of the drug for hydrogel and solvent, which may be the leading parameter for release of guest molecules from polymers. The KDF release from the hydrogels into simulated intestinal fluid decreases when the amount of modified GA increases. This was demonstrated to be due to the higher affinity of KDF for GA‐richer hydrogel, which makes the anti‐inflammatory release less favorable. The analysis of released drug half‐time (t1/2 = 16.10 and 21.51 h) indicated sustained release characteristics. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43319.
Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator
Authors: Nieddu Erika , Pollarolo Benedetta , Mazzei Marco T. , Anzaldi Maria , Schenone Silvia , Pedemonte Nicoletta , Galietta Luis J. V. , Mazzei Mauro
Published: December 2015

The phenylhydrazone RDR‐1 is endowed with moderate activity as F508del‐CFTR corrector; nevertheless, its simple structure enables stimulating developments in this class of correctors. Therefore, we synthesized a number of phenylhydrazones 3 by reacting phenylhydrazine derivatives 1 with furfural derivatives 2. By the same reaction, also the pyridine derivatives 4, the thiophene derivatives 5, and the hydrazides 6 and 7 were prepared. All compounds were tested as F508del‐CFTR correctors in the cystic fibrosis (CF) bronchial epithelial cell line CFBE41o‐, using corr‐4a and VX‐809 as controls. Some of the tested compounds emerged as interesting F508del‐CFTR correctors at 20 μM (3c) and 2 μM (5d). 3c and 5d administered together with VX‐809 produced a satisfactory additivity of action. When the structure of 5d was overlapped with RDR‐1 and five other established correctors, a shared central design was clearly visible. This fact may be of interest in the search for new F508del‐CFTR correctors.
Herd behavior in consumers’ adoption of online reviews
Authors: Shen Xiao‐Liang , Zhang Kem Z.K. , Zhao Sesia J.
Published: December 2015

It has been demonstrated that online consumer reviews are an important source of information that affect individuals’ purchase decision making. To understand the influence of online reviews, this study extends prior research on information adoption by incorporating the perspective of herd behavior. We develop and empirically test a research model using data collected from an existing book review site. We report 2 major findings. First, argument quality and source credibility predict information usefulness, which affects the adoption of online reviews. Second, we determine that the adoption of online reviews is also influenced by 2 herd factors, namely, discounting own information and imitating others. We further identify the key determinants of these herd factors, including background homophily and attitude homophily. The theoretical and practical implications are discussed.
Citation analysis as a literature search method for systematic reviews
Authors: Belter Christopher W.
Published: December 2015

Systematic reviews are essential for evaluating biomedical treatment options, but the growing size and complexity of the available biomedical literature combined with the rigor of the systematic review method mean that systematic reviews are extremely difficult and labor‐intensive to perform. In this article, I propose a method of searching the literature by systematically mining the various types of citation relationships between articles. I then test the method by comparing its precision and recall to that of 14 published systematic reviews. The method successfully retrieved 74% of the studies included in these reviews and 90% of the studies it could reasonably be expected to retrieve. The method also retrieved fewer than half of the total number of publications retrieved by these reviews and can be performed in substantially less time. This suggests that the proposed method offers a promising complement to traditional text‐based methods of literature identification and retrieval for systematic reviews.
Liberating interdisciplinarity from myth. An exploration of the discursive construction of identities in information studies
Authors: Madsen Dorte
Published: December 2015

Recent research in information studies suggests that the tradition of seeing the discipline as weak is still alive and kicking. This is a problem because the discourse of the weak discipline creates conceptual confusion in relation to interdisciplinarity. Considering the growth of the iSchools and what is assumed to be a major institutional redrawing of boundaries, there is a pressing need to conceptualize interdisciplinary practices and boundary work. This paper explores the “weak” discipline through a discourse analytical lens and identifies a myth. Perceiving the discipline as weak is part of a myth, fueled by the ideal of a unitary discipline; the ideal discipline has strong boundaries, and as long as the discourse continues to focus on a need for boundaries, the only available discourse is one that articulates the discipline as weak. Thus, the myth is a vicious circle that can be broken if weakness is no longer ascribed to the discipline by tradition. The paper offers an explanation of the workings of the myth so that its particular way of interpreting the world does not mislead us when theorizing interdisciplinarity. This is a conceptual paper, and the examples serve as an empirical backdrop to the conceptual argument.
Identification of nonliteral language in social media: A case study on sarcasm
Authors: Muresan Smaranda , Gonzalez‐Ibanez Roberto , Ghosh Debanjan , Wacholder Nina
Published: December 2015

