bluuebunny/crossref_metadata_2025 huggingface dataset:
4‐Cyano‐6,7‐dimethoxycarbostyrils with Solvent‐ and pH‐Independent High Fluorescence Quantum Yields and Emission Maxima
Authors: Ahvale Appasaheb B. , Prokopcová Hana , Šefčovičová Jana , Steinschifter Waltraud , Täubl Anna E. , Uray Georg , Stadlbauer Wolfgang
Published: November 2007

Highly fluorescent and stable 6,7‐dimethoxy‐2‐oxoquinoline‐4‐carbonitriles (11) were synthesized starting from appropriate 4‐hydroxyquinolones 3 via reactive 4‐chloroquinolones 8 by using toluenesulfinates as catalysts. In contrast to the well‐described 4‐trifluoromethyl‐substituted analogues 18, N‐substituted derivatives 11 fluoresce in water, polar, and apolar solvents in a narrow 430–440‐nm window with almost constant quantum yield of 0.5. Equal excitation is possible in the broad double maximum between 385 and 410 nm yielding identical data between pH 1 and 11. These properties could lead to a broadly usable fluorescence standard. N‐Alkylation with bromoacetate yields ester 13 in good yields. Reactive succinimidoyl (OSu) ester 15 was prepared by saponification to acid 14. With amino acids or peptides, linking to labeled derivatives 17 was achieved under mild conditions in slightly basic aqueous media. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Stimulus‐contrast‐induced biases in activation order reveal interaction between V1/V2 and human MT+
Authors: Maruyama Masaki , Palomo Daniel D. , Ioannides Andreas A.
Published: November 2007

The luminance contrast of a visual stimulus is known to modulate the response properties of areas V1 and the human MT complex (hMT+), but has not been shown to modulate interactions between these two areas. We examined the direction of information transfer between V1/V2 and hMT+ at different stimulus contrasts by measuring magnetoencephalographic (MEG) responses to moving and stationary stimuli presented centrally or peripherally. To determine the direction of information flow, the different response latencies among stimuli and hemispheres in V1/V2 was compared with those of hMT+. At high contrast, responses to stimulus motion and position began in V1/V2, and were followed in hMT+ with a delay between 34 and 55 ms. However, at low contrast, lateralized responses in hMT+ came first, with those in V1/V2 lagging with a delay of 27 ms. Also, at high contrast, stationary stimuli produced greater responses than motion stimuli in V1/V2, while the reverse was true in hMT+, whose response lagged behind the initial response in V1/V2. The same activation order was found using Mutual Information Analysis of the response variances for each condition. Here, the response variances in hMT+ mimicked and trailed those of V1/V2 at high contrast, whereas the reverse was true at low contrast. Such consistent interactions found using two different methodologies strongly supports a processing link between these two areas. The results also suggest that feedback from hMT+ for low‐contrast stimuli compensates for unresolved processing in V1/V2 when the input of a visual image is weak. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.
Understanding second careers: Lessons from a study of U.S. navy admirals
Authors: Baruch Yehuda , Quick James Campbell
Published: November 2007

We examined the career transition of senior executives from a strong bureaucratic organization into a dynamic business environment. In surveying retired, flag‐rank admirals characterized by the need to start a second career, we found significant support for a career transition model. The retired admirals in this study largely enjoyed a smooth transition into civilian careers. Their traditional career was associated primarily with external success, the contemporary protean career with internal success. The role of the organization proved instrumental for a successful transition. © 2007 Wiley Periodicals, Inc.
Career success after stigmatizing organizational events
Authors: Hamori Monika
Published: November 2007

This article examines the effect of six types of stigmatizing organizational events on employees' career moves to another employer: criticism of the organization in the media; resignation of key individuals from the organization; downsizing; a drop in net income; lawsuits launched by the Securities and Exchange Commission, competitors, or customers; and lawsuits launched by employees. Stigmatizing events that signal the decline of corporate performance are the most devastating for professional career success. Outsiders, on the other hand, are less sensitive to an organization's involvement in lawsuits launched by public authorities or employees. Stigmatizing events affect the career success of every professional in the organization, irrespective of his or her hierarchical level. © 2007 Wiley Periodicals, Inc.
How groups learn, continuously
Authors: London Manuel , Sessa Valerie I.
Published: November 2007

This article examines how groups learn, conditions that affect learning, and interventions to improve the learning process. Adaptive group learning is reacting almost automatically to stimuli to make minor changes in process and outcome. Generative group learning is proactive learning for mastery. Transformative group learning is reconstructing meaning and fundamentally changing the way the group operates. Pressures and opportunities in the environment and group readiness stimulate and support these different types of learning. Group leaders, members, and human resource professionals who facilitate, coach, and provide resources for development can apply this knowledge to diagnose group conditions and encourage continuous learning. © 2007 Wiley Periodicals, Inc.
Enhancement of bio‐compatibility via specific interactions in polyesters modified with a bio‐resourceful macromolecular ester containing polyphenol groups
Authors: Yen Kai‐Cheng , Mandal Tarun K. , Woo E.M.
Published: November 2007

