bluuebunny/crossref_metadata_2025 huggingface dataset:
Amide-Type Local Anesthetics and Human Mesenchymal Stem Cells: Clinical Implications for Stem Cell Therapy
Authors: Dregalla Ryan C. , Lyons Nicolette F. , Reischling Patrick D. , Centeno Christopher J.
Published: January 2014

In the realm of regenerative medicine, human mesenchymal stem cells (hMSCs) are gaining attention as a cell source for the repair and regeneration of tissues spanning an array of medical disciplines. In orthopedics, hMSCs are often delivered in a site-specific manner at the area of interest and may require the concurrent application of local anesthetics (LAs). To address the implications of using hMSCs in combination with anesthetics for intra-articular applications, we investigated the effect that clinically relevant doses of amide-type LAs have on the viability of bone marrow-derived hMSCs and began to characterize the mechanism of LA-induced hMSC death. In our study, culture-expanded hMSCs from three donors were exposed to the amide-type LAs ropivacaine, lidocaine, bupivacaine, and mepivacaine. To replicate the physiological dilution of LAs once injected into the synovial capsule, each anesthetic was reduced to 12.5%, 25%, and 50% of the stock solution and incubated with each hMSC line for 40 minutes, 120 minutes, 360 minutes, and 24 hours. At each time point, cell viability assays were performed. We found that extended treatment with LAs for 24 hours had a significant impact on both hMSC viability and adhesion. In addition, hMSC treatment with three of the four anesthetics resulted in cell death via apoptosis following brief exposures. Ultimately, we concluded that amide-type LAs induce hMSC apoptosis in a time- and dose-dependent manner that may threaten clinical outcomes, following a similar trend that has been established between these particular anesthetics and articular chondrocytes both in vitro and in vivo.
Mesenchymal Stromal Cells Mediate Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation by Inhibition of the Th17 Signaling Pathway
Authors: Lathrop Melissa J. , Brooks Elice M. , Bonenfant Nick R. , Sokocevic Dino , Borg Zachary D. , Goodwin Meagan , Loi Roberto , Cruz Fernanda , Dunaway Chad W. , Steele Chad , Weiss Daniel J.
Published: January 2014

Systemic administration of mesenchymal stromal cells (MSCs) suppresses airway inflammation and methacholine-induced airway hyper-responsiveness (AHR) in mouse models of T helper cell (Th) type 2-mediated eosinophilic allergic airway inflammation (AAI); however, the efficacy of MSCs in mouse models of severe Th17-mediated neutrophilic AAI has not yet been demonstrated. We assessed MSC effects in a mouse model of mixed Th2/Th17 AAI produced by mucosal exposure to Aspergillus fumigatus hyphal extract (AHE). Following sensitization produced by oropharyngeal AHE administration, systemic (tail vein) administration of syngeneic MSCs on the first day of challenge significantly reduced acute AHR predominantly through reduction of Th17-mediated airway inflammation. In parallel experiments, MSCs also mitigated AHR when administered during recurrent challenge 10 weeks after initial sensitization and challenge through reduction in systemic Th17-mediated inflammation. Investigation into potential mechanistic actions of MSCs in this model demonstrated that although T regulatory cells were increased in all AHE-treated mice, MSC administration did not alter T regulatory cell numbers in either the acute or recurrent model. Differential induction of interleukin-17a secretion was observed in ex vivo restimulation of mediastinal lymph node mixed-cell cytokine analyses. Although the mechanisms by which MSCs act to decrease inflammation and AHR in this model are not yet fully elucidated, decrease in Th17-mediated airway inflammation appears to play a significant role. These results provide a basis for further investigations of MSC administration as a potential therapeutic approach for severe refractory neutrophilic asthma.
Human Bone Marrow-Derived Mesenchymal Stem Cells Display Enhanced Clonogenicity but Impaired Differentiation With Hypoxic Preconditioning
Authors: Boyette Lisa B. , Creasey Olivia A. , Guzik Lynda , Lozito Thomas , Tuan Rocky S.
Published: January 2014

Stem cells are promising candidate cells for regenerative applications because they possess high proliferative capacity and the potential to differentiate into other cell types. Mesenchymal stem cells (MSCs) are easily sourced but do not retain their proliferative and multilineage differentiative capabilities after prolonged ex vivo propagation. We investigated the use of hypoxia as a preconditioning agent and in differentiating cultures to enhance MSC function. Culture in 5% ambient O2 consistently enhanced clonogenic potential of primary MSCs from all donors tested. We determined that enhanced clonogenicity was attributable to increased proliferation, increased vascular endothelial growth factor secretion, and increased matrix turnover. Hypoxia did not impact the incidence of cell death. Application of hypoxia to osteogenic cultures resulted in enhanced total mineral deposition, although this effect was detected only in MSCs preconditioned in normoxic conditions. Osteogenesis-associated genes were upregulated in hypoxia, and alkaline phosphatase activity was enhanced. Adipogenic differentiation was inhibited by exposure to hypoxia during differentiation. Chondrogenesis in three-dimensional pellet cultures was inhibited by preconditioning with hypoxia. However, in cultures expanded under normoxia, hypoxia applied during subsequent pellet culture enhanced chondrogenesis. Whereas hypoxic preconditioning appears to be an excellent way to expand a highly clonogenic progenitor pool, our findings suggest that it may blunt the differentiation potential of MSCs, compromising their utility for regenerative tissue engineering. Exposure to hypoxia during differentiation (post-normoxic expansion), however, appears to result in a greater quantity of functional osteoblasts and chondrocytes and ultimately a larger quantity of high-quality differentiated tissue.
The case for addressing primary resistance mutations to non‐nucleoside reverse transcriptase inhibitors to treat children born from mothers living with HIV in sub‐Saharan Africa
Authors: Kébé Khady , Bélec Laurent , Ndiaye Halimatou Diop , Gueye Sokhna Bousso , Diouara Abou Abdallah Malick , Ngom Safiétou , Gueye Ndéye Rama Diagne , Mbaye Ngagne , Signaté Sy Haby , Mboup Souleymane , Kane Coumba Touré
Published: January 2014

