bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary health care reform in Uzbekistan
Authors: Ahmedov Mohir , Rechel Bernd , Alimova Vasila , Azimov Ravshan
Published: August 2007

In recent years, primary health care in Uzbekistan has seen dramatic changes in organization, management and financing. The Soviet multi‐tiered system of primary care is being replaced by a two‐tiered system, consisting in rural areas of rural physician points (SVPs) and outpatient clinics of central rayon hospitals. A state‐guaranteed benefits package of primary care services has been introduced and financing is increasingly based on capitation. In addition, a considerable number of physicians and nurses have been trained in general practice. There are, however, a number of challenges that remain. One of them is the considerable regional differences that exist in health financing. Another challenge is that some rural areas have difficulties attracting primary care workers. Overall, the institutional and financial link between primary and secondary care needs to be strengthened, as at present GPs have an incentive to refer patients to higher levels of care, which is financially inaccessible for large parts of the population. Copyright © 2007 John Wiley & Sons, Ltd.
Perceived purposes of performance appraisal: Correlates of individual‐ and position‐focused purposes on attitudinal outcomes
Authors: Youngcourt Satoris S. , Leiva Pedro I. , Jones Robert G.
Published: August 2007

Performance appraisals have traditionally been directed at individuals, serving either an administrative or developmental purpose. They may serve a role definition purpose as well. This study sought to identify and more broadly define the purposes of performance appraisals to include this role definition purpose. Furthermore, this study examined purposes of performance appraisals as perceived by the role incumbent, as opposed to the stated organizational purposes. The relationships between these perceived purposes with several attitudinal outcomes, including satisfaction with the performance appraisal, job satisfaction, affective commitment, and role ambiguity, are reported. Data from 599 retail service employees were used to test the hypothesized relationships. Results suggested support for a model consisting of three performance appraisal purposes having differential relationships with the outcomes examined, suggesting the purpose of the performance appraisal may influence ratees' perceptions of and attitudes toward their jobs.
The impact of workplace attire on employee self‐perceptions
Authors: Peluchette Joy V. , Karl Katherine
Published: August 2007

This study examined employee preferences for different styles of workplace attire and how wearing various styles of clothing affected their self‐perceptions. Respondents felt most authoritative, trustworthy, and competent when wearing formal business attire but friendliest when wearing casual or business casual attire. Significant two‐way interactions were found between dress preference and mode of dress worn on self‐perceptions of productivity, trustworthiness, creativity, and friendliness. Suggestions for future research and implications for HRD professionals are proposed.
Engaging in personal business on the job: Extending the presenteeism construct
Authors: D'Abate Caroline P. , Eddy Erik R.
Published: August 2007

Presenteeism describes the situation when workers are on the job but, because of illness, injury, or other conditions, they are not functioning at peak levels. Although much of the research on presenteeism appears in the medical literature, we argue that presenteeism also occurs when employees go to work but spend a portion of the workday engaging in personal business while on the job, such as e‐mailing friends, paying personal bills, or making personal appointments. Results of a Web‐based survey of 115 individuals suggest that employees spend approximately one hour and twenty minutes in a typical workday engaged in personal activities, costing their employers an average $8,875 each year in lost productivity per employee. Results suggest that engagement in personal business on the job is not related to self‐reported measures of performance, efficiency, job satisfaction, organizational commitment, or intentions to stay, only to procrastination. Implications of these findings for practice and research are discussed.
Dynamic interactions between two models of team development and learning: Implications for performance and human resource managers
Authors: Hall Jim
Published: August 2007

Team‐based activities have become commonplace in many organizations. Research on team effectiveness has included studies on the effect of several variables, including goals, reward systems, team composition, type of task, and norms conducive to innovation. These all can be seen as the context for a team's ability to develop and learn. This article extends the existing research by briefly reviewing two dominant theories of team development and learning (the stages of development model and the punctuated equilibrium model) and then proposes, using seven propositions, a synthesis of the two models, showing how they need to interact to ensure optimal team effectiveness. Several implications for human resource development are identified.
Social experiences in infancy and early childhood co‐sleeping
Authors: Hayes Marie J. , Fukumizu Michio , Troese Marcia , Sallinen Bethany A. , Gilles Allyson A.
Published: August 2007

Infancy and early childhood sleep–wake behaviours from current and retrospective parental reports were used to explore the relationship between sleeping arrangements and parent–child nighttime interactions at both time points. Children (N=45) from educated, middle‐class families, mostly breastfed in infancy, composed a convenience sample that was recruited from a university preschool in the Northeast US. Parents responded to the Sleep Habits Inventory, a 19‐item Likert‐style inventory measuring sleep‐related behaviours during the last week, and the Sleeping Arrangements Questionnaire, a 30‐question, open‐ended, short‐answer‐style instrument which queries both retrospective infancy and current sleep location, bedtime routine, night waking and parent–child interactions during the sleep period. Co‐sleeping in early childhood was associated with sleep location in infancy (i.e. proximity to the mother's bed) during wake–sleep transitions and night feedings. Security object use during infancy was inversely related to early childhood co‐sleeping (calling for the parents, night waking, poor bedtime routine and fear of the dark). Results showed that early childhood co‐sleeping in this sample was reactive, i.e. associated with current parent‐seeking, night waking and social contact during wake–sleep transitions. These findings suggest that co‐sleeping in early childhood is related to social experiences during infancy, particularly the amount of parent social contact and security object use. Copyright © 2007 John Wiley & Sons, Ltd.
LC/MS identification of 12 intracellular cytoskeletal and inflammatory proteins from monocytes adherent on surface‐adsorbed fibronectin‐derived peptides
Authors: Zuckerman Sean T. , Kao Weiyuan John
Published: August 2007

