bluuebunny/crossref_metadata_2025 huggingface dataset:
Porcine parvovirus removal using trimer and biased hexamer peptides
Authors: Heldt Caryn L. , Gurgel Patrick V. , Jaykus Lee‐Ann , Carbonell Ruben G.
Published: July 2011

Assuring the microbiological safety of biological therapeutics remains an important concern. Our group has recently reported small trimeric peptides that have the ability to bind and remove a model nonenveloped virus, porcine parvovirus (PPV), from complex solutions containing human blood plasma. In an effort to improve the removal efficiency of these small peptides, we created a biased library of hexamer peptides that contains two previously reported trimeric peptides designated WRW and KYY. This library was screened and several hexamer peptides were discovered that also removed PPV from solution, but there was no marked improvement in removal efficiency when compared to the trimeric peptides. Based on simulated docking experiments, it appeared that hexamer peptide binding is dictated more by secondary structure, whereas the binding of trimeric peptides is dominated by charge and hydrophobicity. This study demonstrates that trimeric and hexameric peptides may have different, matrix‐specific roles to play in virus removal applications. In general, the hexamer ligand may perform better for binding of specific viruses, whereas the trimer ligand may have more broadly reactive virus‐binding properties.
Scale‐down/scale‐up studies leading to improved commercial beer fermentation
Authors: Nienow Alvin W. , Nordkvist Mikkel , Boulton Christopher A.
Published: July 2011

Scale‐up/scale‐down techniques are vital for successful and safe commercial‐scale bioprocess design and operation. An example is given in this review of recent studies related to beer production. Work at the bench scale shows that brewing yeast is not compromised by mechanical agitation up to 4.5 W/kg; and that compared with fermentations mixed by CO2 evolution, agitation ≥ 0.04 W/kg is able to reduce fermentation time by about 20%. Work at the commercial scale in cylindroconical fermenters shows that, without mechanical agitation, most of the yeast sediments into the cone for about 50% of the fermentation time, leading to poor temperature control. Stirrer mixing overcomes these problems and leads to a similar reduction in batch time as the bench‐scale tests and greatly reduces its variability, but is difficult to install in extant fermenters. The mixing characteristics of a new jet mixer, a rotary jet mixer, which overcomes these difficulties, are reported, based on pilot‐scale studies. This change enables the advantages of stirring to be achieved at the commercial scale without the problems. In addition, more of the fermentable sugars are converted into ethanol. This review shows the effectiveness of scale‐up/scale‐down studies for improving commercial operations. Suggestions for further studies are made: one concerning the impact of homogenization on the removal of vicinal diketones and the other on the location of bubble formation at the commercial scale.
Neuroimage Evidence and the Insanity Defense
Authors: Schweitzer N. J. , Saks Michael J.
Published: July 2011

The introduction of neuroscientific evidence in criminal trials has given rise to fears that neuroimagery presented by an expert witness might inordinately influence jurors' evaluations of the defendant. In this experiment, a diverse sample of 1,170 community members from throughout the U.S. evaluated a written mock trial in which psychological, neuropsychological, neuroscientific, and neuroimage‐based expert evidence was presented in support of a not guilty by reason of insanity (NGRI) defense. No evidence of an independent influence of neuroimagery was found. Overall, neuroscience‐based evidence was found to be more persuasive than psychological and anecdotal family history evidence. These effects were consistent across different insanity standards. Despite the non‐influence of neuroimagery, however, jurors who were not provided with a neuroimage indicated that they believed neuroimagery would have been the most helpful kind of evidence in their evaluations of the defendant. Copyright © 2011 John Wiley & Sons, Ltd.
Corrections by melatonin of liver mitochondrial disorders under diabetes and acute intoxication in rats
Authors: Cheshchevik Vitali T. , Dremza Iosif K. , Lapshina Elena A. , Zabrodskaya Svetlana V. , Kujawa Jolanta , Zavodnik Ilya B.
Published: July 2011

The aim of the present work was to investigate the mechanisms of oxidative damage of the liver mitochondria under diabetes and intoxication in rats as well as to evaluate the possibility of corrections of mitochondrial disorders by pharmacological doses of melatonin. The experimental (30 days) streptozotocin‐induced diabetes mellitus caused a significant damage of the respiratory activity in rat liver mitochondria. In the case of succinate as a respiratory substrate, the ADP‐stimulated respiration rate V3 considerably decreased (by 25%, p < 0·05) as well as the acceptor control ratio (ACR) V3/V2 markedly diminished (by 25%, p < 0·01). We observed a decrease of the ADP‐stimulated respiration rate V3 by 35% (p < 0·05), with glutamate as substrate. In this case, ACR also decreased (by 20%, p < 0·05). Surprisingly, the phosphorylation coefficient ADP/O did not change under diabetic liver damage. Acute rat carbon tetrachloride‐induced intoxication resulted in considerable decrease of the phosphorylation coefficient because of uncoupling of the oxidation and phosphorylation processes in the liver mitochondria. The melatonin administration during diabetes (10 mg·kg‐1 body weight, 30 days, daily) showed a considerable protective effect on the liver mitochondrial function, reversing the decreased respiration rate V3 and the diminished ACR to the control values both for succinate‐dependent respiration and for glutamate‐dependent respiration. The melatonin administration to intoxicated animals (10 mg·kg−1 body weight, three times) partially increased the rate of succinate‐dependent respiration coupled with phosphorylation. The impairment of mitochondrial respiratory plays a key role in the development of liver injury under diabetes and intoxication. Melatonin might be considered as an effector that regulates the mitochondrial function under diabetes. Copyright © 2011 John Wiley & Sons, Ltd.
BAFF‐R gene induced by IFN‐γ in multiple myeloma cells is related to NF‐κB signals
Authors: Shen Xianjuan , Zhang Xia , Xu Guang , Ju Shaoqing
Published: July 2011