The prevalence of human immunodeficiency virus (HIV) drug resistance mutations (DRMs) was estimated in 25 untreated infants who were living with HIV‐1, younger than 13 months and living in Senegal. Antiretroviral DRMs were detected in 8 of 25 (32%) children. Non‐nucleoside reverse transcriptase inhibitor (NNRTI) DRMs were present in all (100%) children whose viruses harboured DRMs: K103N in 43%; Y181C, K101E and V106M each in 29%; and Y188L in 14%. The D67N thymidine‐analogue mutation was observed in only two children whose mothers had received chemoprophylaxis of mother‐to‐child transmission (MTCT). The proportion of children whose viruses harboured DRMs was then 6.5‐fold higher in children whose mother–child couples had received nevirapine (NVP)‐based chemoprophylaxis than in other couples without prophylaxis [7 of 13 (53.8%) vs. 1 of 12 (8.3%)]. These findings point to the absolute need to address primary resistance mutations in case of virological failure in young children treated by antiretroviral drugs, and to make more effective treatment regimens available to NVP‐exposed infants living with HIV‐1 in Senegal.
CO2 discharge from the bottom of volcanic Lake Rotomahana, New Zealand
Authors: Mazot Agnes , Schwandner Florian M. , Christenson Bruce , de Ronde Cornel E. J. , Inguaggiato Salvatore , Scott Brad , Graham Duncan , Britten Karen , Keeman J. , Tan Karine
Published: January 2014

From April 2010 to February 2011, CO2 flux surveys were performed on Lake Rotomahana, New Zealand. The area has been hydrothermally active with fumaroles and sublacustrine hydrothermal activity before and since the eruption of Mt Tarawera in 1886. The total CO2 emission from the lake calculated by sequential Gaussian simulation is 549 ± 72 t d−1. Two different mechanisms of degassing, diffusion through the water‐air interface and bubbling, are distinguished using a graphical statistical approach. The carbon dioxide budget calculated for the lake confirms that the main source of CO2 to the atmosphere is by diffusion covering 94.5% of the lake area (mean CO2 flux 25 g m−2 d−1) and to a lesser extent, bubbling (mean CO2 flux 1297 g m−2 d−1). Mapping of the CO2 flux over the entire lake, including over lake floor vents detected during the survey, correlates with eruption craters formed during the 1886 eruption. These surveys also follow regional tectonic patterns present in the southeastern sector of Lake Rotomahana suggesting a deep magmatic source (∼10 km) for CO2 and different pathways for the gas to escape to the surface. The values of δ13CCO2 (−2.88 and −2.39‰) confirm the magmatic origin of CO2.
Sea surface topography retrieved from GNSS reflectometry phase data of the GEOHALO flight mission
Authors: Semmling A. M. , Beckheinrich J. , Wickert J. , Beyerle G. , Schön S. , Fabra F. , Pflug H. , He K. , Schwabe J. , Scheinert M.
Published: January 2014

Sea surface topography observations are deduced from an airborne reflectometry experiment. A GNSS (Global Navigation Satellite System) receiver dedicated for reflectometry was set up aboard the German HALO (High Altitude Long Range) research aircraft. Flights were conducted over the Mediterranean Sea about 3500 m above sea level. A signal path model divided into large‐ and small‐scale contributions is used for phase altimetry. The results depict geoid undulations and resolve anomalies of the sea surface topography. For the whole experiment 65 tracks over the Mediterranean Sea are retrieved and compared with a topography model. Tracks differ between right‐handed and left‐handed circular polarization. The difference, however, is not significant for this study. Precision and spatial resolution decrease disproportionately at low elevations. Eight tracks with centimeter precision are obtained between 11° and 33° of elevation. At higher elevation angles the number of tracks is significantly reduced due to surface roughness. In future such retrievals could contribute to ocean eddy detection.
Automatic recognition of type III solar radio bursts in STEREO/WAVES data for onboard real‐time and archived data processing
Authors: Lobzin V. V. , Cairns Iver H. , Zaslavsky A.
Published: January 2014

Type III radio bursts are produced near the local electron plasma frequency and/or near its harmonic by fast electrons ejected from the solar active regions and moving through the corona and solar wind. These bursts have dynamic spectra with frequency rapidly falling with time. This paper presents two new methods developed to detect type III bursts automatically in the data from High Frequency Receiver (HFR) of the STEREO/WAVES radio instrument onboard the STEREO spacecraft. The first technique is applicable to the low‐frequency band (HFR‐1: 125 kHz to 1.975 MHz) only. This technique can possibly be implemented in onboard satellite software aimed at preliminary detection of bursts and identification of time intervals with relatively high solar activity. In the second technique the bursts are detected in both the low‐frequency band and the high‐frequency band (HFR‐2: 2.025 MHz to 16.025 MHz), with the computational burden being higher by 1 order of magnitude as compared with that for the first technique. Preliminary tests of the method show that the performance of the first technique is quite high, PdL=72%±3%. The performance of the second technique is considerably higher, PdL+H=81%±1%, while the number of false alarms does not exceed 10% for one daily spectrum.
The solar wind electric field does not control the dayside reconnection rate
Authors: Borovsky Joseph E. , Birn Joachim
Published: January 2014

