bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of β‐Blocker Dose with Serum Procollagen Concentrations and Cardiac Response to Spironolactone in Patients with Heart Failure
Authors: Cavallari Larisa H. , Momary Kathryn M. , Groo Vicki L. , Viana Marlos A. G. , Camp Joseph R. , Stamos Thomas D.
Published: June 2007

Study Objective. To determine whether β‐blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure.

Design. Prospective clinical study.

Setting. Two heart failure centers.

Patients. Eighty‐eight spironolactone‐naïve patients with heart failure who were taking β‐blockers.

Intervention. In a subset of 29 patients, spironolactone was started at 12.5 mg/day with the dosage titrated to 25 mg/day if tolerated.

Measurements and Main Results. Venous blood samples were collected from each patient. Serum procollagen type I and type III aminoterminal peptides (PINP and PIIINP) were determined by radioimmunoassay and compared between the 25 patients receiving low doses (< 50% of recommended target dose) and the 63 patients receiving high doses (≥ 50% of recommended target dose) of β‐blockers. Patients receiving low‐dose β‐blockers had higher mean ± SD PIIINP concentrations (6.6 ± 3.5 vs 4.9 ± 2.6 μg/L, p=0.03) and tended to have higher PINP concentrations (74.0 ± 44.1 vs 57.1 ± 28.6 μg/L, p=0.10) compared with those receiving high doses. A repeat blood sample was collected from the 29 patients who received spironolactone after 6 months of therapy. Changes in procollagen peptides also were compared in this subset between low‐dose (9 patients) and high‐dose (20 patients) β‐blocker groups. Low β‐blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] −14.3 μg/L [‐9.8 to −19.3 μg/L] vs −2.5 μg/L [5.9 to −9.8 μg/L], p=0.02) and PIIINP (‐1.4 μg/L [‐0.9 to −2.4 μg/L] vs 0.1 μg/L [0.9 to −1.3 μg/L], p=0.045) with spironolactone therapy than high β‐blocker doses. In addition, 100% of the patients in this subset taking low‐dose β‐blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis.

Conclusion. Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of β‐blocker dosages, at least in terms of its effects on cardiac remodeling.
Peginterferon alfa‐2a versus Peginterferon alfa‐2b as Initial Treatment of Hepatitis C Virus Infection: A Cost‐Utility Analysis from the Perspective of the Veterans Affairs Health Care System
Authors: Yeh Wei‐Shi , Armstrong Edward P. , Skrepnek Grant H. , Malone Daniel C.
Published: June 2007

Study Objective. To assess the cost‐utility of peginterferon alfa‐2a plus ribavirin, peginterferon alfa‐2b plus ribavirin, and no therapy for treatment‐naïve patients with chronic hepatitis C virus (HCV) infection from the perspective of the Veterans Affairs (VA) health care system by using patient‐reported utility scores.

Design. Cost‐utility analysis using a Markov model.

Setting. Veterans Affairs health care system.

Data Source. Data for the model were obtained from clinical trials and published literature. Data from the VA health care system were used to define the patient cohorts.

Measurements and Main Results. A Markov model incorporating transition probabilities between disease health states that depend only on the current health state was developed to simulate the progression of HCV disease. The patient cohorts were a 45‐year‐old male cohort and a 55‐year‐old male cohort, each with liver fibrosis but no cirrhosis. The lifetime expected costs, quality‐adjusted life‐years (QALYs) gained, and incremental net monetary benefit (INMB) with HCV treatments were determined for each cohort by genotype (genotype 1, and genotypes 2 and 3). Both peginterferon regimens were significantly more cost‐effective than no treatment, although no significant differences in costs or QALYs were noted between peginterferon regimens. For the 45‐year‐old cohort with a genotype 1 infection, the INMB was $128,583 (95% confidence interval [CI] $79,279–$177,308) and $128,025 (95% CI $80,425–$173,448) versus no treatment for peginterferon alfa‐2a plus ribavirin and peginterferon alfa‐2b plus ribavirin, respectively. Treatment with either peginterferon regimen produced significantly lower lifetime HCV‐related medical costs for genotype 2 or 3 infections, but not genotype 1.

Conclusions. Peginterferon alfa‐2a plus ribavirin and peginterferon alfa‐2b plus ribavirin were found to be cost‐effective treatments for patients with HCV infections, particularly with genotypes 2 and 3. However, no significant differences in costs or efficacy were observed between these peginterferon treatment regimens.
Absence of an Interaction Between Tigecycline and Digoxin in Healthy Men
Authors: Zimmerman James J. , Harper Dawn M. , Matschke Kyle , Speth John L. , Raible Donald G. , Fruncillo Richard J.
Published: June 2007

Study Objective. To evaluate a potential interaction between tigecycline and digoxin using pharmacokinetic and pharmacodynamic assessments.