B‐cell activating factor (BAFF) is a potent cell‐survival factor expressed in many haematopoietic cells. BAFF regulates B‐cell survival, differentiation and proliferation by binding to three tumour necrosis factor receptors: transmembrane activator, calcium modulator and cyclophilin ligand interactor; B‐cell maturation antigen; and BAFF receptor (BAFF‐R). Although BAFF‐R is produced by interferon gamma (IFN‐γ), the underlying mechanism remains elusive. In this study, we examined the effects of IFN‐γ on BAFF‐R expression in cultured human multiple myeloma cells (KM3) both at the transcriptional and posttranscriptional levels. Incubation of KM3 cells with IFN‐γ elevated the expression of BAFF‐R mRNA and protein levels. IFN‐γ elicited marked enhancement of the human BAFF‐R promoter activity and nuclear factor kappa B (NF‐κB) DNA binding activity. NF‐κB dependent on the human BAFF‐R gene might be regulated via a transcriptional event through one putative NF‐κB site on the BAFF‐R gene promoter. These results provide a molecular mechanism for the increase in expression of the BAFF‐R gene that is induced by proinflammatory cytokines in responsive cells. Copyright © 2011 John Wiley & Sons, Ltd.
Biosynthesis of Sesquiterpenes by the Fungus Fusarium verticillioides
Authors: Dickschat Jeroen S. , Brock Nelson L. , Citron Christian A. , Tudzynski Bettina
Published: July 2011

The volatiles of the fungus Fusarium verticillioides were analysed by GC‐MS. Sesquiterpenes dominated, with trichodiene as the principle component. Several other sesquiterpenes were detected in low amounts that were unambiguously identified from their mass spectra and retention indices. The absolute configurations of (R)‐β‐bisabolene, (R)‐cuparene, (+)‐β‐barbatene, (−)‐α‐cedrene, (+)‐β‐cedrene, and (+)‐α‐funebrene originating from different key cationic intermediates, were determined by chiral GC‐MS and proved to be related to the trichodiene stereostructure. The unusual compound (E)‐iso‐γ‐bisabolene was also found corroborating a previously suggested mechanism for the cyclisation of the bisabolyl to the cuprenyl cation that is based on quantum mechanical calculations (Y. J. Hong, D. J. Tantillo, Org. Lett. 2006, 8, 4601–4604). These analyses resulted in a revised biosynthesis scheme to trichodiene and the side products of the responsible terpene cyclase, trichodiene synthase, an enzyme that is well characterised from Fusarium sporotrichioides. Feeding studies with several deuterated mevalonolactone isotopomers unravelled stereochemical aspects of the late cyclisations towards trichodiene.
Milestones to recovery: Preliminary validation of a framework to promote recovery and map progress through the medium secure inpatient pathway
Authors: Doyle Michael , Logan Caroline , Ludlow Andrea , Holloway Josanne
Published: July 2011

Background

Forensic mental health care in the UK has undergone a rapid expansion since the late 1990s. In medium secure units (MSUs), there is growing emphasis on developing care pathways without much theoretical underpinning. We developed a concept of ‘Milestones to Recovery’ (MTR) to measure progress through the MSU pathway.

Aims

Our aim was to validate the MTR framework. Our hypotheses were that patients scoring higher on the MTR Scale would be more likely to be aggressive to others in the following 6 months and resident in the acute areas of the unit and that those scoring lower would be more likely to be discharged within 6 months of the assessment.

Methods

An MTR scale was developed to enable the investigation of the validity of the MTR framework and evaluated with staff evaluations of 80 resident patients using a prospective, longitudinal and naturalistic design.

Results

The results suggest that the MTR framework is valid in discriminating between different stages on the MSU pathway. Therapeutic engagement was particularly important in terms of progress through the MSU, whereas current behaviour was important in predicting future aggression.

Conclusions

Further research is required to test the MTR framework across different levels of security, with larger samples and within different populations.

Implications for practice

Provides a framework to map progress through the service.

Identifies key factors that influence recovery and rehabilitation.

Potential to promote dialogue between patients and staff, and enhance motivation.

Copyright © 2011 John Wiley & Sons, Ltd.
Results of stent implantation for native and recurrent coarctation of the aorta—follow‐up of up to 13 years
Authors: Krasemann Thomas , Bano Maria , Rosenthal Eric , Qureshi Shakeel A.
Published: July 2011

Background: To evaluate the mid and long‐term prognosis after stenting of native or recurrent CoA, we studied the cardiovascular parameters in the follow‐up period up to 13 years. Methods and results: Between 1993 and 2006, 68 patients underwent stent implantation for aortic coarctation (average age 25.5 years, range 5.7–65 years, average weight 65.5 kg, range 32–122 kg). Forty‐six (68%) patients were aged >17 years. Stenting was performed for native coarctation in 41 and for recurrent coarctation in 27 patients, in 23 (34%) patients with a covered stent. Redilation was carried out in 26 (38%) patients. The invasive systolic gradient decreased from mean (±SD) 25 (±15) mm Hg to 5 (±5) mm Hg (P < 0.0005). The descending aorta pressure increased from 80 (±15) mm Hg to 101 (±18) mm Hg. The systolic right arm blood pressure decreased from a mean of 153 (±24) mm Hg to 129 (±18) mm Hg (P < 0.0005). Complications like small dissections were rare. Follow‐up (6 days to 13 years, mean 41 months) was available in 66 patients, in 23 after reintervention at a mean of 71 months, range of 8 months to 10.3 years. Fifty‐one percent remained clinically hypertensive. Conclusions: Stenting of aortic coarctation gives good medium‐term results. Frequent reintervention relate to deliberately under‐dilating stents during the initial procedure. The reintervention rate has reduced since the introduction of covered stents. © 2011 Wiley‐Liss, Inc.
Bioactive Unnatural Somatostatin Analogues through Bioorthogonal Iodo‐ and Ethynyl‐Disulfide Intercalators
Authors: Pfisterer Anne , Eisele Klaus , Chen Xi , Wagner Manfred , Müllen Klaus , Weil Tanja
Published: July 2011