Working toward a physical understanding of how solar wind/magnetosphere coupling works, four arguments are presented indicating that the solar wind electric field vsw × Bsw does not control the rate of reconnection between the solar wind and the magnetosphere. Those four arguments are (1) that the derived rate of dayside reconnection is not equal to solar wind electric field, (2) that electric field driver functions can be improved by a simple modification that disallows their interpretation as the solar wind electric field, (3) that the electric field in the magnetosheath is not equal to the electric field in the solar wind, and (4) that the magnetosphere can mass load and reduce the dayside reconnection rate without regard for the solar wind electric field. The data are more consistent with a coupling function based on local control of the reconnection rate than the Axford conjecture that reconnection is controlled by boundary conditions irrespective of local parameters. Physical arguments that the solar wind electric field controls dayside reconnection are absent; it is speculated that it is a coincidence that the electric field does so well at correlations with geomagnetic indices.
Solution‐Processable Hole‐Generation Layer and Electron‐Transporting Layer: Towards High‐Performance, Alternating‐Current‐Driven, Field‐Induced Polymer Electroluminescent Devices
Authors: Chen Yonghua , Xia Yingdong , Smith Gregory M. , Sun Hengda , Yang Dezhi , Ma Dongge , Li Yuan , Huang Wenxiao , Carroll David L.
Published: January 2014

The effect of solution‐processed p‐type doping of hole‐generation layers (HGLs) and electron‐transporting layer (ETLs) are systematically investigated on the performance of solution‐processable alternating current (AC) field‐induced polymer EL (FIPEL) devices in terms of hole‐generation capability of HGLs and electron‐transporting characteristics of ETLs. A variety of p‐type doping conjugated polymers and a series of solution‐processed electron‐transporting small molecules are employed. It is found that the free hole density in p‐type doping HGLs and electron mobility of solution‐processed ETLs are directly related to the device performance, and that the hole‐transporting characteristics of ETLs also play an important role since holes need to be injected from electrode through ETLs to refill the depleted HGLs in the positive half of the AC cycle. As a result, the best FIPEL device exhibits exceptional performance: a low turn‐on voltage of 12 V, a maximum luminance of 20 500 cd m−2, a maximum current and power efficiency of 110.7 cd A−1 and 29.3 lm W−1. To the best of the authors' knowledge, this is the highest report to date among FIPEL devices driven by AC voltage.
A model‐based approach to the automatic diagnosis of von Willebrand disease
Authors: Galvanin Federico , Barolo Massimiliano , Padrini Roberto , Casonato Alessandra , Bezzo Fabrizio
Published: January 2014

Von Willebrand disease (VWD) is the most common inherited coagulation disorder to be seen in humans. It originates from a deficiency and/or dysfunction of the von Willebrand factor (VWF), a large multimeric glycoprotein playing a central role in the hemostasis process. VWD occurs in a large variety of forms, and its symptoms may range from sporadic nosebleeds and mild bleeding from small lesions in skin, to acute thrombocytopenia or prolonged bleeding episodes. Diagnosing VWD may be complicated because of the heterogeneous nature of the disorder. Two mechanistic models of VWD are proposed in this article, and their performance is assessed using clinical data. Models allow for the automatic detection of the disease, as well as for a quantitative assessment of VWF multimer distribution patterns, thus elucidating the critical pathways involved in the disease recognition and characterization. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1718–1727, 2014
Obtaining model‐independent growth rates from experimental data of dry thermal oxidation of silicon
Authors: Yeow Y. Leong , Liow Jong‐Leng , Leong Yee‐Kwong
Published: January 2014

Empirical time‐oxide layer thickness data of dry thermal oxidation of silicon were converted numerically into instantaneous growth rates by Tikhonov regularization. These growth rates are independent of any assumed kinetics of oxidation or functional form of the original data and can, therefore, be used in model testing of this important industrial process. A number of numerical issues in the Tikhonov regularization computation, for example, the expected monotonic decrease in growth rate with time and the large time span of some of the datasets, are addressed. Numerical results indicate that kinetic data presented in the form of growth rate‐oxide layer thickness plots are more sensitive than the traditional time‐oxide thickness plots for use in model testing and for parameter determination. The advantages of this new approach are demonstrated by three case studies covering the complete oxide thickness spectrum of interest to the microelectronic industry. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1810–1820, 2014
Exacerbation of BMI after cessation of growth hormone therapy in patients with Prader–Willi syndrome
Authors: Oto Yuji , Tanaka Yuriko , Abe Yoshiko , Obata Kazuo , Tsuchiya Takayoshi , Yoshino Atsunori , Murakami Nobuyuki , Nagai Toshiro
Published: January 2014

Long‐term treatment with growth hormone (GH) in patients with Prader–Willi syndrome (PWS) improves not only height velocity, height standard deviation score, and final height, but also the degree of obesity and body composition abnormalities. Anecdotally, PWS patients tend to suffer from severe obesity and its complications after cessation of GH therapy. However, there have been no studies to investigate changes in body mass index (BMI) and adipose tissue distribution after cessation of GH therapy in young PWS patients. Therefore, we investigated changes in the BMI‐standard deviation score (SDS) and adipose tissue distribution after cessation of GH therapy in PWS patients. We evaluated 14 PWS patients. BMI‐SDS was calculated at 0, 6, 12, 18, and 24 months before and after cessation of GH treatment. We also evaluated subcutaneous adipose tissue (SAT) (cm2) and visceral adipose tissue (VAT) (cm2) area in 8 of the 14 study patients with single slice abdominal computed tomography at the level of the umbilicus. The BMI‐SDS significantly increased at 6, 12, 18, and 24 months after cessation of GH therapy (P = 0.039, P = 0.008, P = 0.003, P = 0.003, respectively). There was a tendency toward increases in VAT at 12 and 24 months after cessation of GH therapy, but the increases did not reach statistical significance (P = 0.062, P = 0.125, respectively). Therefore, cessation of GH therapy in PWS patients worsened BMI. To maintain good body composition and prevent complications of obesity, long‐term use of GH in adult PWS patients may be advisable. © 2014 Wiley Periodicals, Inc.
Investigation of association of serotonin transporter and monoamine oxidase‐A genes with Alzheimer's disease and depression in the VITA study cohort: A 90‐month longitudinal study
Authors: Scholz Claus‐Jürgen , Jungwirth Susanne , Danielczyk Walter , Weber Heike , Wichart Ildiko , Tragl Karl Heinz , Fischer Peter , Riederer Peter , Deckert Jürgen , Grünblatt Edna
Published: January 2014