Specific interactions and miscibility are demonstrated in a series of binary miscible blend comprising of bio‐compatible/biodegradable polyesters, such as poly(ϵ‐caprolactone) (PCL), poly(ethylene adipate) (PEA), or poly (butylene adipate) (PBA), and a macromolecular ester with polyphenol groups, tannic acid (TA). Thermal analysis and infrared spectroscopy were used for proving existence of favorable interactions, and polarized‐light optical microscopy was used for characterizing the changes in crystal growth. The appearance of a single composition‐dependent glass transition temperature (Tg) observed by differential scanning calorimetry (DSC) indicated that TA is miscible with PCL, PBA, and PEA, respectively, over the entire range of compositions. Fourier transform infrared (FTIR) spectroscopy confirmed the presence of specific intermolecular hydrogen bonding interactions between the carbonyl groups of polyesters and the phenolic hydroxyl groups of TA. The blend Tg's generally exhibited various extents of positive‐then‐negative deviation from linearity with the compositions. The Tg‐composition relationships for three blend systems could all be fitted by the Kwei equation with large negative q values of −80 to −110 for different polyesters. Significant effects by TA on the spherulitic crystallization growth in the polyester/TA blends were also discussed to support the miscibility and strong interactions. Overall, the behavior of blends of polyesters with TA is similar to that of blends of polyesters with poly(vinyl p‐phenol) (PVPh) that have been more widely studied and reported. However, TA is naturally bio‐resourceful, bio‐compatible, and bio‐degradable but PVPh is not. Synergism of miscibility, natural bio‐compatibility, and biodegradability in these blends by introducing naturally biodegradable macromolecules such as TA may offer greater potential in intended applications. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Pre‐treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves engineered heart tissue
Authors: Radisic Milica , Park Hyoungshin , Martens Timothy P. , Salazar‐Lazaro Johanna E. , Geng Wenliang , Wang Yadong , Langer Robert , Freed Lisa E. , Vunjak‐Novakovic Gordana
Published: November 2007

Native myocardium consists of several cell types, of which approximately one‐third are myocytes and most of the nonmyocytes are fibroblasts. By analogy with monolayer culture in which fibroblasts were removed to prevent overgrowth, early attempts to engineer myocardium utilized cell populations enriched for cardiac myocytes (CMs; ∼80–90% of total cells). We hypothesized that the pre‐treatment of synthetic elastomeric scaffolds with cardiac fibroblasts (CFs) will enhance the functional assembly of the engineered cardiac constructs by creating an environment supportive of cardiomyocyte attachment and function. Cells isolated from neonatal rat ventricles were prepared to form three distinct populations: rapidly plating cells identified as CFs, slowly plating cells identified as CMs, and unseparated initial population of cells (US). The cell fractions (3 × 106 cells total) were seeded into poly(glycerol sebacate) scaffolds (highly porous discs, 5 mm in diameter × 2‐mm thick) using Matrigel™, either separately (CM or CF), concurrently (US), or sequentially (CF pre‐treatment followed by CM culture, CF + CM), and cultured in spinner flasks. The CF + CM group had the highest amplitude of contraction and the lowest excitation threshold, superior DNA content, and higher glucose consumption rate. The CF + CM group exhibited compact 100‐ to 200‐μm thick layers of elongated myocytes aligned in parallel over layers of collagen‐producing fibroblasts, while US and CM groups exhibited scattered and poorly elongated myocytes. The sequential co‐culture of CF and CM on a synthetic elastomer scaffold thus created an environment supportive of cardiomyocyte attachment, differentiation, and contractile function, presumably due to scaffold conditioning by cultured fibroblasts. When implanted over the infarcted myocardium in a nude rat model, cell‐free poly(glycerol sebacate) remained at the ventricular wall after 2 weeks of in vivo, and was vascularized. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Oscillatory perfusion seeding and culturing of osteoblast‐like cells on porous beta‐tricalcium phosphate scaffolds
Authors: Du Dajiang , Furukawa Katsuko , Ushida Takashi
Published: November 2007

Perfusion culture systems have proven to be effective bioreactors for constructing tissue engineered bone in vitro, but existing circuit‐based perfusion systems are complicated and costly for conditioned culture due to the large medium volume required. A compact perfusion system for artificial bone fabrication using oscillatory flow is described here. Mouse osteoblast‐like MC 3T3‐E1 cells were seeded at 1.5 × 106 cells/100 μL and cultured for 6 days in porous ceramic beta‐tricalcium phosphate scaffolds (10 mm in diameter, 8 mm in height) by only 1.5 mL culture media per scaffold. The seeding efficiency, cell proliferation, distribution and viability, and promotion of early osteogenesis by both a static and an oscillatory perfusion method were evaluated. The oscillatory perfusion method generated higher seeding efficiency, alkaline phosphatase activity, and scaffold cellularity (by DNA content) after 6 days of culture. Stereomicroscopic observation of 3(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide staining and Calcein‐AM/propidium iodide double staining also demonstrated homogeneous seeding, proliferation, and viability of cells throughout the scaffolds in the oscillatory perfusion system. By contrast, the static culture yielded polarized seeding and proliferation favoring the outer and upper scaffold surfaces, with only dead cells in the center of the scaffolds. Thus, these results suggest that the oscillatory flow condition not only allow a better seeding efficiency and homogeneity, but also facilitates uniform culture and early osteogenic differentiation. The oscillatory perfusion system could be a simple and effective bioreactor for bone tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Bacterial adhesion and osteoblast function on titanium with surface‐grafted chitosan and immobilized RGD peptide
Authors: Shi Zhilong , Neoh K. G. , Kang E. T. , Poh Chyekhoon , Wang W.
Published: November 2007