With the rapid development of social media, spontaneously user‐generated content such as tweets and forum posts have become important materials for tracking people's opinions and sentiments online. A major hurdle for current state‐of‐the‐art automatic methods for sentiment analysis is the fact that human communication often involves the use of sarcasm or irony, where the author means the opposite of what she/he says. Sarcasm transforms the polarity of an apparently positive or negative utterance into its opposite. Lack of naturally occurring utterances labeled for sarcasm is one of the key problems for the development of machine‐learning methods for sarcasm detection. We report on a method for constructing a corpus of sarcastic Twitter messages in which determination of the sarcasm of each message has been made by its author. We use this reliable corpus to compare sarcastic utterances in Twitter to utterances that express positive or negative attitudes without sarcasm. We investigate the impact of lexical and pragmatic factors on machine‐learning effectiveness for identifying sarcastic utterances and we compare the performance of machine‐learning techniques and human judges on this task.
Incorporation of Hexa‐peri‐hexabenzocoronene (HBC) into Carbazole–Benzo‐2,1,3‐thiadiazole Copolymers to Improve Hole Mobility and Photovoltaic Performance
Authors: Gao Chen , Jiang Pei , Shi Keli , Ma Di , Li Yongfang , Yu Gui , Li Xiaoyu , Wang Haiqiao
Published: December 2015

Hexa‐peri‐hexabenzocoronene (HBC) is a discotic‐shaped conjugated molecule with strong π–π stacking property, high intrinsic charge mobility, and good self‐assembly properties. For a long time, however, organic photovoltaic (OPV) solar cells based on HBC demonstrated low power conversion efficiencies (PCEs). In this study, two conjugated terpolymers, poly[N‐9′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5′‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole)] (PCDTBT)‐5 HBC and PCDTBT‐10 HBC, were synthesized by incorporating different amounts of HBC as the third component into poly[N‐9′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5′‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole)] (PCDTBT) through Suzuki coupling polymerization. For comparison, the donor–acceptor (D–A) conjugated dipolymer PCDTBT was also synthesized to investigate the effect of HBC units on conjugated polymers. The HBC‐containing polymers exhibited higher thermal stabilities, broader absorption spectra, and lower highest‐occupied molecular orbital (HOMO) energy levels. In particular, the field‐effect mobilities were enhanced by more than one order of magnitude after the incorporation of HBC into the conjugated polymer backbone on account of increased interchain π–π stacking interactions. The bulk heterojunction (BHJ) polymer solar cells (PSCs) fabricated with the polymers as donor and PC71BM as acceptor demonstrated gradual improvement of open‐circuit voltage (VOC) and short‐circuit current (JSC) with the increase in HBC content. As a result, the PCEs were improved from 3.21 % for PCDTBT to 3.78 % for PCDTBT‐5 HBC and then to 4.20 % for PCDTBT‐10 HBC.
A Pyrene‐functionalized Polynorbornene for Ratiometric Fluorescence Sensing of Pyrophosphate
Authors: Ge Jin‐Zhu , Liu Zhanghua , Cao Qian‐Yong , Chen Yong , Zhu Jiang‐Hua
Published: December 2015

A novel pyrene‐functionalized polynorbornene (P1) bearing sulfonamide NH and triazolium donors has been synthesized for ratiometric fluorescence sensing of PPi in aqueous solution. In addition, P1 is also used to monitor intracellular PPi and to detect PPi released during polymerase chain reaction.
Regulation of mesenchymal stem cell 3D microenvironment: From macro to microfluidic bioreactors
Authors: Sart Sébastien , Agathos Spiros N. , Li Yan , Ma Teng
Published: December 2015