Alzheimer's disease (AD) and depression (DE) are common psychiatric disorders strongly intertwined with one another. Nevertheless, etiology and early diagnosis of the disorders are still elusive. Several genetic variations have been suggested to associate with AD and DE, particularly in genes involved in the serotonergic system such as the serotonin transporter (SERT/SLC6A4), responsible for the removal from the synaptic cleft, and the monoamine‐oxidase‐A (MAOA), responsible for the presynaptic degradation of serotonin. Here, we attempt to characterize this pleiotropic effect for the triallelic SERT gene‐linked polymorphic region (5HTTLPR) and for the MAOA‐uVNTR, in participants in the Vienna‐Transdanube‐Aging (VITA)‐study. The VITA‐study is a community‐based longitudinal study following a birth cohort (75 years old at baseline examination, n = 606) from Vienna for a period of 90 months with a regular follow‐up interval of 30 months. Our main finding, confirming previous reports, is that the 5HTTLPR S‐allele is a risk allele for DE (OR = 1.55 CI 95% 1.03–2.32) and its carriers had a steeper increase in SGDS sum score. No association to AD was found. MAOA‐uVNTR did not associate with either AD or DE. However, in AD MAOA‐uVNTR S‐allele carriers a steeper increase of HAMD and STAI1 sum scores (P < 0.05) was observed. Although the VITA‐study cohort is rather small with low power to detect gene alterations, the uniqueness of this very thoroughly investigated and homogenous cohort strengthens the results through exceptional data collection. Still, reinvestigation in a larger cohort similar to this, as well as a meta‐analysis, is important to confirm these results. © 2014 Wiley Periodicals, Inc.
Stereoselective Addition of 1,3‐Diketones to β‐Nitroacrylates Catalyzed by Chiral Metal‐Free Bifunctional Catalysts
Authors: Massolo Elisabetta , Benaglia Maurizio , Palmieri Alessandro , Celentano Giuseppe
Published: January 2014

Organocatalytic stereoselective additions of different nucleophiles to β‐nitroacrylates have been investigated. A thiourea‐based cinchona‐derived bifunctional catalyst promotes the addition of 1,3‐diketones to differently substituted nitroacrylates in modest to fair yields and up to 93 % enantioselectivity. The 1,3 dicarbonyl functionality of the addition products was then used to synthesize enantiomerically enriched 3,4,5‐trialkyl substituted pyrazoles via reaction with hydrazine. The stereoselective addition of N‐methylindole to nitroacrylate was also preliminarily studied; the Friedel–Crafts alkylation was successfully organocatalyzed in the presence of an acid additive in very good yields and up to 53 % enantioselectivity.
Verfahren zur Enantiomerentrennung
Authors: Lorenz Heike , Seidel‐Morgenstern Andreas
Published: January 2014

Die Verfügbarkeit reiner Enantiomere ist von steigender Bedeutung für die pharmazeutische Industrie sowie auch für die Agrochemie und Biotechnologie. Generell gibt es zwei konkurrierende Ansätze zur Gewinnung von reinen Enantiomeren. Der “chirale” Ansatz basiert auf der Entwicklung einer asymmetrischen Synthese, die selektiv eines der Enantiomere liefert. Der “racemische” Ansatz basiert auf der Trennung eines Gemischs der beiden Enantiomere, wobei hier in den letzten Jahren bemerkenswerte Fortschritte erzielt werden konnten. Dieser Aufsatz fokussiert insbesondere auf enantioselektive Kristallisationsprozesse und präparative Chromatographie, einschließlich hybrider Trennprozesse und der zusätzlichen Integration von Racemisierungsschritten. Zur Illustration dienen mehrere in unserem Arbeitskreis untersuchte Trennungen.
Processes To Separate Enantiomers
Authors: Lorenz Heike , Seidel‐Morgenstern Andreas
Published: January 2014

The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agrochemistry and biotechnology. In general, there are two rival approaches to provide pure enantiomers. The “chiral” approach is based on developing an asymmetric synthesis of just one of the enantiomers, while the “racemic” approach is based on separating mixtures of the two enantiomers. In the last few years remarkable progress has been achieved in the latter area. This Review focuses in particular on enantioselective crystallization processes and preparative chromatography, including hybrid processes and the incorporation of racemization steps. Several examples from our research are used for illustration purposes.
Dynamic properties of star‐shaped, solution‐polymerized styrene–butadiene rubber and its cocoagulated rubber‐filled with silica/carbon black
Authors: Liu Xiao , Zhao Suhe , Yang Yong , Zhang Xingying , Wu Youping
Published: January 2014

