bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoclonal anti‐A antibody removal by synthetic A antigen immobilized on specific antibody filters
Authors: Gautam Shalini , Korchagina Elena Y. , Bovin Nicolai V. , Federspiel William J.
Published: August 2007

Removal of blood group anti‐A and anti‐B antibodies can prevent hyperacute organ rejection in ABO‐incompatible transplantation. We are developing an extracorporeal‐specific antibody filter (SAF) as an immunoadsorption device for direct removal of ABO blood group antibodies from whole blood, without the need for plasma separation and plasma exchange. A hollow fiber‐based small scale SAF (mini‐SAF) device was fabricated and synthetic A antigen, Atrisaccharide (Atri) conjugated to activated polyacrylic acid, was immobilized on the fiber lumen surface. Monoclonal antibody anti‐A IgM were specifically removed up to 70% of initial antibodies using mini‐SAF device. The monoclonal anti‐A capture experiments on mini‐SAF indicated that antibody removal relative to the initial concentration is independent of inlet concentration in the beginning; however, as the surface starts saturating with bound antibodies, removal becomes dependent on inlet concentration. No significant effect of flow rate on removal rate was observed. The radial diffusion and axial convection‐based mathematical model developed for unsteady state antibody removal was in good agreement with the experimental data and showed that the antibody removal rate can be maximized by increasing the antibody‐binding capacity of the SAF. Biotechnol. Bioeng. 2008;99: 876–883. © 2007 Wiley Periodicals, Inc.
Simultaneous estimation of chlorophyll a and lipid contents in microalgae by three‐color analysis
Authors: Su Chia‐Hung , Fu Chun‐Chong , Chang Yet‐Chung , Nair Giridhar R. , Ye Jun‐Liang , Chu I.‐Ming , Wu Wen‐Teng
Published: August 2007

A method of rapid determination of chlorophyll a and lipid contents of microalgae based on colorimetric analysis of the digital images of the microalgae is proposed. The color variation of microalgae during cultivation is evaluated by the brightness of the three primary colors (red, green, and blue). The brightness values of the three primary colors are modeled as two linear correlation functions (RGB model) for microalgal chlorophyll a and lipid contents, respectively. The chlorophyll a and lipid contents predicted by the proposed model are compared with that determined by the standard methods. The good agreement of the model predictions with experimental results is demonstrated with a squared correlation coefficient (R2) of 0.99 for chlorophyll a and lipid. The reliability of the RGB model was verified in real cultivations of the microalgae in a photobioreactor. Growth dynamics, contents of chlorophyll a and lipid corresponded very well with previously reported studies. Biotechnol. Bioeng. 2008; 99; 1034–1039. © 2007 Wiley Periodicals, Inc.
Silicate mineral dissolution during heap bioleaching
Authors: Dopson Mark , Halinen Anna‐Kaisa , Rahunen Nelli , Boström Dan , Sundkvist Jan‐Eric , Riekkola‐Vanhanen Marja , Kaksonen Anna H. , Puhakka Jaakko A.
Published: August 2007

Silicate minerals are present in association with metal sulfides in ores and their dissolution occurs when the sulfide minerals are bioleached in heaps for metal recovery. It has previously been suggested that silicate mineral dissolution can affect mineral bioleaching by acid consumption, release of trace elements, and increasing the viscosity of the leach solution. In this study, the effect of silicates present in three separate samples in conjunction with chalcopyrite and a complex multi‐metal sulfide ore on heap bioleaching was evaluated in column bioreactors. Fe2+ oxidation was inhibited in columns containing chalcopyrite samples A and C that leached 1.79 and 1.11 mM fluoride, respectively but not in sample B that contained 0.14 mM fluoride. Microbial Fe2+ oxidation inhibition experiments containing elevated fluoride concentrations and measurements of fluoride release from the chalcopyrite ores supported that inhibition of Fe2+ oxidation during column leaching of two of the chalcopyrite ores was due to fluoride toxicity. Column bioleaching of the complex sulfide ore was carried out at various temperatures (7–50°C) and pH values (1.5–3.0). Column leaching at pH 1.5 and 2.0 resulted in increased acid consumption rates and silicate dissolution such that it became difficult to filter the leach solutions and for the leach liquor to percolate through the column. However, column temperature (at pH 2.5) only had a minor effect on the acid consumption and silicate dissolution rates. This study demonstrates the potential negative impact of silicate mineral dissolution on heap bioleaching by microbial inhibition and liquid flow. Biotechnol. Bioeng. 2008;99: 811–820. © 2007 Wiley Periodicals, Inc.
A novel small‐diameter vascular graft: In vivo behavior of biodegradable three‐layered tubular scaffolds
Authors: Zhang Liang , Zhou Jianye , Lu Qingping , Wei Yingjie , Hu Shengshou
Published: August 2007