Biomaterials‐associated infections remain a source of serious complications in modern medicine. When a biomaterial is implanted in the body, the result of successful tissue integration or implant infection depends on the race for the surface between bacteria and tissue cells. One promising strategy to reduce the incidence of infection is the functionalization of the biomaterial surface to inhibit bacterial adhesion and encourage the growth of cells. In this in vitro study, the surface of titanium alloy substrates was first functionalized by covalently grafted chitosan (CS). The cell‐adhesive Arg‐Gly‐Asp (RGD) peptide was then immobilized on the CS‐grafted surface through covalent binding of peptide to the free NH2 groups of CS. Both these functionalized surfaces showed a decrease in adhesion of Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) compared with the pristine substrate. A significant increase in osteoblast cell attachment, proliferation, and alkaline phosphatase activity was observed on the surface with the immobilized Arg‐Gly‐Asp peptide. Thus, utilizing surface‐grafted chitosan in conjunction with the cell‐adhesive peptide to modify the metal surface provides a promising means for enhancing tissue integration of implants by reducing bacterial adhesion and promoting osteoblast functions. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Hemocompatible albumin‐heparin coatings prepared by the layer‐by‐layer technique. The effect of layer ordering on thrombin inhibition and platelet adhesion
Authors: Houska Milan , Brynda Eduard , Solovyev Andrey , Broučková Adéla , Křížová Petra , Vaníčková Martina , Dyr Jan E.
Published: November 2007

Using the layer‐by‐layer technique, ELISA polystyrene plates were coated with multilayer assemblies of albumin with various heparins or with multilayer assemblies of albumin. The coatings containing heparin were tested for their ability to potentiate thrombin inhibition by antithrombin and its dependence on the layer arrangement. The order of activities of surface bound heparins matched their order in solution; however their activity was reduced to less than 10% due to binding. The increasing number of layers increased the activity of the coatings suggesting that heparin inside the assemblies is available for the interaction. The albumin‐heparin assemblies overcoated with albumin layers preserved about half of heparin activity. Platelets adhered in similar amounts to albumin‐heparin and albumin coatings; however, in both cases platelets adhered more to single layer than to multilayer coatings. The adhesion of platelets to single layer coatings was also affected by the crosslinking of the coatings; more platelets adhered to less crosslinked single layer coatings while multilayer coatings remained essentially unaffected by crosslinking. If the coatings were dried and reswollen, a substantial number of platelets adhered to the reconditioned single layer coatings but the two layer coatings were affected much less and the adhesion of platelets to the coatings with three layers was close to normal. A minimum of three albumin‐heparin or albumin layers is apparently required to shield the underlying surface and to achieve proper functioning of the coatings. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Potential of baboon endothelial progenitor cells for tissue engineered vascular grafts
Authors: Hinds Monica T. , Ma MinHui , Tran Noi , Ensley Ann E. , Kladakis Stephanie M. , Vartanian Keri B. , Markway Brandon D. , Nerem Robert M. , Hanson Stephen R.
Published: November 2007

Thrombosis and intimal hyperplasia limit the usefulness of small caliber vascular grafts. While some improvements have been reported for grafts seeded with mature endothelial cells (EC), the harvesting of ECs from autologous sources, for example, veins or adipose tissue, remains problematic. More recently, endothelial progenitor cells (EPCs) have been considered a promising source of ECs because EPCs can be readily isolated from whole blood then rapidly expanded in vitro. Additionally, EPCs are increasingly recognized to play important roles in hemostasis, angiogenesis, and arterial injury repair. However, the characterization of EPCs in relevant animal models remains poorly defined. Accordingly, we have characterized the isolation, growth, and functional characteristics of Baboon EPCs (BaEPCs) to evaluate their potential for an autologous cell source for tissue engineered vascular grafts. BaEPCs were successfully cultured from the peripheral blood with an average population doubling time of 1.17 ± 0.43 days. While the BaEPCs were positive for typical EC markers of vWF, CD31, VE‐cadherin, VEGF‐R2, Thrombomodulin, and E‐selectin, there was reduced eNOS expression. The BaEPCs cell body and actin filaments align in the direction of flow typical of mature ECs. Thus while the lack of eNOS expression is worthy of investigation, EPCs are an attractive cell source for tissue engineered vascular grafts and the baboon model has great potential for continuing evaluations of these cells. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Solubilization and bioconjugation of QDs and their application in cell imaging
Authors: Wang Hai‐Qiao , Zhang Hai‐Li , Li Xiu‐Qing , Wang Jian‐Hao , Huang Zhen‐Li , Zhao Yuan‐Di
Published: November 2007

Quantum dot (QD) solubilization, conjugation with biomolecules, column purification, and labeling of human HepG2 cells with transferrin‐QD (Tf‐QD) conjugates are reported in detail in this article. Water‐soluble QDs (WQDs) were obtained using sodium thiolycolate to replace the surface ligand tri‐n‐octylphosphine oxide (TOPO) on the surface of oil‐soluble QDs, and Tf‐QD conjugates were produced by coupling Tf to WQD. The resulting Tf‐QDs were characterized by UV and luminescence spectrophotometry and purified by Sephadex column. The results indicate that Tf has been conjugated to QD successfully. Based on transferrin/transferrin‐receptor‐mediated delivery system, the Tf‐QD conjugates were used to label human HepG2 cells. After a short incubation, the QDs were mainly localized to the membrane of cells. After 12‐h incubation, QDs appear mainly in the cytoplasm portion. However, QDs were not found in the nucleus of the cells. Furthermore, the fluorescence intensity of QDs in the cells reduces gradually over time, and fluorescence cannot be observed after 10 days. However, the growth of the labeled cells was not markedly affected by the toxicity of QDs, and they are alive for 10 days. These results can be used for further application of QDs in bioscience. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
In vitro engineering of a palatal mucosa equivalent with acellular porcine dermal matrix
Authors: Xiong Xuepeng , Zhao Yifang , Zhang Wei , Xie Weiguo , He Sangang
Published: November 2007

