bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of anticytomegalovirus seropositivity with more severe joint destruction and more frequent joint surgery in rheumatoid arthritis
Authors: Pierer Matthias , Rothe Kathrin , Quandt Dagmar , Schulz Anett , Rossol Manuela , Scholz Roger , Baerwald Christoph , Wagner Ulf
Published: December 2011

Objective

Expansion of autoreactive CD4+CD28null T cells is associated with extraarticular disease manifestations, including rheumatoid vasculitis, and it has recently been demonstrated that expansion of these T cells is associated with anticytomegalovirus (anti‐CMV) seropositivity. This study was undertaken to investigate a possible link between latent CMV infection and rheumatoid arthritis (RA).

Methods

In a retrospective analysis, anti‐CMV antibodies and clinical, serologic, and radiologic parameters of joint destruction were examined in 202 RA patients and 272 healthy controls. In addition, frequencies of CD4+CD28null T cells; concentrations of the cytokines monocyte chemotactic protein 1 (MCP‐1), interferon‐α (IFNα), and IFN‐inducible protein 10; and anti‐CMV–specific T cell responses were analyzed in RA patients.

Results

Overall, no significant difference in the frequency of anti‐CMV seropositivity between RA patients and healthy controls was observed. Among individuals older than age 55 years, however, anti‐CMV IgG antibodies were significantly more frequent in RA patients than controls (65.3% and 54.7%, respectively; P = 0.05). Anti‐CMV seropositivity in RA patients was associated with an increased frequency of CD4+CD28null T cells and increased serum concentrations of MCP‐1. The frequency of anti‐CMV–specific CD4+ T cells producing IFNγ was increased in RA patients compared to controls. Most importantly, anti‐CMV–seropositive RA patients showed radiographic evidence of more advanced joint destruction and had increased frequencies of joint‐related surgical procedures, indicating more severe joint disease.

Conclusion

Our findings indicate that latent CMV infection aggravates the clinical course of RA and is associated with increased frequencies of CD4+CD28null T cells and of CMV‐specific IFNγ‐secreting CD4+ T cells.
Fenestrated endovascular aneurysm repair
Authors: Cross J , Gurusamy K , Gadhvi V , Simring D , Harris P , Ivancev K , Richards T
Published: December 2011

Background

Fenestrated endovascular aneurysm repair (FEVAR) is a technically challenging operation. The duration, blood loss, and risk of limb ischaemia, contrast-induced nephropathy and reperfusion injury are likely to be higher than after standard endovascular aneurysm repair (EVAR). Benefits of FEVAR over open repair may be less than those seen with standard infrarenal EVAR. This paper is a meta-analysis of observational studies of all published data for FEVAR, with the aim to highlight current issues around the evidence for the potential benefit of FEVAR.

Methods

A search was performed for studies describing FEVAR for juxtarenal abdominal aortic aneurysms. Small series of fewer than ten procedures and studies describing predominantly branched endografts or FEVAR for aortic dissection were excluded. Authors of included papers were contacted to eliminate patient duplication.

Results

Eleven studies were identified describing a total of 660 procedures. Definitions of aneurysm morphology were variable, and clear inclusion and exclusion criteria were not always documented. Double fenestrations were more common than triple or quadruple fenestrations. Target vessel perfusion rates ranged from 90·5 to 100 per cent. Eleven deaths occurred within 30 days, giving a 30-day proportional mortality rate of 2·0 per cent. Morbidity was poorly reported.

Conclusion

FEVAR for repair of suprarenal and juxtarenal aneurysms is a viable alternative to open repair. However, there is no level 1 evidence for FEVAR, and current evidence is weak with many unanswered questions.
The never-ending story of dilatation versus surgery for oesophageal achalasia
Authors: Zaninotto G , Patti M G
Published: December 2011

Still no clear winner
Prospective surveillance study of the management of intussusception in UK and Irish infants
Authors: Samad L , Marven S , El Bashir H , Sutcliffe A G , Cameron J C , Lynn R , Taylor B
Published: December 2011

Background

Intussusception is the most common cause of acute intestinal obstruction in infants. This study examined the clinical presentation, management and outcomes of intussusception in this age group.

Methods

Prospective surveillance of intussusception in infants was carried out between March 2008 and March 2009 in the UK and Ireland. Monthly cards were sent to paediatric clinicians who were requested to notify cases of intussusception.

Results

The study identified 261 confirmed cases. The commonest presenting symptom/sign was non-bilious vomiting, in 210 (80·5 per cent) of the infants. Abdominal ultrasonography was done in 247 infants (94·6 per cent) and was diagnostic in 242 (98·0 per cent), compared with plain abdominal X-ray, which was diagnostic in 33 (23·6 per cent) of 140 infants. Enema reduction was carried out in 240 (92·0 per cent) of the 261 infants; the majority (237, 98·8 per cent) had pneumatic reduction with a success rate of 61·2 per cent (145 of 237). Surgery was required in 111 infants (42·5 per cent); 92 operations were as a result of unsuccessful enema reduction, and the remaining 19 infants (17·1 per cent) had primary surgery. Forty-four infants (39·6 per cent of operations) needed a bowel resection. The majority of children (238, 91·2 per cent) recovered uneventfully; 21 (8·0 per cent) had sequelae, one child died (0·4 per cent), and the outcome was unknown for one infant.