Small‐diameter vascular grafts are potential substitutes for damaged vessels in patients, but most biodegradable grafts available now are not strong enough. The present study examined the burst strength, radial compliance, suture retention strength for a novel biodegradable tubular scaffold and investigated its behavior in vivo. The tubular scaffold (6‐mm i.d., 4 cm long) has three layers including porous polylacticglycolic‐ acid in both inner and outer layers, a compact polyurethanes layer in midst. Bone marrow stromal cells (bMSCs) were seeded on the scaffolds and cultured for 7 days in vitro to construct tissue engineered vascular grafts which were then implanted in canine abdominal aorta. After 1, 3, 6, 12 and 24 weeks, the grafts were retrieved and evaluated histologically, angiographically and immunohistochemically. The biodegradable tubular scaffolds showed wall thickness of 0.295 mm to 0.432 mm; radial compliance of 3.80%/100 mmHg ∼0.57%/100mmHg, burst strength of 160 kPa ∼183kPa, and suture retention strength of 1959 N/cm2∼3228N/cm2. The implanted grafts were fully patent without any signs of dilation or obstruction after 3 months' implantation. Scanning electron microscopy revealed a confluence endothelial cell layer spreading on the inner surface of the grafts. Immunohistochemistry of the retrieved grafts showed that vWF‐stainin, αSMA‐staining were positive in the inner and medium layer respectively. Masson's trichrome staining showed that amount of collagen fibers existed in the grafts wall. Overall, these novel three‐layered scaffolds exhibited favourable mechanical strength, long term patency and good remodeling in vivo. Biotechnol. Bioeng. 2008; 99; 1007–1015. © 2007 Wiley Periodicals, Inc.
Fed‐batch cultivation of the marine bacterium Sulfitobacter pontiacus using immobilized substrate and purification of sulfite oxidase by application of membrane adsorber technology
Authors: Muffler Kai , Ulber Roland
Published: August 2007

Sulfitobacter pontiacus, a gram‐negative heterotrophic bacterium isolated from the Black Sea is well known to produce a soluble AMP‐independent sulfite oxidase (sulfite: acceptor oxidoreductase) of high activity. Such an enzyme can be of great help in establishing biosensor systems for detection of sulfite in food and beverages considering the high sensitivity of biosensors and the increasing demand for such biosensor devices. For obtaining efficient amounts of the enzyme, an induction of its biosynthesis by supplementing sufficient concentrations of sodium sulfite to the fermentation broth is required. Owing to the fact that a high initial concentration of sodium sulfite decreases dramatically the enzyme expression, different fed‐batch strategies can be applied to circumvent such inhibition or repression of the enzyme respectively. By the use of sulfite species immobilized in polyvinyl alcohol gels, an approach to the controlled and continuous feeding of sulfite to the cultivation media could be established to diminish inhibitory concentrations. Furthermore, the purification of the enzyme is described by using membrane adsorber technology. Biotechnol. Bioeng. 2008;99: 870–875. © 2007 Wiley Periodicals, Inc.
Impact of the smallest surgical margin on local control in soft tissue sarcoma
Authors: Sampo M , Tarkkanen M , Huuhtanen R , Tukiainen E , Böhling T , Blomqvist C
Published: August 2007

Background

The aim was to review a single-institution experience of a prospective treatment protocol for soft tissue sarcoma of the extremity and trunk wall, with particular focus on the smallest surgical margin leading to local control.

Methods

The study included 270 patients who had surgery for soft tissue sarcoma at Helsinki University Central Hospital between 1987 and 1997. Resection margins were measured prospectively from tumour specimens. Radiotherapy was administered if the smallest margin measured less than 2·5 cm, irrespective of tumour grade.

Results

With a median follow-up of 6·6 years, the 5-year local control rate was 76·4 per cent. On multivariable analysis, the smallest surgical margin around the sarcoma (after radiotherapy) was prognostic for local control. A margin of at least 2·5 cm was associated with a local recurrence-free rate of 89·2 per cent at 5 years. Tumour size, depth or grade and patient's age had no independent prognostic effect on local control.

Conclusion

Surgical margin had independent prognostic value for local control. A surgical margin of 2–3 cm provided reasonable local control of soft tissue sarcoma, even without radiotherapy. Radiotherapy is recommended for smaller margins, irrespective of tumour grade.
Simultaneous quantitation of three major triterpenoid glycosides in Centella asiatica extracts by high performance liquid chromatography with evaporative light scattering detection
Authors: Zhang Feng‐Lun , Wei Ying‐Jie , Zhu Jia , Gong Zhu‐Nan
Published: August 2007

A high‐performance liquid chromatography method with evaporative light scattering detection was established for simultaneous determination of three major triterpenoid glycosides, i.e. asiaticoside, madecassoside and asiaticoside‐B, in Centella asiatica extracts. The optimal chromatographic conditions were achieved on a COSMOSIL 5C18‐MS‐II column by constant elution with water (0.01% trifluoroacetic acid, v/v) and acetonitrile (1.0% methyl tert‐butyl ether, 0.01% trifluoroacetic acid, v/v) (78:22) as mobile phase at a flow rate of 1.0 mL/min; the column temperature was 30°C. The evaporative light scattering detector was set at an evaporating temperature of 40°C and nitrogen gas pressure of 3.5 bar. The validation of the method included tests of linearity, sensitivity, precision, repeatability, stability and accuracy. All calibration curves showed good linear regression (r2 > 0.9993) within test ranges. The established method showed good precision and accuracy with overall intra‐day and inter‐day variations of 1.73–3.06 and 3.89%–4.92%, respectively, and overall recoveries of 97.63–99.39% for the three compounds analyzed. The method developed was successfully applied to quantify the main triterpenoid glycosides in Centella asiatica extracts from different companies. Copyright © 2007 John Wiley & Sons, Ltd.
Fluorescence determination of N‐acetylaspartic acid in the rat cerebrum homogenate using high‐performance liquid chromatography with pre‐column fluorescence derivatization
Authors: Fukushima Takeshi , Arai Kotaro , Tomiya Masayuki , Mitsuhashi Shogo , Sasaki Tsukasa , Santa Tomofumi , Imai Kazuhiro , Toyo'oka Toshimasa
Published: August 2007