Iodo‐ and ethynyl‐containing bisalkylating bioconjugation agents 5 and 8 were achieved and allow the introduction of reactive unnatural substituents into proteins and peptides whilst the bioactive 3D structure is retained. Derivatives of the peptide hormone somatostatin bearing a single iodo or ethynyl group were prepared through intercalation into the disulfide bridge. For the first time, the exact reaction mechanism of the intercalation was elucidated by applying 2D NMR experiments and it was shown that, during the reaction, somatostatin diastereomers were formed. Site‐directed modification of the ethynyl‐modified peptide with a coumarin chromophore was achieved through a [1,3] dipolar Huisgen cycloaddition reaction; this suggests that such a derivative could serve as an attractive platform to prepare artificial somatostatin compound libraries. The biological activity and specificity of a representative modified somatostatin derivative was demonstrated and efficient receptor‐mediated cell uptake occurred in a dose‐dependent manner into receptor positive cells only. The iodo and ethynyl bioconjugation reagents presented herein could be applied for introducing such substituents into alternative peptides and proteins and, in principle, could facilitate the efficient design of a broad variety of artificial protein and peptide analogues with previously unknown bioactivities.
Hydrophobic Interactions and Clustering in a Porous Capsule: Option to Remove Hydrophobic Materials from Water
Authors: Schäffer Christian , Todea Ana Maria , Bögge Hartmut , Petina Olga A. , Rehder Dieter , Haupt Erhard T. K. , Müller Achim
Published: July 2011

The investigation of hydrophobic interactions under confined conditions is of tremendous interdisciplinary interest. It is shown that based on porous capsules of the type {(pentagon)}12{(linker)}30 ≡ {(Mo)Mo5}12{Mo2(ligand)}30, which exhibit different hydrophobic interiors—achieved by coordinating related ligands to the internal sites of the 30 {Mo2} type linkers—there is the option to study systematically interactions with different uptaken/encapsulated hydrophobic molecules like long‐chain alcohols as well as to prove the important correlation between the sizes of the related hydrophobic cavities and the option of water encapsulations. The measurements of 1D‐ and 2D‐NMR spectra (e.g. ROESY, NOESY and HSQC) allowed the study of the interactions especially between encapsulated n‐hexanol molecules and the hydrophobic interior formed by propionate ligands present in a new synthesized capsule. Future detailed studies will focus on interactions of a variety of hydrophobic species with different deliberately constructed hydrophobic capsule interiors.
Enantioselective Friedel–Crafts reaction of indoles with trifluoroacetaldehyde catalyzed by Cinchona alkaloids
Authors: Borkin Dmitry A. , Landge Shainaz M. , Török Béla
Published: July 2011

The first direct asymmetric synthetic preparation of trifluoro‐1‐(indol‐3‐yl)ethanols (TFIEs) is described by an enantioselective organocatalytic method from indoles and inexpensive trifluoroacetaldehyde methyl hemiacetal. The reaction is catalyzed by hydroquinine to produce TFIEs in an almost quantitative yield and with enantioselectivities up to 75% at room temperature. The enantioselectivity is strongly dependent on the concentration of substrates and catalyst due to the competitive noncatalyzed reaction. Chirality, 2011. © 2011 Wiley‐Liss, Inc.
A Partial Convergence in Action of Methylene Blue and Artemisinins: Antagonism with Chloroquine, a Reversal with Verapamil, and an Insight into the Antimalarial Activity of Chloroquine
Authors: Haynes Richard K. , Cheu Kwan‐Wing , Li Ka‐Yan , Tang Maggie Mei‐Ki , Wong Ho‐Ning , Chen Min‐Jiao , Guo Zu‐Feng , Guo Zhi‐Hong , Coghi Paolo , Monti Diego
Published: July 2011

Artemisinins rapidly oxidize leucomethylene blue (LMB) to methylene blue (MB); they also oxidize dihydroflavins such as the reduced conjugates RFH2 of riboflavin (RF), and FADH2 of the cofactor flavin adenine dinucleotide (FAD), to the corresponding flavins. Like the artemisinins, MB oxidizes FADH2, but unlike artemisinins, it also oxidizes NAD(P)H. Like MB, artemisinins are implicated in the perturbation of redox balance in the malaria parasite by interfering with parasite flavoenzyme disulfide reductases. The oxidation of LMB by artemisinin is inhibited by chloroquine (CQ), an inhibition that is abruptly reversed by verapamil (VP). CQ also inhibits artemisinin‐mediated oxidation of RFH2 generated from N‐benzyl‐1,4‐dihydronicotinamide (BNAH)–RF, or FADH2 generated from NADPH or NADPH–Fre, an effect that is also modulated by verapamil. The inhibition likely proceeds by the association of LMB or dihydroflavin with CQ, possibly involving donor–acceptor or π complexes that hinder oxidation by artemisinin. VP competitively associates with CQ, liberating LMB or dihydroflavin from their respective CQ complexes. The observations explain the antagonism between CQ–MB and CQ–artemisinins in vitro, and are reconcilable with CQ perturbing intraparasitic redox homeostasis. They further suggest that a VP–CQ complex is a means by which VP reverses CQ resistance, wherein such a complex is not accessible to the putative CQ‐resistance transporter (PfCRT).
Current awareness of piperazines: pharmacology and toxicology
Authors: Elliott Simon
Published: July 2011

