bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the technical and clinical performance of the Elecsys® HBsAg II assay with the Architect®, AxSym®, and Advia® Centaur HBsAg screening assays
Authors: Louisirirotchanakul S. , Khupulsup K. , Akraekthalin S. , Chan K.P. , Saw S. , Aw T.C. , Cho D.‐H. , Shin M.‐G. , Lim J.
Published: March 2010

South East Asia has some of the highest prevalence rates of hepatitis B virus (HBV) infection (≥8%) in the world, and the emergence of hepatitis B surface antigen (HBsAg) mutant strains is a growing problem. Assays with the highest levels of sensitivity, including mutant detection, should be used for routine HBsAg screening. In this large multicenter study, the clinical and technical performance of the fully automated Elecsys HBsAg II assay was compared with the Architect, AxSYM, and Advia Centaur HBsAg assays for HBsAg screening. Nine laboratories (three each from Thailand, Korea, and Singapore) compared the Elecsys HBsAg II assay with their routine HBsAg screening assay against a range of stored and routine clinical samples, including recombinant mutants. The Elecsys HBsAg II assay demonstrated equivalent sensitivity and specificity to the Architect HBsAg assay. However, the Elecsys HBsAg II assay recognized a native mutant sample (L94S, L97V, L98V, T123A) that the Architect HBsAg assay failed to detect. The AxSYM and Advia Centaur HBsAg assays appeared less sensitive for the detection of early HBV infection and also failed to detect some of the recombinant mutant strains. There was almost complete agreement between the Elecsys HBsAg II assay and comparator assays with respect to routine serum samples. The results of this study demonstrate that the Elecsys HBsAg II assay is a highly sensitive and specific screening assay for HBsAg and detects reliably the most important and clinically relevant HBV mutants and genotypes. It is suitable for routine HBsAg screening in Asia. J. Med. Virol. 82: 755–762, 2010. © 2010 Wiley‐Liss, Inc.
Mechanism of HIV‐1‐TAT induction of interleukin‐1β from human monocytes: Involvement of the phospholipase C/protein kinase C signaling cascade
Authors: Yang Yongbo , Wu Jianguo , Lu Yuanan
Published: March 2010

Human immunodeficiency virus TAT plays an important role in the disregulation of cytokine production associated with the neurological disorders that follow HIV infection. IL‐1β is one of the important inflammatory cytokines secreted by immune‐activated monocytes/macrophages. Previous reports have shown that extracellular TAT stimulates IL‐1β expression in monocytes/macrophages. However, little is known about the mechanisms and possible TAT‐responsive elements within the IL‐1β promoter. The present study shows that TAT increases the production of IL‐1β in human monocytes; PLC‐PKC pathway‐dependent phosphorylation of p44/42 and JNK MAP kinases participates partially in IL‐1β induction by TAT; specific C/EBP and NF‐κB transcription factor binding elements within the IL‐1β promoter are involved in TAT regulation of IL‐1β production. This study identifies a signaling mechanism for HIV‐1‐induced IL‐1β production in human monocytes that may be involved in the neuropathogenesis of HIV‐associated dementia. J. Med. Virol. 82: 735–746, 2010. © 2010 Wiley‐Liss, Inc.
Norovirus GII‐4 2006b variant circulating in patients with acute gastroenteritis in Thailand during a 2006–2007 study
Authors: Kittigul Leera , Pombubpa Kannika , Taweekate Yuthana , Diraphat Pornphan , Sujirarat Dusit , Khamrin Pattara , Ushijima Hiroshi
Published: March 2010

Noroviruses (NoVs) are recognized as a significant cause of acute gastroenteritis in children and adults. A 14‐month study, from January 2006 to February 2007, was undertaken in a hospital in Thailand to determine the prevalence and genetic characterization of NoVs in patients of all ages with acute gastroenteritis. Based on reverse transcription‐nested polymerase chain reaction (RT‐nested PCR), NoVs were detected in 122 of 273 (44.7%) collected stool samples. Of the 122 NoV‐positive samples, 28 (23%) belonged to GI, 79 (64.8%) belonged to GII, and 15 (12.2%) were mixed infections of GI and GII strains. Three NoV GI‐positive and 42 NoV GII‐positive samples were characterized successfully by DNA sequencing of the RT‐nested PCR products and phylogenetic analysis. For NoV GI, two genotypes were identified: GI‐2 (one sample) and GI‐6 (two samples). NoV GII could be classified further into five distinct genotypes: GII‐2 (1 sample), GII‐3 (3 samples), GII‐4 (14 samples), GII‐6 (3 samples), and GII‐17 (2 samples), and one unclassified genotype (19 samples). All NoV GII‐4 strains showed 88–98% nucleotide identity with NoV GII‐4 2006b variants reported worldwide. Among genotypes of NoV characterized, one co‐infected stool sample exhibited NoVs GI‐6 and GII‐4 2006b. This study suggests that there is an important role of NoVs as etiologic agents in patients with acute gastroenteritis. The predominant circulating genotype of NoV infections is GII‐4 2006b variant. J. Med. Virol. 82: 854–860, 2010. © 2010 Wiley‐Liss, Inc.
B2 attenuates polyglutamine‐expanded androgen receptor toxicity in cell and fly models of spinal and bulbar muscular atrophy
Authors: Palazzolo Isabella , Nedelsky Natalia B. , Askew Caitlin E. , Harmison George G. , Kasantsev Aleksey G. , Taylor J. Paul , Fischbeck Kenneth H. , Pennuto Maria
Published: March 2010