The objective of this study was to develop a palatal mucosa equivalent composed of multilayered oral keratinocytes grown on the acellular porcine dermal matrix. Acellular porcine dermal matrix was prepared through a series of procedures and assessed by histological, immunohistochemical, and scanning electron microscopy examination. The palatal mucosa equivalent was fabricated by seeding oral keratinocytes, which cultured from human palate mucosa, onto the acellular dermal matrix. After 4 days submerged in medium, this composite was raised to the air–liquid interface for another 7 or 14 days of cultivation. The results demonstrated the processed porcine dermal matrix was totally cell‐free. The resultant palatal mucosa equivalent showed a multilayered oral epithelium that had been formed, and the number of cell layers was correlated with the culture period at the air–liquid interface. Oral keratinocytes infiltrated into the empty hair follicles of the acellular porcine dermal matrix and formed an anchor‐like structure, which exhibited resemblance to the rete ridges of the native palate mucosa. Immunohistochemical staining for CK10/13, CK19, Ki‐67 nuclear antigen, and Heparan sulphate indicated the cultured palatal mucosa equivalent shared the same characteristics with that of the native palate mucosa. In conclusion, our fabricated palatal mucosa equivalent exhibited the characteristics of the native counterpart, and this equivalent might be useful for recovery of the wounds in the palate secondary to palatoplasty. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Polyubiquitylation of PARP‐1 through ubiquitin K48 is modulated by activated DNA, NAD+, and dipeptides
Authors: Wang Tao , Simbulan‐Rosenthal Cynthia M. , Smulson Mark E. , Chock P. Boon , Yang David C.H.
Published: November 2007

Poly(ADP‐ribose) polymerase‐1 (PARP‐1) is the most abundant and the best‐studied isoform of a family of enzymes that catalyze the polymerization of ADP‐ribose from NAD+ onto target proteins. PARP‐1 is well known to involve in DNA repair, genomic stability maintenance, transcription regulation, apoptosis, and necrosis. Polyubiquitylation targets proteins towards degradation and regulates cell cycle progression, transcription, and apoptosis. Here we report polyubiquitylation of PARP‐1 in mouse fibroblasts in the presence of proteasome inhibitor and in full‐length recombinant PARP‐1 in vitro under standard ubiquitylation assay conditions by immunoprecipitation and immunoblotting. Mutation of ubiquitin K48R but not ubiquitin K63R abolishes polyubiquitylation of PARP‐1, indicating that K48 of ubiquitin was used in the formation of polyubiquitin chain and that ubiquitylated PARP‐1 is likely destined for degradation. Full‐length PARP‐1 was ubiquitylated most likely at the N‐terminal 24 kDa domain of PARP‐1 as suggested by the inhibition of ubiquitylation by activated DNA and the absence of polyubiquitin in the C‐terminal 89 kDa PARP‐1 derived from caspase‐catalyzed cleavage. NAD+ inhibited ubiquitylation of PARP‐1, while dipeptides ArgAla and LeuAla enhanced ubiquitylation of PARP‐1. ATP inhibited the synthesis of poly(ADP‐ribose) by PARP‐1 and affinity purified polyubiquitylated PARP‐1 was active in PAR synthesis. The results suggest polyubiquitylation of PARP‐1 could regulate poly(ADP‐ribosyl)ation of nuclear proteins by PARP‐1 and consequently apoptosis and PARP‐1 regulated cellular processes through ubiquitin‐dependent degradation pathways. J. Cell. Biochem. 104: 318–328, 2008. © 2007 Wiley‐Liss, Inc.
Detection and characterization of vascular endothelial growth factors and their receptors in a series of angiosarcomas
Authors: Itakura Eijun , Yamamoto Hidetaka , Oda Yoshinao , Tsuneyoshi Masazumi
Published: November 2007

Background

Angiosarcomas are malignant mesenchymal neoplasms, including sarcomas of presumptive vascular endothelial origin and sarcomas of probable lymphatic origin. It is, however, often difficult to determine whether they are from blood vascular or lymphatic endothelium. The majority of angiosarcomas are thought to originate from vascular endothelia and spread via bloodstream to lung, but lymphatic metastases can occur.

Methods

We investigated immunohistochemical expression of vascular endothelial growth factors (VEGF‐A, VEGF‐C) and their receptors (VEGFR‐1, VEGFR‐2, VEGFR‐3) in a series of 34 angiosarcomas.

Results

VEGF‐A was expressed by 32/34 (94%), VEGF‐C by 4/34 (12%), VEGFR‐1 by 32/34 (94%), VEGFR‐2 by 22/34 (65%), and VEGFR‐3 by 27/34 (79%). Patients who expressed low or no VEGFR‐2 showed a significantly unfavorable prognosis by log‐rank test (P = 0.010) and multivariate analysis (hazard ratio, 5.16; 95% CI, 1.40–19.04; P = 0.014). VEGFR‐1 and VEGFR‐3 were not significantly associated with patients' prognosis.