Conclusion

This study described current treatment patterns for intussusception in infancy; these represent a benchmark for improved standards of care for this condition.
Effect of sodium butyrate on autophagy and apoptosis in Chinese hamster ovary cells
Authors: Seong Lee Jae , Lee Gyun Min
Published: December 2011

Sodium butyrate (NaBu), which is widely used in recombinant Chinese hamster ovary cell (rCHO) cultures for high‐level expression of therapeutic proteins, is known to induce apoptosis in a dose‐dependent manner. Lately, the significance of autophagy has increased in the field of CHO cell culture due to the fact that autophagy is related to the programmed cell death mechanism. To determine the effect of NaBu on autophagy as well as apoptosis of rCHO cells, rCHO cells producing erythropoietin were subjected to NaBu treatment. NaBu treatment up to 5 mM increased cleaved forms of PARP, caspase‐3, and Annexin V positive population, confirming the previous results that NaBu induces apoptosis. Concurrently, NaBu treatment increased the level of accumulation of the autophagic marker, LC3‐II, independently of nutrient depletion, suggesting that NaBu induces autophagy. To elucidate the potential role of autophagy induced by NaBu, a representative autophagy inducer (rapamycin) or an inhibitor (bafilomycin A1) was added to cultures together with NaBu. It was found that autophagy had the potential role of a positive cell survival mechanism under NaBu treatment. Furthermore, gradual reduction in mitochondrial membrane potential/mass and recruitment of a mitophagy protein, Parkin, to the mitochondria were observed under NaBu treatment, suggesting that this positive function of autophagy might be mediated by the autophagic removal of damaged mitochondria. Taken together, autophagy was observed in rCHO cell culture under NaBu treatments and the results obtained here support the positive effects of autophagy induced by NaBu treatments. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012
Further views from professors, state directors, and analysts
Authors: Cohen Arthur M.
Published: December 2011

This chapter surveys state directors and professors in community college leadership programs, as well as the writings of key analysts of higher education, for the challenges, opportunities, and central concerns they identify in the present and future of community colleges.
Raman optical activity study on insulin amyloid‐ and prefibril intermediate
Authors: Yamamoto Shigeki , Watarai Hitoshi
Published: December 2011

The amyloid fibril of bovine insulin and its renaturing intermediates were studied by using Raman optical activity (ROA). In the spectrum of the amyloid, the sharp +/− ROA couplet of amide I band characteristic of the β‐sheet‐rich proteins was observed, together with a sharp peak at 1271 cm−1 characteristic of a turn structure. The shoulder ROA peak of the native insulin at ∼ 1340 cm−1, which was assigned to the hydrated α‐helix, was not observed in the amyloid, suggesting that the hydrated α‐helix was converted to the parallel β‐sheet structure in the amyloid. Recovery of the amyloid to the native state was also monitored by ROA. The intermediate states showed distinct features from the amyloid or native ones. The intermediates did not show a characteristic ROA peak of the poly(L‐proline) II helix at ∼ 1318 cm−1. The hydrated α‐helix ROA peak was not recovered in the intermediate states. In a process of the amyloid formation, at first the hydrated α‐helix of the native insulin is converted to a specific partially unfolded structure, and then, it was converted to the parallel β‐sheet structure with many turns. Chirality, 2012. © 2011 Wiley Periodicals, Inc.
Absolute stereochemistry of altersolanol a and alterporriols
Authors: Kanamaru Saki , Honma Miho , Murakami Takanori , Tsushima Taro , Kudo Shinji , Tanaka Kazuaki , Nihei Ken‐Ichi , Nehira Tatsuo , Hashimoto Masaru
Published: December 2011

The absolute stereochemistry of altersolanol A (1) was established by observing a positive exciton couplet in the circular dichroism (CD) spectrum of the C3,C4‐O‐bis(2‐naphthoyl) derivative 10 and by chemical correlations with known compound 8. Before the discussion, the relative stereochemistry of 1 was confirmed by X‐ray crystallographic analysis. The shielding effect at C7′‐OMe group by C1‐O‐benzoylation established the relative stereochemical relationship between the C8‐C8′ axial bonding and the C1‐C4/C1′‐C4′ polyol moieties of alterporriols E (3), an atropisomer of the C8‐C8′ dimer of 1. As 3 could be obtained by dimerization of 1 in vitro, the absolute configuration of its central chirality elements (C1‐C4) must be identical to those of 1. Spectral comparison between the experimental and theoretical CD spectra supported the above conclusion. Axial stereochemistry of novel C4‐O‐deoxy dimeric derivatives, alterporriols F (4) and G (5), were also revealed by comparison of their CD spectra to those of 2 and 3. Chirality, 2012. © 2011 Wiley Periodicals, Inc.
Optimal design of a thermally coupled fluidised bed heat exchanger reactor for hydrogen production and octane improvement in the catalytic naphtha reformers
Authors: Pourazadi E. , Vakili R. , Iranshahi D. , Jahanmiri A. , Rahimpour M. R.
Published: December 2011