The extent and duration of the host response determines device efficacy, yet the mechanism is poorly understood. U937 promonocytic cells were cultured on peptide‐adsorbed tissue‐culture polystyrene to better understand surface‐modulated intracellular events. Phosphotyrosine proteins were enriched by immunoprecipitation and analyzed by nanospray HPLC‐coupled tandem mass spectrometry (LC/MS). Tyrosine‐phosphorylated proteins were chosen based on physiological significance and previous densitometry results, which identified a set of proteins ranging from ∼200 to ∼23 kDa showing altered phosphorylation levels in response to various surface‐adsorbed ligands and phosphorylation inhibitor AG18. Although LC/MS has been used for nearly a decade, its application to the field of biomaterials is relatively novel. Twelve intracellular proteins identified by nanospray LC/MS are potentially related to the host response. Eight of the twelve proteins are related to the cytoskeleton including: moesin, heat shock protein 90β, α‐tubulin, elongation factor 1α, β actin, vimentin, plasminogen activator inhibitor 2, and heterogeneous ribonuclear protein A2. The remaining four proteins: high mobility group box 1, caspase recruitment domain 5, glycoprotein 96, and heterogeneous nuclear ribonucleoprotein D0 modulate inflammation. The specific effect each peptide has upon modulating the phosphorylation state of these proteins cannot be determined from this work; however, 12 viable targets have been identified for further investigation into the role each plays in the surface‐mediated monocyte response. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Structure–property relations and cytotoxicity of isosorbide‐based biodegradable polyurethane scaffolds for tissue repair and regeneration
Authors: Gogolewski Sylwester , Gorna Katarzyna , Zaczynska Ewa , Czarny Anna
Published: August 2007

Microporous scaffolds with potential applications for tissue engineering were produced from the biodegradable aliphatic isosorbide‐based polyurethane using a combined salt leaching–solvent evaporation–coagulation process. Alkaline sodium phosphate heptahydrate crystals were used as a solid porogene, and acetone–water mixture was used as a nonsolvent–coagulant. The scaffolds used in this study had interconnected pores with sizes in the range of 70–120 μm and a pore‐to‐volume ratio of 87%. The XPS measurements showed that the residence of the scaffold in an aqueous solution of the alkaline porogene changed its surface atomic composition, that is increased the surface concentration of oxygen and nitrogen and reduced the surface concentration of hydrocarbons relative to the control material. This also enhanced the hydrophilicity of the scaffold's surfaces as assessed from contact angle measurements. The alkaline porogene did not affect the polymer's molecular weight. The MTT cytotoxicity assay showed that the isosorbide‐based polyurethane scaffold is noncytotoxic. The amounts of interleukin‐6 and interlukin‐8 proinflammatory cytokines released from human blood leukocytes exposed to the polyurethane scaffolds in vitro were comparable and/or lower than the amount of the cytokines released by leukocytes exposed to the culture‐grade polystyrene control. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Amphotericin B‐loaded poly(ethylene glycol)–poly(lactide) micelles: Preparation, freeze‐drying, and in vitro release
Authors: Yang Zhuo Li , Li Xin Ru , Yang Ke Wei , Liu Yan
Published: August 2007

Polymeric micelles prepared from a series of poly(ethylene glycol)–poly(lactide) (PEG–PLA) diblock copolymers with various PLA chain lengths were designed as drug carriers for water insoluble drug amphotericin B (AmB). Physicochemical properties of AmB‐loaded micelles were evaluated. Micelles were freeze‐dried to obtain long‐time stable formulations. The redispersibility of the freeze‐dried samples was poor when the weight ratio of PLA block was bigger than the PEG block of the copolymer. Various types of lyoprotectants including saccharides and PEGs with different molecular weight were tested to improve the redispersion performance of the freeze‐dried samples. PEG was proved to be more effective than saccharides on stabilizing the micelles during lyophilization when the weight ratio of PLA block was bigger than PEG block. The sustained release in vitro of AmB was evidenced. About 80% of AmB was released in 80 h. The in vitro release behavior could be best described by the first‐order equation. The release rate was reduced as enhancing PLA chain length due to the stronger interaction between poorly water‐soluble AmB and longer hydrophobic chain length of PLA. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Staphylococcus epidermidis is cleared from biomaterial implants but persists in peri‐implant tissue in mice despite rifampicin/vancomycin treatment
Authors: Broekhuizen Corine A.N. , de Boer Leonie , Schipper Kim , Jones Christopher D. , Quadir Shan , Vandenbroucke‐Grauls Christina M.J.E. , Zaat Sebastian A.J.
Published: August 2007