Conclusions

VEGF‐A and VEGFR‐1 were detected in diverse subtypes of angiosarcomas. In cooperation, VEGF‐A and VEGF‐C are likely to be involved in the development of angiosarcoma associated with lymphedema. VEGF‐C expression may cause susceptibility to lymphatic metastasis through tumor lymphangiogenesis. Angiosarcoma of the scalp, which is traditionally considered as a true hemangiosarcoma, may include some cases of lymphatic origin. J. Surg. Oncol. 2008;97:74–81. © 2007 Wiley‐Liss, Inc.
Experimental Correlation between Mechanical Non‐Linearity in LAOS Flow and Capillary Flow Instabilities for Linear and Branched Commercial Polyethylenes
Authors: Filipe Susana , Vittorias Iakovos , Wilhelm Manfred
Published: November 2007

An experimental correlation between the non‐linear behaviour of commercial polyethylene melts in LAOS flow, and the pressure fluctuations associated with melt flow instabilities developed in capillary rheometry are presented. Polyethylene melts with enhanced non‐linear behaviour under LAOS conditions present larger pressure fluctuations during capillary extrusion, and consequently, larger surface distortions on the extrudate. The combination of both methods can be a tool to predict the development of melt flow instabilities in the extrusion process of polyethylene melts, and can elucidate their correlation with material structural properties ($\overline M _{\rm w}$, MWD and topology).

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Diabetes mellitus and female lower urinary tract symptoms: A review
Authors: Hill Simon R. , Fayyad Abdalla M. , Jones Geraint R.
Published: November 2007

Diabetes mellitus (DM) has reached epidemic proportions world wide. Many chronic complications of DM, including neuropathy, retinopathy and nephropathy, have been well studied and although urologic complications have been recognized since 1935, little is known about DM as a pathophysiological risk factor for development of lower urinary tract symptoms (LUTS) in women. Diabetic nephropathy, a life‐threatening condition, has received considerable attention in the last few years. Diabetic cystopathy, on the other hand, has received far less attention despite having a significant impact on quality of life, and with significant individual health risks. Initial studies suggested that long standing DM causes paralysis of the detrusor muscle leading to voiding difficulties and this has been the received wisdom regarding diabetic cystopathy for many years. In this review, we discuss what is currently known about lower urinary tract function and urinary incontinence in diabetic females, with a critical analysis of the available evidence and suggest areas for future research. Neurourol. Urodynam. 27:362–367, 2008. © 2007 Wiley‐Liss, Inc.
Bladder voiding by combined high frequency electrical pudendal nerve block and sacral root stimulation
Authors: Boger Adam , Bhadra Narendra , Gustafson Kenneth J.
Published: November 2007

Aims

Uncoordinated contraction of the external urethral sphincter is prevalent in individuals with spinal cord injury and can prevent bladder voiding. The aim of this study was to demonstrate that complete and reversible sinusoidal high frequency alternating current (HFAC) conduction block of the pudendal nerves (PN) can eliminate external urethral sphincter activation and produce low residual bladder voiding.

Methods

In four cats, tripolar nerve cuff electrodes were implanted bilaterally on both pudendal nerves and on both extradural S2 roots. Bladder and urethral pressures, bladder volumes and flow were recorded. Bilateral HFAC was applied to determine voltage and frequency parameters resulting in bilateral PN conduction block. Sacral root stimulation provided bladder activation. Randomized sets of voiding trials were conducted with and without HFAC PN block. Additional voiding trials were conducted following bilateral PN neurotomy to eliminate somatic sphincter resistance and provide an estimate of voiding with complete block.

Results

Effective bilateral PN block and voiding was obtained in three of four animals. Application of bilateral PN HFAC stimulation improved voiding from 2 ± 4% to 77 ± 18% of the initial bladder volume and significantly (P < 0.001) reduced maximum bladder pressure during voiding. Voiding in trials with PN block was not significantly different from voiding following PN neurotomy (82 ± 19%, P = 0.51).

Conclusions

These results demonstrate that bilateral HFAC block of the PN can produce effective voiding. Neural prostheses using this approach may provide an alternative method for producing micturition for people with spinal cord injury. Neurourol. Urodynam. 27:435–439, 2008. © 2007 Wiley‐Liss, Inc.
Surfactant assisted polymerization of tetrafluoroethylene in supercritical carbon dioxide with a pilot scale batch reactor
Authors: Giaconia Alberto , Scialdone Onofrio , Apostolo Marco , Filardo Giuseppe , Galia Alessandro
Published: November 2007

Chain‐free radical polymerization of tetrafluoroethylene (TFE) was carried out in supercritical carbon dioxide (scCO2), at 50 °C and 121–133 bar, with tertiary‐amyl‐per‐pivalate as a free radical initiator, using a 5‐L pilot scale batch reactor. Experiments were carried out both in the absence and in the presence of perfluoropolyether (PFPE) carboxylate surfactants. Stabilizers were employed under the free acid form and as sodium and calcium salts. An expanded fibrillated poly(TFE) was obtained in all experiments. In the case of surfactant‐free polymerizations, the product was mainly constituted by irregular shape macroparticles having size in the range 200–500 μm. Quite interestingly, when the free acid surfactant was used, a clear acceleration of the polymerization rate was observed and smaller polymer particles with more regular quasi‐spherical morphology were obtained. Melt fusion crystallinity of as‐polymerized poly(TFE) seemed not substantially affected by the presence of the stabilizers and was rather high (80–86%) suggesting that polymerization mainly occurs at polymer particle surface. All these elements suggest that FLUOROLINK® 7004H PFPE carboxylic acid decreases coagulation of primary polymer particles leading to an increase in polymer surface area. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 257–266, 2008
Synthesis and characterization of water‐soluble gold nanoparticles stabilized by comb‐shaped copolymers
Authors: Han De‐Hui , Pan Cai‐Yuan
Published: November 2007