The dynamic properties, including the dynamic mechanical properties, flex fatigue properties, dynamic compression properties, and rolling loss properties, of star‐shaped solution‐polymerized styrene–butadiene rubber (SSBR) and organically modified nanosilica powder/star‐shaped styrene–butadiene rubber cocoagulated rubber (N‐SSBR), both filled with silica/carbon black (CB), were studied. N‐SSBR was characterized by 1H‐NMR, gel permeation chromatography, energy dispersive spectrometry, and transmission electron microscopy. The results show that the silica particles were homogeneously dispersed in the N‐SSBR matrix. In addition, the N‐SSBR/SiO2/CB–rubber compounds' high bound rubber contents implied good filler–polymer interactions. Compared with SSBR filled with silica/CB, the N‐SSBR filled with these fillers exhibited better flex fatigue resistance and a lower Payne effect, internal friction loss, compression permanent set, compression heat buildup, and power loss. The nanocomposites with excellent flex fatigue resistance showed several characteristics of branched, thick, rough, homogeneously distributed cross‐sectional cracks, tortuous flex crack paths, few stress concentration points, and obscure interfaces with the matrix. Accordingly, N‐SSBR would be an ideal matrix for applications in the tread of green tires. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40348.
Tailoring the crystalline morphologies and mechanical properties of high‐density polyethylene parts by a change in the fluid flow pattern under gas‐assisted injection molding
Authors: Zhang Quanping , Wang Long , Xia Xiaochao , Feng Jianmin , Fu Xiaorong , Yang Mingbo
Published: January 2014

In this study, an increase in the cooling rate of high‐density polyethylene parts was carried out via a change in the fluid flow pattern to introduce gas cooling under a gas‐assisted injection‐molding process; this was conducive to the retention of orientation chains shaped during the injection stage and further developed into much more oriented crystals. Morphological observation showed that the parts without gas cooling (WOGC) were composed of oriented crystals except the gas channel zone, whereas the parts with gas cooling (WGC) were full of oriented crystals, especially much more interlocking shish‐kebab structures in the subskin zone. The WGC parts had a higher degree of orientation than the corresponding zone of the WOGC parts. Although the lower crystallinity, the wider orientation regions, and much more interlocking shish‐kebab structures led to considerable increases from 32 and 990 MPa in the WOGC parts to 36 and 1150 MPa in the WGC parts for the yield strength and elastic modulus, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40349.
Antitumor efficacy of doxorubicin encapsulated within PEGylated poly(amidoamine) dendrimers
Authors: Liao Huihui , Liu Hui , Li Yulin , Zhang Mengen , Tomás Helena , Shen Mingwu , Shi Xiangyang
Published: January 2014

We report here a general approach to using poly(amidoamine) (PAMAM) dendrimers modified with polyethylene glycol (PEG) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for in vitro cancer therapy applications. In this approach, PEGylated PAMAM dendrimers were synthesized by conjugating monomethoxypolyethylene glycol with carboxylic acid end group (mPEG‐COOH) onto the surface of generation 5 amine‐terminated PAMAM dendrimer (G5.NH2), followed by acetylation of the remaining dendrimer terminal amines. By varying the molar ratios of mPEG‐COOH/G5.NH2, G5.NHAc‐mPEGn (n = 5, 10, 20, and 40, respectively) with different PEGylation degrees were obtained. We show that the PEGylated dendrimers are able to encapsulate DOX with approximately similar loading capacity regardless of the PEGylation degree. The formed dendrimer/DOX complexes are water soluble and stable. In vitro release studies show that DOX complexed with the PEGylated dendrimers can be released in a sustained manner. Further cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc‐mPEGn/DOX complexes display effective antitumor activity, and the DOX molecules encapsulated within complexes can be internalized into the cell nucleus, similar to the free DOX drug. Findings from this study suggest that PEGylated dendrimers may be used as a general drug carrier to encapsulate various hydrophobic drugs for different therapeutic applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40358.
Rheological and thermal properties of saponified cassava starch‐g‐poly(acrylamide) superabsorbent polymers varying in grafting parameters and absorbency
Authors: Parvathy Prabha C. , Jyothi Alummoottil. N.
Published: January 2014

Cassava starch‐graft‐poly(acrylamide) superabsorbent polymers (SAPs) with varying absorbencies were synthesized. Weight average molecular weight (Mw) of the hydrolyzed starch‐graft‐copolymers ranged from 1.6 × 106to 2.8 × 106g/mol, the largest being shown by the sample with highest percentage grafting. The storage (G′) and loss modulus (G″) of hydrogels were determined as a function of frequency.G″ was larger thanG′ for the hydrogels with higher absorbencies and exhibited a liquid‐like behavior. However, hydrogels with lower absorbencies showed a reverse viscoelastic behavior. The viscosity of hydrogels determined using a Brookfield viscometer at different shear rates was found to be larger for the hydrogels with higher absorbencies. The melting temperature (Tm) and enthalpy change of fusion (ΔHf) of the SAPs ranged from 149.7 to 177.7°C and 65 to 494.9 J/g, respectively and showed a positive correlation with grafting parameters andMw. Heavy metal ion removal capacity of hydrogel followed the order Cu2+ > Pb2+ > Zn2+. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2014,131, 40368.
Transition‐Metal‐Catalyzed CS Bond Coupling Reaction
Authors: Lee Chin‐Fa , Liu Yi‐Chen , Badsara Satpal Singh
Published: January 2014

Sulfur‐containing molecules such as thioethers are commonly found in chemical biology, organic synthesis, and materials chemistry. While many reliable methods have been developed for preparing these compounds, harsh reaction conditions are usually required in the traditional methods. The transition metals have been applied in this field, and the palladium‐catalyzed coupling of thiols with aryl halides and pseudo halides is one of the most important methods in the synthesis of thioethers. Other metals have also been used for the same purpose. Here, we summarize recent efforts in metal‐catalyzed CS bond cross‐coupling reactions, focusing especially on the coupling of thiols with aryl‐ and vinyl halides based on different metals.
Fluorescence enhancement of europium (III) perchlorate by 1,10‐phenanthroline on the 1‐(naphthalen‐2‐yl)‐2‐(phenylsulthio)ethanone complex and luminescence mechanism
Authors: Li Wen‐Xian , Xin Xiao‐Dong , Feng Shu‐Yan , Liu Yu , Zhang Jing , Ao Bo‐Yang , Li Ying‐Jie
Published: January 2014