Although many piperazine derivatives exist, only a limited number have been studied, whereby they have been found to be generally stimulant in nature resulting from dopaminergic, noradrenergic, and predominantly serotoninergic effects in the brain. Reported toxic effects include agitation, anxiety, cardiac symptoms (e.g. tachycardia) and sometimes seizures. As for many drugs, they are primarily metabolized by cytochrome P450 with subsequent possible glucuronidation and/or sulfation. Their abuse has been relatively recently observed in the last decade with only a few identified in biological fluid (primarily 1‐benzylpiperazine (BZP) and 1‐(3‐trifluoromethylphenyl)piperazine (3‐TFMPP)) despite publications of a number of analytical methods. Even when detected, however, the toxicological significance of their presence is often difficult to ascertain as many cases involve other drugs as well as a wide and overlapping range of concentrations found in blood (both in life and after death). This paper reviews the current pharmacological and toxicological information for piperazine derivatives and also includes new ante‐mortem and post‐mortem blood data. Copyright © 2011 John Wiley & Sons, Ltd.
Social, policy, and public health perspectives on new psychoactive substances
Authors: Sumnall H.R. , Evans‐Brown M. , McVeigh J.
Published: July 2011

New psychoactive substances pose a particular challenge to those formulating drugs policy and related public health responses. This paper outlines some of the main issues arising from their use, with a particular focus on user perspectives. Such substances are often (at least initially) produced and distributed for different reasons than controlled drugs. They emerge in users' repertoires undetected by most monitoring systems and general population drug surveys. While reasons for use by innovators and early adopters are often in the spirit of self‐experimentation, such substances may rapidly diffuse to the recreational arena as a result of enthusiastic user propagation where they act as substitutes or complements to controlled drugs. The majority of substances are believed to be sourced, albeit not exclusively, from manufacturers based in China. They are retailed to consumers through the Internet and physical shops (such as ‘head’ and ‘smart’ shops), as well as traditional ‘street dealers’ (although data on the significance of this latter route of supply are limited). The data required for risk assessment of the harms such substances may pose, as well as information required for accurate user‐derived harm reduction advice, are often limited. Moreover, some involved in the commercial supply have deliberately misbranded products, including substituting the active substance, in apparent attempts to circumvent regulatory frameworks. This leaves users susceptible to both health and criminal justice harms. Despite various attempts to restrict the supply, they often continue to be available through the illicit market, although it is not yet possible to predict whether they will join other drugs such as MDMA and LSD as mainstays of the recreational pharmacopeia. Copyright © 2011 John Wiley & Sons, Ltd.
Aminoindanes—the next wave of ‘legal highs’?
Authors: Sainsbury P.D. , Kicman A.T. , Archer R.P. , King L.A. , Braithwaite R.A.
Published: July 2011

Due to its closed ring system, 2‐aminoindane is a conformationally rigid analogue of amphetamine. Internet websites offering synthetic compounds as ‘research chemicals’ have recently been advertising 5,6‐methylenedioxy‐2‐aminoindane (MDAI), 5, 6‐methylenedioxy‐N‐methyl‐2‐aminoindane (MDMAI), 5‐iodo‐2‐aminoindane (5‐IAI), and 5‐methoxy‐6‐methyl‐2‐aminoindane (MMAI). The chemistry, pharmacology, and toxicological aspects of this new class of psychoactive substances are reviewed, as these could become the next wave of ‘legal highs’. Copyright © 2011 John Wiley & Sons, Ltd.
Electrostatic Interaction of Negatively Charged Core–Shell Nanoparticles with Antitumoral Cationic Platinum‐Based Complexes
Authors: Gál Miroslav , Híveš Ján , Laus Michele , Sparnacci Katia , Ravera Mauro , Gabano Elisabetta , Osella Domenico
Published: July 2011

We report herein on the interaction between two cationic antiproliferative platinum compounds [namely cis‐[PtCl(NH3)2(py)]Cl (1) and trans,trans‐[(NH3)2Pt{NH2(CH2)4NH2}PtCl(NH3)2](Cl)2 (2)] and novel poly(methyl methacrylate) core–shell nanoparticles (MS) bearing anionic SO3– arms, studied to determine whether such particles might serve as drug carriers for Pt drugs. Electrostatic forces hold together the resulting adducts such that in the presence of higher concentrations of other cations the Pt drug should be released quickly and easily. As expected from their electric charges, we found that the formation constant of the MS‐2 adduct is significantly higher than that of MS‐1. Moreover, the stability of both adducts depends on the ionic strength and surface charge density of competing cations in the medium. The stability of the conjugates and the consequent retention and release of the drug from the nanoparticles will thus depend on both blood and extracellular fluid composition.
A Highly Versatile Catalytic System forN‐Arylation of Amines with Aryl Chlorides in Water
Authors: Huang Manna , Lin Xiaoqin , Zhu Xinhai , Peng Weili , Xie Jianwei , Wan Yiqian
Published: July 2011

The C–N coupling between nucleophiles and aryl chlorides, which are less expensive, less reactive, and more abundant than their bromide and iodide counterparts, is challenging but of great interest for industrial applications. An oxalyldihydrazide/hexane‐2,5‐dione (100–150 mol‐%)/CuO system was found to enable the reaction of a wide range of nucleophiles with a variety of aryl chlorides in water for the first time.
2‐Diphenylaminofluoren‐7‐ylstyrene Derivatives with Various Aromatic End‐Capping Groups for Highly Efficient Blue and White Organic Light‐Emitting Diodes
Authors: Lee Kum Hee , Son Chang Seok , Lee Jin Yong , Kang Sunwoo , Yook Kyoung Soo , Jeon Soon Ok , Lee Jun Yeob , Yoon Seung Soo
Published: July 2011