The water‐soluble gold nanoparticles stabilized by well‐defined comb‐shaped copolymers have been synthesized successfully. The hybrid nanoparticles consist of gold core and poly[poly(ethylene oxide) methyl ether acrylate]‐block‐poly(N‐isopropylacrylamide) [P(A‐MPEO)‐block‐PNIPAM] shell. The water‐soluble comb‐shaped copolymers, P(A‐MPEO)‐block‐PNIPAM with PNIPAM as a handle, were successfully synthesized via a macromonomer technique using reversible addition fragmentation chain transfer (RAFT) polymerization method. The terminal dithioester group of the comb‐shaped copolymer was reduced to a thiol end group forming SH‐terminated copolymers, P(A‐MPEO)‐block‐PNIPAM‐SH. Successively they were used to stabilize gold nanoparticles by the “grafting‐to” approach. The hybrid nanoparticles were characterized by TEM, UV–vis, and HRTEM. Because of the thermosensitive property of PNIPAM in aqueous solution, the comblike copolymer‐tethered gold nanoparticles show a sharp and reversible phase transition at 30 °C in aqueous solution, which was determined by microdifferential scanning calorimetry. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 341–352, 2008
CO escape from myoglobin with metadynamics simulations
Authors: Ceccarelli Matteo , Anedda Roberto , Casu Mariano , Ruggerone Paolo
Published: November 2007

The relatively small size of myoglobin makes it suitable for the investigation of the ligand escape process in respiratory proteins and, in general, an ideal model system for the study of the more general structure‐function paradigm. In this work, we use Molecular Dynamics simulations combined with an accelerated algorithm, the metadynamics, to probe the escape of CO from myoglobin. Our approach permits to quantitatively describe the escape process via the reconstruction of the associated free energy surface. Additionally, hints on the involvement of a larger numbers of residues than hitherto assumed in the gating process are extracted from our data. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Modeling of metal interaction geometries for protein–ligand docking
Authors: Seebeck Birte , Reulecke Ingo , Kämper Andreas , Rarey Matthias
Published: November 2007

The accurate modeling of metal coordination geometries plays an important role for structure‐based drug design applied to metalloenzymes. For the development of a new metal interaction model, we perform a statistical analysis of metal interaction geometries that are relevant to protein–ligand complexes. A total of 43,061 metal sites of the Protein Data Bank (PDB), containing amongst others magnesium, calcium, zinc, iron, manganese, copper, cadmium, cobalt, and nickel, were evaluated according to their metal coordination geometry. Based on statistical analysis, we derived a model for the automatic calculation and definition of metal interaction geometries for the purpose of molecular docking analyses. It includes the identification of the metal‐coordinating ligands, the calculation of the coordination geometry and the superposition of ideal polyhedra to identify the optimal positions for free coordination sites. The new interaction model was integrated in the docking software FlexX and evaluated on a data set of 103 metalloprotein‐ligand complexes, which were extracted from the PDB. In a first step, the quality of the automatic calculation of the metal coordination geometry was analyzed. In 74% of the cases, the correct prediction of the coordination geometry could be determined on the basis of the protein structure alone. Secondly, the new metal interaction model was tested in terms of predicting protein–ligand complexes. In the majority of test cases, the new interaction model resulted in an improved docking accuracy of the top ranking placements. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Estimating quality of template‐based protein models by alignment stability
Authors: Chen Hao , Kihara Daisuke
Published: November 2007

The error in protein tertiary structure prediction is unavoidable, but it is not explicitly shown in most of the current prediction algorithms. Estimated error of a predicted structure is crucial information for experimental biologists to use the prediction model for design and interpretation of experiments. Here, we propose a method to estimate errors in predicted structures based on the stability of the optimal target‐template alignment when compared with a set of suboptimal alignments. The stability of the optimal alignment is quantified by an index named the SuboPtimal Alignment Diversity (SPAD). We implemented SPAD in a profile‐based threading algorithm and investigated how well SPAD can indicate errors in threading models using a large benchmark dataset of 5232 alignments. SPAD shows a very good correlation not only to alignment shift errors but also structure‐level errors, the root mean square deviation (RMSD) of predicted structure models to the native structures (i.e. global errors), and local errors at each residue position. We have further compared SPAD with seven other quality measures, six from sequence alignment‐based measures and one atomic statistical potential, discrete optimized protein energy (DOPE), in terms of the correlation coefficient to the global and local structure‐level errors. In terms of the correlation to the RMSD of structure models, when a target and a template are in the same SCOP family, the sequence identity showed a best correlation to the RMSD; in the superfamily level, SPAD was the best; and in the fold level, DOPE was best. However, in a head‐to‐head comparison, SPAD wins over the other measures. Next, SPAD is compared with three other measures of local errors. In this comparison, SPAD was best in all of the family, the superfamily and the fold levels. Using the discovered correlation, we have also predicted the global and local error of our predicted structures of CASP7 targets by the SPAD. Finally, we proposed a sausage representation of predicted tertiary structures which intuitively indicate the predicted structure and the estimated error range of the structure simultaneously. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Stabilization of antibody structure upon association to a human carbonic anhydrase IX epitope studied by X‐ray crystallography, microcalorimetry, and molecular dynamics simulations
Authors: Král Vlastimil , Mader Pavel , Collard Renata , Fábry Milan , Hořejší Magdaléna , Řezáčová Pavlína , Kožíšek Milan , Závada Jan , Sedláček Juraj , Rulíšek Lubomír , Brynda Jiří
Published: November 2007