Human mesenchymal stem cells (hMSCs) have emerged as an important cell type in cell therapy and tissue engineering. In these applications, maintaining the therapeutic properties of hMSCs requires tight control of the culture environments and the structural cell organizations. Bioreactor systems are essential tools to achieve these goals in the clinical‐scale expansion and tissue engineering applications. This review summarizes how different bioreactors provide cues to regulate the structure and the chemico‐mechanical microenvironment of hMSCs with a focus on 3D organization. In addition to conventional bioreactors, recent advances in microfluidic bioreactors as a novel approach to better control the hMSC microenvironment are also discussed. These advancements highlight the key role of bioreactor systems in preserving hMSC's functional properties by providing dynamic and temporal regulation of in vitro cellular microenvironment.
Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation
Authors: Kim J M , Kwon C H D , Joh J-W , Han S B , Sinn D H , Choi G-S , Kang E-S , Lee J H , Kim G S , Lee S-K
Published: December 2015

Background

ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and patient survival between ABO-compatible (ABO-C) and ABO-I LDLT. The aim was to compare the outcomes of ABO-I LDLT with those of ABO-C LDLT using the matched-pairs method.

Methods

Patients who underwent ABO-I LDLT procedures between 2010 and 2013 were studied. They were matched for significant variables with patients who had ABO-C LDLT (1 : 2 matching).

Results

Forty-seven ABO-I LDLT procedures were included. Ninety-four patients who had ABO-C LDLT were selected as a comparator group. The incidence of cytomegalovirus, bacterial and fungal infections during the first 3 months was similar after ABO-I LDLT and ABO-C LDLT (85 versus 76 per cent, 28 versus 37 per cent, and 13 versus 20 per cent, respectively). Antibody-mediated rejection occurred after two procedures within 2 weeks of transplantation, but liver function improved with plasma exchange in both patients. There were no differences in the rate of acute rejection and biliary complications between ABO-I and ABO-C groups (P = 0·478 and P = 0·511 respectively). Three patients who had ABO-I LDLT developed diffuse intrahepatic biliary complications and progressed to graft failure. The 1-, 2- and 3-year patient survival rates after ABO-I LDLT and ABO-C LDLT were 89 versus 87 per cent, 85 versus 83 per cent, and 85 versus 79 per cent, respectively.

Conclusion

The short-term outcomes of ABO-I LDLT were comparable to those of ABO-C LDLT in this study. ABO-I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.
Clinical outcomes of left hepatic trisectionectomy for hepatobiliary malignancy
Authors: Farid S G , White A , Khan N , Toogood G J , Prasad K R , Lodge J P A
Published: December 2015

Background

Left hepatic trisectionectomy (LHT) is a challenging major anatomical hepatectomy with a high complication rate and a worldwide experience that remains limited. The aim of this study was to describe changes in surgical practice over time, to analyse the outcomes of patients undergoing LHT for hepatobiliary malignancy, and to identify factors associated with morbidity and mortality.

Methods

A cohort study was undertaken of patients who underwent LHT at a single tertiary hepatobiliary referral centre between January 1993 and March 2013. Univariable and multivariable analysis was used to identify factors associated with short- and long-term outcomes following LHT.

Result

Some 113 patients underwent LHT for colorectal liver metastasis (57), hilar cholangiocarcinoma (22), intrahepatic cholangiocarcinoma (12) and hepatocellular carcinoma (11); 11 patients had various other indications. Overall morbidity and 90-day mortality rates were 46·0 and 9·7 per cent respectively. Overall 1- and 3-year survival rates were 71·3 and 44·4 per cent respectively. Total hepatic vascular exclusion and intraoperative blood transfusion were independent predictors of postoperative morbidity, whereas blood transfusion was the only factor predictive of in-hospital mortality. Time period analysis revealed a decreasing trend in blood transfusion, duration of hospital stay, and postoperative morbidity and mortality in the last 5 years.

Conclusion

Morbidity, mortality and long-term survival after LHT support its use in selected patients with a significant tumour burden.
Reactivation of Paraoxon‐inhibited Acetylcholinesterase by Monoquaternary Pyridinium Oximes with N‐Alkylbromide Side Chains
Authors: Lee Hyun Myung , Shin Jin Soo , Han Soo Bong , Jung Yu Kyoung , Kim Meeheyin , Lee Sang‐Ho , Hur Gyeunghaeng , Jung Young‐Sik
Published: December 2015