The present study combines simultaneously the definition of fluidisation and process intensification (thermally coupled heat exchanger reactor) concept and determines the optimum operational conditions in both sides of the reactor, using Differential Evolution (DE) optimisation approach. The exothermic hydrogenation of nitrobenzene to aniline takes place in a set of tubular reactors which is placed inside the naphtha reactors and thermally handle the endothermic reaction of reforming. A single objective function consists of four terms including aromatic mole fraction of the reformate and hydrogen production from each reactor in the endothermic side as well as the total molar flow rate of aniline and nitrobenzene conversion in the exothermic side is defined. Seven decision variables such as inlet temperature of exothermic and endothermic sides, exothermic molar flow rates for the first and the second reactors and the number of tubes are considered during the optimisation procedure. Temperature constraints have been considered in both sides during the optimisation in order to reduce the possibility of rapid catalyst deactivation by sintering. Results show approximately 464.4 and 598.9 kg/h increase in aromatic and aniline production rates in optimised thermally coupled fluidised bed naphtha reactor (OTCFBNR) compared with non‐optimised case (TCFBNR), respectively. Such a theoretical study is necessary prior to designing new pilot plants and revamping industrial units. © 2011 Canadian Society for Chemical Engineering
Modelling and simulation of trickle‐bed reactors using computational fluid dynamics: A state‐of‐the‐art review
Authors: Wang Yining , Chen Jinwen , Larachi Faical
Published: December 2011

Trickle‐bed reactors (TBRs), which accommodate the flow of gas and liquid phases through packed beds of catalysts, host a variety of gas–liquid–solid catalytic reactions, particularly in the petroleum/petrochemical industry. The multiphase flow hydrodynamics in TBRs are complex and directly affect the overall reactor performance in terms of reactant conversion and product yield and selectivity. Non‐ideal flow behaviours, such as flow maldistribution, channelling or partial catalyst wetting may significantly reduce the effectiveness of the reactor. However, conventional TBR modelling approaches cannot properly account for these non‐ideal behaviours owing to the complex coupling between fluid dynamics and chemical kinetics. Recent advances in the application of computational fluid dynamics (CFD) to three‐phase TBR systems have shown promise of achieving a deeper understanding of the interactions between multiphase fluid dynamics and chemical reactions. This study is intended to give a state‐of‐the‐art overview of the progress achieved in the field of CFD simulation of TBRs over the past two decades. The fundamental modelling framework of multiphase flow in TBRs, advances in important constitutive models, and the application of CFD models are discussed in detail. Directions for future research are suggested.
Micellar enhanced ultrafiltration: A comparative study
Authors: Jadhav S. V. , Marathe K. V.
Published: December 2011

A pilot plant study was carried out to evaluate the performance of continuous cross flow micellar enhanced ultrafiltration (MEUF) method for the simultaneous separation of phenol and ortho‐cresol from the aqueous phase using a cationic surfactant, cetyltrimethyl ammonium bromide. The membranes used in this study are polysulfone tubular hollow fibre membrane with 6 kDa and a ceramic membrane having pore diameter 50 nm with an active layer of microporous zirconia (ZrO2) supported on α‐alumina, respectively. The work includes comparing the effectiveness of membranes based on pollutants structural parameters, membrane properties and membrane modules. The characteristic parameters such as the distribution coefficient (D), micelle binding constant (Kp) and micelle loading (Lm) were obtained at optimal experimental conditions. High initial rejections were observed (above 95%) for both the membranes and the permeate flux remained almost constant at 17 LMH. It was found that the polysulfone material membrane suited better for MEUF with higher and steady rejections over a period of time. High micelle leakage was observed in ceramic membrane. The energy consumption for hollow fibre polysulfone membrane was less than the ceramic membrane. © 2011 Canadian Society for Chemical Engineering
Response Surface Analysis to Improve Dispersed Crude Oil Biodegradation
Authors: Zahed Mohammad A. , Aziz Hamidi A. , Isa Mohamed H. , Mohajeri Leila
Published: December 2011

In this research, the bioremediation of dispersed crude oil, based on the amount of nitrogen and phosphorus supplementation in the closed system, was optimized by the application of response surface methodology and central composite design. Correlation analysis of the mathematical‐regression model demonstrated that a quadratic polynomial model could be used to optimize the hydrocarbon bioremediation (R2 = 0.9256). Statistical significance was checked by analysis of variance and residual analysis. Natural attenuation was removed by 22.1% of crude oil in 28 days. The highest removal on un‐optimized condition of 68.1% were observed by using nitrogen of 20.00 mg/L and phosphorus of 2.00 mg/L in 28 days while optimization process exhibited a crude oil removal of 69.5% via nitrogen of 16.05 mg/L and phosphorus 1.34 mg/L in 27 days therefore optimization can improve biodegradation in shorter time with less nutrient consumption.
Adjusting Chlorine Dosage and to Prevent Bio‐Growth and Minimize Trihalomethanes in Reverse Osmosis Filtrate in a Wastewater Reclamation Process
Authors: Hsu Yi‐Che , Wang Yu‐Hsuan , Wu Shuo‐Chuan , Wu Chuen‐Mei , Chu Ching‐Ping , Chung Yu‐Jen , Huang Yong‐Tang , Wang Kuo‐Liang
Published: December 2011