Infections associated with implanted biomedical devices (BAI) are predominantly caused by Staphylococcus epidermidis. We previously observed in murine experimental BAI that S. epidermidis persists in peri‐implant tissue rather than on the implanted biomaterial itself (Boelens et al., J Infect Dis 2000;181:1337–1349; Broekhuizen et al., Infect Immun 2007;75:1129–1136). To investigate the efficacy of rifampicin/vancomycin to clear S. epidermidis from implants and peri‐implant tissues, mice with two implants were challenged with 107 cfu S. epidermidis per implant and received daily injections of rifampicin (25 mg/kg) and vancomycin (50 mg/kg). On the day of termination, implants and peri‐implant tissue were collected and processed for culture and histology. After 1 and 8 days, implants of control mice were culture positive in 14/18 and 5/16 cases, respectively, and tissue biopsies were all culture positive. In the antibiotic‐treated mice, bacteria were recovered from only 1/18 and 1/16 implants after 1 and 8 days, respectively, whereas the tissues were culture positive in 14/18 and 7/16 biopsies, respectively. In microscopy, bacteria were seen in the tissue at a distance of several cell layers from the tissue‐implant interface, colocalized with host cells. Thus, although a regimen of rifampicin/vancomycin sterilized the implants, S. epidermidis persisted in peri‐implant tissue, which might be an as yet unrecognized reservoir in the pathogenesis of BAI. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Effects of confinement on the mechanical properties of self‐assembled articular cartilage constructs in the direction orthogonal to the confinement surface
Authors: Elder Benjamin D. , Athanasiou Kyriacos A.
Published: August 2007

This study examined the effects of radial confinement and passive axial compression‐induced vertical confinement, on the biomechanical, biochemical, and histological properties of self‐assembled chondrocyte constructs. The self‐assembled constructs, engineered without the use of an exogenous scaffold, exhibited significant increases in stiffness in the direction orthogonal to that of the confinement surface. With radial confinement, the significantly increased aggregate modulus was accompanied by increased collagen organization in the direction perpendicular to the articular surface, with no change in collagen or glycosaminoglycan (GAG) content. Additionally, radial confinement was most beneficial when applied before 2 weeks. With passive axial compression, the significantly increased Young's modulus and ultimate tensile strength were accompanied by a significant increase in collagen production. This study is the first to demonstrate the beneficial effects of confinement on tissue engineered constructs in the direction orthogonal to that of the confinement surface. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:238–246, 2008
Visitor and non‐visitor images of Central and Eastern Europe: a qualitative analysis
Authors: Hughes Howard L. , Allen Danielle
Published: August 2007

This study examines the image of Central and Eastern Europe (CEE) as a holiday destination. The countries are linked by having had communist governments and being inaccessible to tourists from outside the communist bloc. Currently, they seek new tourist markets and this study examines the views of a number of UK residents about destination image of CEE. The study examines, through semi‐structured interviews, images held by people who have and who have not visited CEE. The data is analysed qualitatively. Few significant differences were found between views of visitors and non‐visitors; most views were positive and associated favourably with ‘culture’. Negative images were usually associated with the eastern part of the area especially ex‐Yugoslavia. Copyright © 2007 John Wiley & Sons, Ltd.
Explaining hump‐shaped inflation responses to monetary policy shocks
Authors: Yetman James
Published: August 2007

According to conventional wisdom, the output effects of a monetary policy shock commence within months of the shock, while most inflationary effects lag significantly. We demonstrate a simple model that can explain the conventional wisdom and is consistent with profit maximizing price setting decisions by firms, based on the assumption that renegotiating existing contracts is costly. Thus, firms jointly choose both their price and the expected length of time for which that price will hold each time they re‐contract. We show that such a ‘sticky contracting’ assumption, combined with menu costs, generates a hump‐shaped inflation response to monetary policy shocks. Copyright © 2007 John Wiley & Sons, Ltd.
Production, inventory and waiting time
Authors: Epstein Gil S.
Published: August 2007

In this paper, I introduce the idea of adjusting waiting time as an alternative to price adjustment in order to study the relationship between waiting time, demand, profits and inventories. In the model, demand depends on both price and waiting time. Consumers are willing to pay more if they do not have to wait long. I derive the conditions under which a monopoly may profit from utilizing the option of holding inventory by changing the waiting time facing the consumers. Copyright © 2007 John Wiley & Sons, Ltd.
The frequency and costs of individual price adjustment
Authors: Wolman Alexander L.
Published: August 2007

How often do the nominal prices of individual goods change? What is the nature of costs of price adjustment? How big are these costs? Answering these questions may be important for constructing macroeconomic models that are useful for monetary policy analysis. The empirical literature reveals that many prices do change infrequently, in part because of physical costs of price adjustment. However, infrequent price adjustment also seems to be related to costs of decision making, to relationships between buyers and sellers, and to strategic behavior among sellers, all in ways that are not yet well understood. Copyright © 2007 John Wiley & Sons, Ltd.
Limited stability in cell culture medium and hydrogen peroxide formation affect the growth inhibitory properties of delphinidin and its degradation product gallic acid
Authors: Kern Melanie , Fridrich Diana , Reichert Julia , Skrbek Susanne , Nussher Anja , Hofem Sabine , Vatter Sandra , Pahlke Gudrun , Rüfer Corinna , Marko Doris
Published: August 2007