Design. Open‐label, three‐period, one‐sequence crossover study.

Setting. Hospital‐affiliated, inpatient clinical pharmacology unit.

Subjects. Twenty healthy men.

Intervention. Tigecycline 100 mg was administered intravenously as a single dose on day 1 (period 1). Digoxin was administered as a 0.5‐mg oral loading dose on day 7, followed by 0.25 mg/day on days 8–14 (period 2). Digoxin 0.25 mg/day was continued on days 15–19; in addition, on day 15, a loading dose of tigecycline 100 mg was administered intravenously, followed by 50 mg every 12 hours starting on the evening of day 15 through the morning of day 19 (period 3).

Measurements and Main Results. Pharmacokinetic assessments were performed on days 1 and 19 for tigecycline and on days 14 and 19 for digoxin. Electrocardiographic parameters were measured at baseline and on days 1, 14, and 19 to assess digoxin pharmacodynamics. Serum tigecycline concentrations were determined by liquid chromatography with tandem mass spectrometry detection, and plasma and urine digoxin concentrations were determined by radioimmunoassay. Tigecycline area under the concentration‐time curve (AUC), AUC from 0–12 hours (AUC0–12), weight‐normalized clearance, and mean resistance time were not affected by concomitant multiple‐dose digoxin administration, but tigecycline half‐life was decreased during period 1, apparently due to fewer detectable terminal concentrations in some subjects. Digoxin steady‐state AUC0–24, weight‐normalized oral dose clearance, cumulative amount of drug excreted in urine over 24 hours, renal clearance, and QTc (change from baseline) were not affected by multiple‐dose tigecycline administration.

Conclusion. No significant effects of tigecycline on digoxin pharmacokinetics and pharmacodynamics were noted, but a small effect of digoxin on tigecycline pharmacokinetics cannot be ruled out due to design issues with period 1 of the study.
Pancreatic Enzyme Pharmacotherapy
Authors: Ferrone Marcus , Raimondo Massimo , Scolapio James S.
Published: June 2007

Supplemental pancreatic enzyme preparations are provided to patients with conditions of pancreatic exocrine deficiency such as chronic pancreatitis and cystic fibrosis. These patients frequently experience steatorrhea, which occurs from inadequate fat absorption. The delivery of sufficient enzyme concentrations into the duodenal lumen simultaneously with meals can reduce nutrient malabsorption, improve the symptoms of steatorrhea, and in some cases alleviate the pain associated with chronic pancreatitis. Current clinical practices dictate administration of lipase 25,000–40,000 units/meal by using pH‐sensitive pancrelipase microspheres, along with dosage increases, compliance checks, and differential diagnosis in cases of treatment failure. Despite the large number of specialty enzyme replacements available commercially, many patients remain dissatisfied with standard therapy, and future developments are needed to optimize treatment in these individuals.
A Febrile Neutropenic Patient with Enterococcus gallinarum Sepsis Treated with Daptomycin and Gentamicin
Authors: Barber Gerard R. , Lauretta Joseph , Saez Ruben
Published: June 2007

Gram‐positive pathogens are increasingly implicated in today's changing epidemiology of hospital‐acquired infections. Staphylococci, streptococci, and enterococci are among the most frequently identified causes of surgical site, complicated skin‐structure, and bloodstream infections. In accordance, the use of antimicrobial agents with gram‐positive activity, especially those with activity against resistant organisms, has also increased. We describe a septic, neutropenic patient with bacteremia due to Enterococcus gallinarum. Therapeutic options were restricted due to resistance factors of the organism, limited guidance in the medical literature, and the patient's history and underlying condition. Despite these challenges, the patient was successfully treated with a combination of daptomycin and gentamicin and replacement of her indwelling central line. As antimicrobial stewards and diagnosticians, we must bear in mind that selective pressures exerted by the increasing use of agents with gram‐positive activity may result in an increased prevalence of organisms such as E. gallinarum.
Assessment of ground improvement work using radioisotope cone penetrometers
Authors: Shrivastava A. K.
Published: June 2007

The effectiveness of radioisotope cone penetrometers (RIcones) under various soil conditions is now well established. This paper briefly describes the design of RI-cones, and the advantages associated with their use. Two case histories are presented in which these cone penetrometers were utilised to investigate their effectiveness in ground improvement works. Both case histories involve land reclamation work. In one, reclamation was effected by hydraulically placing the fly ash obtained from a nearby coal-fired power plant, and in the other, the reclamation of land from sea was effected by pluviating sand by a conveyor belt system. It has been shown that RI-cones can detect any small changes in the density profile, which can result in large savings in a project involving millions of cubic metres of sand.