Highly efficient blue fluorescent materials with a 2‐diphenylaminofluoren‐7‐ylstyrene emitting unit and various aromatic end‐capping groups were synthesized and characterized. A 2‐methyl‐9,10‐bis(2‐naphthyl)anthracene host was doped with these blue materials as the blue dopants in the emitting layer of organic light‐emitting diode (OLED) devices. All devices exhibited highly efficient blue electroluminescence with high external quantum efficiency (4.38–6.2 % at 20 mA cm–2). In particular, two deep blue OLEDs using 7‐[3,5‐bis(naphthalen‐1‐yl)styryl]‐9,9‐diethyl‐2‐N,N‐diphenylamino‐9H‐fluorene (1f) and 7‐{4‐[1′‐(2′,3′,4′,5′‐tetraphenyl)phenyl]styryl}‐9,9‐diethyl‐2‐N,N‐diphenylamino‐9H‐fluorene (1g) as dopants in the emitting layer showed high external quantum efficiencies of 4.63 and 5.96 % at 20 mA cm–2 with the color coordinates (0.148, 0.134) and (0.147, 0.144), respectively. A sky‐blue OLED using7‐{4‐[9,9′‐spirobi(fluoren)‐2‐yl]styryl}‐9,9‐diethyl‐2‐N,N‐diphenylamino‐9H‐fluorene (1e) exhibited a high quantum efficiency of 6.20 % at 20 mA cm–2 with the color coordinates (0.148, 0.195). Moreover, efficient white OLEDs with an external quantum efficiency, luminous efficiency, and color coordinates of 6.50 %, 10.3 cd A–1 at 20 mA cm–2 and (0.357, 0.310) at 1000 cd m–2 were demonstrated by exploiting this highly efficient blue fluorescent material (1e) as a dopant in the blue‐emitting layer.
Use of Sagaun sawdust as an adsorbent for the removal of crystal violet dye from simulated wastewater
Authors: Khattri S.D. , Singh M.K.
Published: July 2011

Removal of dye crystal violet from wastewater by a low‐cost abundantly available adsorbent was investigated. By varying the parameters such as agitation time, dye concentration, adsorbent dose, pH and temperature, potential feasibility for the removal of crystal violet by Sagaun sawdust was explored. The adsorption efficiencies were found to be pH dependent. A greater percentage of dye was removed with a decrease in the initial concentration of dye and increase in the amount of adsorbent. Characterization of the adsorbent by infrared spectroscopy was undertaken. Kinetic study showed that the adsorption of dye on sawdust was a gradual process. The equilibrium adsorption capacity of adsorbent for dye removal was measured which followed Langmuir isotherm. The dimensionless factor, RL
revealed that the adsorption process is favorable in nature. © 2011 American Institute of Chemical Engineers Environ Prog, 2011
Field observations of infragravity waves and their behaviour on rock shore platforms
Authors: Beetham Edward P. , Kench Paul S.
Published: July 2011

Infragravity wave (IGW) transformation was quantified from field measurements on two shore platforms on New Zealand's east coast, making this the first study to describe the presence, characteristics and behaviour of IGWs on rock platform coasts. Data was collected using a cross‐shore array of pressure transducers during a 22 hour experiment on Oraka shore platform and a 36 hour experiment at Rothesay Bay shore platform. A low pass Fourier filter was used to remove gravity wave frequency oscillations, allowing separate analysis of IGWs and the full wave spectrum. Offshore IGW heights were measured to be 7 cm (Oraka) and 9 cm (Rothesay Bay), which were 21% (Oraka) and 7.5% (Rothesay Bay) the height of incident wave height. At the cliff toe, significant IGW height averaged 15 cm at Oraka and 13 cm at Rothesay Bay. This increase in IGW height over the platform during both experiments is attributed to shoaling of 40 to 55% over the last 50–60 m before the cliff toe, respectively. Shoaling across the platform was quantified as the change in IGW height from the platform edge to cliff toe, resulting in a maximum increase of 1·88 and 2·63 on Rothesay Bay and Oraka platforms. IGW height at the cliff toe showed a strong correlation with incident wave height. The proportional increase in IGW height shows a strong correlation to water level on each platform. The rate of shoaling of long period waves on the shallow, horizontal platforms increased at higher water levels resulting in a super elevation in water level at the cliff toe during high tide. Greater IGW shoaling was also observed on the wider (Oraka) shore platform. Results from this study show the first measurements of IGWs on shore platforms and identify long wave motion a significant process in a morphodynamic understanding of rock coast. Copyright © 2011 John Wiley & Sons, Ltd.
Cahn–Hilliard modeling of particles suspended in two‐phase flows
Authors: Choi Young Joon , Anderson Patrick D.
Published: July 2011

In this paper, we present a model for the dynamics of particles suspended in two‐phase flows by coupling the Cahn–Hilliard theory with the extended finite element method (XFEM). In the Cahn–Hilliard model the interface is considered to have a small but finite thickness, which circumvents explicit tracking of the interface. For the direct numerical simulation of particle‐suspended flows, we incorporate an XFEM, in which the particle domain is decoupled from the fluid domain. To cope with the movement of the particles, a temporary ALE scheme is used for the mapping of field variables at the previous time levels onto the computational mesh at the current time level. By combining the Cahn–Hilliard model with the XFEM, the particle motion at an interface can be simulated on a fixed Eulerian mesh without any need of re‐meshing. The model is general, but to demonstrate and validate the technique, here the dynamics of a single particle at a fluid–fluid interface is studied. First, we apply a small disturbance on a particle resting at an interface between two fluids, and investigate the particle movement towards its equilibrium position. In particular, we are interested in the effect of interfacial thickness, surface tension, particle size and viscosity ratio of two fluids on the particle movement towards its equilibrium position. Finally, we show the movement of a particle passing through multiple layers of fluids. Copyright © 2011 John Wiley & Sons, Ltd.
Numerical simulations of negatively buoyant jets in an immiscible fluid using the Particle Finite Element Method
Authors: Mier‐Torrecilla M. , Geyer A. , Phillips J. C. , Idelsohn S. R. , Oñate E.
Published: July 2011

Negatively buoyant jets consist in a dense fluid injected vertically upward into a lighter ambient fluid. The numerical simulation of this kind of buoyancy‐driven flows is challenging as it involves multiple fluids with different physical properties. In the case of immiscible fluids, it requires, in addition, to track the motion of the interface between fluids and accurately represent the discontinuities of the flow variables.