In the present study we investigated the stability of anthocyanidins under cell culture conditions and addressed the question whether degradation products might contribute to the cellular effects assigned to the parent compounds. Substantial degradation was found already after 30 min, measured by HPLC/DAD. However, the decrease of detectable anthocyanidins exceeded by far the formation of the respective phenolic acids. From the formed phenolic acids only gallic acid (GA) exhibited growth inhibitory properties. However, also GA was found to be degraded rapidly. Furthermore, the incubation with delphinidin (DEL) or GA resulted in a substantial formation of hydrogen peroxide. The suppression of hydrogen peroxide accumulation by catalase modified significantly the growth inhibitory effects of DEL and GA, indicating that hydrogen peroxide formation might generate experimental artefacts. In summary, the results show that the phenolic acids formed by the degradation of cyanidin (CY), pelargonidin (PG), peonidin (PN) and malvidin (MV) do not contribute to the growth inhibitory effect of the parent compound. The degradation of DEL generates a phenolic acid with substantial growth inhibitory properties (GA). However, taken into account the small proportion of generated GA and its lacking stability, the contribution of GA to the growth inhibitory properties of DEL might be limited.
New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor
Authors: Pfohl‐Leszkowicz Annie , Tozlovanu Mariana , Manderville Richard , Peraica Maja , Castegnaro Marcel , Stefanovic Vladislav
Published: August 2007

To find out whether ochratoxin A (OTA), citrinin (CIT), aristolochic acids (AA) are etiologic agents of Balkan endemic nephropathy (BEN) or Chinese herbal nephrotoxicity, and associated urinary tract tumor (UTT), we have compared (i) in human kidney cell culture, the DNA adduct formation and persistence of OTA/CIT and AA adducts (ii) analyzed DNA adduct in several tumors from human kidney suspected to be exposed to either OTA and CIT, or AAs (iii) analyzed OTA, CIT, and AA in food. In kidney cell cultures, formation of specific OTA‐DNA adduct and AA‐DNA adduct were detected in the same range (around 10 adducts/109nucleotides) and were time‐ and dose‐dependent. After 2 days all disappeared. DNA adduct related to OTA and CIT are found in human kidney tissues from Balkans, France, and Belgium whereas no DNA adducts related to AA could be found in any tumors of BEN patients from Croatia, Bulgaria, or Serbia. No DNA adduct was found in kidney biopsy or necropsy of the French women suspected to be exposed to AA. OTA and CIT are more frequently found in rural area. AA was never detected. All these plead for implication of mycotoxins, especially OTA, in BEN and UTT.
Comparison of various density functional methods for distinguishing stereoisomers based on computed 1H or 13C NMR chemical shifts using diastereomeric penam β‐lactams as a test set
Authors: Wiitala Keith W. , Cramer Christopher J. , Hoye Thomas R.
Published: August 2007

Full 1H and 13C NMR chemical shift assignments were made for two sets of penam β‐lactams: namely, the diastereomeric (2S, 5S, 6S)‐, (2S, 5R, 6R)‐, (2S, 5S, 6R)‐, and (2S, 5R, 6S)‐methyl 6‐(1,3‐dioxoisoindolin‐2‐yl)‐3,3‐dimethyl‐7‐oxo‐4‐thia‐1‐aza‐bicyclo[3.2.0]heptane‐2‐carboxylates (1–4) and (2S, 5R, 6R)‐, (2S, 5S, 6R)‐, and (2S, 5R, 6S)‐6‐(1,3‐dioxoisoindolin‐2‐yl)‐3,3‐dimethyl‐7‐oxo‐4‐thia‐1‐aza‐bicyclo[3.2.0]heptane‐2‐carboxylic acids (6–8). Each penam was then modeled as a family of conformers obtained from Monte Carlo searches using the AMBER* force field followed by IEFPCM/B3LYP/6‐31G(d) geometry optimization of each conformer using chloroform solvation. 1H and 13C chemical shifts for each conformer were computed at the WP04, WC04, B3LYP, and PBE1 density functional levels as Boltzmann averages of IEFPCM/B3LYP/6‐311 + G(2d,p) energies over each family. Comparisons between experimental and theoretical chemical shift data were made using the total absolute error (|Δδ | T) criterion. For the 1H shift data, all methods were sufficiently accurate to identify the proper stereoisomers. Computed 13C shifts were not always successful in identifying the correct stereoisomer, regardless of which DFT method was used. The relative ability of each theoretical approach to discriminate among stereoisomers on the basis of proton shifts was also evaluated. Copyright © 2007 John Wiley & Sons, Ltd.
Coupled hydrogen‐bonding interactions between β‐carboline derivatives and acetic acid
Authors: Reyman D. , Hallwass F. , da Cruz Gonçalves Simone M. , Camacho J. J.
Published: August 2007

In this work, we have analysed the tendency of two β‐carboline derivatives, harmane and norharmane, in the formation of hydrogen bonds. We obtained the 1H and 13C NMR spectra of different mixtures of these derivatives with acetic acid (AcOH) in CDCl3. A cyclic 1:3 complex is proposed between harmane and AcOH, while a 1:2 complex is proposed for norharmane.

Chemical shifts at temperatures between 233 and 323 K were measured: lowering the temperature produces the same effect as increasing the amount of AcOH in solution.