Feasibility of effluent reclamation for the Futian municipal WWTP in Taichung Taiwan was evaluated using an “SF‐UF‐RO” pilot plant. The optimal parameters of each unit were obtained during the pilot plant test. The pilot plant started the operation in late October 2008 and operated until January 2011. The reverse osmosis (RO) system produces 75 m3 water daily, and the produced water quality was comparable to the city water in Taichung. Chlorine dosed in the sand filtration (SF) inlet and ultrafiltration (UF) backwash had the most significant effect on the stability of system performance. When the chlorine was underdosed, biofilm clogged the bag filter (prefilter of UF) and led to the flow rate decay of the UF. The prefilter needed replacement every 1 or 2 weeks resulting in increased process cost. On the other hand, when the chlorine dosage was increased to mitigate the biofilm growth, the residual chlorine not only reacted with TOC and derived trihalomethanes (THMs) in the RO product water (more than 20 µg/L), but it also damaged the RO membrane. After trial and error, the chlorine concentration was optimized as 0.7 mg/L in SF inlet to prevent growth of biofilm as well as to control the residual chlorine in the RO inlet and THMs in the RO product water. It is suggested that cautiously adjusting chlorine dosage is essential for stably operating such a hybrid membrane system to reclaim the municipal wastewater.
Adsorption of Basic Dyes from Aqueous Solutions by Depolymerization Products of Post‐Consumer PET Bottles
Authors: Acar Işıl , Bal Ayça , Güçlü Gamze
Published: December 2011

The purpose of this work is the removal of basic dyes (Safranine T and Brilliant Green) from aqueous media by depolymerization products (DP) obtained from aminoglycolysis of waste poly(ethylene terephthalate) (PET). The surface morphology and physical properties of depolymerization product were also determined. Adsorption behaviors (adsorption capacities, adsorption kinetics and adsorption isotherms) of these samples were realized at room temperature. Then, the amounts of residual dye concentrations were measured using Visible Spectrophotometer at 530 and 618 nm for Safranine T (ST) and Brilliant Green (BG), respectively. All adsorption experiments were carried out for different depolymerization products (DP1, DP2, DP3, and DP4). Adsorption capacities of depolymerization products for both of dyes decrease with following order: DP2 > DP4 > DP1 > DP3. The maximum adsorption capacities for ST and BG onto DP2 sample were found to be 29 and 33 mg g−1, respectively. In addition, the adsorption kinetic results show that the pseudo‐second‐order kinetic model is more suitable than pseudo‐first‐order model for the adsorption of basic dyes onto DP samples. Adsorption data were evaluated using Langmuir and Freundlich adsorption isotherm models. The results revealed that the adsorption of basic dyes onto DP sample fit very well Langmuir isotherm model. In conclusion, the depolymerization products of post‐consumer PET bottles can be used as low cost adsorbent for the removal of basic dyes from wastewaters.
Dispersive Liquid–Liquid Microextraction for Preconcentration and Determination of Nickel in Water
Authors: Lemos Valfredo A. , dos Santos Vieira Emanuel V. , dos Santos Silva Eldevan , dos Santos Liz O.
Published: December 2011

A method for the determination of nickel in water was developed. The procedure involves preconcentration of nickel by using dispersive liquid–liquid microextraction. The Ni(II) ions were extracted in chloroform in the form of complex with the reagent 2‐(2′‐benzothiazolylazo)‐p‐cresol. Ethanol was used as the disperser solvent. After injection of the extracting mixture in a solution of nickel, a cloudy mixture was observed. A quick centrifugation induces phase separation and thus the settling of rich phase. The nickel content in the rich phase is measured by flame atomic absorption spectrometry. Under optimal conditions, the limit of detection and quantification obtained were 1.4 and 4.7 µg L−1, respectively. Some parameters used to characterize preconcentration systems, such as enrichment factor and consumption index were calculated and resulted in 29 and 0.34 mL, respectively. After optimization of variables and determination of analytical characteristics, the method was used for the analysis of certified reference materials (BCR‐713: wastewater, effluent and BCR‐414: plankton) and real water samples.
Effects of Rhizosphere Ventilation on Soil Enzyme Activities of Potted Tomato under Different Soil Water Stress
Authors: Niu Wen‐Quan , Zang Xuan , Jia Zong‐Xia , Shao Hong‐Bo
Published: December 2011

In order to improve the growing environment of root zone, and investigate the effects of different rhizosphere ventilation environments on soil enzyme activities, we supplied gas for potted tomato by air compressor, and set three irrigation levels (70–90% field capacity). Each irrigation level has different ventilation volume coefficient (0.4, 0.8, 1.2, and 1.6) with the reference standard as 50% soil porosity. The results showed that the changing trend of soil catalase, urease, and dehydrogenase activity showed the first increase and then the decrease in the tomato growth period, and activities of soil catalase, urease, and dehydrogenase under the ventilation treatment are higher than those of the non‐ventilation. When the irrigation level was 80% the field capacity and the ventilation coefficient was 0.8, the activities of three soil enzyme reached the highest value. Their activities of soil catalase, urease, and dehydrogenase were particularly sensitive to rhizosphere ventilation in fruit expanding process. Tomato had more dry matter accumulation and output under the ventilation treatment than that of the non‐ventilation. The results prove that rhizosphere ventilation can improve the potted tomato root zone environment, increase the soil enzyme activity, and promote the nutrients uptake, thus promoting plant growth and fruit output and improving soil quality.
Structures and Fragmentation of [Cu(Uracil‐H)(Uracil)]+ in the Gas Phase
Authors: Ali Osama Y. , Fridgen Travis D.
Published: December 2011