Expanded polyglutamine tracts cause neurodegeneration through a toxic gain‐of‐function mechanism. Generation of inclusions is a common feature of polyglutamine diseases and other protein misfolding disorders. Inclusion formation is likely to be a defensive response of the cell to the presence of unfolded protein. Recently, the compound B2 has been shown to increase inclusion formation and decrease toxicity of polyglutamine‐expanded huntingtin in cultured cells. We explored the effect of B2 on spinal and bulbar muscular atrophy (SBMA). SBMA is caused by expansion of polyglutamine in the androgen receptor (AR) and is characterized by the loss of motor neurons in the brainstem and spinal cord. We found that B2 increases the deposition of mutant AR into nuclear inclusions, without altering the ligand‐induced aggregation, expression, or subcellular distribution of the mutant protein. The effect of B2 on inclusions was associated with a decrease in AR transactivation function. We show that B2 reduces mutant AR toxicity in cell and fly models of SBMA, further supporting the idea that accumulation of polyglutamine‐expanded protein into inclusions is protective. Our findings suggest B2 as a novel approach to therapy for SBMA. © 2010 Wiley‐Liss, Inc.
Low levels of mutant ubiquitin are degraded by the proteasome in vivo
Authors: van Tijn Paula , Verhage Marian C. , Hobo Barbara , van Leeuwen Fred W. , Fischer David F.
Published: March 2010

The ubiquitin‐proteasome system fulfills a pivotal role in regulating intracellular protein turnover. Impairment of this system is implicated in the pathogenesis of neurodegenerative diseases characterized by ubiquitin‐ containing proteinaceous deposits. UBB+1, a mutant ubiquitin, is one of the proteins accumulating in the neuropathological hallmarks of tauopathies, including Alzheimer's disease, and polyglutamine diseases. In vitro, UBB+1 properties shift from a proteasomal ubiquitin‐fusion degradation substrate at low expression levels to a proteasome inhibitor at high expression levels. Here we report on a novel transgenic mouse line (line 6663) expressing low levels of neuronal UBB+1. In these mice, UBB+1 protein is scarcely detectable in the neuronal cell population. Accumulation of UBB+1 commences only after intracranial infusion of the proteasome inhibitors lactacystin or MG262, showing that, at these low expression levels, the UBB+1 protein is a substrate for proteasomal degradation in vivo. In addition, accumulation of the protein serves as a reporter for proteasome inhibition. These findings strengthen our proposition that, in healthy brain, UBB+1 is continuously degraded and disease‐related UBB+1 accumulation serves as an endogenous marker for proteasomal dysfunction. This novel transgenic line can give more insight into the intrinsic properties of UBB+1 and its role in neurodegenerative disease. © 2010 Wiley‐Liss, Inc.
Effect of thermal adaptation on seasonal outdoor thermal comfort
Authors: Lin Tzu‐Ping , de Dear Richard , Hwang Ruey‐Lung
Published: March 2010

Thermal perceptions and preferences of individuals outdoors cannot be entirely explained by the energy balance of the human body. They are also affected by psychological and behavioural factors or the so‐called thermal adaptation. To examine the effect of thermal adaptation on seasonal outdoor thermal comfort, 1644 interviews with concurrent micrometeorological measurements were conducted outdoors in central Taiwan. Results indicate a deviation of 1.3 °C standard effective temperature (SET*) in neutral temperatures between hot and cool seasons, and a deviation of 1.8 °C SET* in preferred temperature between hot and cool seasons. Additionally, although subjects' temperature and sunshine preferences were highly correlated with SET*, they diverged between seasons for identical SET* exposures in the two seasons. Analysis reveals that people's thermal perceptions were strongly related to the air temperature (Ta) and mean radiant temperature (Tmrt), but not significant to air speed and air humidity. These results demonstrate that thermal adaptation markedly influences seasonal outdoor thermal comfort, knowledge of which may be useful in the planning and design of outdoor environments in hot–humid regions. Copyright © 2010 Royal Meteorological Society
An East Coast winter storm precipitation climatology
Authors: Frankoski Nicholas J. , DeGaetano Arthur T.
Published: March 2010

Using a previously compiled climatology of East Coast winter storms (ECWS), an ECWS precipitation climatology was developed for the eastern United States from 1951–1952 to 2005–2006, using an automated procedure. Non‐ECWS precipitation that may have occurred during ECWS events was excluded through the development of a decision process based on knowledge of the characteristics of extratropical storms and aided by ECWS case study analyses. The main components used by this decision process were the location of precipitation and pressure gradients, and the presence of additional cyclones, not meeting the ECWS criteria. A sensitivity analysis of the ECWS precipitation climatology was conducted, which considered the change in the climatology if non‐ECWS precipitation was not excluded by the decision process. The highest average percentages of snowfall from ECWS occur in the Middle Atlantic and southern New England regions. These heavily populated metropolitan areas typically receive 45% of snowfall from ECWS. The highest average percentages of annual precipitation from ECWS are generally 20–25% and are located along the East Coast from Virginia northward to Maine. For the metropolitan centres of the Northeast, and for northern New England, El Niño years seem to indicate above average precipitation and snowfall amounts from ECWS, as well as an above average overall percentage of precipitation and snowfall from ECWS. Copyright © 2010 Royal Meteorological Society
A New Approach for in vitro Imaging of Breast Cancer Cells by Anti‐Metadherin Targeted PVA‐Pyrene
Authors: Medine E. Ilker , Odaci Dilek , Gacal Bahadir N. , Gacal Burcin , Sakarya Serhan , Unak Perihan , Timur Suna , Yagci Yusuf
Published: March 2010