L'efficacité des pénétrateurs cônes radio-isotopes (cônes RI) est désormais bien établie, et ce dans des conditions de sol variées. Cet article décrit brièvement la conception des cônes RI et les avantages associés à leur utilisation. Il présente deux études de cas dans lesquelles ces pénétromètres cônes ont é té utilisés pour évaluer leur efficacité dans des travaux d'amélioration de terrain. Ces deux é tudes comportaient des travaux de réhabilitation de terrain. Dans le premier scénario, la réhabilitation est réalisée par la déposition hydraulique de cendres volantes issues d'une centrale électrique au charbon à proximité. Dans le second, elle est effectuée par pluviation de sable par un système de courroie transporteuse. Il est ici démontré que les cônes RI peuvent détecter même de faibles changements dans le profil de densité, ce qui peut permettre de réaliser d'importantes économies dans un projet impliquant des millions de mètres cubes de sable.
Mitigation of liquefaction hazard by dynamic compaction
Authors: Majdi A. , Soltani A. Sharifi , Litkouhi S.
Published: June 2007

The tendency to apply soil improvement techniques in comparison with conventional remedial methods has been widely increasing in Iran, especially over the past decade. This is because these techniques are less time-consuming and more cost-effective. The risk of liquefaction at the Caspian Sea Republics Oil Swap (CROS) project site for loose saturated sandy layers down to 13 m was revealed subsequent to completion of the geotechnical investigations. Following a detailed study, dynamic compaction was selected to be the best option, especially for the foundations of the nine oil tanks at the site. To determine the dynamic compaction pattern, including the optimum number of drops, total energy and height of drop, a detailed trial programme was carried out. This included drilling boreholes, cone penetration test and standard penetraiton test performance and trial tamping as well as heave tests. The results were quite satisfactory, and the liquefaction hazard was well mitigated. Because of the lack of time, no ageing effect was investigated.

L'approche consistant à appliquer des techniques d'amé-lioration des sols en comparaison avec les méthodes de traitement conventionnelles s'est répandue en Iran, particuliè rement ces dix dernières années. En effet, ces techniques sont plus économiques et permettent de ne pas perdre de temps. Les études géotechniques réalisées sur le site du projet CROS ont permis de révéler le risque de liquéfaction pour les couches sableuses saturées et meubles jusqu'à 13 m de profondeur. Après une é tude détaillèe, il a é té décidé que la compaction dynamique offrait la meilleure solution, en particulier pour les fondations des neufs réservoirs de pétrole sur le site. Un programme d'essais détaillé a été mis en place pour déterminer le profil de compaction dynamique, y compris le nombre optimal de chutes de pilon et l'énergie totale et la hauteur de chute. Il comprenait le creusement de trous de forage, la réalisation de tests de performance CPT et SPT, un damage d'essai et des tests de soulèvement. Les résultats obtenus sont satisfaisants et le risque de liquéfaction a puêtre bien atténué. En raison du manque de temps à disposition, il n'a pas é té possible d'étudier les effets du vieillissement.
Effect of preloading on the cyclic strength of reconstituted sand
Authors: Stamatopoulos C. , Stamatopoulos A.
Published: June 2007

The effect of preloading on the cyclic soil strength under level ground was investigated by cyclic direct-shear tests where horizontal shear stress oscillated about a zero mean value. Tests on reconstituted samples were performed on two different sands and at varying prestress ratios, densities and vertical stresses. Test results showed a marked increase of the cyclic soil strength with the prestress ratio. The effect is more pronounced for the looser specimens. Arelationship giving the increase of the cyclic strength of sands with the prestress ratio is proposed. This relationship predicted reasonably well the increase in cyclic soil strength measured in previous laboratory studies. The domain of validity of this equation and the manner in which it can be used for ground modification projects under earthquakes are discussed.

On étudie ici l'effet du préchargement sur la résistance cyclique du sol en dessous de la surface à niveau au moyen d'essais cycliques de cisaillement direct où la contrainte de cisaillement oscillait autour d'une valeur moyenne nulle. Des tests, réalisés sur des échantillons reconstitués, ont étéeffectués sur deux types de sables et pour des rapports de précontrainte, densités et contraintes verticales variables. Les résultats ainsi obtenus montrent une augmentation significative de la résistance cyclique du sol avec le rapportde précontrainte. Ce phénoméne est encore plus marqué pour les échantillons les plus meubles. Il est proposé uneéquation donnant l'augmentation de la résistance cyclique des sables en fonction du rapport de prélcontrainte. Cetterelation a permis de prédire de maniére relativement satisfaisante l'augmentation de résistance cyclique du solmesurée dans des é tudes de laboratoire précédentes. Ondiscute ici également du domaine de validité de cette équation et de la façon dont elle peut être appliquée auxprojets d'amélioration des sols soumis à des tremblementsde terre.
Settlement of circular foundations on stone-column-reinforced grounds
Authors: Elshazly H. , Hafez D. , Mossaad M.
Published: June 2007