The 13C data confirm a delocalisation of the π electron density towards the pyridinic ring that occurs when AcOH is added. Copyright © 2007 John Wiley & Sons, Ltd.
A predictive tool for assessing 13C NMR chemical shifts of flavonoids
Authors: Burns Darcy C. , Ellis David A. , March Raymond E.
Published: August 2007

Herein are presented the 1H and 13C NMR data for seven monohydroxyflavones (3‐, 5‐, 6‐, 7‐, 2′‐, 3′‐, and 4′‐hydroxyflavone), five dihydroxyflavones (3,2′‐, 3,3′‐, 3,4′‐, 3,6‐, 2′,3′‐dihydroxyflavone), a trihydroxyflavone (apigenin; 5,7,4′‐trihydroxyflavone), a tetrahydroxyflavone (luteolin; 5,7,3′,4′‐tetrahydroxyflavone), and three glycosylated hydroxyflavones (orientin; luteolin‐6C‐β‐D‐glucoside, homoorientin; luteolin‐8C‐β‐D‐glucoside, vitexin; apigenin‐8C‐β‐D‐glucoside). When these NMR spectra are compared, it is possible to assess the impact of flavone modification and to elucidate detailed structural and electronic information for these flavonoids. A simple predictive tool for assigning flavonoid 13C chemical shifts, which is based on the cumulative differences between the monohydroxyflavones and flavone 13C chemical shifts, is demonstrated. The tool can be used to accurately predict 13C flavonoid chemical shifts and it is expected to be useful for rapid assessment of flavonoid 13C NMR spectra and for assigning substitution patterns in newly isolated flavonoids. Copyright © 2007 John Wiley & Sons, Ltd.
Application of unsymmetrical indirect covariance NMR methods to the computation of the 13C↔15N HSQC‐IMPEACH and 13C↔15N HMBC‐IMPEACH correlation spectra
Authors: Martin Gary E. , Hilton Bruce D. , Irish Patrick A. , Blinov Kirill A. , Williams Antony J.
Published: August 2007

Utilization of long‐range 1H15N heteronuclear chemical shift correlation has continually grown in importance since the first applications were reported in 1995. More recently, indirect covariance NMR methods have been introduced followed by the development of unsymmetrical indirect covariance processing methods. The latter technique has been shown to allow the calculation of hyphenated 2D NMR data matrices from more readily acquired nonhyphenated 2D NMR spectra. We recently reported the use of unsymmetrical indirect covariance processing to combine 1H13C GHSQC and 1H15N GHMBC long‐range spectra to yield a 13C15N HSQC‐HMBC chemical shift correlation spectrum that could not be acquired in a reasonable period of time without resorting to 15N‐labeled molecules. We now report the unsymmetrical indirect covariance processing of 1H13C GHMBC and 1H15N IMPEACH spectra to afford a 13C15N HMBC‐IMPEACH spectrum that has the potential to span as many as six to eight bonds. Correlations for carbon resonances long‐range coupled to a protonated carbon in the 1H13C HMBC spectrum are transferred via the long‐range 1H15N coupling pathway in the 1H15N IMPEACH spectrum to afford a much broader range of correlation possibilities in the 13C15N HMBC‐IMPEACH correlation spectrum. The indole alkaloid vincamine is used as a model compound to illustrate the application of the method. Copyright © 2007 John Wiley & Sons, Ltd.
Baseline mannose binding lectin levels may not predict infection among children with leukemia
Authors: Rubnitz Jeffrey E. , Howard Scott C. , Willis Jennifer , Pui Ching‐Hon , Pounds Stanley , Hayden Randall T.
Published: August 2007

We measured baseline serum mannose binding lectin (MBL) levels in 91 patients with childhood leukemia to determine their predictive value for the development of febrile neutropenia or specific infections. Median MBL levels did not differ significantly between patients who developed febrile neutropenia, bacterial infection, or disseminated fungal infection and those who did not. In addition, low MBL levels were not associated with an increased cumulative incidence of infection or with a shorter time to first infection. This preliminary study suggests that baseline MBL levels may not be clinically useful to identify pediatric leukemia patients who are at increased risk of infection. Additional studies are required to determine whether serial MBL measurements may be valuable for this purpose. Pediatr Blood Cancer 2008;50:866–868. © 2007 Wiley‐Liss, Inc.
Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV‐1 protease
Authors: Altman Michael D. , Nalivaika Ellen A. , Prabu‐Jeyabalan Moses , Schiffer Celia A. , Tidor Bruce
Published: August 2007

Drug resistance in HIV‐1 protease, a barrier to effective treatment, is generally caused by mutations in the enzyme that disrupt inhibitor binding but still allow for substrate processing. Structural studies with mutant, inactive enzyme, have provided detailed information regarding how the substrates bind to the protease yet avoid resistance mutations; insights obtained inform the development of next generation therapeutics. Although structures have been obtained of complexes between substrate peptide and inactivated (D25N) protease, thermodynamic studies of peptide binding have been challenging due to low affinity. Peptides that bind tighter to the inactivated protease than the natural substrates would be valuable for thermodynamic studies as well as to explore whether the structural envelope observed for substrate peptides is a function of weak binding. Here, two computational methods—namely, charge optimization and protein design—were applied to identify peptide sequences predicted to have higher binding affinity to the inactivated protease, starting from an RT–RH derived substrate peptide. Of the candidate designed peptides, three were tested for binding with isothermal titration calorimetry, with one, containing a single threonine to valine substitution, measured to have more than a 10‐fold improvement over the tightest binding natural substrate. Crystal structures were also obtained for the same three designed peptide complexes; they show good agreement with computational prediction. Thermodynamic studies show that binding is entropically driven, more so for designed affinity enhanced variants than for the starting substrate. Structural studies show strong similarities between natural and tighter‐binding designed peptide complexes, which may have implications in understanding the molecular mechanisms of drug resistance in HIV‐1 protease. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Second step of hydrolytic dehalogenation in haloalkane dehalogenase investigated by QM/MM methods
Authors: Otyepka Michal , Banáš Pavel , Magistrato Alessandra , Carloni Paolo , Damborský Jiří
Published: August 2007