In this paper, we investigate numerically the injection of a negatively buoyant jet into a homogenous immiscible ambient fluid using the Particle Finite Element Method and compare the two‐dimensional numerical results with experiments on the injection of a jet of dyed water through a nozzle in the base of a cylindrical tank containing rapeseed oil. In both simulations and experiments, the fountain inlet flow velocity and nozzle diameter have been varied to cover a wide range of Froude Fr and Reynolds Re numbers ( 0.1 < Fr < 30, 8 < Re < 1350), reproducing both weak and strong laminar fountains.

The flow behaviors observed for the different numerical simulations fit in the regime map based on the Re and Fr values of the experiments, and the maximum fountain height is in good agreement with the experimental observations, suggesting that particle finite element method is a useful tool for the study of immiscible two‐fluid systems. Copyright © 2011 John Wiley & Sons, Ltd.
High‐resolution genomic analysis of the 11q13 amplicon in breast cancers identifies synergy with 8p12 amplification, involving the mTOR targets S6K2 and 4EBP1
Authors: Karlsson Elin , Waltersson Marie Ahnström , Bostner Josefine , Pérez‐Tenorio Gizeh , Olsson Birgit , Hallbeck Anna‐Lotta , Stål Olle
Published: July 2011

The chromosomal region 11q13 is amplified in 15–20% of breast cancers; an event not only associated with estrogen receptor (ER) expression but also implicated in resistance to endocrine therapy. Coamplifications of the 11q13 and 8p12 regions are common, suggesting synergy between the amplicons. The aim was to identify candidate oncogenes in the 11q13 region based on recurrent amplification patterns and correlations to mRNA expression levels. Furthermore, the 11q13/8p12 coamplification and its prognostic value, was evaluated at the DNA and the mRNA levels. Affymetrix 250K NspI arrays were used for whole‐genome screening of DNA copy number changes in 29 breast tumors. To identify amplicon cores at 11q13 and 8p12, genomic identification of significant targets in cancer (GISTIC) was applied. The mRNA expression levels of candidate oncogenes in the amplicons [RAD9A, RPS6KB2 (S6K2), CCND1, FGF19, FGF4, FGF3, PAK1, GAB2 (11q13); EIF4EBP1 (4EBP1), PPAPDC1B, and FGFR1 (8p12)] were evaluated using real‐time PCR. Resulting data revealed three main amplification cores at 11q13. ER expression was associated with the central 11q13 amplification core, encompassing CCND1, whereas 8p12 amplification/gene expression correlated to S6K2 in a proximal 11q13 core. Amplification of 8p12 and high expression of 4EBP1 or FGFR1 was associated with a poor outcome in the group. In conclusion, single nucleotide polymorphism arrays have enabled mapping of the 11q13 amplicon in breast tumors with high resolution. A proximal 11q13 core including S6K2 was identified as involved in the coamplification/coexpression with 8p12, suggesting synergy between the mTOR targets S6K2 and 4EBP1 in breast cancer development and progression. © 2011 Wiley‐Liss, Inc.
Identification of miR‐374a as a prognostic marker for survival in patients with early‐stage nonsmall cell lung cancer
Authors: Võsa Urmo , Vooder Tõnu , Kolde Raivo , Fischer Krista , Välk Kristjan , Tõnisson Neeme , Roosipuu Retlav , Vilo Jaak , Metspalu Andres , Annilo Tarmo
Published: July 2011

Lung cancer is one of the deadliest types of cancer proven by the poor survival and high relapse rates after surgery. Recently discovered microRNAs (miRNAs), small noncoding RNA molecules, play a crucial role in modulating gene expression networks and are directly involved in the progression of a number of human cancers. In this study, we analyzed the expression profile of 858 miRNAs in 38 Estonian nonsmall cell lung cancer (NSCLC) samples (Stage I and II) and 27 adjacent nontumorous tissue samples using Illumina miRNA arrays. We found that 39 miRNAs were up‐regulated and 33 down‐regulated significantly in tumors compared with normal lung tissue. We observed aberrant expression of several well‐characterized tumorigenesis‐related miRNAs, as well as a number of miRNAs whose function is currently unknown. We show that low expression of miR‐374a in early‐stage NSCLC is associated with poor patient survival. The combinatorial effect of the up‐ and down‐regulated miRNAs is predicted to most significantly affect pathways associated with cell migration, differentiation and growth, and several signaling pathways that contribute to tumorigenesis. In conclusion, our results demonstrate that expression of miR‐374a at early stages of NSCLC progression can serve as a prognostic marker for patient risk stratification and may be a promising therapeutic target for the treatment of lung cancer. © 2011 Wiley‐Liss, Inc.
Mechanisms of GABA release from human astrocytes
Authors: Lee Moonhee , McGeer Edith G. , McGeer Patrick L.
Published: July 2011