Poly(vinyl alcohol)‐pyrene‐anti‐metadherin (PVA‐Py‐(Anti‐MTDH)), a novel antibody based water soluble probe containing both fluorescent and target sites in the structure for in vitro imaging of breast cancer cells is reported here. Since breast cancer cells have an excess of MDTH protein expressed on the surface, a PVA‐Py prepared by “Click chemistry” approach is targeted by Anti‐MTDH antibody and applied to the MCF‐7 cell line. After characterization, the designed architecture was evaluated in terms of cell incorporation efficiency and compared with a non‐targeted structure (PVA‐Py). Atomic force microscopy (AFM) and fluorescence microscopy images of cells after incubation of the probe molecules were also obtained to monitor the interaction of the probes with the cancerous cells.

magnified image
New Amphiphilic Conjugates of Mono‐ and Bis(carboxy)‐PEG2,000 Polymers with Lipoamino Acids as Surface Modifiers of Colloidal Drug Carriers
Authors: Pignatello Rosario , Pantò Valentina , Basile Livia , Impallomeni Giuseppe , Ballistreri Alberto , Pistarà Venerando , Craparo Emanuela F. , Puglisi Giovanni
Published: March 2010

Linking PEG2,000 polymers ending in 1 or 2 carboxylic groups to lipoamino acids (LAAs) gives mono‐ and homo‐disubstituted PEG‐LAA conjugates. They show an identical solubility to parent PEGs in water and organic solvents. By DSC the degree and depth of interaction of these conjugates with a biomembrane model is studied, gaining information about their future incorporation in drug‐loaded nanocarriers. The ability of PEG‐LAA conjugates to adopt an ordinate arrangement on the surface of particles and efficiently cover them is demonstrated, compared to DSPE‐PEG, by measuring the zeta potential values of negatively charged liposomes prepared in their presence.

magnified image
Organostibine‐Mediated Controlled/Living Radical Polymerization of Methyl Methacrylate and Styrene in Ionic Liquidsa
Authors: Cui Guoyou , Li Jun , Liu Zhengping , Dou Junyan
Published: March 2010

Organostibine‐mediated controlled/living radical polymerization of MMA was successfully achieved in room temperature ionic liquids (RTILs) [bmim]Tf2N and [bmim]PF6. The ln([M]0/[M]) increased linearly with increasing reaction time. The number‐average molecular weights of PMMA increased linearly with conversion, and the polydispersity indices were less than 1.15 and narrower in RTILs than in bulk. The living characters of SBRP were further demonstrated by chain extension of PMMA and preparation of copolymer PMMA‐b‐PS in RTILs. Recycle and reuse of RTILs were efficient with well‐controlled PMMA produced in the recycled RTILs. SBRP of St in RTILs was also discussed. The polymerization could be controlled only at low St conversion due to the heterogeneous reaction.

magnified image
Poly(p‐phenylenevinylene) Derivatives with Defined Conjugation Segments and Post‐Polymerization Modification with Sterically Enshrouded Chromophores
Authors: Buelt Ashley A. , Colberg Allison J. , Dennis Ashlyn E. , Jecen Kristine M. , Morgan Brad P. , Smith Rhett C.
Published: March 2010

Two poly(p‐phenylenevinylene) derivative alternating copolymers (P1‐I and P2‐I) have been prepared featuring iodo substituents and m‐phenylene units to periodically disrupt conjugation. P1‐I was derivatized with various chromophores to yield P1a‐f. In P1a‐f, the chromophores were positioned within a sterically protected pocket shielding them from interchain interactions so that intrachain interactions between polymer segments could be observed. Solution and film properties of polymers have been examined. Post‐polymerization chromophore modification leads to new photophysical properties such as intramolecular charge transfer and fluorescent resonance energy transfer processes in some cases.

magnified image
To try or to calculate – Operating fatigue strength and zero fracture line
Authors: Köhler J.
Published: March 2010

Eine Prognose für die Betriebsfestigkeit von Bauteilen in der Entwicklungsphase wird erstellt. An einem Beispiel mit einfachen Lastsequenzen wird die Entwicklung der Bruchwahrscheinlichkeit bis zur Nullbruchlinie dargestellt. Die Nullbruchlinie wird als Grenzlinie der zulässigen Ausfallhäufigkeit definiert.

During the design phase of products a forecasting of operating strength is calculated. The development of the fracture probability until reaching the zero fracture line is shown in an example with simple load sequences. The zero fracture line is defined as the border line of acceptable failure frequency.
Effect of PVD process parameters on nucleation and structure of CrN layers
Authors: Slomski E. M. , Scheerer H. , Troßmann T. , Berger C.
Published: March 2010