Mechanistic studies on the hydrolytic dehalogenation catalyzed by haloalkane dehalogenases are of importance for environmental and industrial applications. Here, Car‐Parrinello (CP) and ONIOM hybrid quantum‐mechanical/molecular mechanics (QM/MM) are used investigate the second reaction step of the catalytic cycle, which comprises a general base‐catalyzed hydrolysis of an ester intermediate (EI) to alcohol and free enzyme. We focus on the enzyme LinB from Sphingomonas paucimobilis UT26, for which the X‐ray structure at atomic resolution is available. In agreement with previous proposals, our calculations suggest that a histidine residue (His272), polarized by glutamate (Glu132), acts as a base, accepting a proton from the catalytic water molecule and transferring it to an alcoholate ion. The reaction proceeds through a metastable tetrahedral intermediate, which shows an easily reversed reaction to the EI. In the formation of the products, the protonated aspartic acid (Asp108) can easily adopt conformation of the relaxed state found in the free enzyme. The overall free energy barrier of the reaction calculated by potential of the mean force integration using CP‐QM/MM calculations is equal to 19.5 ± 2 kcal · mol−1. The lowering of the energy barrier of catalyzed reaction with respect to the water reaction is caused by strong stabilization of the reaction intermediate and transition state and their preorganization by electrostatic field of the enzyme. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Conformational stability and DNA binding energetics of the rat thyroid transcription factor 1 homeodomain
Authors: Del Vecchio Pompea , Carullo Paola , Barone Guido , Pagano Bruno , Graziano Giuseppe , Iannetti Alessio , Acquaviva Renato , Leonardi Antonio , Formisano Silvestro
Published: August 2007

The conformational stability of the rat thyroid transcription factor 1 homeodomain, TTF‐1HD, has been investigated by means of circular dichroism (CD) and differential scanning calorimetry (DSC) measurements at pH 5.0 as a function of KCl concentration. Thermal unfolding of TTF‐1HD is a reversible two‐state transition. The protein is not stable against temperature, showing a denaturation temperature of 32°C in the absence of salt and 50°C at 75 mMKCl. The binding energetics of TTF‐1HD to its target DNA sequence has been characterized by means of isothermal titration calorimetry (ITC) measurements, complemented with CD data. At 25°C, pH 5.0 and 75 mMKCl, the binding constant amounts to 1.5 × 108M−1and the binding enthalpy change amounts to −41 kJ mol−1. The process is enthalpy driven, but also the entropy change is favorable to complex formation. To gain a molecular level understanding of the interactions determining the association of TTF‐1HD to the target DNA sequence structural information would be requested, but it is not yet available. Therefore, structural models of two complexes, TTF‐1HD with the target DNA sequence and TTF‐1HD with a modified DNA sequence, have been constructed by using as a template the NMR structure of the complex between NK‐2 HD and its target DNA, and by performing molecular dynamics simulations 3.5 ns long. Analysis of these models allows one to shed light on the origin of the DNA binding specificity characteristic of TTF‐1HD. Proteins 2008. © 2007 Wiley‐Liss, Inc.
The noncatalytic triad of α‐amylases: A novel structural motif involved in conformational stability
Authors: Marx Jean‐Claude , Poncin Johan , Simorre Jean‐Pierre , Ramteke Pramod W. , Feller Georges
Published: August 2007

Chloride‐activated α‐amylases contain a noncatalytic triad, independent of the glycosidic active site, perfectly mimicking the catalytic triad of serine‐proteases and of other active serine hydrolytic enzymes. Mutagenesis of Glu, His, and Ser residues in various α‐amylases shows that this pattern is a structural determinant of the enzyme conformation that cannot be altered without losing the intrinsic stability of the protein. 1H‐15N NMR spectra of a bacterial α‐amylase reveal proton signals that are identical with the NMR signature of catalytic triads and especially a deshielded proton involving a protonated histidine and displaying properties similar to that of a low barrier hydrogen bond. It is proposed that the H‐bond between His and Glu of the noncatalytic triad is an unusually strong interaction, responsible for the observed NMR signal and for the weak stability of the triad mutants. Furthermore, a stringent template‐based search of the Protein Data Bank demonstrated that this motif is not restricted to α‐amylases, but is also found in 80 structures from 33 different proteins, amongst which SH2 domain‐containing proteins are the best representatives. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Lipid transfer proteins from Brassica campestris and mung bean surpass mung bean chitinase in exploitability
Authors: Lin Peng , Xia Lixin , Wong Jack H. , Ng T. B. , Ye Xiuyun , Wang Shaoyun , Xiangzhu Shi
Published: August 2007