A novel ligand, 1‐(naphthalen‐2‐yl)‐2‐(phenylsulthio)ethanone was synthesized using a new method and its two europium (Eu) (III) complexes were synthesized. The compounds were characterized by elemental analysis, coordination titration analysis, molar conductivity, infrared, thermo gravimetric analyzer‐differential scanning calorimetry (TGA‐DSC), 1H NMR and UV spectra. The composition was suggested as EuL5 · (ClO4)3 · 2H2O and EuL4 · phen(ClO4)3 · 2H2O (L = C10H7COCH2SOC6H5). The fluorescence spectra showed that the Eu(III) displayed strong characteristic metal‐centered fluorescence in the solid state. The ternary rare earth complex showed stronger fluorescence intensity than the binary rare earth complex in such material. The strongest characteristic fluorescence emission intensity of the ternary system was 1.49 times as strong as that of the binary system. The phosphorescence spectra were also discussed. Copyright © 2014 John Wiley & Sons, Ltd.
Unique Crystal Structure of a Novel Surfactant Protein from the Foam Nest of the Frog Leptodactylus vastus
Authors: Cavalcante Hissa Denise , Arruda Bezerra Gustavo , Birner‐Gruenberger Ruth , Paulino Silva Luciano , Usón Isabel , Gruber Karl , Maciel Melo Vânia Maria
Published: January 2014

Breeding by releasing eggs into stable biofoams (“foam nests”) is a peculiar reproduction mode within anurans, fish, and tunicates; not much is known regarding the biochemistry or molecular mechanisms involved. Lv‐ranaspumin (Lv‐RSN‐1) is the predominant protein from the foam nest of the frog Leptodactylus vastus. This protein shows natural surfactant activity, which is assumed to be crucial for stabilizing foam nests. We elucidated the amino acid sequence of Lv‐RSN‐1 by de novo sequencing with mass‐spectrometry and determined the high‐resolution X‐ray structure of the protein. It has a unique fold mainly composed of a bundle of 11 α‐helices and two small antiparallel β‐strands. Lv‐RSN‐1 has a surface rich in hydrophilic residues and a lipophilic cavity in the region of the antiparallel β‐sheet. It possesses intrinsic surface‐active properties, reducing the surface tension of water from 73 to 61 mN m−1 (15 μg mL−1). Lv‐RSN‐1 belongs to a new class of surfactants proteins for which little has been reported regarding structure or function.
Tuning the Selectivity in the Aerobic Oxidation of Cumene Catalyzed by Nitrogen‐Doped Carbon Nanotubes
Authors: Liao Shixia , Chi Yumei , Yu Hao , Wang Hongjuan , Peng Feng
Published: January 2014

In this study it is demonstrated that carbon nanotubes (CNTs) with doped nitrogen atoms in graphitic domains (NCNTs) can act as a new class of metal‐free catalysts exhibiting excellent activity in the aerobic oxidation of cumene. We proved that NCNTs can promote the decomposition of hydroperoxide cumene with exceptionally high activity, resulting in strongly increased cumene conversion and extraordinarily high selectivity to acetophenone and 2‐benzyl‐2‐propanol. The incorporation of nitrogen altered the surface electron structure of the CNTs and tuned the reactivity and selectivity. DFT calculations revealed that the remarkable improvement of catalytic performance of NCNTs is caused by the strong interaction between hydroperoxide cumene and the NCNTs. NCNTs also exhibited desirable recyclability after four cycling tests. This study not only provides a novel method for the cumene oxidation to high‐value‐added products at moderate reaction temperatures and oxygen atmospheric pressure, but also gives new insights into the effect of surface nitrogen doping on carbon‐catalyzed liquid‐phase oxidation of aromatic hydrocarbons.
Whole‐Cell Carboxylate Reduction for the Synthesis of 3‐Hydroxytyrosol
Authors: Napora‐Wijata Kamila , Robins Karen , Osorio‐Lozada Antonio , Winkler Margit
Published: January 2014

3‐Hydroxytyrosol (3‐HT) is a phenolic antioxidant that has a number of beneficial effects on human health and is a valuable building block in the synthesis of various pharmaceuticals. Herein, we report a new method for the production of 3‐HT through reduction of 3,4‐dihydroxyphenylacetic acid. The reduction was performed in whole Escherichia coli BL21 (DE3) cells overexpressing carboxylic acid reductase from Nocardia and phosphopantetheinyl transferase from E. coli. An endogenous E. coli aldehyde reducing activity turned out to be highly efficient for further reduction of the aldehyde intermediate to the desired alcohol. The influence of different buffer components, cofactors, and cofactor recycling systems was investigated. A very economic combination of glucose, citrate, and air proved sufficient for recycling of the essential cofactors ATP and NAD(P)H. Selected crucial parameters were then further optimized within a “design of experiments” approach. Finally, first preparative‐scale bioreductions resulted in pure 3‐HT.
A Pyrimidopyrimidine Janus‐AT Nucleoside with Improved Base‐Pairing Properties to both A and T within a DNA Duplex: The Stabilizing Effect of a Second Endocyclic Ring Nitrogen
Authors: Largy Eric , Liu Wenbo , Hasan Abid , Perrin David M.
Published: January 2014