Störstellen in Bauteiloberflächen wirken sich negativ auf die Schichtnukleation bei PVD‐Schichtsystemen aus. Sie können im anschließenden Schichtwachstum zu Defekten in der Schichtstruktur führen. Die Konsequenz ist eine Minderung der lokalen Haftfestigkeit, höhere Reibwerte und Fehlstellen in der Schicht. Diese begünstigen in korrosiven Medien die Entstehung von Korrosion. CrN‐Schichten sind für ihre hohe Härte und ihre guten Verschleißeigenschaften bekannt. Zudem weisen sie eine bessere Korrosionsbeständigkeit als Titan basierte Nitride auf. Die strukturellen und mechanischen Eigenschaften dieser Schichtsysteme können unter anderem durch die Veränderung der Biasspannung und des Stickstoffgehalts während des Schichtwachstums beeinflusst werden. Durch gezielte Variation dieser Beschichtungsparameter wurden CrN‐Schichten mit den bevorzugten Kristallgitterstrukturen (111) und (200) abgeschieden, mit dem Ziel deren Abdeckungsfähigkeit von Störstellen zu untersuchen. Für die gezielte Untersuchung und Vergleichbarkeit der Ergebnisse wurden Vickerseindrücke HV 0,5 als bewusst gestaltete Störstellen auf der Grundwerkstoffoberfläche aufgebracht. Als Grundwerkstoff diente niedriglegierter Stahl (100Cr6). Die Kristallgitterorientierungen der abgeschiedenen Schichten wurden zunächst anhand von röntgenographischen Messungen (XRD) identifiziert. Anhand weiterer rasterelektronenmikroskopischer Aufnahmen (REM) wurden die bewusst erzeugten Störstellen in Form von Vickerseindrücken und Ritzspuren sichtbar gemacht, mit dem Ziel die Schichtqualität und die Mikrostruktur um Fehlstellen zu beschreiben.

Imperfections on substrate surfaces can cause growth defects in hard coatings prepared by magnetron sputtering, leading to local loss of adhesion, higher friction, voids and corrosion at coating defects. CrN‐coatings are known for their high hardness and good wear resistance. In addition CrN‐coatings are better corrosion resistant than Ti based nitrides. The structure and the mechanical properties of those coatings can be influenced by varying bias voltage and gas flow during film growth. Due to variation of those parameters CrN‐coatings were deposited with preferred crystallized lattice orientations (111) and (200). The main objective of investigation is the potential to cover imperfections. Vickers indentations (HV 0.5) were applied as designed imperfections. As base material low alloyed steel was used (100Cr6). At first crystallized lattice orientations were identified by X‐ray diffraction (XRD). Further scanning electron microscope analysis (SEM) was applied to identify and study crystallized lattice orientations near those imperfections.
Effect of quenching temperature on microstructure and performance of Al‐bearing cast boron steel
Authors: Hou J. , Fu H. , Lei Y. , Yi D. , Xing J.
Published: March 2010

The effects of quenching temperature on microstructure and performance of Al‐bearing cast boron steel (ACBS) containing 0.25–0.45%C, 1.5–1.8%B and 1.4–1.6%Al were investigated by means of the optical microscopy (OM), the scanning electron microscopy (SEM), X‐ray diffraction (XRD), Rockwell hardness and Vickers micro‐hardness tester. The results show that the solidification structures of cast steel consist of high hardness boride, ferrite, pearlite and a small quantity of martensite when 1.5–1.8%B and 1.4–1.6%Al are added into the carbon steel. The metallic matrix of ACBS changes into single martensite from the mixed structure of ferrite, pearlite and martensite along with the increase of quenching temperature. The increase of quenching temperature also leads to the transformation of boride from continuous shape to isolated shape. Moreover, the micro‐hardness of matrix and macroscopical hardness increase with the increase of quenching temperature. When the quenching temperature excels 1000°C, the hardness has a slight decrease. ACBS has good comprehensive properties after heat treatment at 1000°C.
Corrosion analysis of a heat‐exchanger in epichlorophydrin production process
Authors: Wang L. L. , Chen H. J.
Published: March 2010

The failure of E230 heat‐exchanger in the production of epichlorophydrin (ECH) form dichloropropanol (DCP) was analyzed and material solutions are recommended. The analysis indicates that the combined effect of stress corrosion cracking (SCC) and dissolution of HCl and HClO in the DCP mixture solution in the E230 heat‐exchanger chamber to the tube surface and chamber wall contributes to the failure of heat‐exchanger tubes and the perforation of E230 heat‐exchanger chamber. It is recommended to reduce the content of Cl– in the DCP mixture solution and to increase its pH. Titanium, Type 316L stainless steel (SS), and electroless Ni‐P coating can be considered as the candidate materials. Also, the process can be divided into two series step with one step heating the temperature from 30°C to 60°C, and the other step heating the temperature from 60°C to 90°C. For the lower temperature step, the Type 316L SS or electroless Ni‐P coating can be used. For the higher temperature step, Titanium can be applied. Periodic cleaning of the tube surface and chamber inner surface deposit is necessary. Intensifying the in‐service inspection and monitoring is also required.
Experimental investigation on heat treatment of a high‐speed steel for hot rolling roll mill
Authors: Li X. , Du Z. , Fu H. , Feng Z. , Zhao H.
Published: March 2010

The authors describe the researching results to optimise the hardening and tempering of the high carbon high‐speed steel for rolls containing 2.38%C, 5.07%V, 6.34%Mo, 5.09%Cr, 1.20%Ni, 1.17%Nb, 0.09%Ti and 0.05%RE by means of light optical microscope (LOM), scanning electron microscope (SEM), backscattered electron image (BSE), X‐ray diffraction (XRD), and hardness, tensile strength, impact toughness and wear testers. The results show that the microstructure of above casting high‐speed steel is given by a tempered martensitic matrix surrounded by eutectic carbides. Casting high‐speed steel has higher hardness quenching at 1280 K–1340 K, and it has higher hardness, tensile strength, impact toughness, and abrasive wear resistance tempering at 793 K–833 K. The comprehensive properties of casting high‐speed steel is the best while air‐cooling quenching about 1340 K and tempering about 813 K.
A novel splice variant of the β‐tropomyosin (TPM2) gene in prostate cancer
Authors: Assinder Stephen J. , Au Edith , Dong Qihan , Winnick Clare
Published: March 2010