Most of the available methods of settlement prediction for foundations on stone-column-reinforced grounds assume infinitely extended foundations on infinite grids of columns. Nevertheless, the real performance of a foundation with finite size is believed to differ from that of a corresponding foundation with infinite size. In the current paper, foundations with real sizes in the common engineering range are analysed. To cover various site conditions, both homogeneous and stratified weak soils are considered. In order to obtain reliable results, a well-tested advanced nonlinear finite element code is used in the modelling. Moreover, field load test results are utilised to calibrate the mathematical model. In the simulation, the post-installation in situ stress state is included in order to ensure that the mathematical model is capable of reproducing the field settlement records. It was shown that composite grounds with the same stone replacement ratio under structures with different sizes lead to different settlement improvement degrees.

La plupart des méthodes disponibles pour la prédiction du tassement des fondations sur un terrain renforcé par des colonnes de pierre prennent pour hypothèse des fondations étendues à l'infini selon des maillages infinis de colonnes. On pense cependant que les performances réelles d'une fondation de dimension finie diffèrent de celles d une fondation correspondante de dimension infinie. Cet article étudie des fondations de dimensions réelles dans le domaine d ingénierie courant. Afin de couvrir diverses conditions de site, on examine des sols mous stratifiés et homogènes. Pour obtenir des résultats fiables, on applique dans la modélisation un code d analyse linéaire élaboré à éléments finis parfaitement éprouvé. Des résultats d'essais de charge in situ sont également utilisés pour étalonner le modèle mathématique. La simulation intègre l état de contrainte in situ après installation afin de s assurer que le modèle mathématique est capable de reproduire les relevés de tassement sur le terrain. Il a été montré que des sols composites avec le même taux de remplacement de pierre sous des structures de dimensions différentes atteignent des niveaux d'amélioration du tassement différents.
Modeling Earthquake Risk via Extreme Value Theory and Pricing the Respective Catastrophe Bonds
Authors: Zimbidis Alexandros A. , Frangos Nickolaos E. , Pantelous Athanasios A.
Published: June 2007

The aim of the paper is twofold. Firstly, to analyze the historical data of the earthquakes in the boarder area of Greece and then to produce a reliable model for the risk dynamics of the magnitude of the earthquakes, using advanced techniques from the Extreme Value Theory. Secondly, to discuss briefly the relevant theory of incomplete markets and price earthquake catastrophe bonds, combining the model found for the earthquake risk and an appropriate model for the interest rate dynamics in an incomplete market framework. The paper ends by providing some numerical results using Monte Carlo simulation techniques and stochastic iterative equations.
Tire Energy Loss from Obstacle Impact
Authors: Rhyne Timothy B. , Cron Steven M.
Published: June 2007

Tires in actual service conditions operate on rough roads with a random distribution of obstacles. Rolling resistance, however, is typically measured on smooth surfaces. This paper considers the nature of tire energy loss when impacting obstacles. It is demonstrated by a simple example that translational energy can be “lost,” even in purely elastic impacts, by trapping energy in structural vibrations that cannot return the energy to translation during the restitution phase of the impact. Tire simulations and experiments demonstrate that this dynamic energy loss can be very large in tires if the impact times are short. Impact times indicating the potential for large energy loss are found to be in the range of normal highway speeds.
Eichenförderungsmassnahmen im Niderholz (Kanton Zürich): Auswirkungen auf Bestand und Bruthöhlenstandorte von Mittel- und Buntspecht | Measures to promote the growth of oak trees in the Niderholz (Canton Zurich): Impact on population size and location of breeding cavities of the middle spotted and great spotted woodpeckers
Authors: Miranda Beatrice , Schiegg Karin , Bühlmann Jost , Pasinelli Gilberto
Published: June 2007

From 1997–2003, forest management measures in favour of the vulnerable middle spotted woodpecker were conducted in an oak-hornbeam forest in northern Switzerland. In this study,we examine the consequences of these measures on population size and location of breeding cavities of middle spotted and great spotted woodpeckers. We found that population sizes of both species remained stable despite considerable forestry action taken in old oaks stands of vital importance for these woodpeckers. In areas where the two management measures «coppice-with-standards» and «thinning of coppicewith-standards stands» were applied, no differences in the number of breeding cavities of both species immediately before and after management intervention measures could be found. However, the proportion of breeding cavities of the great spotted woodpecker increased in old oak stands which were not subjected to management measures, while middle spotted woodpeckers used such stands as expected from their availability. We conclude that the two forest management measures are, at least on the short run, appropriate to the ecological requirements of the two woodpecker species.
Zehn Jahre Landschaftsverzeichnis im Kanton Glarus | Ten year register of the landscape in Canton Glarus
Authors: Steiner Regula
Published: June 2007