Janus bases are heterocyclic nucleic acid base analogs that present two different faces able to simultaneously hydrogen bond to nucleosides that form Watson–Crick base pairs. The synthesis of a Janus‐AT nucleotide analogue, NJAT, that has an additional endocyclic ring nitrogen and is thus more capable of efficiently discriminating T/A over G/C bases when base‐pairing in a standard duplex‐DNA context is described. Conversion to a phosphoramidite ultimately afforded incorporation into an oligonucleotide. In contrast to the first generation of carbocyclic Janus heterocycles, it remains in its unprotonated state at physiological pH and, therefore, forms very stable Watson–Crick base pairs with either A or T bases. Biophysical and computational methods indicate that NJAT is an improved candidate for sequence‐specific genome targeting.
Enzyme Design from the Bottom Up: An Active Nickel Electrocatalyst with a Structured Peptide Outer Coordination Sphere
Authors: Reback Matthew L. , Buchko Garry W. , Kier Brandon L. , Ginovska‐Pangovska Bojana , Xiong Yijia , Lense Sheri , Hou Jianbo , Roberts John A. S. , Sorensen Christina M. , Raugei Simone , Squier Thomas C. , Shaw Wendy J.
Published: January 2014

Catalytic, peptide‐containing metal complexes with a well‐defined peptide structure have the potential to enhance molecular catalysts through an enzyme‐like outer coordination sphere. Here, we report the synthesis and characterization of an active, peptide‐based metal complex built upon the well‐characterized hydrogen production catalyst [Ni(PPh2NPh)2]2+ (PPh2NPh=1,3,6‐triphenyl‐1‐aza‐3,6‐diphosphacycloheptane). The incorporated peptide maintains its β‐hairpin structure when appended to the metal core, and the electrocatalytic activity of the peptide‐based metal complex (≈100,000 s−1) is enhanced compared to the parent complex ([Ni(PPh2NAPPA)2]2+; ≈50,500 s‐1). The combination of an active molecular catalyst with a structured peptide provides a scaffold that permits the incorporation of features of an enzyme‐like outer‐coordination sphere necessary to create molecular electrocatalysts with enhanced functionality.
HPLC‐PDA‐ORD Bioassay of S‐(+) and R‐(−) Clopidogrel on Rat Dried Blood Spots
Authors: Nageswara Rao Ramisetti , Prasad Katuri Guru , Bindu Priya Pullakandam , Bijarji Shriharsh
Published: January 2014

A simple and rapid chiral high‐performance liquid chromatography (HPLC) method was developed and validated for bioanalysis of clopidogrel enantiomers on rat dried blood spots (DBS). Clopidogrel enantiomers were extracted from DBS using ethanol: methanol (80:20, v/v) and separated on a Chiralcel OJ‐H column containing cellulose tris (4‐methly benzoate) as a polysaccharide stationary phase using n‐hexane–ethanol‐diethylamine (70:30, 0.1 v/v) as a mobile phase at a flow rate of 1.0 mL/min. The detection was carried out at 220 nm using a photodiode array (PDA) detector while the elution order of the enantiomers was determined by a polarimeter connected to PDA in series. The effect of hematocrit on extraction of clopidogrel enantiomers from DBS was evaluated and no interference from endogenous substances was noticed. The overall accuracy of (R) and (S) enantiomers of clopidogrel from DBS were 91.6 and 89.2%, respectively. The calibration curves were linear over the concentration range of 1–500 µg/mL for both enantiomers. The results show that the method is specific, precise, and reproducible (intra‐ and interday precision relative standard deviations (RSDs) <10.0%). The stability of racemic clopidogrel was performed under all storage conditions and the results were found to be well within the acceptance limits. Chirality 26:102–107, 2014.© 2014 Wiley Periodicals, Inc.
Adsorption of Racemic Pharmaceuticals on Nano‐Scale Substrates
Authors: Bolten Dennis , Staudt Reiner , Türk Michael
Published: January 2014

Eine neue Prozessidee zur Auftrennung racemischer Wirkstoffe unter Verwendung nanoskaliger AlO(OH)‐Hohlkugeln als Adsorbens und überkritischen Kohlenstoffdioxides (sc‐CO2) als Lösungsmittel wird vorgestellt. Zur Auslegung des Prozesses werden Untersuchungen zur Abscheidung der racemischen Wirkstoffe (RS)‐Flurbiprofen, (RS)‐Ibuprofen, (RS)‐Ketoprofen und den reinen Enantiomeren (R)‐Flurbiprofen, (S)‐Ibuprofen und (S)‐Ketoprofen an AlO(OH)‐Hohlkugeln präsentiert und bewertet. Zudem werden Adsorptionsdaten von gasförmigem CO2 an den Hohlkugeln und kommerziellen AlO(OH)‐Partikeln, die mit einer Magnetschwebewaage ermittelt wurden, verglichen. Abschließend werden erste Ergebnisse von orientierenden Versuchen zur Adsorption von racemischem Flurbiprofen aus sc‐CO2 an den Hohlkugeln vorgestellt.
Removal of Hg(II) and CH3Hg(I) Using Rasped Pith Sago Residue Biosorbent
Authors: Saman Norasikin , Johari Khairiraihanna , Tien Song Shiow , Mat Hanapi
Published: January 2014

Rasped pith sago residue (RPSR) was used as a biosorbent for inorganic (Hg(II)) and organic (CH3Hg(I)) mercury removal from aqueous solutions. In biosorbent preparation, the RPSR having particle size range of 0.06–0.10 was washed with deionized water repeatedly to eliminate impurities, dried in an oven at 50°C for two days, followed with drying in a vacuum oven for 3 h. The performance of RPSR as a novel biosorbent for removing mercury was evaluated in batch adsorption. The adsorption of mercury ions was found to highly dependent on the pH of the solutions. The Hg(II) adsorption was high at pH > 4, while the CH3Hg(I) adsorption was found higher at pH < 5. The higher adsorption capacity for Hg(II) and CH3Hg(I) was 0.288 and 0.213 mmol/g, respectively. Both mercury adsorptions equilibrium and kinetics were fitted to the Langmuir isotherm model and pseudo‐second‐order kinetic model, respectively. These results indicate the RPSR has a potential to be a low‐cost biosorbent for mercury removal process from aqueous solutions.
Disi Water Use for Irrigation – a False Decision and Its Consequences
Authors: Salameh Elias , Alraggad Marwan , Tarawneh Arwa
Published: January 2014