N‐Acetyl‐l‐aspartic acid (NAA) is an endogenous compound, and its brain concentration is suggested to be altered in neurological disorders. In the present study, a fluorescence determination method for NAA was developed by employing reversed‐phase high‐performance liquid chromatography (HPLC) with pre‐column fluorescence derivatization using 4‐N,N‐dimethylaminosulfonyl‐7‐N‐(2‐aminoethyl)amino‐2,1,3‐benzoxadiazole (DBD‐ED). Using methylsuccinic acid as the internal standard, a linear calibration curve for NAA was constructed in the range 125–1000 µm (n = 3). The detection limit on the column was approximately 5.0 fmol (signal‐to‐noise ratio 3). The proposed HPLC method was applied to determine NAA in the rat cerebrum homogenate. Cerebrum NAA was successfully determined using 10 µL of the homogenate, and the validation data for the proposed HPLC method demonstrated satisfactory results. Intra‐ and inter‐day precision and accuracy were within 1.1–7.0 and −8.1–6.3%, respectively. The concentration of NAA in the male rat cerebrum (13 weeks old) was 84 ± 4.6 µmol/mg protein (n = 3). Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis of 4‐[2‐(N,N‐dimethylamino)ethylaminosulfonyl]‐7‐N‐methylhydrazino‐2,1,3‐benzoxadiazole (DAABD‐MHz) as a derivatization reagent for aldehydes in liquid chromatography/electrospray ionization–tandem mass spectrometry
Authors: Santa Tomofumi , Al‐Dirbashi Osama Y , Ichibangase Tomoko , Rashed Mohamed S , Fukushima Takeshi , Imai Kazuhiro
Published: August 2007

Benzofurazan derivatization reagent, 4‐[2‐(N,N‐dimethylamino)ethylaminosulfonyl]‐7‐N‐methylhydrazino‐2,1,3‐benzoxadiazole (DAABD‐MHz), for aldehydes in liquid chromatography/electrospray ionization–tandem mass spectrometry (LC/ESI‐MS/MS), was synthesized. DAABD‐MHz reacted with aliphatic aldehydes under mild conditions. The generated derivatives were separated on a reversed‐phase column and detected by ESI‐MS/MS with detection limits of 30–60 fmol on‐column. Upon collision‐induced dissociation, a single and intense fragment ion at m/z 151 was observed. These results suggested that DAABD‐MHz was suitable as a derivatization reagent in LC/ESI‐MS/MS. Copyright © 2007 John Wiley & Sons, Ltd.
Validation of a simple HPLC method for assay of haplamine and its metabolites in plasma suitable for pharmacokinetic application in rats
Authors: Ea Sompheary , Aubert Claude , Giacometti Sarah , Ciccolini Joseph , Siv Chhan , Bun Hot
Published: August 2007

A simple HPLC method with ultraviolet detection has been developed and validated for the simultaneous determination of haplamine and its metabolites (trans/cis‐3,4‐dihydroxyhaplamine) in rat. A liquid–liquid extraction was used to extract the compounds from rat plasma. The analysis was performed on a C18 Nucleosil Nautilus column. The mobile phase consisted of water (A) and a mixture of methanol and acetonitrile (85:15; v/v) (B) used in gradient mode (38–40% B for 10 min, 40–58% B for 49 min, 58–38% B for 1 min, and 38% for 5 min) pumped at 1 mL/min. The calibration curves showed good linearity with correlation coefficients greater than 0.999 for the analytes in the investigated concentration range. The lower limit of detection was 0.007, 0.008 and 0.009 µg/mL and the lower limit of quantification was 0.014, 0.017 and 0.018 µg/mL for haplamine, and trans/cis‐3,4‐dihydroxyhaplamine, respectively. The method was applied to a preliminary pharmacokinetic study in rats. This method proved to meet fully the standards required of experimental pharmacokinetic studies and should be used in further preclinical investigation. Copyright © 2007 John Wiley & Sons, Ltd.
Quantitative retention–activity relationship models for quinolones using biopartitioning micellar chromatography
Authors: Wu Li‐Ping , Chen Yu , Wang Shu‐Rong , Chen Cong , Ye Li‐Ming
Published: August 2007

A simple and reproducible quantitative retention–activity relationship (QRAR) model utilizing biopartitioning micellar chromatography was developed for the biological parameter estimation of drugs. The correlation between retention factors of quinolones obtained in physiological conditions (pH, ionic strength) and biological activities was investigated using different second‐order polynomial models. The predictive and interpretative ability of the chromatographic models was evaluated in terms of cross‐validated data (RMSEC, RMSECV and RMSECVi). The aim was to obtain adequate QRAR models of half‐life, clearance, volume of distribution, plasma protein combination rate, area under concentration–time curve and toxicity (LD50) of quinolones, and to elucidate the advantages and limitations of using a single parameter as independent variable for describing and estimating the activities. Copyright © 2007 John Wiley & Sons, Ltd.
Gas Holdup from the Free Surface of Liquids Subjected to a Vertically Vibrating Plate
Authors: Grinis L. , Kholmer V.
Published: August 2007

Gas holdup is an important factor in the various technological processes involving the interaction between liquid and gaseous systems. The goal of the present research is to study the effect of vibration parameters and plate design on the gas holdup efficiency in a vibrating plate column. The gas bubbles were generated by the vibrating plate, which was sufficiently close to the liquid surface. An analytical model for the calculation of the gas holdup was developed. A device for the introduction of the gas and the vertical vibration of the liquid was designed and used in this research. The experimental data obtained are in good agreement with the theoretical calculations. The results show the possibility of enhancing the gas holdup by changing the vibration parameters and optimizing the vibrating plate unit design parameters.
Indium‐Mediated Selective Introduction of a 1,3‐Butadien‐2‐yl Group at the C4‐Position in 2‐Azetidinones and Application of 1,3‐Diene‐Tethered 2‐Azetidinones in the Diels–Alder Reaction
Authors: Lee Kooyeon , Lee Phil Ho
Published: August 2007