Antifungal peptides with a molecular mass of 9 kDa and an N‐terminal sequence demonstrating remarkable similarity to those of nonspecific lipid transfer proteins (nsLTPs) were isolated from seeds of the vegetable Brassica campestris and the mung bean. The purified peptides exerted an inhibitory action on mycelial growth in various fungal species. The antifungal activity of Brassica and mung bean nsLTPs were thermostable, pH‐stable, and stable after treatment with pepsin and trypsin. In contrast, the antifungal activity of mung bean chitinase was much less stable to changes in pH and temperature. Brassica LTP inhibited proliferation of hepatoma Hep G2 cells and breast cancer MCF 7 cells with an IC50 of 5.8 and 1.6 µM, respectively, and the activity of HIV‐1 reverse transcriptase with an IC50 of 4 µM. However, mung bean LTP and chitinase were devoid of antiproliferative and HIV‐1 reverse transcriptase inhibitory activities. In contrast to the mung bean LTP, which exhibited antibacterial activity, Brassica LTP was inactive. All three antifungal peptides lacked mitogenic activity toward splenocytes. These results indicate that the two LTPs have more desirable activities than the chitinase and that there is a dissociation between the antifungal and other activities of these antifungal proteins. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Fast Fmoc synthesis of hAmylin1–37 with pseudoproline assisted on‐resin disulfide formation
Authors: Page Karen , Hood Christina A. , Patel Hirendra , Fuentes German , Menakuru Mahendra , Park Jae H.
Published: August 2007

Human amylin (1–37) and the (1–13) fragment were synthesized with and without pseudoproline dipeptides. Thallium (III) trifluoroacetate, a mild oxidant, was used to cyclize the peptides by forming a disulfide bridge from C2 to C7. On the basis of our model studies, incorporation of a pseudoproline dipeptide decreases the amount of time necessary for the crude linear amylin (1–13) to cyclize on the resin. Without pseudoproline dipeptides, the 1–37 crude linear amylin was not pure enough to undergo the cyclization reaction. Following the cyclization studies, the synthesis time of the linear human amylin (1–37) was systematically reduced from 58 h to 8.5 h by shortening the reaction times. Cyclization and cleavage times were also reduced to 1.5 h. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.
Binding energy of an off‐centre hydrogenic donor impurity in a spherical quantum dot
Authors: Mikhail I. F. I. , Ismail I. M. M.
Published: August 2007

A variational calculation is given of the binding energy of an off‐centre hydrogenic donor impurity placed in a spherical quantum dot. The study is restricted to the ground state binding energy in the quantum dot. The cases of both infinite and finite confining potentials are considered. The variation of the binding energy as a function of the dot radius and as a function of the impurity position has been investigated. In the case of high finite confining potentials, the initial deviation of the binding energy from the result of infinite potential has been derived. The critical impurity location at which the deviation in the binding energy due to any finite confining potential changes its sign has been determined. The maximum binding energy and the dot radius at which it occurs have further been calculated for any confining potential or any impurity location. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Magnon energy gap in a three‐layer ferromagnetic superlattice
Authors: Qiu Rong‐ke , Zhang Zhi‐dong , Han Li , Ma Guang‐kun , Zhang Xu‐dong
Published: August 2007

The magnon energy band in a three‐layer ferromagnetic superlattice is studied by using the linear spin‐wave approach and Green's function technique. It is found that two modulated energy gaps exist in the magnon energy band along Kx direction perpendicular to the plane of the superlattice. The spin quantum numbers and the interlayer exchange couplings all affect the two energy gaps. The disappearance of one of the energy gaps corresponds to a high symmetry among the interlayer exchange couplings, while the vanishing of another energy gap corresponds to a high symmetry of the system, which belongs to the type III Shubnikov group or the polychromatic group of magnetic group. This magnetically structural symmetry includes not only the symmetry of crystallographic point‐groups or space‐groups, but also the symmetry of strength and direction of spins. Comparing with the previous results for a three‐layer ferrimagnetic superlattice, it is concluded that the energy gap of the ferromagnetic/ferrimagnetic superlattices is dominated by different symmetries originated from ferromagnetic/antiferromagnetic interlayer exchange couplings. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fermi surface and momentum spin density of the half metal CrO2
Authors: Biasini M. , Rusz J.
Published: August 2007

We calculated the Fermi surface and the electron‐positron momentum spin density resulting from the measurement of the 2‐dimensional angular correlation of the electron positron annihilation radiation (2D‐ACAR) of the half metal CrO2. Inclusion of spin orbit interaction yields a negligible deviation from half metallicity. Furthermore, although the up and down momentum spin densities are heavily modulated by the effect of the non uniform positron density, their difference, resulting in the net momentum spin density, shows a nearly complete cancellation of positron effects and reveals the Fermi surface with great detail. We point out that the large cancellation of the electron‐positron matrix elements, which in paramagnetic multiatomic systems plague the interpretation of the experiments, yields a great effectiveness of 2D‐ACAR experiments with polarized positrons to all the ferromagnetic substances and particularly to half metals. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
PALSfit: A new program for the evaluation of positron lifetime spectra
Authors: Olsen J. V. , Kirkegaard P. , Pedersen N. J. , Eldrup M.
Published: August 2007

PALSfit is a new Windows program for the analysis of positron lifetime spectra. PALSfit combines into one interactive Windows program the features of our previous PATFIT program package, such as data input, least‐squares fitting routines as well as graphical displays. A number of options are available, including constraints on positron lifetimes, intensities, background and area, and corrections for annihilation in the positron source. In addition, a number of new features have been included. The Windows user‐interface makes to a large extent the various features of the program self‐explanatory, and using the program is straightforward. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
First test of LSO scintillators for Positron Lifetime Spectroscopy
Authors: Haaks M. , Valentini R. , Vianden R.
Published: August 2007