We have previously demonstrated that human astrocytes are GABAergic cells. Throughout the adult human brain, they express the GABA synthesizing enzyme GAD 67, the GABA metabolizing enzyme GABA‐T, and the GABAA and GABAB receptors. GABA modulates the actions of microglia, indicating an important role for astrocytes beyond that of influencing neurotransmitter function. Here we report on the mechanisms by which astrocytes release GABA. Astrocytes were found to express the mRNA and protein for multiple GABA transporters, and multiple receptors for glutamate, GABA, and glycine. In culture, untreated human astrocytes maintained an intracellular GABA level of 2.32 mM. They exported GABA into the culture medium so that an intracellular‐extracellular gradient of 3.64 fold was reached. Inhibitors of the GABA transporters GAT1, GAT2, and GAT3, significantly reduced this export in a Ca2+‐independent fashion. Intracellular GABA levels were enhanced by treatment with the GABA‐T inhibitors gabaculine or vigabatrin. Treatment with glutamate increased GABA release in a concentration‐dependent fashion. This was partially inhibited by blockers of N‐methyl‐D‐aspartate and kainate receptors. Conversely, glycine and D‐serine, co‐agonists of NMDA receptors, enhanced the GABA release. GABA release was accompanied by an increase in intracellular Ca2+ concentration ([Ca2+]i) and was reduced by adding the Ca2+ chelator, BAPTA‐AM to the medium. These data indicate that astrocytes continuously synthesize GABA and that there are multiple mechanisms which can mediate its release. Each of these may play a role in the physiological functioning of astrocytes. © 2011 Wiley‐Liss, Inc.
Evidence that compromised K+ spatial buffering contributes to the epileptogenic effect of mutations in the human kir4.1 gene (KCNJ10)
Authors: Haj‐Yasein Nadia Nabil , Jensen Vidar , Vindedal Gry Fluge , Gundersen Georg Andreas , Klungland Arne , Ottersen Ole Petter , Hvalby Øivind , Nagelhus Erlend Arnulf
Published: July 2011

Mutations in the human Kir4.1 potassium channel gene (KCNJ10) are associated with epilepsy. Using a mouse model with glia‐specific deletion of Kcnj10, we have explored the mechanistic underpinning of the epilepsy phenotype. The gene deletion was shown to delay K+ clearance after synaptic activation in stratum radiatum of hippocampal slices. The activity‐dependent changes in extracellular space volume did not differ between Kcnj10 mutant and wild‐type mice, indicating that the Kcnj10 gene product Kir4.1 mediates osmotically neutral K+ clearance. Combined, our K+ and extracellular volume recordings indicate that compromised K+ spatial buffering in brain underlies the epilepsy phenotype associated with human KCNJ10 mutations. © 2011 Wiley‐Liss, Inc.
Identification of a cut‐off for the macis score to predict the prognosis of differentiated thyroid carcinoma in children and young adults
Authors: Jang Hye Won , Lee Ji In , Kim Hee Kyung , Oh Young Lyun , Choi Yoon–La , Jin Dong–Kyu , Kim Jung–Han , Chung Jae Hoon , Kim Sun Wook
Published: July 2011

Background

The metastases, age at diagnosis, completeness of resection, invasion, size of the tumor (MACIS) scoring system was developed to predict disease‐specific survival in patients with differentiated thyroid carcinoma (DTC), mainly for adults, with a cut‐off score of 6. The purpose of this study was to evaluate its ability to predict prognosis of DTC in children and young adults.

Methods

The medical records of 66 children and young adult (<21 years old) patients with DTC were reviewed retrospectively. Receiver operating characteristic (ROC) analysis was performed to determine the cut‐off for predicting poor prognosis.

Results

Extrathyroidal invasion and regional lymph node metastasis were noted in 64% each, and distant metastases were found in 8%. The optimal cut‐off for the MACIS score for poor prognosis was 4 (93% sensitivity, 67% specificity). The overall 10‐year recurrence‐free survival was better in patients with MACIS score <4 than score ≥4 (p < .05).

Conclusion

A MACIS score of more than 4 was associated with a poor prognosis in children and young adult patients with DTC. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2 −/− ( Abcb4 −/−) mouse cholangiopathy model by promoting biliary HCO Symbol output
Authors: Baghdasaryan Anna , Claudel Thierry , Gumhold Judith , Silbert Dagmar , Adorini Luciano , Roda Aldo , Vecchiotti Stefania , Gonzalez Frank J. , Schoonjans Kristina , Strazzabosco Mario , Fickert Peter , Trauner Michael
Published: July 2011

Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. The nuclear farnesoid X receptor (FXR) and the membrane G protein-coupled receptor, TGR5, regulate bile acid (BA) homeostasis and inflammation. Therefore, we hypothesized that activation of FXR and/or TGR5 could ameliorate liver injury in

Mdr2

−/− (

Abcb4

−/−) mice, a model of chronic cholangiopathy. Hepatic inflammation, fibrosis, as well as bile secretion and key genes of BA homeostasis were addressed in

Mdr2

−/− mice fed either a chow diet or a diet supplemented with the FXR agonist, INT-747, the TGR5 agonist, INT-777, or the dual FXR/TGR5 agonist, INT-767 (0.03% w/w). Only the dual FXR/TGR5 agonist, INT-767, significantly improved serum liver enzymes, hepatic inflammation, and biliary fibrosis in

Mdr2

−/− mice, whereas INT-747 and INT-777 had no hepatoprotective effects. In line with this, INT-767 significantly induced bile flow and biliary HCO
Symbol
output, as well as gene expression of carbonic anhydrase 14, an important enzyme able to enhance HCO
Symbol
transport, in an Fxr-dependent manner. In addition, INT-767 dramatically reduced bile acid synthesis via the induction of ileal

Fgf15

and hepatic

Shp

gene expression, thus resulting in significantly reduced biliary bile acid output in

Mdr2

−/− mice.