Organophosphorus nerve agents cause neurotoxicity through the inhibition of acetylcholinesterase (AChE) in the human body. Various oxime reactivators were found to reactivate the inhibited AChE. Pralidoxime (2‐PAM) is one such representative oxime antidotes. However, its reactivation ability, as well as its action on the inhibited AChE of the central nervous system, is not sufficient, and therefore the discovery of new oxime reactivators is required. Here, oximes with N‐bromoalkyl groups were synthesized, and their reactivation potency on AChE inhibited by paraoxon was evaluated.
d‐lactic acid production from renewable lignocellulosic biomass via genetically modified Lactobacillus plantarum
Authors: Zhang Yixing , Kumar Amit , Hardwidge Philip R. , Tanaka Tsutomu , Kondo Akihiko , Vadlani Praveen V.
Published: December 2015

d‐lactic acid is of great interest because of increasing demand for biobased poly‐lactic acid (PLA). Blending poly‐l‐lactic acid with poly‐d‐lactic acid greatly improves PLA's mechanical and physical properties. Corn stover and sorghum stalks treated with 1% sodium hydroxide were investigated as possible substrates for d‐lactic acid production by both sequential saccharification and fermentation and simultaneous saccharification and cofermentation (SSCF). A commercial cellulase (Cellic CTec2) was used for hydrolysis of lignocellulosic biomass and an l‐lactate‐deficient mutant strain Lactobacillus plantarum NCIMB 8826 ldhL1 and its derivative harboring a xylose assimilation plasmid (ΔldhL1‐pCU‐PxylAB) were used for fermentation. The SSCF process demonstrated the advantage of avoiding feedback inhibition of released sugars from lignocellulosic biomass, thus significantly improving d‐lactic acid yield and productivity. d‐lactic acid (27.3 g L−1) and productivity (0.75 g L−1 h−1) was obtained from corn stover and d‐lactic acid (22.0 g L−1) and productivity (0.65 g L−1 h−1) was obtained from sorghum stalks using ΔldhL1‐pCU‐PxylAB via the SSCF process. The recombinant strain produced a higher concentration of d‐lactic acid than the mutant strain by using the xylose present in lignocellulosic biomass. Our findings demonstrate the potential of using renewable lignocellulosic biomass as an alternative to conventional feedstocks with metabolically engineered lactic acid bacteria to produce d‐lactic acid. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:271–278, 2016
Conjugation of melanotransferrin antibody on solid lipid nanoparticles for mediating brain cancer malignancy
Authors: Kuo Yung‐Chih , Chao In‐Wei
Published: December 2015

Solid lipid nanoparticles (SLNs) comprising complex internal lipids were conjugated with melanotransferrin antibody (MA) to carry anticancer etoposide across the blood–brain barrier (BBB) for managing glioblastoma multiforme (GBM). MA was crosslinked on the surface of etoposide‐loaded SLNs (ETP‐SLNs) to target human brain‐microvascular endothelial cells (HBMECs) and U87MG cells. The experimental evidences showed that an increase in the tripalmitin weight percentage in lipids enhanced the particle size and viability of U87MG cells, however decreased the etoposide loading efficiency, MA conjugation efficiency, and permeability coefficient for etoposide across the BBB. A high level of MA on the particle surface increased the atomic ratio of nitrogen to phosphorus and permeability coefficient for propidium iodide and etoposide across the BBB, however reduced the MA conjugation efficiency, transendothelial electrical resistance, and viability of U87MG cells. Based on immunochemical staining, we found that MA on ETP‐SLNs triggered the melanotransferrin‐mediated transcytosis and promoted the growth‐inhibitory efficacy to U87MG cells. MA‐conjugated ETP‐SLNs can be a promising colloidal delivery system for malignant GBM pharmacotherapy. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:480–490, 2016
Monitoring the ex‐vivo expansion of human mesenchymal stem/stromal cells in xeno‐free microcarrier‐based reactor systems by MIR spectroscopy
Authors: Rosa Filipa , Sales Kevin C. , Carmelo Joana G. , Fernandes‐Platzgummer Ana , da Silva Cláudia L. , Lopes Marta B. , Calado Cecília R. C.
Published: December 2015