Disi water has been utilized during the last 2.5 decades in irrigation purposes in a very dry country, very short of water resources and where the groundwater in Disi represents the only strategic water reserve. After 25 years of exploitation, groundwater levels dropped by around 25 m signalizing aquifer emptying. Disi aquifer receives an average water replenishment of 50 million cubic meters per year (MCM/y), but this amount is lost as natural outflow. Therefore, groundwater extraction is quasi a mining process. During the last 25 years, about 2 billion m3 of groundwater were exploited from Disi for irrigation purposes with a value of around US$ 2 billion. The only input from Jordan in these irrigation projects has been water. The environmental consequences of groundwater extractions in Disi are: dropping water levels, mobilization of some salty water bodies in geologic units connected vertically with Disi aquifer such as Khureim Formation and irrigation return flow waters with their high salt contents, biocides, and fertilizers concentrations. In the meantime, it has been recognized that Jordan's drinking water needs in the coming few decades can only be satisfied by utilizing Disi groundwater. But Disi aquifer cannot supply the water amounts for both drinking and irrigation. Recently, the government decided not to renew the licenses for Disi irrigation projects which is a very sound decision to protect the national water resources. It represents a reversal of a former decision which was based on a wrong policy built on false and distorted information.
A Chemical Tool for In Vitro and In Vivo Precipitation of Lysine Methyltransferase G9a
Authors: Konze Kyle D. , Pattenden Samantha G. , Liu Feng , Barsyte‐Lovejoy Dalia , Li Fengling , Simon Jeremy M. , Davis Ian J. , Vedadi Masoud , Jin Jian
Published: January 2014

Here we report the design, synthesis, and biochemical characterization of a new chemical tool, UNC0965. UNC0965 is a biotinylated version of our previously reported G9a chemical probe, UNC0638. Importantly, UNC0965 maintains high in vitro potency and is cell penetrant. The biotinylated tag of UNC0965 enables “chemiprecipitation” of G9a from whole cell lysates. Further, the cell penetrance of UNC0965 allowed us to explore the localization of G9a on chromatin both in vitro and in vivo through chemical inhibitor‐based chromatin immunoprecipitation (chem‐ChIP).
On the Structures, Lifetimes, and Infrared Spectra of Alkylmercury Hydrides
Authors: Benidar Abdessamad , Montero‐Campillo M. Merced , Lamsabhi Al Mokhtar , Yáñez Manuel , Bouilloud Michaelle , Guillemin Jean‐Claude , Mó Otilia
Published: January 2014

A series of six small alkylmercury hydrides of the general formula RHgH with R=methyl, ethyl,n‐propyl, isopropyl,n‐butyl, and 3‐butenyl were obtained by reduction in vacuo of the corresponding mercury halide with tributyltin hydride in the presence of a radical inhibitor. These very reactive compounds, which have to be removed from the reaction mixture as they are formed, were characterized by1H NMR and13C NMR spectroscopy. The IR spectra ofn‐propyl‐, isopropyl‐,n‐butyl‐, and 3‐butenylmercury hydride were recorded for the first time. All compounds were then studied by density functional theory calculations on the basis of a recent theoretical assessment for alkylmercury compounds performed by our group. Comparison of the experimental and theoretical results allowed the assignment of the vibrational modes in an unambiguous way, in spite of the low intrinsic stability of some of the derivatives investigated. The experimental procedure implemented for registering the IR spectra of these unstable species in the gas phase allowed us to obtain reasonable estimates of their lifetimes.
Assessing eating disorder symptoms in adolescence: Is there a role for multiple informants?
Authors: Swanson Sonja A. , Aloisio Kate M. , Horton Nicholas J. , Sonneville Kendrin R. , Crosby Ross D. , Eddy Kamryn T. , Field Alison E. , Micali Nadia
Published: January 2014

Objectives

Studies of adolescent psychiatric disorders often collect information from adolescents and parents, yet most eating disorder epidemiologic studies only rely on adolescent report.

Method

We studied the eating disorder symptom reports, from questionnaires sent at participants' ages 14 and 16 years, provided by 7,968 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), and their parents. Adolescents and parents were asked questions about the adolescent's eating disorder symptoms (binge eating, vomiting, laxative use, fasting, and thinness). We assessed cross‐sectional concordance and prevalence using kappa coefficients and generalized estimating equations. Generalized estimating equations were used to assess prospective associations between symptom reports and adolescent weight outcomes measured at a face‐to‐face assessment at 17.5 years.

Results

Parents and adolescents were largely discordant on symptom reports cross‐sectionally (kappas < 0.3), with the parent generally less likely to report bulimic symptoms than the adolescent but more likely to report thinness. Female adolescents were more likely to report bulimic symptoms than males (e.g., two to four times more likely to report binge eating), while prevalence estimates according to parent reports of female vs. male adolescents were similar. Both informants' symptom reports were predictive of body mass and composition measures at 17.5 years; compared to adolescent report, parentally reported binge eating was more strongly predictive of body mass index.

Discussion

Parent report of eating disorder symptoms seemed to measure different, but potentially important, aspects of these symptoms during adolescence. Epidemiologic eating disorder studies should consider the potential value added from incorporating parental reports, particularly in studies of males. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:475–482)