Specific antibodies interfere with the function of human tumor‐associated carbonic anhydrase IX (CA IX), and show potential as tools for anticancer interventions. In this work, a correlation between structural elements and thermodynamic parameters of the association of antibody fragment Fab M75 to a peptide corresponding to its epitope in the proteoglycan‐like domain of CA IX, is presented. Comparisons of the crystal structures of free Fab M75 and its complex with the epitope peptide reveal major readjustments of CDR‐H1 and CDR‐H3. In contrast, the overall conformations and positions of CDR‐H2 and CDR‐L2 remain unaltered, and their positively charged residues may thus present a fixed frame for epitope recognition. Adoption of the altered CDR‐H3 conformation in the structure of the complex is accompanied by an apparent local stabilization. Analysis of domain mobility with translation‐libration‐screw (TLS) method shows that librations of the entire heavy chain variable domain (VH) decrease and reorient in the complex, which correlates well with participation of the heavy chain in ligand binding. Isothermal titration microcalorimetry (ITC) experiments revealed a highly unfavorable entropy term, which can be attributed mainly to the decrease in the degrees of freedom of the system, the loss of conformational freedom of peptide and partially to a local stabilization of CDR‐H3. Moreover, it was observed that one proton is transferred from the environment to the protein‐ligand complex upon binding. Molecular dynamics simulations followed by molecular mechanics/generalized Born surface area (MM‐GBSA) calculations of the ligand (epitope peptide) binding energy yielded energy values that were in agreement with the ITC measurements and indicated that the charged residues play crucial role in the epitope binding. Theoretical arguments presented in this work indicate that two adjacent arginine residues (ArgH50 and ArgH52) are responsible for the observed proton transfer. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Large scale analysis of protein‐binding cavities using self‐organizing maps and wavelet‐based surface patches to describe functional properties, selectivity discrimination, and putative cross‐reactivity
Authors: Kupas Katrin , Ultsch Alfred , Klebe Gerhard
Published: November 2007

A new method to discover similar substructures in protein binding pockets, independently of sequence and folding patterns or secondary structure elements, is introduced. The solvent‐accessible surface of a binding pocket, automatically detected as a depression on the protein surface, is divided into a set of surface patches. Each surface patch is characterized by its shape as well as by its physicochemical characteristics. Wavelets defined on surfaces are used for the description of the shape, as they have the great advantage of allowing a comparison at different resolutions. The number of coefficients to describe the wavelets can be chosen with respect to the size of the considered data set. The physicochemical characteristics of the patches are described by the assignment of the exposed amino acid residues to one or more of five different properties determinant for molecular recognition. A self‐organizing neural network is used to project the high‐dimensional feature vectors onto a two‐dimensional layer of neurons, called a map. To find similarities between the binding pockets, in both geometrical and physicochemical features, a clustering of the projected feature vector is performed using an automatic distance‐ and density‐based clustering algorithm. The method was validated with a small training data set of 109 binding cavities originating from a set of enzymes covering 12 different EC numbers. A second test data set of 1378 binding cavities, extracted from enzymes of 13 different EC numbers, was then used to prove the discriminating power of the algorithm and to demonstrate its applicability to large scale analyses. In all cases, members of the data set with the same EC number were placed into coherent regions on the map, with small distances between them. Different EC numbers are separated by large distances between the feature vectors. A third data set comprising three subfamilies of endopeptidases is used to demonstrate the ability of the algorithm to detect similar substructures between functionally related active sites. The algorithm can also be used to predict the function of novel proteins not considered in training data set. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Artificial Neural Networks: Useful Aid in Diagnosing Acute Appendicitis
Authors: Prabhudesai S. G. , Gould S. , Rekhraj S. , Tekkis P. P. , Glazer G. , Ziprin P.
Published: November 2007

Backround

The purpose of the study was to assess the role of artificial neural networks (ANNs) in the diagnosis of appendicitis in patients presenting with acute right iliac fossa (RIF) pain and comparing its performance with the assessment made by experienced clinicians and the Alvarado score.

Methods

After training and testing an ANN, data from 60 patients presenting with suspected appendicitis over a 6‐month period to a teaching hospital was collected prospectively. Accuracy of diagnosing appendicitis by the clinician, the Alvarado score, and the ANN was compared.

Results

The sensitivity, specificity, and positive and negative predictive values of the ANN were 100%, 97.2%, 96.0%, and 100% respectively. The ability of the ANN to exclude accurately the diagnosis of appendicitis in patients without true appendicitis was statistically significant compared to the clinical performance (p = 0.031) and Alvarado score of ≥6 (p = 0.004) and nearly significant compared to the Alvarado score of ≥7 (p = 0.063).