The reaction of 4‐acetoxy‐2‐azetidinones with organoindium reagents generated in situ from indium and 1,4‐dibromo‐2‐butyne in the presence of LiCl in DMF selectively produced 2‐azetidinones which contain a 1,3‐butadienyl‐2‐yl group at the C4‐position in good yields. The Diels–Alder reaction of 4‐[(1‐methylene)prop‐2‐enyl]‐2‐azetidinones with a variety of dienophiles provided 2‐azetidinones with valuable functional‐group‐substituted six‐membered rings at the C4‐position in good yields.
Verbesserung des Wasserabscheidungswirkungsgrades im Kondensator für Flugzeugklimaanlagen durch die Nutzung ionenimplantierter Kondensatoroberflächen
Authors: Rausch M. H. , Krzeminski K. , Fröba A. P. , Leipertz A.
Published: August 2007

Zur Optimierung des Wärmeübergangs und der damit verbundenen Wasserabscheidung aus strömender feuchter Luft in Klimatisierungssystemen wurde die Verringerung der Benetzbarkeit relevanter Aluminiumlegierungen durch Oberflächenmodifikation mittels Ionenimplantation erprobt. Ein Maß für eine deutliche Reduzierung der Benetzbarkeit ist die Einstellung von Tropfenkondensation unter Sattdampfbedingungen, was an der Legierung Al 6951 erstmals durch die Implantation von Stickstoffionen reproduzierbar gelang. Wärmetechnische Untersuchungen unter Sattdampfbedingungen zeigten, dass selbst beim Auftreten von Tropfenkondensation auf nur etwa 50 % einer Kondensatoroberfläche mehr als eine Verdopplung des Wärmeübergangskoeffizienten für die Kondensation möglich ist. Anschließend wurden Untersuchungen mit dem Arbeitsmedium feuchte Luft in einer Laborklimaanlage durchgeführt, in der einzelne in technischen Kondensatoren eingesetzte Finschichten unter realistischen Betriebsbedingungen hinsichtlich der Wasserabscheidung visuell und wärmetechnisch analysiert werden können. Vergleichende Versuche mit unbehandelten und durch Ionenimplantation modifizierten Fins unter identischen Randbedingungen zeigten keine Unterschiede in der auftretenden Kondensationsform. Am implantierten Fin wurden leicht verbesserte Wasserabscheidungswirkungsgrade ermittelt.
Dose intensity and hematologic toxicity in older cancer patients receiving systemic chemotherapy
Authors: Shayne Michelle , Culakova Eva , Poniewierski Marek S. , Wolff Debra , Dale David C. , Crawford Jeffrey , Lyman Gary H.
Published: August 2007

BACKGROUND.

This prospective study was undertaken to evaluate patient and treatment characteristics that contribute to hematologic toxicity in older cancer patients.

METHODS.

A nationwide study of 115 community oncology practices was conducted between 2002 and 2005 with data collected on 976 patients who had received chemotherapy for common malignancies, including lung cancer, colorectal cancer, breast cancer, ovarian cancer, genitourinary cancer, and lymphoma. Primary outcomes included severe neutropenia (SN) and febrile neutropenia (FN). Secondary outcomes included delivered relative dose intensity (RDI) <85%, dose delays ≥15% days, and reductions ≥15%.

RESULTS.

Approximately 50% of both patients with early‐stage disease and patients with advanced‐stage disease received an actual RDI <85%, and this rate reached 60% in the oldest group (aged >80 years). Increasing age was associated with lower actual RDI (P = .030) and averaged 87.5% across all elderly age groups. A decreasing trend in SN or FN events occurred with increasing age (P for trend = .039), with the majority of initial neutropenic events occurring in Cycle 1 for all age groups. Among the patients who received an actual RDI ≥85%, there was no significant difference in SN or FN by age group or disease stage. Independent risk factors for the development of SN or FN included cancer type, planned RDI ≥85%, body surface area ≤2m2, anthracycline‐ or platinum‐based regimens, previous chemotherapy, elevated blood urea nitrogen, and alkaline phosphatase. Neutropenic complications decreased significantly with primary colony‐stimulating factor (CSF) prophylaxis (coefficient of determination [R2] = 0.260; c‐statistic = 0.782).

CONCLUSIONS.

Among cancer patients aged ≥70 years, 50% of whom received relatively full‐dose chemotherapy, increasing age alone did not increase the risk of hematologic toxicity. Cancer 2007. © 2007 American Cancer Society.
Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors
Authors: Nicholson H. Stacy , Kretschmar Cynthia S. , Krailo Mark , Bernstein Mark , Kadota Richard , Fort Daniel , Friedman Henry , Harris Michael B. , Tedeschi‐Blok Nicole , Mazewski Claire , Sato Judith , Reaman Gregory H.
Published: August 2007

BACKGROUND.

Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors.

METHODS.

Temozolomide was administered orally as monthly 5‐day courses at doses of 200 mg/m2/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m2/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles.

RESULTS.

The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1–23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high‐grade astrocytoma, 1 of 21 with low‐grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain‐stem glioma, or other CNS tumors. Notably, 41% of patients with low‐grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity was infrequent.

CONCLUSIONS.

Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low‐grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy. Cancer 2007. © 2007 American Cancer Society.
Design and analysis of a scalable algorithm to monitor chord‐based p2p systems at runtime
Authors: Binzenhöfer Andreas , Kunzmann Gerald , Henjes Robert
Published: August 2007

Peer‐to‐peer (p2p) systems are a highly decentralized, fault tolerant, and cost‐effective alternative to the classic client–server architecture. Yet companies hesitate to use p2p algorithms to build new applications. Due to the decentralized nature of such a p2p system the carrier does not know anything about the current size, performance, and stability of its application. In this paper, we present an entirely distributed and scalable algorithm to monitor a running p2p network. The snapshot of the system enables a telecommunication carrier to gather information about the current performance parameters of the running system as well as to react to discovered errors. Copyright © 2007 John Wiley & Sons, Ltd.
Transcriptional control of human T‐BET expression: The role of Sp1
Authors: Yu Jianhua , Wei Min , Boyd Zachary , Lehmann Esther B. , Trotta Rossana , Mao Hsiaoyin , Liu Shujun , Becknell Brian , Jaung Michael S. , Jarjoura David , Marcucci Guido , Wu Lai‐Chu , Caligiuri Michael A.
Published: August 2007

Murine T‐bet (T‐box expressed in T cells) is a master regulator of IFN‐γ gene expression in NK and T cells. T‐bet also plays a critical role in autoimmunity, asthma and other diseases. However, cis elements or trans factors responsible for regulating T‐bet expression remain largely unknown. Here, we report on our discovery of six Sp1‐binding sites within the proximal human T‐BET promoter that are highly conserved among mammalian species. Electrophoretic mobility shift assays demonstrate a physical association between Sp1 and the proximal T‐BET promoter with a direct dose response between Sp1 expression and T‐BET promoter activity. Ectopic overexpression of Sp1 also enhanced T‐BET expression and cytokine‐induced IFN‐γ secretion in NK cells and T cells. Mithramycin A, which blocks the binding of Sp1 to the T‐BET promoter, diminished both T‐BET expression and IFN‐γ protein production in monokine‐stimulated primary human NK cells. Collectively, our results suggest that Sp1 is a positive transcriptional regulator of T‐BET. As T‐BET and IFN‐γ are critically important in inflammation, infection, and cancer, targeting Sp1, possibly with mithramycin A, may be useful for preventing and/or treating diseases associated with aberrant T‐BET or IFN‐γ expression.
β‐Defensins chemoattract macrophages and mast cells but not lymphocytes and dendritic cells: CCR6 is not involved
Authors: Soruri Afsaneh , Grigat Jasmin , Forssmann Ulf , Riggert Joachim , Zwirner Jörg
Published: August 2007

β‐Defensins are natural peptide antibiotics whose immunomodulatory functions are poorly understood. In the present study, macrophages were found to migrate to human β‐defensins (HBD)‐1 to ‐4 using Gαi proteins as well as MAPK ERK, p38 and JNK as signal transducers. In addition, mast cells responded to HBD‐1 to ‐4 with calcium fluxes as well as chemotaxis, which increased upon stimulation with IgE plus antigen or ionomycin. In contrast, human β‐defensins were unable to induce migration of memory lymphocytes and dendritic cells (DC). Similar to HBD, the murine β‐defensin (mBD)‐8 mobilized macrophages and lacked the ability to recruit memory T cells. These findings were unexpected as CCR6 on memory T cells and DC has been previously observed to be a receptor for human β‐defensins. In support of our findings, however, RBL‐2H3 as well as 300.19 cells stably expressing CCR6 proved to be unresponsive to HBD‐2 and ‐3. Intriguingly, our observation of a PKC‐independent homologous desensitization between HBD‐1 to ‐4 suggests a common receptor for HBD. In summary, chemoattraction of macrophages and mast cells is evolutionary conserved within the β‐defensin family despite a considerable sequence variation and distinct antimicrobial activities. However, CCR6 is not a functional receptor for β‐defensins.
Extensive HLA class I allele promiscuity among viral CTL epitopes
Authors: Frahm Nicole , Yusim Karina , Suscovich Todd J. , Adams Sharon , Sidney John , Hraber Peter , Hewitt Hannah S. , Linde Caitlyn H. , Kavanagh Daniel G. , Woodberry Tonia , Henry Leah M. , Faircloth Kellie , Listgarten Jennifer , Kadie Carl , Jojic Nebojsa , Sango Kaori , Brown Nancy V. , Pae Eunice , Zaman M. Tauheed , Bihl Florian , Khatri Ashok , John Mina , Mallal Simon , Marincola Francesco M. , Walker Bruce D. , Sette Alessandro , Heckerman David , Korber Bette T. , Brander Christian
Published: August 2007

Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I‐restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well‐defined viral epitopes were tested in 100 subjects regardless of the individuals’ HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I‐restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I‐restricted antigen presentation and vaccine development.
Preparation of Thiocarboxylate, Thiocarbamate and Xanthate Complexes of Pentacoordinate Nickel(II): Insertion of Heterocumulenes Into Nickel(II) Hydroxido Complexes
Authors: Santana M. Dolores , Sáez‐Ayala Magalí , García Luís , Pérez José , García Gabriel
Published: August 2007