Complexes of copper (II) ions and uracil were studied using tandem mass spectrometry (Fourier transform ion cyclotron resonance, FTICR, mass spectrometry) including extensive isotopic labeling as well as theoretical calculations. Positive ion electrospray mass spectra of aqueous solutions of CuCl2 and uracil show that the [Cu(Ura‐H)(Ura)]+ ion is the most abundant ion even at low concentrations of uracil. Sustained off‐resonance irradiation collision‐induced dissociation (SORI‐CID) experiments show that the lowest energy decomposition pathway for [Cu(Ura‐H)(Ura)]+, surprisingly, is not the loss of uracil, but the loss of HNCO followed by HCN as the most abundant secondary fragmentation product. MSn studies identified primary, secondary and tertiary fragmentation products. Extensive isotopic labeling studies, as well as computational studies allowed for a detailed fragmentation scheme for the [Cu(Ura‐H)(Ura)]+ ion, beginning with the lowest energy structure.
Signaling by SHH rescues facial defects following blockade in the brain
Authors: Chong H. Jonathan , Young Nathan M. , Hu Diane , Jeong Juhee , McMahon Andrew P. , Hallgrimsson Benedikt , Marcucio Ralph S.
Published: December 2011

Background: The Frontonasal Ectodermal Zone (FEZ) is a signaling center in the face that expresses Sonic hedgehog (Shh) and regulates patterned growth of the upper jaw. Blocking SHH in the forebrain blocks Shh expression in the FEZ and creates malformations resembling holoprosencephaly (HPE), while inhibition of BMP signaling in the mesenchyme blocks FEZ formation and causes similar dysmorphology. Thus, the brain could regulate FEZ formation by SHH or BMP signaling, and if so, activating one of these pathways in the face might alleviate the effects of repression of SHH in the brain. Results: We blocked SHH signaling in the brain while adding SHH or BMP between the neural and facial ectoderm of the frontonasal process. When applied early, SHH restored Shh expression in the FEZ and significantly improved shape outcomes, which contrasts with our previous experiments that showed later SHH treatments have no effect. BMP‐soaked beads introduced early and late caused apoptosis that exacerbated malformations. Finally, removal of Smoothened from neural crest cells did not inhibit Shh expression in the FEZ. Conclusions: Collectively, this work suggests that a direct, time‐sensitive SHH signal from the brain is required for the later induction of Shh in the FEZ. We propose a testable model of FEZ activation and discuss signaling mediators that may regulate these interactions. Developmental Dynamics 241:247–256, 2012. © 2012 Wiley Periodicals, Inc.
Superparamagnetic Core‐Shell‐Type Fe3O4/Ru Nanoparticles as Catalysts for the Selective Hydrogenation of an Unconstrained α,β‐Unsaturated Ketone
Authors: Khan Farooq‐Ahmad , Süss‐Fink Georg
Published: December 2011

Superparamagnetic core‐shell‐type Fe3O4/Ru nanoparticles (particle size ca. 15 nm) synthesized by co‐precipitation, adsorption and reduction methods were found to selectively hydrogenate the carbon‐oxygen double bond in trans‐4‐phenyl‐3‐penten‐2‐one (conversion 100 %, selectivity > 90 %) with a catalytic turnover of 900 under mild reaction conditions (30 °C, 15 bar H2). The finely dispersed catalyst can be separated from the reaction mixture by using an external magnet, recycled, and reused without significant loss of activity and selectivity.
Enantioselective Annulation Reactions of Bisenolates Prepared Through Dearomatization Reactions of Aromatic and Heteroaromatic Diesters
Authors: Pérez‐Vázquez Jaime , Veiga Alberte X. , Prado Gustavo , Sardina F. Javier , Paleo M. Rita
Published: December 2011

A one‐pot, enantioselective strategy for the dearomatization–annulation of aromatic diesters to give a range of highly functionalized polycyclic molecules with excellent enantioselectivity is presented. This methodology is based on the reaction of bisenolates, prepared by treating aromatic diesters with trialkyltin lithium reagents, which involves a stanna‐Brook rearrangement, with 1,ω‐dihaloalkanes and other biselectrophiles. We have also developed experimental conditions for performing these reactions with substoichiometric amounts of the required tin reagent by in situ recycling of Me6Sn2 into Me3SnLi with excess lithium metal, and provide a study of the scope and limitations of this synthetic methodology.
Concerted functions of HDAC1 and microRNA‐574‐5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells
Authors: Meyers‐Needham Marisa , Ponnusamy Suriyan , Gencer Salih , Jiang Wenhui , Thomas Raquela J. , Senkal Can E. , Ogretmen Besim
Published: December 2011

Histone deacetylases (HDACs) and microRNAs (miRs) have pro‐survival roles, but the mechanism behind this is unclear. Repression of ceramide synthase 1 (CerS1), altering C18‐ceramide generation, was linked to drug resistance and metastasis. Here we report that the CerS1 promoter was repressed by HDAC1‐dependent inhibition of Sp1 recruitment to two specific GC‐boxes spanning the −177 and −139 region. Moreover, an alternatively spliced variant CerS1 mRNA (CerS1‐2) was detected mainly in cancer cells or primary tumour tissues compared to controls, which was targeted by miR‐574‐5p for degradation. A specific 3′UTR‐targeting site, localized within the retained intron between exons 6 and 7, was identified, and its mutation, or miR‐574‐5p knockdown prevented the degradation of CerS1‐2 mRNA. Interference with HDAC1 and miR‐574‐5p reconstituted CerS1‐2 expression and C18‐ceramide generation in multiple human cancer cell lines, which subsequently inhibited proliferation and anchorage‐independent growth. Accordingly, knockdown of CerS1 partially protected cancer cells from MS‐275/miR‐574‐5p siRNA‐mediated growth inhibition. Thus, these data suggest that the HDAC1/miR‐574‐5p axis might provide a novel therapeutic target to reconstitute tumour suppressor CerS1/ceramide signalling.
Spatial threshold exceedance analysis through marked point processes
Authors: Madrid A.E. , Angulo J.M. , Mateu J.
Published: December 2011