Lutetium oxyorthosilicate (LSO) was employed as scintillator material in a positron lifetime (PALS) fast‐slow spectrometer. Compared to the widely used BaF2 scintillator material, LSO has a single exponential decay with 40 ns, a high density of 7.49 g/cm3, an effective nuclear charge of 65.8 and a superb light output. With this features photon rates above 5 × 106 should be possible, which affords to obtain lifetime spectra within a period of minutes. The physical and mechanical properties make LSO attractive as scintillator material for PALS measurements. The capability of LSO for PALS was studied and compared to BaF2. As a first test of the spectrometer, a lifetime spectrum of well annealed nickel was measured and analyzed. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity
Authors: Remsberg Connie M. , Yáñez Jaime A. , Ohgami Yusuke , Vega‐Villa Karina R. , Rimando Agnes M. , Davies Neal M.
Published: August 2007

The present study evaluated the preclinical pharmacokinetics and pharmacodynamics of trans‐pterostilbene, a constituent of some plants. Right jugular vein cannulated male Sprague‐Dawley rats were dosed i.v. with 20 mg/kg of pterostilbene and samples were analysed by the reverse phase HPLC method. Serum AUC, serum t1/2, urine t1/2, Cltotal and Vdβ were 17.5 ± 6.6 µg/h/mL, 1.73 ± 0.78 h, 17.3 ± 5.6 h, 0.960 ± 0.025 L/h/kg and 2.41 ± 1.13 L/kg (mean ± SEM), respectively. A pterostilbene glucuronidated metabolite was detected in both serum and urine. The in vitro metabolism in rat liver microsomes furthermore suggests phase II metabolism of pterostilbene. Pterostilbene demonstrated concentration‐dependent anticancer activity in five cancer cell lines (1–100 µg/mL). An in vitro colitis model showed concentration‐dependent suppression of PGE2 production in the media of HT‐29 cells. Antiinflammatory activity was examined by inducing inflammation in canine chondrocytes followed by treatment with pterostilbene (1–100 µg/mL). The results showed decreased levels of MMP‐3, sGAG and TNF‐α compared with control levels. Pterostilbene exhibited concentration‐dependent antioxidant capacity measured by the ABTS method. Pterostilbene increased the latency period to response in both tail‐flick and hot‐plate analgesic tests. Copyright © 2007 John Wiley & Sons, Ltd.
Peanut (Arachis hypogaea) consumption improves Glutathione and HDL‐cholesterol levels in experimental diabetes
Authors: Emekli‐Alturfan Ebru , Kasikci Emel , Yarat Aysen
Published: August 2007

The aim of this investigation was to assess the influence of peanut (Arachis hypogaea) consumption on oxidant‐antioxidant status and lipid profile in Streptozotocin (STZ) induced diabetic rats. 32 rats were divided into 4 groups as control, control+peanut, diabetic, diabetic+peanut. Control and diabetic groups were fed on standard rat chow whereas control+peanut and diabetic+peanut were fed on standard rat chow supplemented with 0.63 g % peanut for 12 weeks. Serum glucose levels, lipids, Glutathione (GSH), lipid peroxidation (LPO) and atherogenic index (AI) levels were determined at the end of the experiment. In the diabetic group TG (Triglyceride), TC (Total cholesterol), LDL‐C (LDL‐cholesterol) levels and atherogenic indexes increased significantly whereas HDL‐C (HDL‐cholesterol) level decreased significantly compared to the control group. The supplementation with peanut in the diabetic group led to significantly higher HDL‐C levels and lower AI levels compared to diabetic group. Peanut consumption increased GSH levels significantly both in control and diabetic groups. In conclusion, this study shows that peanut consumption may improve oxidant‐antioxidant status in healthy and diabetic status without increasing blood lipids. Moreover, increased HDL‐C levels and decreased AI levels in diabetic rats indicate that, peanut consumption may have protective effects against cardiovascular complications of diabetes. Copyright © 2007 John Wiley & Sons, Ltd.
Postnatal development of pups from nursing rats treated with Gingko biloba
Authors: Faria Dieime Elaine Pereira de , Borges Luciana Valente , Peters Vera Maria , Reis João Evangelista de Paula , Ribeiro Luiz Cláudio , de Cássia da Silveira e Sá Rita , Guerra Martha de Oliveira
Published: August 2007

The Gingko biloba extract is contraindicated during pregnancy and lactation due to the lack of information about its effects on these reproductive phases. Previous studies have shown that G. biloba extract contains components with estrogenic and antiestrogenic activities, thus nursing dams treated with the extract of this plant could show reduction in milk production, resulting in malnutrition and poor development of pups. This work analyzes the postnatal development of pups, whose mothers were treated with G. biloba extract during the lactation period. Nursing Wistar rats received 3.5 mg/kg/day of G. biloba aqueous extract, corresponding to the highest human dose. Clinical signs of maternal toxicity were evaluated. The growth rate, viability, survival during treatment and lactation indices of the pups were calculated. The physical, motor and sensorial development of the pups was also evaluated. No maternal signs of toxicity were observed. As there were no biological differences between control and G. biloba treated pups, it is possible to assume that, in this experimental design, the administration of G. biloba aqueous extract to nursing rats during the lactation period seems to be devoid of toxic effect to mothers and to the physical, motor and sensory development of the pups. Copyright © 2007 John Wiley & Sons, Ltd.