Decreased expression of high molecular weight isoforms of tropomyosin (Tm) is associated with oncogenic transformation and is evident in cancers, with isoform Tm1 seemingly an important tumor suppressor. Tm1 expression in prostate cancer has not previously been described. In this study, while demonstrating suppressed levels of Tm1 in the prostate cancer cell lines LNCaP, PC3, and DU‐145 compared to normal prostate epithelial cell primary isolates (PrEC), a novel splice variant of the TPM2 gene was identified. Quantitative RT‐PCR determined significantly greater levels of the transcript variant in all three prostate cancer cell lines than in normal prostate epithelial cells. Characterization of this novel variant demonstrated it to include exon 6b, previously thought unique to the muscle‐specific β‐Tm isoform, with an exon arrangement of 1–2–3–4–5–6a–6b–7–8–10. Inclusion of exon 6b introduces a premature stop codon directly following the 6a–6b exon boundary. Western blot analysis demonstrated the presence of a truncated protein in prostate cancer cell lines that was absent in normal prostate epithelial cells. It is hypothesized that this truncated protein will result in suppression of Tm1 polymer formation required for actin filament association. The lack of Tm polymer–actin association will result in loss of the stable actin microfilament organization and stress fiber formation, a state associated with cell transformation. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.
Quantifying uncertainty using robustness analysis in the application of ORESTE to sewer rehabilitation projects prioritization—Brussels case study
Authors: Ana Eliseo , Bauwens Willy , Broers Olivier
Published: March 2010

Sewer systems are considered extremely important components of the urban water infrastructure due to their function and capital‐intensive nature. These systems, however, have been undergoing aging and deterioration, thus needing repair or rehabilitation. Historically, the budgets for sewer rehabilitation are often scarce and too limited to address the requirements, requiring utility managers to prioritize the competing projects. In this paper, the application of ORESTE to the prioritization of sewer rehabilitation projects for the Brussels, Belgium network was demonstrated. The 43 proposed projects were ranked based on a set of 16 criteria. In addition, a methodology was introduced to investigate the robustness of the ORESTE solution. The inclusion of the robustness analysis into the technique allowed for the quantification of the uncertainties associated with the priority rankings. This type of information is very important in developing confidence among decision makers as to their decision on the priority ranking of sewer rehabilitation projects. Copyright © 2010 John Wiley & Sons, Ltd.
6‐Shogaol is more effective than 6‐gingerol and curcumin in inhibiting 12‐O‐tetradecanoylphorbol 13‐acetate‐induced tumor promotion in mice
Authors: Wu Hou , Hsieh Min‐Chi , Lo Chih‐Yu , Liu Cheng Bin , Sang Shengmin , Ho Chi‐Tang , Pan Min‐Hsiung
Published: March 2010

We previously reported that 6‐shogaol strongly suppressed lipopolysaccharide‐induced overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in murine macrophages. In this study, we further compared curcumin, 6‐gingerol, and 6‐shogaol's molecular mechanism of action and their anti‐tumor properties. We demonstrate that topical application of 6‐shogaol more effectively inhibited 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐stimulated transcription of iNOS and COX‐2 mRNA expression in mouse skin than curcumin and 6‐gingerol. Pretreatment with 6‐shogaol has resulted in the reduction of TPA‐induced nuclear translocation of the nuclear factor‐κB subunits. 6‐Shogaol also reduced TPA‐induced phosphorylation of IκBα and p65, and caused subsequent degradation of IκBα. Moreover, 6‐shogaol markedly suppressed TPA‐induced activation of extracellular signal‐regulate kinase1/2, p38 mitogen‐activated protein kinase, JNK1/2, and phosphatidylinositol 3‐kinase/Akt, which are upstream of nuclear factor‐κB and AP‐1. Furthermore, 6‐shogaol significantly inhibited 7,12‐dimethylbenz[a]anthracene/TPA‐induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 wk. Presented data reveal for the first time that 6‐shogaol is an effective anti‐tumor agent that functions by down‐regulating inflammatory iNOS and COX‐2 gene expression in mouse skin. It is suggested that 6‐shogaol is a novel functional agent capable of preventing inflammation‐associated tumorigenesis.
Characterization of three saponins from a fraction using 1D DOSY as a solvent signal suppression tool. Agabrittonosides E–F. Furostane Saponins from Agave brittoniana Trel. spp. Brachypus
Authors: Macías Francisco A. , Guerra José O. , Simonet Ana M. , Pérez Andy J. , Nogueiras Clara
Published: March 2010

A careful NMR analysis, especially by 1D TOCSY and 1D ROESY, of a refined saponin fraction allowed us to determine the structure of three saponins from a polar extract of Agave brittoniana Trel. spp. Brachypus leaves. The use of 1D DOSY for the suppression of the solvent signal was useful to obtain the chemical shifts of anomeric signals. A full assignment of the 1H and 13C spectral data for the new saponins, agabrittonosides E–F (1–2) and the well‐known Karatavioside C (3) and their methoxyl derivatives, is reported. The structures were established using a combination of 1D and 2D (1H, 1H‐COSY, TOCSY, ROESY, g‐HSQC, g‐HMBC and g‐HSQC‐TOCSY) NMR techniques and ESI–MS. In addition, the methoxylation of these furostane saponins in the presence of MeOH was studied. Copyright © 2010 John Wiley & Sons, Ltd.
Clinical quality measures for electrodiagnosis in suspected carpal tunnel syndrome
Authors: Sandin Karl J. , Asch Steven M. , Jablecki Charles K. , Kilmer David D. , Nuckols Teryl K.
Published: March 2010