Indicators of recurrence, persistence and, in general, distribution patterns of extremal events defined by random field threshold exceedances provide relevant information on critical phenomena for risk assessment. Such indicators are directly related to geometrical properties describing the structure of the corresponding excursion sets. Given the intrinsic nature of the latter, spatial marked point processes provide a natural approach to analyze distribution patterns of such extremal events in relation to specific characteristics of interest. In this paper, on the basis of simulations from flexible models separating memory and fractality effects, the structure of threshold exceedances is analyzed in terms of various second‐order characteristics. In particular, the study is focused on the variations in size, boundary roughness, and distance heterogeneities in the components of excursion sets, as well as in clustering/inhibition patterns, depending on both the underlying model parameters and the threshold specifications. The methodology proposed is applied to a real data set on surface reflected solar radiation. Copyright © 2011 John Wiley & Sons, Ltd.
A hierarchical zero‐inflated Poisson regression model for stream fish distribution and abundance
Authors: Boone E.L. , Stewart‐Koster B. , Kennard M.J.
Published: December 2011

Ecologists are frequently confronted with the challenge of accurately modelling species abundance. However, this task requires one to deal with both presence/absence as well as abundance. Traditional Poisson regression models are not adequate when attempting to deal with both issues simultaneously. Zero‐inflated regression models have been proposed to deal with this problem with much success. We extend these models to incorporate both a multilevel hierarchical structure and spatial correlation. The model is illustrated using a dataset concerning the Hypseleotris galii (Fire‐tailed Gudgeon), a native species to eastern Australia. Copyright © 2011 John Wiley & Sons, Ltd.
Nonparametric methods for spatial regression. An application to seismic events
Authors: Francisco‐Fernández Mario , Quintela‐del‐Río Alejandro , Fernández‐Casal Rubén
Published: December 2011

Nonparametric regression estimation is a powerful tool to handle multidimensional data. When a dependent data set is analyzed, classical techniques need to be modified to provide useful results. In this work, different approximations to take the spatial dependence into account are exposed. A bandwidth selection technique that adjusts the generalized cross‐validation criterion for the effect of spatial correlation, in the case of bivariate local polynomial regression, is considered. Moreover, a bootstrap algorithm is designed to assess the variability of the estimated spatial maps, and also to estimate the probability of obtaining a response variable larger than or equal to a given threshold, for a specific point. A simulation study checks the validity of the presented approaches in practice. The broad applicability of the procedures is demonstrated on a data set of earthquakes in the Iberian Peninsula. Copyright © 2011 John Wiley & Sons, Ltd.
Wnt transmembrane signaling and long‐term spatial memory
Authors: Tabatadze Nino , Tomas Caroline , McGonigal Rhona , Lin Brian , Schook Andrew , Routtenberg Aryeh
Published: December 2011

Transmembrane signaling mechanisms are critical for regulating the plasticity of neuronal connections underlying the establishment of long‐lasting memory (e.g., Linden and Routtenberg (1989) Brain Res Rev 14:279–296; Sossin (1996) Trends Neurosci 19:215–218; Mayr and Montminy (2001) Nat Rev Mol Cell Biol 2:599–609; Chen et al. (2011) Nature 469:491–497). One signaling mechanism that has received surprisingly little attention in this regard is the well‐known Wnt transmembrane signaling pathway even though this pathway in the adult plays a significant role, for example, in postsynaptic dendritic spine morphogenesis and presynaptic terminal neurotransmitter release (Inestrosa and Arenas (2010) Nat Rev Neurosci 11:77–86). The present report now provides the first evidence of Wnt signaling in spatial information storage processes. Importantly, this Wnt participation is specific and selective. Thus, spatial, but not cued, learning in a water maze selectively elevates the levels in hippocampus of Wnt 7 and Wnt 5a, but not the Wnt 3 isoform, indicating behavioral selectivity and isoform specificity. Wnt 7 elevation is subfield‐specific: granule cells show an increase with no detectable change in CA3 neurons. Wnt 7 elevation is temporally specific: increased Wnt signaling is not observed during training, but is seen 7 days and, unexpectedly, 30 days later. If the Wnt elevation after learning is activity‐dependent, then it may be possible to model this effect in primary hippocampal neurons in culture. Here, we evaluate the consequence of potassium or glutamate depolarization on Wnt signaling. This represents, to our knowledge, the first demonstration of an activation‐dependent elevation of Wnt levels and surprisingly an increased number of Wnt‐stained puncta in neurites suggestive of trafficking from the cell body to neuronal processes, probably dendrites. It is proposed that Wnt signaling pathways regulate long‐term information storage in a behavioral‐, cellular‐, and isoform‐specific manner. © 2011 Wiley Periodicals, Inc.
Dorsal versus ventral hippocampal contributions to trace and contextual conditioning: Differential effects of regionally selective nmda receptor antagonism on acquisition and expression
Authors: Czerniawski Jennifer , Ree Fredrick , Chia Chester , Otto Tim
Published: December 2011