A register of the landscapes of regional importance in Canton Glarus was initiated in 1966. In this article, both the impact and the experiences drawn from this countryside register are discussed with reference to three specific examples.
Memories of a 'decision‐map': Recall of a real‐life decision
Authors: Galotti Kathleen M.
Published: June 2007

First‐year students in college who had participated in a study of college‐decision‐making 8 to 20 months earlier were asked to recall the criteria they had used and the alternatives they had considered in making the decision. They were also asked to describe the criteria they thought, in retrospect, that they ought to have used, and to rate their satisfaction with the decision‐making process and its outcome. Two hundred and seven of the original 322 participants responded to a follow‐up questionnaire through the mail. Participants recalled about half of the criteria they originally reported using, and about two‐thirds of the schools they originally reported considering. Their recall of criteria was affected by their current view of teh criteria they should have used, providing a replication for previous findings. No gender or academic ability effects were found. Somewhat surprisingly, given existing literature, recall was unaffected by emotional responses to the decision, either those reported during the decision‐making process or those reported retrospectively. Overall, the pattern of results suggests that memory is affected by a decision‐maker's current cognitive framework of the decision, specifically, their retrospective view of how they ought to have made the decision. Moreover, memory is far from perfect, even for stimuli that the decision‐maker generated her‐ or himself, and to which presumably, they gave significant amounts of thought.
Measures of feeling‐of‐knowing accuracy: A new look at an old problem
Authors: Schraw Gregory
Published: June 2007

Two ordinal measures of feeling‐of‐knowing performance appropriate for n × n data arrays are reviewed. Goodman and Kruskal's gamma provides a measure of association between recognition performance and feeling‐of‐knowing judgements. The Hamann coefficient provides a measure of agreement accuracy. The relative strengths and weaknesses of each measure are compared at length. A proof is provided, which reveals a lack of one‐to‐one relation between the two and suggests that they may be independent under most circumstances. It is concluded that both measures should be reported together as complementary indices as each captures a different facet of feeling‐of‐knowing performance. Alternative measures for gamma and the Hamann coefficient are considered and a number of recommendations are made for future research.
The overjustification effect: A meta‐analysis
Authors: Tang Shu‐Hua , Hall Vernon C.
Published: June 2007

This article reports the results of a meta‐analysis using 50 experimental studies (256 effect sizes) of the overjustification effect. In general, we found support for the effect across age, dependent measure, and design type in specific situations where it is predicted to occur. Findings are less supportive of the theory for situations where there should be no difference between experimental and control groups (e. g. non‐contingent or unexpected reward). Suggestions for future research are made.
Highly Enantioselective Synthesis of Arylaliphatic Tertiary Alcohols using Mutants of an Esterase from Bacillus subtilis
Authors: Kourist Robert , Bartsch Sebastian , Bornscheuer Uwe T.
Published: June 2007

The kinetic resolution of a series of acetates of arylaliphatic tertiary alcohols was studied using recombinant esterase variants from Bacillus subtilis (BS2) expressed in E. coli. Highest enantioselectivities (E>100) were achieved in the synthesis of 1,1,1‐trifluoro‐2‐phenylbut‐3‐yn‐2‐ol and three para‐substituted analogues using BS2 mutant G105A. With mutant E188D only two compounds were converted with E>100. For a thiophene analogue or compounds with small variations in the aliphatic chain substantially lower conversions and/or enantioselectivity were observed, which also varied with the BS2 variant used. Thus, small changes in the substrate structure and point mutations in the esterase had a remarkable influence on both activity and enantioselectivity.
Stereo‐Complementary Two‐Step Cascades Using a Two‐Enzyme System Leading to Enantiopure Epoxides
Authors: Seisser Birgit , Lavandera Iván , Faber Kurt , Spelberg Jeffrey H. Lutje , Kroutil Wolfgang
Published: June 2007

A novel one‐pot, two‐step, two‐enzyme cascade is described. Pro‐chiral α‐chloro ketones are stereoselectively reduced to the corresponding halohydrins as an intermediate by a biocatalytic hydrogen transfer process. The intermediate is transformed to the corresponding epoxide by a non‐enantioselective halohydrin dehalogenase. Thus, by combining a Prelog‐ or anti‐Prelog alcohol dehydrogenase with a non‐selective halohydrin dehalogenase, enantiopure (R)‐ as well as (S)‐epoxides were obtained.
Enzyme‐Promoted Desymmetrisation of Prochiral Bis(cyanomethyl) Sulfoxide
Authors: Kiełbasiński Piotr , Rachwalski Michał , Mikołajczyk Marian , Szyrej Małgorzata , Wieczorek Michał W. , Wijtmans Roel , Rutjes Floris P. J. T.
Published: June 2007