Extensive research has documented that medical care in the United States is not of optimal quality, meaning that well‐established care processes are not consistently provided to the patients who would benefit from them. To assess and improve quality of care, specific measures are needed. The objective of this study was to develop quality measures for electrodiagnostic testing in suspected carpal tunnel syndrome (CTS). We used a variation of the well‐established RAND/UCLA Appropriateness Method to develop the measures. A physiatrist and quality measurement experts developed draft measures based on guidelines and literature. Subsequently, in a two‐round, modified‐Delphi process, a multidisciplinary panel of 11 national experts in CTS reviewed a summary of the evidence and then rated the measures for validity and feasibility. Seven draft measures were developed. The expert panel combined two, modified the others, and then judged all resulting measures to be valid and feasible. The measures cover compelling indications for testing, essential test components when CTS is suspected, skin temperature measurement and normalization, and the appropriate interpretation of test results. These measures define a minimum standard of care for the use of electrodiagnostic tests in suspected CTS and are consistent with recent guidelines developed by the American Association of Neuromuscular and Electrodiagnostic Medicine. Provider organizations, insurance companies, and professional societies can use these measures in efforts to monitor and improve quality of care for this common and disabling condition. Muscle Nerve, 2010
Periodic railway timetabling with event flexibility
Authors: Caimi Gabrio , Fuchsberger Martin , Laumanns Marco , Schüpbach Kaspar
Published: March 2010

This article addresses the problem of generating conflict‐free periodic train timetables for large railway networks. We follow a two‐level approach, where a simplified track topology is used to obtain a macrolevel schedule, and the detailed topology is considered locally on the microlevel. To enlarge the solution space in the interface of the two levels, we propose an extension of the well‐known periodic event scheduling problem (PESP) such that it allows to generate flexible time slots for the departure and arrival times instead of exact times. This flexible periodic event scheduling problem (FPESP) formulation increases the chance to obtain feasible solutions (exact train routings) subsequently on the microlevel, in particular for stations with dense peak traffic. Total trip time and the time slot sizes are used as multiple objectives and weighted and/or constrained to allocate the flexibility where it is most useful. Tests on medium‐size instances of the Swiss Federal Railways' 2007 service intention demonstrate the advantage of the FPESP model, while it only moderately increases its solution time in most cases. A trade‐off analysis of the two conflicting objectives is presented and discussed for different scenarios. Finally, we present the Flexbox model, which generalizes the single event flexibilities of the FPESP to arbitrary subsets of events. These Flexboxes can make use of natural dependencies in the timetable and can considerably increase the total flexibility of the timetable. © 2010 Wiley Periodicals, Inc. NETWORKS, 2011
How to find good night train connections
Authors: Gunkel Thorsten , Schnee Mathias , Müller–Hannemann Matthias
Published: March 2010

The search for attractive night train connections is fundamentally different from ordinary search: the primary objective of a customer of a night train is to have a reasonably long sleeping period without interruptions due to train changes. For most passengers it is also undesirable to reach the final destination too early in the morning. These objectives are in sharp contrast to standard information systems which focus on minimizing the total travel time. In this article, we present and compare two new approaches to support queries for night train connections. These approaches have been integrated into the Multi‐Objective Traffic Information System (MOTIS), which is currently being developed by our group. Its purpose is to find all train connections which are attractive from a customer point of view. Using a computational study, we demonstrate that our specialized algorithms for night train connections are able to satisfy customer queries much better than standard methods. This can be achieved with reasonable computational costs: a specialized night train search requires only a few seconds of CPU time. © 2010 Wiley Periodicals, Inc. NETWORKS, 2011
HTAPP: High‐throughput autonomous proteomic pipeline
Authors: Yu Kebing , Salomon Arthur R.
Published: March 2010

Recent advances in the speed and sensitivity of mass spectrometers and in analytical methods, the exponential acceleration of computer processing speeds, and the availability of genomic databases from an array of species and protein information databases have led to a deluge of proteomic data. The development of a lab‐based automated proteomic software platform for the automated collection, processing, storage, and visualization of expansive proteomic data sets is critically important. The high‐throughput autonomous proteomic pipeline described here is designed from the ground up to provide critically important flexibility for diverse proteomic workflows and to streamline the total analysis of a complex proteomic sample. This tool is composed of a software that controls the acquisition of mass spectral data along with automation of post‐acquisition tasks such as peptide quantification, clustered MS/MS spectral database searching, statistical validation, and data exploration within a user‐configurable lab‐based relational database. The software design of high‐throughput autonomous proteomic pipeline focuses on accommodating diverse workflows and providing missing software functionality to a wide range of proteomic researchers to accelerate the extraction of biological meaning from immense proteomic data sets. Although individual software modules in our integrated technology platform may have some similarities to existing tools, the true novelty of the approach described here is in the synergistic and flexible combination of these tools to provide an integrated and efficient analysis of proteomic samples.
Proteomic analysis of Medicago truncatula root plastids
Authors: Daher Zeina , Recorbet Ghislaine , Valot Benoît , Robert Frank , Balliau Thierry , Potin Sophie , Schoefs Benoît , Dumas‐Gaudot Eliane
Published: March 2010