The hydroxido complexes [Ni(N3‐mc)(μ‐OH)]2[PF6]2 [N3‐mc = 2,4,4‐trimethyl‐1,5,9‐triazacyclododec‐1‐ene (N3‐mc1) or 2,4,4,9‐tetramethyl‐1,5,9‐triazacyclododec‐1‐ene (N3‐mc2)] react in the presence of alcohols with CS2 or PhNCS to yield xanthate [(N3‐mc)Ni{S2C(OR′)}][PF6] or O‐alkyl N‐phenylthiocarbamate [(N3‐mc)Ni{PhNC(OR′)S}][PF6] complexes; these compounds represent the first examples of N,S‐chelating thiocarbamates bound to nickel(II). The reactions of [Ni(N3‐mc)(μ‐OH)]2[PF6]2 with thiocarboxylic acids yield the corresponding thiocarboxylate derivatives [(N3‐mc)Ni{SC(O)R′}][PF6]. These paramagnetic nickel(II) complexes were characterized by both one‐ and two‐dimensional (COSY) 1H NMR spectroscopic techniques. The crystal structures of [(N3‐mc2)Ni(S2COCH3)][PF6] (2), [(N3mc2)Ni{PhNC(OCH2CH3)S}][PF6] (8), [(N3‐mc2)Ni{SC(O)CH3}][PF6] (10) and [(N3‐mc1)Ni{SC(O)Ph}][PF6] (11) were determined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
In‐line liquid‐phase microextraction for selective enrichment and direct electrophoretic analysis of acidic drugs
Authors: Nozal Leonor , Arce Lourdes , Simonet Bartolomé M. , Ríos Ángel , Valcárcel Miguel
Published: August 2007

This work describes an efficient in‐line extraction‐preconcentration unit coupled to the electrophoretic capillary based on a liquid‐phase microextraction (LPME) process, which can be directly assembled to the cartridge of the commercial CE equipment. The unit permits analyte extraction, preconcentration and electrophoretic separation to be automatically performed in the commercial CE equipment without the need for additional hardware or software. This new approach was usefully used for the separation and determination of nonsteroidal anti‐inflammatory drugs in human urine permitting at least to analyze 30 consecutive real samples. The LODs were lower than 2 μg/L and the reproducibility, expressed as RSD, was 3.1% for the same unit and only 4.8% between different units.
Novel hydroxyethylcellulose‐graft‐poly acrylamide copolymer for separation of double‐stranded DNA fragments by CE
Authors: Yang Runmiao , Wang Yanmei , Zhou Dan
Published: August 2007

A novel separation medium, hydroxyethylcellulose‐graft‐polyacrylamide (HEC‐g‐PAM) synthesized by atom transfer radical polymerization (ATRP), used for dsDNA separation by CE is presented. The separation performance of HEC‐g‐PAM, which has the same graft density and different graft length, has been investigated in Tris–boric acid–EDTA (TBE) buffer solvent mixtures. The temperature‐dependent rheological behavior of HEC‐g‐PAM was also studied by steady‐shear rheometry. The results showed that dsDNA fragments between 72 and 1353 bp was achieved with a 30 cm effective capillary length at 150 V/cm using this type of graft copolymer as a separation medium in bare fused‐silica capillaries, and separation improvement is obtained in HEC‐g‐PAM compared with HEC and poly(dimethylacrylamide (PDMA).
On‐line chemical generation of tris(2,2′‐bipyridyl)ruthenium(III) and its application in CE with chemiluminescence detection
Authors: Ji Xinghu , He Zhike , Pang Daiwen
Published: August 2007

A novel tris(2,2′‐bipyridyl)ruthenium(III) [Ru(bipy)33+]‐based chemiluminescence (CL) detection in CE using an on‐line chemical generation scheme has been demonstrated. Two continuous streams respectively containing solutions of Ru(bipy)32+ and acidic cerium(IV) used as a homogeneous chemical oxidant are employed to generate Ru(bipy)33+, which is delivered into the reaction capillary of a coaxial flow interface and then reacted with analytes at the end of the separation capillary to yield light. The important operational parameters for separation and detection are identified and optimized. Four α‐ketocarboxylic acids used as models, outside of the amine‐containing compounds, are successfully separated and detected to evaluate the feasibility of the approach. The excellent resolution and detection sensitivity was achieved by using 50 mmol/L phosphate running buffer (pH 9.5) with 0.7 mmol/L CTAB, and CL reagent solution streams containing 0.15 mmol/L Ru(bipy)32+ and 0.8 mmol/L cerium(IV) (0.25 mol/L H2SO4), respectively. The concentration detection limits for α‐ketocarboxylic acids were below 3.7×10−8 mol/L (S/N = 3). The proposed method was applied to the determination of α‐ketocarboxylic acids in five different honey samples with satisfactory results.
Mammalian ATPsynthase monomer versus dimer profiled by blue native PAGE and activity stain
Authors: Bisetto Elena , Di Pancrazio Francesca , Simula Maria Paola , Mavelli Irene , Lippe Giovanna
Published: August 2007

Studies into the effects of oligomerization on F0F1ATPsynthase function are contradictory. We optimized the in‐gel ATPase assay to investigate the functional differences of monomers versus dimers. In Triton X‐100 extracts of heavy bovine heart mitochondria (HBHM) and mitoplasts, but not submitochondrial particles (MgATP‐SMP), dimers had greater specific activity than monomers: at 30°C, the dimer/monomer activity ratios were 2.3, 1.4, and 1.0, respectively. These differences in HBHM and mitoplasts extracts were enhanced at 37°C but lost at 20°C. In mitoplasts but not in MgATP‐SMP, dimers were selectively shielded from limited chymotrypsin degradation of F1 α subunit, possibly due to interactions with other proteins or ligands in the native inner membrane. Despite these differences, all three preparations had similar percentages of dimers and similar contents of the native inhibitor IF1 in Vm (monomer) and (dimer) Vd. These results suggest that, in native membrane, monomers and dimers are functionally distinct.
Compensation of actuator delay and dynamics for real‐time hybrid structural simulation
Authors: Ahmadizadeh M. , Mosqueda G. , Reinhorn A. M.
Published: August 2007