Conclusion:

This study shows that FXR activation improves liver injury in a mouse model of chronic cholangiopathy by reduction of biliary BA output and promotion of HCO
Symbol
-rich bile secretion. (Hepatology 2011;54:1303–1312)
The antiviral protein viperin inhibits hepatitis C virus replication via interaction with nonstructural protein 5A
Authors: Helbig Karla J. , Eyre Nicholas S. , Yip Evelyn , Narayana Sumudu , Li Kui , Fiches Guillaume , McCartney Erin M. , Jangra Rohit K. , Lemon Stanley M. , Beard Michael R.
Published: July 2011

The interferon-stimulated gene, viperin, has been shown to have antiviral activity against hepatitis C virus (HCV) in the context of the HCV replicon, although the molecular mechanisms responsible are not well understood. Here, we demonstrate that viperin plays an integral part in the ability of interferon to limit the replication of cell-culture–derived HCV (JFH-1) that accurately reflects the complete viral life cycle. Using confocal microscopy and fluorescence resonance energy transfer (FRET) analysis, we demonstrate that viperin localizes and interacts with HCV nonstructural protein 5A (NS5A) at the lipid-droplet (LD) interface. In addition, viperin also associates with NS5A and the proviral cellular factor, human vesicle-associated membrane protein-associated protein subtype A (VAP-A), at the HCV replication complex. The ability of viperin to limit HCV replication was dependent on residues within the C-terminus, as well as an N-terminal amphipathic helix. Removal of the amphipathic helix-redirected viperin from the cytosolic face of the endoplasmic reticulum and the LD to a homogenous cytoplasmic distribution, coinciding with a loss of antiviral effect. C-terminal viperin mutants still localized to the LD interface and replication complexes, but did not interact with NS5A proteins, as determined by FRET analysis. Conclusion: In conclusion, we propose that viperin interacts with NS5A and the host factor, VAP-A, to limit HCV replication at the replication complex. This highlights the complexity of the host control of viral replication by interferon-stimulated gene expression. (Hepatology 2011;)
Conditional disruption of mouse HFE2 gene: Maintenance of systemic iron homeostasis requires hepatic but not skeletal muscle hemojuvelin
Authors: Gkouvatsos Konstantinos , Wagner John , Papanikolaou George , Sebastiani Giada , Pantopoulos Kostas
Published: July 2011

Mutations of the HFE2 gene are linked to juvenile hemochromatosis, a severe hereditary iron overload disease caused by chronic hyperabsorption of dietary iron. HFE2 encodes hemojuvelin (Hjv), a membrane-associated bone morphogenetic protein (BMP) coreceptor that enhances expression of the liver-derived iron regulatory hormone hepcidin. Hjv is primarily expressed in skeletal muscles and at lower levels in the heart and the liver. Moreover, a soluble Hjv form circulates in plasma and is thought to act as a decoy receptor, attenuating BMP signaling to hepcidin. To better understand the regulatory function of Hjv, we generated mice with tissue-specific disruption of this protein in hepatocytes or in muscle cells. The hepatic ablation of Hjv resulted in iron overload, quantitatively comparable to that observed in ubiquitous Hjv−/− mice. Serum iron and ferritin levels, transferrin saturation, and liver iron content were significantly (P < 0.001) elevated in liver-specific Hjv−/− mice. Hepatic Hjv mRNA was undetectable, whereas hepcidin expression was markedly suppressed (12.6-fold; P < 0.001) and hepatic BMP6 mRNA up-regulated (2.4-fold; P < 0.01), as in ubiquitous Hjv−/− counterparts. By contrast, the muscle-specific disruption of Hjv was not associated with iron overload or altered hepcidin expression, suggesting that muscle Hjv mRNA is dispensable for iron metabolism. Our data do not support any significant iron-regulatory function of putative muscle-derived soluble Hjv in mice, at least under physiological conditions. Conclusion: The hemochromatotic phenotype of liver-specific Hjv−/− mice suggests that hepatic Hjv is necessary and sufficient to regulate hepcidin expression and control systemic iron homeostasis. (Hepatology 2011;)
Retreatment with telaprevir combination therapy in hepatitis C patients with well-characterized prior treatment response
Authors: Muir Andrew J. , Poordad Fred F. , McHutchison John G. , Shiffman Mitchell L. , Berg Thomas , Ferenci Peter , Heathcote Jenny E. , Pawlotsky Jean-Michel , Zeuzem Stefan , Reesink Henk W. , Dusheiko Geoffrey , Martin Emily C. , George Shelley , Kauffman Robert S. , Adda Nathalie
Published: July 2011

Retreatment with peginterferon alpha and ribavirin (PR) offers a limited chance of sustained virologic response (SVR) in patients who did not achieve SVR with prior PR treatment. This study evaluated the safety and efficacy of telaprevir-based treatment in combination with PR in well-characterized patients who did not achieve SVR in the control arms of three Phase II clinical trials. Patients eligible to enroll in this open-label nonrandomized study either met on-treatment criteria for nonresponse or relapsed after 48 weeks of treatment in the control arm of the three Phase II PROVE studies. The initial protocol was a 24-week regimen: 12 weeks of telaprevir and PR followed by an additional 12 weeks of PR. During the study the protocol was amended to extend PR to 48 weeks for patients with previous null response. All other patients with undetectable hepatitis C virus (HCV) RNA at weeks 4 and 12 received 24 weeks of therapy. Those with detectable HCV RNA at weeks 4 or 12 received a total of 48 weeks of therapy. The overall SVR rate was 59% (69/117). SVR rates with T12PR were 37% (19/51) in prior null responders, 55% (16/29) in prior partial responders, 75% (6/8) in prior breakthroughs, and 97% (28/29) in prior relapsers. The overall relapse rate was 16% (13/83). Adverse events were similar to those in previous trials with telaprevir, with 9% of patients discontinuing due to an adverse event (most commonly rash and anemia). Conclusion: This study demonstrated the benefit of retreatment with a telaprevir-based regimen for patients with well-characterized nonresponse (null and partial) or relapse to a prior course of PR treatment. (Hepatology 2011;)