Despite the recognized importance of non‐photosynthetic plastids in a wide array of plant processes, the root plastid proteome of soil‐grown plants still remains to be explored. In this study, we used a protocol allowing the isolation of Medicago truncatula root plastids with sufficient protein recovery and purity for their subsequent in‐depth analysis by nanoscale capillary LC‐MS/MS. Besides providing the first picture of a root plastid proteome, the results obtained highlighted the identification of 266 protein candidates whose functional distribution mainly resembled that of wheat endosperm amyloplasts and tobacco proplastids together with displaying major differences to those reported for chloroplasts. Most of the identified proteins have a role in nucleic acid‐related processes (16%), carbohydrate (15%) and nitrogen/sulphur (12%) metabolisms together with stress response mechanisms (10%). It is noteworthy that BLAST searches performed against the proteins reported in different plastidomes allowed detecting 30 putative root plastid proteins for which homologues were previously unsuspected as plastid‐located, most of them displaying a common putative role in participating in the plant cell responses against abiotic and/or biotic stresses. Taken together, the data obtained provide new insights into the functioning of root plastids and reinforce the emerging idea for an important role of these organelles in sustaining plant defence reactions.
Protein expression changes induced in murine peritoneal macrophages by Group B Streptococcus
Authors: Susta Federica , Chiasserini Davide , Fettucciari Katia , Orvietani Pier Luigi , Quotadamo Flavia , Noce Rosina , Bartoli Andrea , Marconi Pierfrancesco , Corazzi Lanfranco , Binaglia Luciano
Published: March 2010

Protein expression changes induced in thioglycolate‐elicited peritoneal murine macrophages (MΦ) by infection with type III Group B Streptococcus (GBS) are described. Proteins from control MΦ and MΦ incubated 2 h with live or heat‐inactivated GBS were separated by 2‐DE. Proteins whose expression was significantly different in infected MΦ, as compared with control cells, were identified by MS/MS analysis. Changes in the expression level of proteins involved in both positive and negative modulation of phagocytic functions, stress response and cell death were induced in MΦ by GBS infection. In particular, expression of enzymes playing a key role in production of reactive oxygen species was lowered in GBS‐infected MΦ. Significant alterations in the expression of some metabolic enzymes were also observed, most of the glycolytic and of the pentose‐cycle enzymes being down‐regulated in MΦ infected with live GBS. Finally, evidence was obtained that GBS infection affects the expression of enzymes or enzyme subunits involved in ATP synthesis and in adenine nucleotides interconversion processes.
Identification of ciliary neurotrophic factor receptor α as a mediator of neurotoxicity induced by α‐synuclein
Authors: Liu Jun , Shi Min , Hong Zhen , Zhang JianPeng , Bradner Joshua , Quinn Thomas , Beyer Richard P. , Mcgeer Patrick L. , Chen ShengDi , Zhang Jing
Published: March 2010

Accumulating evidence suggests that extracellular α‐synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques – stable isotope labeling of amino acid in cell cultures (SILAC), biotin labeling of plasma membrane proteins followed by affinity purification, and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor, which appeared to modulate eSNCA‐mediated neurotoxicity via mechanisms related to JAK1/STAT3 signaling but independent of eSNCA endocytosis.
Identification of breast cancer biomarkers in transgenic mouse models: A proteomics approach
Authors: Rodenburg Wendy , Pennings Jeroen L. A. , van Oostrom Conny T. M. , Roodbergen Marianne , Kuiper Raoul V. , Luijten Mirjam , de Vries Annemieke
Published: March 2010

Purpose: Transgenic mouse models for cancer circumvent many challenges that hamper human studies aimed at biomarker discovery. Lower biological variances among mice combined with controllable factors such as food uptake and health status may enable the detection of more subtle protein expression differences. This is envisioned to result in the identification of biomarkers better discriminating cancer cases from controls.

Experimental design: The current study used two innovative mouse models for breast‐cancer to identify new serum biomarkers. Multi‐analyte profiling technique was used to analyze 70 proteins in individual serum samples of non‐tumor and mammary tumor‐bearing Tg.NK (MMTV/c‐neu) mice.

Results: A small set of proteins fully differentiated tumor samples from controls. These comprised osteopontin, interleukin‐18, cystatin C and CD40 antigen. Comparison of protein expression in another breast‐cancer mouse model, the humanized p53.R270H mice, showed common discriminatory expression of osteopontin. However, other biomarkers showed distinct expression in the two different breast‐cancer models, indicating that different mammary tumor sub‐types with respect to molecular and estrogen receptor status reveal divergent serum biomarker sets.

Conclusions and clinical relevance: The current study supports the concept that serum proteins can discriminate mammary tumor cases from controls, and yielded interesting biomarkers that need further testing and validation in human studies.
Deep plasma proteomic analysis of patients with left ventricular remodeling after a first myocardial infarction
Authors: Fertin Marie , Beseme Olivia , Duban Sophie , Amouyel Philippe , Bauters Christophe , Pinet Florence
Published: March 2010

Purpose: Depletion of major blood proteins is one of the most promising approaches to accessing low abundance biomarkers for proteomics studies. The use of combinatorial peptide ligand library (CPLL) for accessing these low abundance proteins in plasma from patients with a myocardial infarction (MI) was tested to identify candidate protein biomarkers of left ventricular remodeling (LVR).

Experimental design: Serial blood samples of MI patients followed for one year (at inclusion, 1 month, 3 months, and 1 year) were treated with CPLL and analyzed by SELDI‐TOF‐MS.

Result: The use of CPLL increased resolution, with loss of most abundant plasma proteins, reproducibly and improved the intensity of low‐abundance proteins. Longitudinal information allowed us to reduce by 55% the final number of peaks identified as significantly modulated throughout the 1‐year follow‐up after MI. Interestingly, 19 of the 26 peaks finally selected were detected only in samples treated from CPLL. The 2777 m/z peak, found in less elevated level in high remodeling patients, was identified as being DAHKSEVAHR FKDLGEENFKALVL, the N‐terminal peptide (24–48 aa) generated from albumin by pepsin cleavage.