Human mesenchymal stem/stromal cells (MSCs) have received considerable attention in the field of cell‐based therapies due to their high differentiation potential and ability to modulate immune responses. However, since these cells can only be isolated in very low quantities, successful realization of these therapies requires MSCs ex‐vivo expansion to achieve relevant cell doses. The metabolic activity is one of the parameters often monitored during MSCs cultivation by using expensive multi‐analytical methods, some of them time‐consuming. The present work evaluates the use of mid‐infrared (MIR) spectroscopy, through rapid and economic high‐throughput analyses associated to multivariate data analysis, to monitor three different MSCs cultivation runs conducted in spinner flasks, under xeno‐free culture conditions, which differ in the type of microcarriers used and the culture feeding strategy applied. After evaluating diverse spectral preprocessing techniques, the optimized partial least square (PLS) regression models based on the MIR spectra to estimate the glucose, lactate and ammonia concentrations yielded high coefficients of determination (R2 ≥ 0.98, ≥0.98, and ≥0.94, respectively) and low prediction errors (RMSECV ≤ 4.7%, ≤4.4% and ≤5.7%, respectively). Besides PLS models valid for specific expansion protocols, a robust model simultaneously valid for the three processes was also built for predicting glucose, lactate and ammonia, yielding a R2 of 0.95, 0.97 and 0.86, and a RMSECV of 0.33, 0.57, and 0.09 mM, respectively. Therefore, MIR spectroscopy combined with multivariate data analysis represents a promising tool for both optimization and control of MSCs expansion processes. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:447–455, 2016
Characterization of the cellulolytic secretome of Trichoderma harzianum during growth on sugarcane bagasse and analysis of the activity boosting effects of swollenin
Authors: A. L. Rocha Vanessa , N. Maeda Roberto , Pereira Nei , F. Kern Marcelo , Elias Luisa , Simister Rachael , Steele‐King Clare , Gómez Leonardo D. , McQueen‐Mason Simon J.
Published: December 2015

This study demonstrates the production of an active enzyme cocktail produced by growing Trichoderma harzianum on sugarcane bagasse. The component enzymes were identified by LCMS‐MS. Glycosyl hydrolases were the most abundant class of proteins, representing 67% of total secreted protein. Other carbohydrate active enzymes involved in cell wall deconstruction included lytic polysaccharide mono‐oxygenases (AA9), carbohydrate‐binding modules, carbohydrate esterases and swollenin, all present at levels of 1%. In total, proteases and lipases represented 5 and 1% of the total secretome, respectively, with the rest of the secretome being made up of proteins of unknown or putative function. This enzyme cocktail was efficient in catalysing the hydrolysis of sugarcane bagasse cellulolignin to fermentable sugars for potential use in ethanol production. Apart from mapping the secretome of T. harzianum, which is a very important tool to understand the catalytic performance of enzyme cocktails, the gene coding for T. harzianum swollenin was expressed in Aspergillus niger. This novel aspect in this work, allowed increasing the swollenin concentration by 95 fold. This is the first report about the heterologous expression of swollenin from T. harzianum, and the findings are of interest in enriching enzyme cocktail with this important accessory protein which takes part in the cellulose amorphogenesis. Despite lacking detectable glycoside activity, the addition of swollenin of T. harzianum increased by two‐fold the hydrolysis efficiency of a commercial cellulase cocktail. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:327–336, 2016
MicroRNA‐185 inhibits angiogenesis in human microvascular endothelial cells through targeting stromal interaction molecule 1
Authors: Hou Jiayin , Liu Liang , Zhu Qian , Wu Yingbiao , Tian Bei , Cui Li , Liu Ying , Li Xinming
Published: December 2015

Angiogenesis is a vital biological mechanism representing the adaptive response to a variety of pathological stimuli such as hypoxia. It is regulated by several pro‐angiogenic and anti‐angiogenic microRNAs. Studies have demonstrated an altered microRNA‐185 (miR‐185) expression in endothelial cells under hypoxic conditions; however, its role in angiogenesis has not been elucidated. We investigated the role of miR‐185 in angiogenesis and found that miR‐185 had an inhibitory effect on cell proliferation, migration, and tube formation. Stromal interaction molecule 1 (STIM1) appeared to be a direct target of miR‐185 by computational prediction; this was confirmed by luciferase reporter assay. Silencing of the STIM1 gene was found to mimic miR‐185‐mediated inhibition of angiogenesis. STIM1 overexpression eliminated the anti‐angiogenic effect of miR‐185. Our study results suggest a direct interaction between miR‐185 and STIM1 mRNA in microvascular endothelial cells. MicroRNA‐185 acted as a negative regulator of angiogenesis in microvascular endothelial cells through downregulation of the STIM1 protein.
Meta‐analysis of randomized controlled trials comparing percutaneous coronary intervention with aspiration thrombectomy Vs. Conventional percutaneous coronary intervention during ST‐segment elevation myocardial infarction
Authors: Dominguez Abel Casso , Bittl John A. , El‐Hayek Georges , Contreras Elizabeth , Tamis‐Holland Jacqueline E.
Published: December 2015