Prochiral bis(cyanomethyl) sulfoxide has been successfully transformed into the corresponding optically active mono amide and mono acid with enantiomeric excesses ranging from low (10 %) to very high (up to 99 %) using a broad spectrum of nitrile‐hydrolysing enzymes.
Laccase‐Catalyzed Dimerization of Hydroxystilbenes
Authors: Ponzoni Chiara , Beneventi Elisa , Cramarossa Maria Rita , Raimondi Stefano , Trevisi Giulia , Pagnoni Ugo Maria , Riva Sergio , Forti Luca
Published: June 2007

A series of hydroxystilbenes, analogues of the bioactive phytoalexin resveratrol, were synthesized and submitted to the catalytic action of a laccase from Trametes pubescens in a biphasic system made of ethyl acetate and acetate buffer. Oxidation took place at the 4′‐hydroxy (4‐hydroxy) position of the hydroxystilbenic moieties, followed by radical‐radical coupling dimerization reactions. Most of the products were isolated in good yields and fully characterized. Depending on the substrates, three different dimeric products could be identified, the main products usually being 4‐O‐α‐ß‐5 (dihydrofuran‐like) dimers.
Altering the Substrate Specificity and Enantioselectivity of Phenylacetone Monooxygenase by Structure‐Inspired Enzyme Redesign
Authors: Pazmiño Daniel E. Torres , Snajdrova Radka , Rial Daniela V. , Mihovilovic Marko D. , Fraaije Marco W.
Published: June 2007

Of all presently available Baeyer–Villiger monooxygenases, phenylacetone monooxygenase (PAMO) is the only representative for which a structure has been determined. While it is an attractive biocatalyst because of its thermostability, it is only active with a limited number of substrates. By means of a comparison of the PAMO structure and a modeled structure of the sequence‐related cyclopentanone monooxygenase, several active‐site residues were selected for a mutagenesis study in order to alter the substrate specificity. The M446G PAMO mutant was found to be active with a number of aromatic ketones, amines and sulfides for which wild‐type PAMO shows no activity. An interesting finding was that the mutant is able to convert indole into indigo blue: a reaction that has never been reported before for a Baeyer–Villiger monooxygenase. In addition to an altered substrate specificity, the enantioselectivity towards several sulfides was dramatically improved. This newly designed Baeyer–Villiger monooxygenase extends the scope of oxidation reactions feasible with these atypical monooxygenases.
Branched‐Chain Keto Acid Decarboxylase from Lactococcus lactis (KdcA), a Valuable Thiamine Diphosphate‐Dependent Enzyme for Asymmetric CC Bond Formation
Authors: Gocke Dörte , Nguyen Cong Luan , Pohl Martina , Stillger Thomas , Walter Lydia , Müller Michael
Published: June 2007

The thiamine diphosphate‐dependent, branched‐chain 2‐keto acid decarboxylase from Lactococcus lactis sup. cremoris B1157 (KdcA) is a new valuable enzyme for the synthesis of chiral 2‐hydroxy ketones. The gene was cloned and the enzyme was expressed as an N‐terminal hexahistidine fusion protein in Escherichia coli. It has a broad substrate range for the decarboxylation reaction including linear and branched‐chain aliphatic and aromatic keto acids as well as phenyl pyruvate and indole‐3‐pyruvate. The dimeric structure of recombinant KdcA is in contrast to the tetrameric structure of other 2‐keto acid decarboxylases. The enzyme is stable between pH 5 and 7 with a pH optimum of pH 6–7 for the decarboxylation reaction. While KdcA is sufficiently stable up to 40 °C it rapidly looses activity at higher temperatures. In this work the carboligase activity of KdcA is demonstrated for the first time. The enzyme shows an exceptionally broad substrate range and, most strikingly, it catalyzes the carboligation of different aromatic aldehydes as well as CH‐acidic aldehydes such as phenylacetaldehyde and indole‐3‐acetaldehyde with aliphatic aldehydes such as acetaldehyde, propanal, and cyclopropanecarbaldehyde, yielding chiral 2‐hydroxy ketones in high enantiomeric excess. Noteworthy, the donor‐acceptor selectivity is strongly influenced by the nature of the respective substrate combination.
An Enzyme Module System for in situ Regeneration of Deoxythymidine 5′‐Diphosphate (dTDP)‐Activated Deoxy Sugars
Authors: Rupprath Carsten , Kopp Maren , Hirtz Dennis , Müller Rolf , Elling Lothar
Published: June 2007