Conclusions and clinical relevance: This finding shows the potential of CPLL in accessing low‐abundance proteins to select and identify candidate biomarkers in patients with LVR.
Identification of diabetic nephropathy‐selective proteins in human plasma by multi‐lectin affinity chromatography and LC‐MS/MS
Authors: Ahn Jung‐Mo , Kim Byung‐Gyu , Yu Myong‐Hee , Lee In‐Kyu , Cho Je‐Yoel
Published: March 2010

Purpose: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Microalbuminuria has been established as a risk factor for the development of diabetic renal disease. Recently, microalbuminuria has been reported to have limitations in determining disease risk and predicting DN. Therefore, identification of more specific biomarkers for prediction of DN is needed.

Experimental design: When kidney damage is initiated, glycoprotein leakage into the blood may occur, thus altering the glycoproteome profile of the blood. Here, we have used a combined approach of glycoprotein enrichment of plasma with a proteomic analysis to discover potential DN biomarkers. We isolated glycoproteins from plasma provided by six type 2 diabetes control (DC) and six type 2 DN patients using multi‐lectin affinity chromatography. Captured glycoproteins were resolved by 1‐D PAGE and tryptic digests of isolated proteins were analyzed by LC‐MS/MS.

Results: From the comparative and semi‐quantitative proteome analysis, we identified 13 up‐ and 14 down‐regulated glycoproteins in DN plasma. Among the up‐regulated glycoproteins, the levels of lumican, vasorin and retinol binding protein‐4 were verified by Western blot analysis of individual plasma samples.

Conclusion and clinical relevance: Collectively, our findings show that biomarker discovery has considerable potential for predicting diabetic nephropathy in diabetic patients.
Combinatorial vascular targeting in translational medicine
Authors: Staquicini Fernanda I. , Moeller Benjamin J. , Arap Wadih , Pasqualini Renata
Published: March 2010

In the post‐genomic era, the phage display technology surfaces as an alternative approach for large‐scale study of tissue‐specific protein interactions with direct clinical and therapeutic applications. The unbiased identification of molecular complexes expressed on the surface of cells and blood vessels of organs and tissues may eventually lead to a considerably improved understanding of cellular and vascular proteomics. The ultimate value of this technology consists in the conception of a new ligand‐directed pharmacology, with broad implications for both treatment and molecular imaging of cancer patients. In this review, we describe the use and applications of phage display for efficient development of targeted drug discovery and design.
The short‐chain oxidoreductase Q9HYA2 from Pseudomonas aeruginosa PAO1 contains an atypical catalytic center
Authors: Huether Robert , Mao Qilong , Duax William L. , Umland Timothy C.
Published: March 2010

The characteristic oxidation or reduction reaction mechanisms of short‐chain oxidoreductase (SCOR) enzymes involve a highly conserved Asp‐Ser‐Tyr‐Lys catalytic tetrad. The SCOR enzyme Q9HYA2 from the pathogenic bacterium Pseudomonas aeruginosa was recognized to possess an atypical catalytic tetrad composed of Lys118‐Ser146‐Thr159‐Arg163. Orthologs of Q9HYA2 containing the unusual catalytic tetrad along with conserved substrate and cofactor recognition residues were identified in 27 additional species, the majority of which are bacterial pathogens. However, this atypical catalytic tetrad was not represented within the Protein Data Bank. The crystal structures of unligated and NADPH‐complexed Q9HYA2 were determined at 2.3 Å resolution. Structural alignment to a polyketide ketoreductase (KR), a typical SCOR, demonstrated that Q9HYA2's Lys118, Ser146, and Arg163 superimposed upon the KR's catalytic Asp114, Ser144, and Lys161, respectively. However, only the backbone of Q9HYA2's Thr159 overlapped KR's catalytic Tyr157. The Thr159 hydroxyl in apo Q9HYA2 is poorly positioned for participating in catalysis. In the Q9HYA2–NADPH complex, the Thr159 side chain was modeled in two alternate rotamers, one of which is positioned to interact with other members of the tetrad and the bound cofactor. A chloride ion is bound at the position normally occupied by the catalytic tyrosine hydroxyl. The putative active site of Q9HYA2 contains a chemical moiety at each catalytically important position of a typical SCOR enzyme. This is the first observation of a SCOR protein with this alternate catalytic center that includes threonine replacing the catalytic tyrosine and an ion replacing the hydroxyl moiety of the catalytic tyrosine.
Type IIB orientifolds, D‐brane instantons and the LARGE volume scenario
Authors: Plauschinn E.
Published: March 2010

This review article is concerned with three topics important for the construction of four‐dimensional models of particle physics in the context of type II String Theories. Special emphasis is put on a consistent presentation of these topics as well as on highlighting their interconnections. The first of the three topics deals with the tadpole cancellation conditions and the cancellation of chiral anomalies for type IIB orientifolds with orientifold three‐ and seven‐planes. The second topic is related to non‐perturbative effects originating from D‐brane instantons. In particular, in the presence of a realistic particle physics sector, a chiral zero‐mode constraint for contribution of instantons to the superpotential arises. The third topic is about moduli stabilisation in type IIB string compactifications. Two scenarios, the KKLT and Large Volume Scenario, are reviewed and a model for the latter scenario with the chiral zero‐mode constraint taken into account is presented.