Compensation of delay and dynamic response of servo‐hydraulic actuators is critical for stability and accuracy of hybrid experimental and numerical simulations of seismic response of structures. In this study, current procedures for compensation of actuator delay are examined and improved procedures are proposed to minimize experimental errors. The new procedures require little or no a priori information about the behavior of the test specimen or the input excitation. First, a simple approach is introduced for rapid online estimation of system delay and actuator command gain, thus capturing the variability of system response through a simulation. Second, an extrapolation procedure for delay compensation, based on the same kinematics equations used in numerical integration procedures is examined. Simulations using the proposed procedures indicate a reduction in high‐frequency noise in force measurements that can minimize the excitation of high‐frequency modes. To further verify the effectiveness of the compensation procedures, the artificial energy added to a hybrid simulation as a result of actuator tracking errors is measured and used for demonstrating the improved accuracy in the simulations. Copyright © 2007 John Wiley & Sons, Ltd.
Downstream variation in bed sediment size along the East Carpathian rivers: evidence of the role of sediment sources
Authors: Rădoane Maria , Rădoane Nicolae , Dumitriu Dan , Miclăuş Crina
Published: August 2007

Taking as an example six main rivers that drain the western flank of the Eastern Carpathians, a conceptual model has been developed, according to which fluvial bed sediment bimodality can be explained by the overlapping of two grain size distribution curves of different origins.

Thus, for Carpathian tributaries of the Siret, coarse gravel joins an unimodal distribution presenting a right skewness with enhanced downstream fining. The source of the coarse material distributions is autohtonous (by abrasion and hydraulic sorting mechanisms). A second distribution with a sandy mode is, in general, skewed to the left. The source of the second distribution is allohtonous (the quantity of sand that reaches the river‐bed through the erosion of the hillslope basin terrains). The intersection of the two distributions occurs in the area of the 0·5–8 mm fractions, where, in fact, the right skewness (for gravel) and left skewness (for sand) histogram tails meet. This also explains the lack of particles in the 0·5–8 mm interval. For rivers where fine sediment sources are low, the 0·5–8 mm fractions have a higher proportion than the fractions under 1 mm.

For the Siret River itself, bed sediment bimodality is greatly enhanced due to the fact that the second mode is more than 25% of the full sample. As opposed to its tributaries, the source of the first mode, of gravel, is allohtonous to the Siret river, generated by the massive input of coarse sediment through the Carpathian tributaries, while the second mode, of the sands, is local. In this case we can also observe that the two distributions of particles of different origins overlap in the 0·5–8 mm fraction domain, creating the illusion of ‘particle lack’ in the fluvial bed sediments. Copyright © 2007 John Wiley & Sons, Ltd.
Effects of forest harvesting on the occurrence of landslides and debris flows in steep terrain of central Japan
Authors: Imaizumi Fumitoshi , Sidle Roy C. , Kamei Rieko
Published: August 2007

Landslides and debris flows associated with forest harvesting can cause much destruction and the influence of the timing of harvesting on these mass wasting processes therefore needs to be assessed in order to protect aquatic ecosystems and develop improved strategies for disaster prevention. We examined the effects of forest harvesting on the frequency of landslides and debris flows in the Sanko catchment (central Japan) using nine aerial photo periods covering 1964 to 2003. These photographs showed a mosaic of different forest ages attributable to the rotational management in this area since 1912. Geology and slope gradient are rather uniformly distributed in the Sanko catchment, facilitating assessment of forest harvesting effects on mass wasting without complication of other factors. Trends of new landslides and debris flows correspond to changes in slope stability explained by root strength decay and recovery; the direct impact of clearcutting on landslide occurrence was greatest in forest stands that were clearcut 1 to 10 yr earlier with progressively lesser impacts continuing up to 25 yr after harvesting. Sediment supply rate from landslides in forests clearcut 1 to 10 yr earlier was about 10‐fold higher than in control sites. Total landslide volume in forest stands clearcut 0 to 25 yr earlier was 5·8 × 103 m3 km−2 compared with 1·3 × 103 m3 km−2 in clearcuts >25 yr, indicating a fourfold increase compared with control sites during the period when harvesting affected slope stability. Because landslide scars continue to produce sediment after initial failure, sediment supply from landslides continues for 45 yr in the Sanko catchment. To estimate the effect of forest harvesting and subsequent regeneration on the occurrence of mass wasting in other regions, changes in root strength caused by decay and recovery of roots should be investigated for various species and environmental conditions. Copyright © 2007 John Wiley & Sons, Ltd.
ERK1/2 and p38 MAP kinases control prion protein fragment 90–231‐induced astrocyte proliferation and microglia activation
Authors: Thellung Stefano , Villa Valentina , Corsaro Alessandro , Pellistri Francesca , Venezia Valentina , Russo Claudio , Aceto Antonio , Robello Mauro , Florio Tullio
Published: August 2007