A highly flexible enzyme module system (EMS) was developed which allows for the first time the in situ regeneration of deoxythymidine 5′‐diphosphate (dTDP)‐activated deoxy sugars and furthermore enables us to produce novel sorangiosides in a combinatorial biocatalytic approach using three enzyme modules. The SuSy module with the recombinant plant enzyme sucrose synthase (SuSy) and the deoxy sugar module consisting of the enzymes RmlB (4,6‐dehydratase), RmlC (3,5‐epimerase) and RmlD (4‐ketoreductase) from the biosynthetic pathway of dTDP‐β‐L‐rhamnose were combined with the glycosyltransferase module containing the promiscuous recombinant glycosyltransferase SorF from Sorangium cellulosum So ce12. Kinetic data and the catalytic efficiency were determined for the donor substrates of SorF: dTDP‐α‐D‐glucose, dTDP‐β‐L‐rhamnose, uridine diphosphate (UDP)‐α‐D‐glucose (Glc), and dTDP‐6‐deoxy‐4‐keto‐α‐D‐glucose. The synthesis of glucosyl‐sorangioside with in situ regeneration of dTDP‐Glc was accomplished by combination of SuSy and SorF. The potential of the EMS is demonstrated by combining SuSy, RmlB, RmlC, RmlD with SorF in one‐pot for the in situ regeneration of dTDP‐activated (deoxy) sugars. The HPLC/MS analysis revealed the formation of rhamnosyl‐sorangioside and glucosyl‐sorangioside, demonstrating the in situ regeneration of dTDP‐β‐L‐rhamnose and dTDP‐α‐D‐glucose and a cycle number for dTDP higher than 9. Furthermore, NADH (reduced form of nicotinamdie adenine dinucleotide) regeneration with formate dehydrogenase in the reduction step catalyzed by the 4‐ketoreductase RmlD could be integrated in the one‐pot synthesis yielding similar conversion rates and cycle numbers. In summary, we have established the first in situ regeneration cycle for dTDP‐activated (deoxy) sugars by a highly flexible EMS which allows simple exchange of enzymes in the deoxy sugar module and exchange of glycosyltransferases as well as aglycones in the glycosyltransferase module to synthesize new hybrid glycosylated natural products in one‐pot.
Comparison of Three Enoate Reductases and their Potential Use for Biotransformations
Authors: Chaparro‐Riggers Javier F. , Rogers Thomas A. , Vazquez‐Figueroa Eduardo , Polizzi Karen M. , Bommarius Andreas S.
Published: June 2007

Enoate reductases (ERs) selectively reduce carbon‐carbon double bonds in α,β‐unsaturated carbonyl compounds and thus can be employed to prepare enantiomerically pure aldehydes, ketones, and esters. Most known ERs, most notably Old Yellow Enzyme (OYE), are biochemically very well characterized. Some ERs have only been used in whole‐cell systems, with endogenous ketoreductases often interfering with the ER activity. Not many ERs are biocatalytically characterized as to specificity and stability. Here, we cloned the genes and expressed three non‐related ERs, two of them novel, in E. coli: XenA from Pseudomonas putida, KYE1 from Kluyveromyces lactis, and Yers‐ER from Yersinia bercovieri. All three proteins showed broad ER specificity and broad temperature and pH optima but different specificity patterns. All three proteins prefer NADPH as cofactor over NADH and are stable up to 40 °C. By coupling Yers‐ER with glucose dehydrogenase (GDH) to recycle NADP(H), conversion of >99 % within one hour was obtained for the reduction of 2‐cyclohexenone. Upon lowering the loadings of Yers‐ER and GDH, we discovered rapid deactivation of either enzyme, especially of the thermostable GDH. We found that the presence of enone substrate, rather than oxygen or elevated temperature, is responsible for deactivation. In summary, we successfully demonstrate the wide specificity of enoate reductases for a range of α,β‐unsaturated carbonyl compounds as well as coupling to glucose dehydrogenase for recycling of NAD(P)(H); however, the stability limitations we found need to be overcome to envision large‐scale use of ERs in synthesis.
Säulen griechischer Tempel unter Erdbebenbeanspruchung
Authors: Vayas Ioannis , Dasiou Maria‐Eleni , Marinelli Aikaterini
Published: June 2007

Säulen antiker griechischer Tempel bestehen aus übereinanderliegenden Wirbeln im Trockenbau. Die Kontaktflächen sind perfekt bearbeitet und absolut zentriert. Das Verhalten solcher Wirbelkonstruktionen unter Erdbebenbeanspruchung ist grundlegend anders als der modernen monolithischen Bauten. Ihre Standsicherheit wird durch unabhängiges Gleiten und Kippen der Wirbel bestimmt, die einen externen Energiedissipationsmechanismus bilden. In diesem Aufsatz werden numerische Untersuchungen zum dynamischen Verhalten antiker Säulen vorgestellt das starke Nichtlinearitäten aufweist. Verschiedene Modellierungsmöglichkeiten werden untersucht und an Versuchsergebnissen kalibriert. Es läßt sich feststellen, dass antike Säulen weniger gefährdet gegenüber Erdbeben als moderne Konstruktionen sein können. Es zeigt sich, dass die Perfektion der Ausbildung die Anforderungen an sthetik, Architektur und Tragfunktion vereinen könnte.
The effectiveness and generalization of a cognitive‐behavioral group treatment to reduce impulsive/aggressive behavior for boys in a residential setting
Authors: Nardone Maria J. , Tryon Warren W. , O'Connor Kevin
Published: June 2007