Conclusions

ANNs can be an effective tool for accurately diagnosing appendicitis and may reduce unnecessary appendectomies.
Family Support and Cardiac Rehabilitation: A Comparative Study of the Experiences of South Asian and White-European Patients and Their Carer's Living in the United Kingdom
Authors: Astin Felicity , Atkin Karl , Darr Aliya
Published: November 2007

Background: Effective lifestyle modification facilitated by cardiac rehabilitation is known to reduce the occurrence of adverse coronary events and mortality. South Asians have poorer outcomes after a myocardial infarction than the general UK population, but little is known about their experiences of family support, cardiac rehabilitation and lifestyle change.

Aims: To explore the nature of family support available to a sample of South Asian and White-European cardiac patients and to highlight similarities and differences between these groups with regard to cardiac rehabilitation and lifestyle modification.

Methods: Using a qualitative approach, semi-structured interviews (in 1 of 6 languages) were conducted by researchers with; 45 South Asian patients and 37 carers and 20 White-European patients and 17 carers. Interviews were conducted in a home setting, up to eighteen months after discharge from hospital following myocardial infarction, coronary artery bypass surgery or unstable angina.

Results: The main themes that emerged related to the provision of advice and information, family support and burden, dietary change and exercise regimes.

Conclusions: Several cultural and ethnic differences were identified between patients and their families alongside similarities, irrespective of ethnicity. These may represent generic characteristics of recovery after a cardiac event. Health professionals should develop a cultural repertoire to engage with diversity and difference. Not every difficulty a person encounters as they try to access appropriate service delivery can be attributed to ethnic background. By improving services generally, support for South Asian populations can be improved. The challenge is to know when ethnicity makes a difference and mediates a person's relationship with service support and when it does not.
p38MAP Kinase activity is required for human primary adipocyte differentiation
Authors: Aouadi M. , Jager J. , Laurent K. , Gonzalez T. , Cormont M. , Binétruy B. , Le Marchand-Brustel Y. , Tanti J.-F. , Bost F.
Published: November 2007

Little is known about the role of p38MAPK in human adipocyte differentiation. Here we showed that p38MAPK activity increases during human preadipocytes differentiation. Pharmacological inhibition of p38MAPK during adipocyte differentiation of primary human preadipocytes markedly reduced triglycerides accumulation and adipocyte markers expression. Cell cycle arrest or proliferation was not affected by p38MAPK inhibition. Although induction of C/EBPβ was not altered by the p38MAPK inhibitor, its phosphorylation on Threonine188 was decreased as well as PPARγ expression. These results indicate that p38MAPK plays a positive role in human adipogenesis through regulation of C/EBPβ and PPARγ factors.
Taurine increases cell proliferation and generates an increase in [Mg2+]i accompanied by ERK 1/2 activation in human osteoblast cells
Authors: Jeon Seol-Hee , Lee Mun-Young , Kim Shang-Jin , Joe Sung-Gun , Kim Gi-Beum , Kim In-Shik , Kim Nam-Soo , Hong Chul-Un , Kim Sung-Zoo , Kim Jin-Shang , Kang Hyung-Sub
Published: November 2007

Taurine has been reported to influence bone metabolism, and its specific transport system, the taurine transporter, is expressed in osteoblasts. The mean [Mg2+]i was 0.51 ± 0.01 mM in normal culture media. Taurine caused an increase in [Mg2+]i by 0.72 ± 0.04 mM in human osteoblast (HOB) cells. This increment in [Mg2+]i was inhibited significantly by PD98059, nifedipine, lidocaine, and imipramine. Taurine was also shown to stimulate the activation of ERK 1/2. This taurine‐stimulated ERK 1/2 activation was inhibited by PD98059. In the present study, taurine was shown to increase cell proliferation and generate an increase in [Mg2+]i accompanied by ERK 1/2 activation in HOB cells.
Phosphatidic acid plays a special role in stabilizing and folding of the tetrameric potassium channel KcsA
Authors: Raja Mobeen , Spelbrink Robin E.J. , de Kruijff Ben , Killian J. Antoinette
Published: November 2007

In this study, we investigated how the presence of anionic lipids influenced the stability and folding properties of the potassium channel KcsA. By using a combination of gel electrophoresis, tryptophan fluorescence and acrylamide quenching experiments, we found that the presence of the anionic lipid phosphatidylglycerol (PG) in a phosphatidylcholine (PC) bilayer slightly stabilized the tetramer and protected it from trifluoroethanol‐induced dissociation. Surprisingly, the presence of phosphatidic acid (PA) had a much larger effect on the stability of KcsA and this lipid, in addition, significantly influenced the folding properties of the protein. The data indicate that PA creates some specificity over PG, and that it most likely stabilizes the tetramer via both electrostatic and hydrogen bond interactions.
PPARδ as a therapeutic target in metabolic disease
Authors: Reilly Shannon M. , Lee Chih-Hao
Published: November 2007

PPARδ is the only member in the PPAR subfamily of nuclear receptors that is not a target of current drugs. Animal studies demonstrate PPARδ activation exerts many favorable effects, including reducing weight gain, increasing skeletal muscle metabolic rate and endurance, improving insulin sensitivity and cardiovascular function and suppressing atherogenic inflammation. These activities stem largely from the ability of PPARδ to control energy balance, reduce fat burden and protect against lipotoxicity caused by ectopic lipid deposition. Therefore, PPARδ represents a novel therapeutic target and the development of PPARδ gonists/modulators may be useful for treating the whole spectrum of metabolic syndrome.