Astrogliosis and microglial activation are a common feature during prion diseases, causing the release of chemoattractant and proinflammatory factors as well as reactive free radicals, involved in neuronal degeneration. The recombinant protease‐resistant domain of the prion protein (PrP90–231) displays in vitro neurotoxic properties when refolded in a β‐sheet‐rich conformer. Here, we report that PrP90–231 induces the secretion of several cytokines, chemokines, and nitric oxide (NO) release, in both type I astrocytes and microglial cells. PrP90–231 elicited in both cell types the activation of ERK1/2 MAP kinase that displays, in astrocytes, a rapid kinetics and a proliferative response. Conversely, in microglia, PrP90–231‐dependent MAP kinase activation was delayed and long lasting, inducing functional activation and growth arrest. In microglial cells, NO release, dependent on the expression of the inducible NO synthase (iNOS), and the secretion of the chemokine CCL5 were Ca2+ dependent and under the control of the MAP kinases ERK1/2 and p38: ERK1/2 inhibition, using PD98059, reduced iNOS expression, while p38 blockade by PD169316 inhibited CCL5 release. In summary, we demonstrate that glial cells are activated by extracellular misfolded PrP90–231 resulting in a proliferative/secretive response of astrocytes and functional activation of microglia, both dependent on MAP kinase activation. In particular, in microglia, PrP90–231 activated a complex signalling cascade involved in the regulation of NO and chemokine release. These data argue in favor of a causal role for misfolded prion protein in sustaining glial activation and, possibly, glia‐mediated neuronal death. © 2007 Wiley‐Liss, Inc.
Crb1 is a determinant of retinal apical Müller glia cell features
Authors: van de Pavert Serge A. , Sanz Alicia Sanz , Aartsen Wendy M. , Vos Rogier M. , Versteeg Inge , Beck Susanne C. , Klooster Jan , Seeliger Mathias W. , Wijnholds Jan
Published: August 2007

Mutations in the human Crumbs homologue‐1 (CRB1) gene cause retinal blinding diseases, such as Leber congenital amaurosis and retinitis pigmentosa. In the previous studies we have shown that Crb1 resides in retinal Müller glia cells and that loss of Crb1 results in retinal degeneration (particularly in the inferior temporal quadrant of the mouse eye). Degeneration is increased by exposure to white light. Here, we studied the role of light and aging to gain a better understanding of the factors involved in the progress of retinal disease. Our data reveal that light is neither sufficient nor required to induce retinal disorganization and degeneration in young Crb1−/− mutant mice, suggesting that it rather modulates the retinal phenotype. Gene expression profiling showed that expression of five genes is altered in light‐exposed Crb1−/− mutant retinas. Three of the five genes are involved in chromosome stabilization (Pituitary tumor transforming gene 1 or Pttg1, Establishment of cohesion 1 homolog 1 or Esco1, and a gene similar to histone H2B). In aged retinas, degeneration of photoreceptors, inner retinal neurons, and retinal pigment epithelium was practically limited to the inferior temporal quadrant. Loss of Crb1 in Müller glia cells resulted in an irregular number and size of their apical villi. We propose that Crb1 is required to regulate number and size of these Müller glia cell villi. The subsequent loss of retinal integrity resulted in neovascularization, in which blood vessels of the choroid protruded into the neural retina. © 2007 Wiley‐Liss, Inc.
Are numbers special? Comparing the generation of verbal materials from ordered categories (months) to numbers and other categories (animals) in an fMRI study
Authors: Ischebeck Anja , Heim Stefan , Siedentopf Christian , Zamarian Laura , Schocke Michael , Kremser Christian , Egger Karl , Strenge Hans , Scheperjans Filip , Delazer Margarete
Published: August 2007

Months, days of the week, and numbers differ from other verbal concepts because they are ordered in a sequence, whereas no order is imposed on members of other categories, such as animals or tools. Recent studies suggest that numbers activate a representation of their quantity within the intraparietal sulcus (IPS) automatically, that is, in tasks that do not require the processing of quantity. It is unclear, however, whether ordered verbal materials in general and not only numbers activate the IPS in such tasks. In the present functional magnetic resonance imaging study word generation of months, numbers, and animals were compared. Word generation of numbers and nonnumerical materials from an ordered category (months) activated the IPS more strongly than generating items from a not‐ordered category such as animals or the verbal control conditions. An ROI analysis of three subregions within the anterior IPS revealed that the most anterior and lateral of these regions, human intraparietal area hIP2, shows a greater sensitivity to ordered materials than the other two areas, hIP1 and hIP3. Interestingly, no difference in activation was observed within the IPS between numbers and months suggesting that the activation of the IPS might not be modulated by the additional quantity information carried by numbers. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Pancreatic and duodenal homeobox gene 1 induces hepatic dedifferentiation by suppressing the expression of CCAAT/enhancer-binding protein β
Authors: Meivar-Levy Irit , Sapir Tamar , Gefen-Halevi Shiraz , Aviv Vered , Barshack Iris , Onaca Nicholas , Mor Eytan , Ferber Sarah
Published: August 2007

It is believed that adult tissues in mammals lack the plasticity needed to assume new developmental fates because of the absence of efficient pathways of dedifferentiation. However, the well-documented ability of the transcription factor pancreatic and duodenal homeobox gene 1 (

PDX
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1

) to activate pancreatic lineage development and insulin production following ectopic expression in liver suggests a surprising degree of residual plasticity in adult liver cells. This study seeks a mechanistic explanation for the capacity of

PDX
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1

to endow liver cells with pancreatic characteristics and function. We demonstrate that

PDX
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1

, previously shown to play an essential role in normal pancreatic organogenesis and pancreatic β-cell function and to possess the potential to activate multiple pancreatic markers in liver, can also direct hepatic dedifferentiation.

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1

represses the adult hepatic repertoire of gene expression and activates the expression of the immature hepatic marker α-fetoprotein. We present evidence indicating that

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1

triggers hepatic dedifferentiation by repressing the key hepatic transcription factor CCAAT/enhancer-binding protein β. Hepatic dedifferentiation is necessary though not sufficient for the activation of the mature pancreatic repertoire in liver.

Conclusion:

Our study suggests a dual role for

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1

in liver: inducing hepatic dedifferentiation and activating the pancreatic lineage. The identification of dedifferentiation signals may promote the capacity to endow mature tissues in mammals with the plasticity needed for acquiring novel developmental fates and functions to be implemented in the field of regenerative medicine. (Hepatology 2007.)