The dorsal and ventral subregions of the hippocampus likely play dissociable roles in some forms of learning. For example, we have previously demonstrated that temporary inactivation of ventral, but not dorsal, hippocampus dramatically impaired the acquisition of trace fear conditioning, while temporary inactivation of dorsal, but not ventral, hippocampus impaired spatially guided reinforced alternation (Czerniawski et al. (2009) Hippocampus 19:20–32). Importantly, emerging data suggest that lesions, temporary inactivation, and NMDA receptor antagonism within these subregions can produce quite different patterns of behavioral effects when administered into the same region. Specifically, while neither lesions nor temporary inactivation of dorsal hippocampus impair the acquisition of trace fear conditioning, learning in this paradigm is severely impaired by pre‐training administration of the NMDA receptor antagonist dl‐2‐phosphonovaleric acid (APV) in dorsal hippocampus; the effect of NMDA receptor antagonism within ventral hippocampus on the acquisition and expression of trace conditioning, or on learning in general, has not yet been systematically explored. The present study extends our previous work examining the differential effect of lesions or inactivation of the dorsal and ventral hippocampal subregions by systematically examining the effect of regionally selective pre‐training or pre‐testing administration of APV on the acquisition and expression of trace and contextual fear conditioning. The results of these studies demonstrate that while pre‐training NMDA receptor antagonism within either the dorsal or ventral subregion of the hippocampus impaired the acquisition of both trace and contextual conditioning, pre‐testing NMDA receptor antagonism within ventral, but not dorsal, hippocampus impaired the expression of previously‐acquired trace and contextual fear conditioning. These data suggest that selectively manipulating the integrity of individual subregions may result in compensatory mechanisms that can support learning, and that NMDA‐dependent plasticity within both dorsal and ventral hippocampus is normally required for the acquisition and maintenance of memory in trace and contextual fear conditioning. © 2011 Wiley Periodicals, Inc.
Influence of heterogeneity on unsaturated hydraulic properties (2) – percentage and shape of heterogeneity
Authors: Wu Cheng‐Mau , Chen Pen‐Yuan , Chen Chu‐Hui , Hsu Nien‐Sheng , Wen Jet‐Chau
Published: December 2011

In subsurface porous media, the soil water retention curve (WRC) and unsaturated hydraulic conductivity curve (UHC) are two important soil hydraulic property curves. Spatial heterogeneity is ubiquitous in nature, which may significantly affect soil hydraulic property curves. The main theme of this paper is to investigate how spatial heterogeneities, including their arrangements and amounts in soil flumes, affect soil hydraulic property curves. This paper uses a two‐dimensional variably saturated flow and solute transport finite element model to simulate variations of pressure and moisture content in soil flumes under a constant head boundary condition. To investigate the behavior of soil hydraulic property curves owing to variations of heterogeneities and their arrangements as well, cases with different proportions of heterogeneities are carried out. A quantitative evaluation of parameter variations in the van Genuchten model (VG model) resulting from heterogeneity is presented. Results show that the soil hydraulic properties are strongly affected by variations of heterogeneities and their arrangements. If the pressure head remains at a specific value, the soil moisture increases when heterogeneities increase in the soil flumes. On the other hand, the unsaturated hydraulic conductivity decreases when heterogeneities increase in the soil flumes under a constant pressure head. Moreover, results reveal that parameters estimated from both WRC and UHC also are affected by shapes of heterogeneity; this indicates that the parameters obtained from the WRC are not suitable for predicting the UHC of different shapes in heterogeneous media. Copyright © 2011 John Wiley & Sons, Ltd.
Organ differences in the impact of p27kip1 deficiency on carcinogenesis induced by N‐methyl‐N‐nitrosourea
Authors: Ogawa Kumiko , Murasaki Toshiya , Sugiura Satoshi , Nakanishi Makoto , Shirai Tomoyuki
Published: December 2011

To evaluate the impact of p27 on carcinogenesis in various organs, N‐methyl‐N‐nitrosourea (MNU), a direct‐acting alkylating agent, was given to p27 knock‐out mice. Groups of 20–40 male and female mice with null, hetero‐ or wild‐type p27 alleles were given drinking water containing 240 ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27‐null males as compared with both wild‐ and hetero‐type animals. Moreover, in both p27+/+ and p27+/− cases, the rates for p27‐positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27‐positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU‐induced carcinogenesis. Copyright © 2011 John Wiley & Sons, Ltd.
Chlorpyrifos exposure reduces reproductive capacity owing to a damaging effect on gametogenesis in the nematode Caenorhabditis elegans
Authors: Ruan Qin‐Li , Ju Jing‐Juan , Li Yun‐Hui , Li Xiao‐Bo , Liu Ran , Liang Ge‐Yu , Zhang Juan , Pu Yue‐Pu , Wang Da‐Yong , Yin Li‐Hong
Published: December 2011