Objectives

Evaluate the impact of aspiration thrombectomy (AT) during primary coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI) on clinical outcomes.

Background

AT during PCI for STEMI may improve microvascular reperfusion, but its impact on clinical outcomes has remained controversial.

Methods

We searched Pubmed, EMBASE, Medline, Scopus, CENTRAL, andClinicalTrials.gov databases on March 31, 2015 for randomized controlled trials that evaluated the use of AT with PCI compared with PCI alone for STEMI. The primary end point was all‐cause mortality. Secondary end points included major adverse cardiac events (MACE, consisting of death, myocardial infarction, and target‐vessel revascularization), recurrent myocardial infarction (MI), target‐vessel revascularization (TVR), stent thrombosis and stroke.

Results

Eighteen randomized controlled trials (n = 21,501) fulfilled the inclusion criteria. A total of 10,544 patients were treated with AT and PCI, compared to 10,957 control patients. The use of AT was not associated with a significant decrease in all‐cause mortality (RR 0.88; 95% CI 0.78–1.01; P = 0.07), MACE (RR 0.93; 95% CI 0.86‐1.00; P = 0.06), recurrent MI (RR 0.97: 95% CI 0.81–1.17; P = 0.77), TVR (RR 0.93; 95% CI 0.82–1.05; P = 0.23), stent thrombosis (RR 0.84; 95% CI 0.66–1.07; P = 0.17), or stroke (RR 1.35; 95% CI 0.86–2.11; P = 0.19).

Conclusions

Using the totality of evidence available through 2015, this meta‐analysis failed to show that the routine use of aspiration thrombectomy in patients with ST‐elevation myocardial infarction significantly reduces all‐cause mortality, MACE, recurrent MI, TVR, or stent thrombosis. The role of aspiration thrombectomy in selected patients with angiographic evidence of large thrombus burden requires further clinical investigation. © 2015 Wiley Periodicals, Inc.
Comparison of long‐term patency after endovascular therapy for superficial femoral artery occlusive disease between patients with and without hemodialysis
Authors: Matsumi Junya , Tobita Kazuki , Shishido Koki , Mizuno Shingo , Yamanaka Futoshi , Murakami Masato , Tanaka Yutaka , Takahashi Saeko , Akasaka Takeshi , Saito Shigeru
Published: December 2015

Objective

To compare long‐term patency after endovascular therapy (EVT) for superficial femoral artery (SFA) occlusive disease between patients with hemodialysis (HD; HD+) and those without HD (HD−).

Background

Long‐term patency after EVT for SFA occlusive disease in HD+ remains unknown. Methods: EVT to SFA was successfully performed in 382 consecutive patients during 2004–2011. Cox proportional hazard model estimated the hazard ratio (HR) for the loss of primary patency (PP), secondary patency (SP), and amputation‐free survival (AFS) in HD+. Binominal logistic regression analysis calculated the propensity score (PS) for covariates with a P value of <0.2 for HD as a dependent variable. HRs were adjusted for PS in multivariate analysis using the Cox proportional hazard model.

Results

PP and SP in HD+ and HD− were 47.9 and 79.4% and 68.4 and 92.5%, respectively, 4 years after EVT. There were no procedure‐related amputations or in‐hospital deaths. Adjusted HRs for the loss of PP, SP, and AFS were as follows: loss of PP, adjusted HR 2.010, 95% CI 1.157–3.492, P = 0.013; loss of SP, adjusted HR 2.927, 95% CI 1.236–6.933, P = 0.015; and loss of AFS, adjusted HR 1.665, 95% CI 0.994–2.791, P = 0.053.

Conclusions

Although HD+ had more than double the risks for loss of PP and SP than HD−, EVT to SFA in HD+ was found to be safe with an acceptable PP and SP. © 2015 Wiley Periodicals, Inc.
Ruthenium Nanoparticles in High‐Throughput Studies of Chemoselective Carbonyl Hydrogenation Reactions
Authors: Gmeiner Julia , Behrens Silke , Spliethoff Bernd , Trapp Oliver
Published: December 2015

Small (≤1.4 nm) and very active Ru nanoparticles, stabilized in a polysiloxane matrix, were prepared and studied in hydrogenation reactions by the integration of catalysis and analysis. We used our strategy to combine catalytic activity and separation selectivity in a capillary microreactor, installed in a GC–MS instrument, to develop a fast and reliable screening tool for catalysis over Ru nanoparticles. A high conversion using a low catalyst loading of 0.3 mol % and temperature and long‐term stability of the catalytically active column were observed for the hydrogenation of various carbonyl compounds, which included aldehydes, ketones, and pyruvates. Additionally, we observed a high chemoselectivity for aromatic carbonyl systems. Comprehensive measurements were performed in this high‐throughput experimental setup to gain important insights into the kinetics of hydrogenation reactions at the interface between heterogeneous and homogeneous catalysis.
Three Keggin‐Type Transition Metal‐Substituted Polyoxometalates as Pure Inorganic Photosensitizers for p‐Type Dye‐Sensitized Solar Cells
Authors: Guo Xiang‐Wei , Li Jian‐Sheng , Sang Xiao‐Jing , Chen Wei‐Lin , Su Zhong‐Min , Wang En‐Bo
Published: December 2015

In light of the serious challenge of severe global energy shortages, p‐type dye‐sensitized solar cells (p‐DSSCs) have attracted increasing levels of interest. The potential of three Keggin‐type transition metal‐substituted polyoxometalates, TBA8Na2[SiW9O37{Co(H2O)3}]⋅ 11 H2O (SiW9Co3), TBA4[(SiO4)W10MnIII2O36H6]⋅1.5 CH3CN⋅ 2 H2O (SiW10MnIII2), and TBA3.5H5.5[(SiO4)W10MnIII/IV2O36]⋅ 10 H2O⋅0.5 CH3CN (SiW10MnIII/IV2) has been explored as pure inorganic dye photosensitizers for p‐DSSCs (TBA=(n‐C4H9)4N+). The three dyes show overall conversion efficiencies of 0.038, 0.029, and 0.027 %, respectively, all of which are higher than that of coumarin 343 (0.017 %). These polyoxometalates are the first three pure inorganic dyes reported for use with p‐DSSCs and therefore demonstrate a new strategy for designing efficient dyes, especially pure inorganic dyes. Moreover, they broaden the range of applications for polyoxometalates.
HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat
Authors: Angelika Ihle Michaela , Merkelbach‐Bruse Sabine , Hartmann Wolfgang , Bauer Sebastian , Ratner Nancy , Sonobe Hiroshi , Nishio Jun , Larsson Olle , Åman Pierre , Pedeutour Florence , Taguchi Takahiro , Wardelmann Eva , Buettner Reinhard , Schildhaus Hans‐Ulrich
Published: December 2015

Histone deacetylases (HDAC) are key players in epigenetic regulation of gene expression and HDAC inhibitor (HDACi) treatment seems to be a promising anticancer therapy in many human tumours, including soft tissue sarcomas. HR23b has been shown to be a potential biomarker for sensitivity to HDACi therapy in cutaneous T‐cell lymphoma and hepatocellular carcinoma. We aimed to evaluate HR23b as a candidate biomarker for HDACi response in sarcomas and gastrointestinal stromal tumours (GIST). Therefore, HR23b expression was analysed comprehensively by western blot in sarcoma and GIST cell lines covering all major clinically relevant subtypes. MTT assay and ApoTox‐GloTM Triplex assay were performed after treatment with vorinostat, belinostat, mocetinostat and entinostat. HR23b protein expression was measured under HDACi treatment. Furthermore, HR23b expression levels were immunohistochemically determined in a large set of 523 clinical samples from sarcoma and GIST patients. Western blot analyses showed that sarcomas differ significantly in their expression of HR23b protein. All HDACi were able to regulate proliferation and apoptosis in vitro. Sensitivity to vorinostat correlated significantly with HR23b protein expression. Immunohistochemical prevalence screening in clinical samples of relevant adult‐type tumours revealed that 12.5% of sarcomas (among them malignant peripheral nerve sheath tumours, pleomorphic liposarcomas, leiomyosarcomas, dedifferentiated liposarcomas, synovial sarcomas and angiosarcomas) and 23.2% of GIST show high HR23b expression. Therefore, HDACi have antiproliferative and proapoptotic effects in sarcomas depending on the expression level of HR23b. These findings suggest that HR23b represents a candidate biomarker for HDACi sensitivity in certain sarcoma types and in GIST.
N‐Phenylbenzamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore
Authors: Roy Sudeshna , Šileikytė Justina , Neuenswander Benjamin , Hedrick Michael P. , Chung Thomas D. Y. , Aubé Jeffrey , Schoenen Frank J. , Forte Michael A. , Bernardi Paolo
Published: December 2015