Previous studies have revealed that chlorpyrifos exposure adversely affects the reproductive capacity of male rodents. The present study investigated the reproductive toxicity of chlorpyrifos exposure and possible related mechanisms using the nematode Caenorhabditis elegans. L4 nematode larvae were exposed to chlorpyrifos at concentrations of 0.003, 0.03, 0.3 and 3.0 mg l−1 for different durations. In addition to decreased brood size, reduced spermatid size, increased percentage of abnormal spermatids, suppressed spermatid activation and motility of sperm, damaged oocyte morphology, increased numbers of apoptotic cells and unfertilized oocytes were observed in nematodes exposed to various concentrations of chlorpyrifos. Moreover, expression patterns of the genes spe‐10, spe‐15, fer‐1, prg‐1, glp‐1, mlh‐1, cyb‐3, ced‐3, ced‐4 and ced‐9 (which are associated with spermatid size, spermatid activation and morphology, oocyte morphology, oocyte function, and apoptosis) were altered after chlorpyrifos exposure. Therefore, chlorpyrifos exposure may adversely affect fertility in nematodes by influencing both spermatogenesis and oogenesis. Alterations in the expression patterns of genes involved in gametogenesis may explain the corresponding changes in gametogenesis in nematodes exposed to chlorpyrifos. Hence, the model organism Caenorhabditis elegans is recommended for assessment of reproductive toxicity relating to gametogenesis. Copyright © 2011 John Wiley & Sons, Ltd.
Rapid acquisition of Raman spectral maps through minimal sampling: applications in tissue imaging
Authors: Rowlands Christopher J. , Varma Sandeep , Perkins William , Leach Iain , Williams Hywel , Notingher Ioan
Published: December 2011

A method is presented for acquiring high‐spatial‐resolution spectral maps, in particular for Raman micro‐spectroscopy (RMS), by selectively sampling the spatial features of interest and interpolating the results. This method achieves up to 30 times reduction in the sampling time compared to raster‐scanning, the resulting images have excellent correlation with conventional histopathological staining, and are achieved with sufficient spectral signal‐to‐noise ratio to identify individual tissue structures. The benefits of this selective sampling method are not limited to tissue imaging however; it is expected that the method may be applied to other techniques which employ point‐by‐point mapping of large substrates. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the effect of a variation of the force field, spatial boundary condition and size of the QM region in QM/MM MD simulations
Authors: Meier Katharina , Thiel Walter , van Gunsteren Wilfred F.
Published: December 2011

During the past years, the use of combined quantum–classical, QM/MM, methods for the study of complex biomolecular processes, such as enzymatic reactions and photocycles, has increased considerably. The quality of the results obtained from QM/MM calculations is largely dependent on five aspects to be considered when setting up a molecular model: the QM Hamiltonian, the MM Hamiltonian or force field, the boundary and coupling between the QM and MM regions, the size of the QM region and the boundary condition for the MM region. In this study, we systematically investigate the influence of a variation of the molecular mechanics force field and the size of the QM region in QM/MM MD simulations on properties of the photoactive part of the blue light photoreceptor protein AppA. For comparison, we additionally performed classical MD simulations and studied the effect of a variation of the type of spatial boundary condition. The classical boundary conditions and the force field used in a QM/MM MD simulation are shown to have non‐neglegible effects upon the structural and energetic properties of the protein which makes it advisable to minimize computational artifacts in QM/MM MD simulations by application of periodic boundary conditions and a thermodynamically calibrated force field. A comparison of the structural and energetic properties of MD simulations starting from two alternative, different X‐ray structures for the blue light utilizing flavin protein in its dark state indicates a slight preference of the two force fields used for the so‐called Anderson structure over the Jung structure. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012
Thermodynamics and kinetics of large‐time‐step molecular dynamics
Authors: Rao Francesco , Spichty Martin
Published: December 2011

Molecular dynamics (MD) simulations provide essential information about the thermodynamics and kinetics of proteins. Technological advances in both hardware and algorithms have seen this method accessing timescales that used to be unreachable only few years ago. The quest to simulate slow, biologically relevant macromolecular conformational changes, is still open. Here, we present an approximate approach to increase the speed of MD simulations by a factor of ∼4.5. This is achieved by using a large integration time step of 7 fs, in combination with frozen covalent bonds and look‐up tables for nonbonded interactions of the solvent. Extensive atomistic MD simulations for a flexible peptide in water show that the approach reproduces the peptide's equilibrium conformational changes, preserving the essential properties of both thermodynamics and kinetics. Comparison of this approximate method with state‐of‐the‐art implicit solvation simulations indicates that the former provides a better description of the underlying free‐energy surface. Finally, simulations of a 33‐residue peptide show that these fast MD settings are readily applicable to investigate biologically relevant systems. © 2011 Wiley Periodicals, Inc.
A Novel and Efficient Synthesis of Dronedarone Hydrochloride, an Antiarrhythmic Drug Substance
Authors: Mohanarangam Saravanan , Satyanarayana Bollikonda , Elati Chandrashekar R. , Vijayabhaskar Bolugoddu , Pratap Reddy Padi
Published: December 2011

A novel and efficient synthesis of dronedarone hydrochloride starting from 2‐n‐butyl‐5‐nitrobenzofuran by employing mild and selective reaction conditions is described. The synthetic approach is operationally simple and suitable for industrial application.
Predicting the Activity of Peptides Based on Amino Acid Information
Authors: Wang Xiao‐Yu , Wang Juan , Hu Yong , Lin Yong , Shu Mao , Wang Li , Cheng Xiao‐Ming , Lin Zhi‐Hua
Published: December 2011

A set of amino acid descriptors including hydrophobic, stereo and electrical properties were applied to construct quantitative structure‐activity relationships (QSARs) models of three peptides datasets (angiotensin‐converting enzyme inhibitor dipeptides, bactericidal peptides and oxytocin peptides) with stepwise multiple regression combined partial least squares regression (SMR‐PLS). The results of QASRs models are very robust, with multiple correlation coefficients (R2), and cross validation (Q2) equal to 0.687, 0.671; 0.977, 0.890 and 0.950, 0.802 respectively. The robust models show the descriptors can be further expanded for polypeptides and serve as a useful quantitative tool for the rational drug design and discovery.