Persistent opening of the mitochondrial permeability transition pore (PTP), an inner membrane channel, leads to mitochondrial dysfunction and renders the PTP a therapeutic target for a host of life‐threatening diseases. Herein, we report our effort toward identifying small‐molecule inhibitors of this target through structure–activity relationship optimization studies, which led to the identification of several potent analogues around the N‐phenylbenzamide compound series identified by high‐throughput screening. In particular, compound 4 (3‐(benzyloxy)‐5‐chloro‐N‐(4‐(piperidin‐1‐ylmethyl)phenyl)benzamide) displayed noteworthy inhibitory activity in the mitochondrial swelling assay (EC50=280 nm), poor‐to‐very‐good physicochemical as well as in vitro pharmacokinetic properties, and conferred very high calcium retention capacity to mitochondria. From the data, we believe compound 4 in this series represents a promising lead for the development of PTP inhibitors of pharmacological relevance.
Neoadjuvant combination chemotherapy for unresectable stage III non–small cell lung cancer
Authors: Bunn Paul A. , Gaspar Laurie E. , Weyant Michael J. , Mitchell John D.
Published: December 2015

Neoadjuvant chemotherapy and chemoradiation therapy can be considered for patients with potentially resectable stage III Non–Small cell lung cancer. The use of antiangiogenic agents, the best systemic therapy, and the best radiation field and dose require further study.
Acute respiratory infections in children and adolescents with acute lymphoblastic leukemia
Authors: Hakim Hana , Dallas Ronald , Zhou Yinmei , Pei Dequing , Cheng Cheng , Flynn Patricia M. , Pui Ching‐Hon , Jeha Sima
Published: December 2015

BACKGROUND

Knowledge regarding the incidence, clinical course, and impact of respiratory viral infections in children with acute lymphoblastic leukemia (ALL) is limited.

METHODS

A retrospective cohort of patients with newly diagnosed ALL who were treated on the Total Therapy XVI protocol at St Jude Children's Research Hospital between 2007 and 2011 was evaluated.

RESULTS

Of 223 children, 95 (43%) developed 133 episodes of viral acute respiratory illness (ARI) (incidence, 1.1 per 1000 patient‐days). ARI without viral etiology was identified in 65 patients (29%) and no ARI was detected in 63 patients (28%). There were no significant associations noted between race, sex, age, or ALL risk group and the development of ARI. Children receiving induction chemotherapy were found to be at the highest risk of viral ARI (incidence, 2.3 per 1000 patient‐days). Influenza virus was the most common virus (38%) followed by respiratory syncytial virus (33%). Of 133 episodes of viral ARI, 61% of patients were hospitalized, 26% experienced a complicated course, 80% had their chemotherapy delayed, and 0.7% of patients died. Twenty‐four patients (18%) developed viral lower respiratory tract infections (LRTI), 5 of whom (21%) had complications. Patients with viral LRTI had a significantly lower nadir absolute lymphocyte count; were sicker at the time of presentation; and were more likely to have respiratory syncytial virus, to be hospitalized, and to have their chemotherapy delayed for longer compared with those with viral upper respiratory tract infections.

CONCLUSIONS

Despite the low incidence of viral ARI in children with ALL, the associated morbidity, mortality, and delay in chemotherapy remain clinically significant. Viral LRTI was especially associated with high morbidity requiring intensive care‐level support. Cancer 2016;122:798–805. © 2015 American Cancer Society.