Twenty of 150 boys living in a residential setting who were emitting high levels of impulsive/aggressive behavior participated in a study of the effectiveness of a cognitive‐behavioral group treatment procedure designed to equip them with skills conducive to alternate and more socially appropriate behavior. Treatment involved 13 meetings of 55 minutes duration over a six‐week period. The results indicated significant behavioral changes in school regarding: (1) the intensity of physical fighting, (2) the frequency and intensity of verbal fighting, (3) noncompliance, and (4) being in an inappropriate location. These behavioral changes did not generalize beyond the school setting. Significant increases in the number of identified logical consequences of aggressive behavior and in the number of alternative responses to aggressive behavior were observed compared to control boys. The behavioral changes observed in school largely extinguished during the five weeks between the last treatment session and the follow‐up observations.
Predicting the nursing care needs of children in an inpatient psychiatry unit
Authors: Mabe P. Alex , Read Elizabeth E.
Published: June 2007

This study examined factors that could be used in the prediction of nursing care needs of the child or adolescent requesting admission into an inpatient psychiatric unit. Using a time sampling observer methodology, nursing care activities provided to 40 child/adolescent inpatients were recorded and used as estimates of nursing care needs. Results indicated a great deal of variability in the nursing care needs of the inpatients. An encouraging finding of this study was that with relatively little difficulty, information can be obtained that is predictive of the child's or adolescent's nursing care needs. Significant predictive contributions were particularly noted for information pertaining to the sex of the child/adolescent, ratings of intellectual functioning, and history of possible abuse and/or neglect.
Marital dissolution and distress in a psychiatric population: A longitudinal design
Authors: Beach Steven R. H. , Winters Ken C. , Weintraub Sheldon
Published: June 2007

There has been interest in recent years in the relationship between marital distress and psychopathology. It has been rare, however, for investigators to follow patients after their release from the hospital and observe the course of their marital relationships. The present study included patients meeting criteria for three DSM III DISORDERS (MAjor depressive, bipolar, and schizophrenic) and a normal control sample, all of whom are participants in an ongoing longitudinal study of children at risk for psychopathology (Stony Brook High‐Risk Project; Weintraub & Neale, 1984). Marital Adjustment Test (MAT; Locke & Wallace, 1959) scores were collected on patients at entry into the project (Phase I) and at a three year follow‐up (Phase II). Course of marriage was defined as negative if the couple's marital adjustment was rated as poor at Phase II or resulted in divorce or separation at Phase II. It was found that only the depressed group differed from the normal group in having significantly worse course of marital relationship; 84% of the depressive couples showed a “negative” course of marital change over time. However, all three patient groups had significantly higher rates of divorce by Phase II. MAT scores at Phase I successfully predicted course of marital relationship for all diagnostic groups. Implications for aftercare of psychiatric inpatients are discussed.
Relationships between patients' perceived improvement and their evaluations of treatment components in a behaviorally‐oriented psychiatric inpatient unit
Authors: Merkel William T. , Wiener Richard L.
Published: June 2007

Patients on a behaviorally‐oriented inpatient psychiatric unit were asked to rate their perceptions of treatment outcome and the value of 16 program components in producing that outcome. Significant correlations were found between perceived outcome and positive evaluations of the overall behavioral treatment plan, individual meetings with nursing staff, individual meetings with team psychologists, assertion group training, and daily group therapy. Patients perceived individual meetings with the nursing staff to be the single most valuable program component among those related to favorable outcome. Implications for the increased utilization of nursing staff during a time of dwindling resources for mental health are discussed.
Behavioral skills workshop for staff and supervisor in a community residence for developmentally handicapped adults
Authors: Davis John R. , McEachern Mary Anne , Christensen Joanna , Voort Catherine Vant
Published: June 2007

A behavioral skills workshop for counselors and a supervisor in a community group home was developed and evaluated. The workshop included group skills training, individual supervised in vivo practice, and supervisor training. Supervisor training taught behavioral staff management skills that were delivered in a multiple baseline design across subjects. Positive changes in staff behavior occurred for each group only after supervisor intervention. Significant positive changes occurred by the end of the workshop and were maintained at follow‐up for staff self‐evaluations of expertise and confidence to resolve problems, severity of client problems, and behavioral observations of positive client behaviors.
Cues‐pause‐point language training: Structuring trainer statements to provide students with correct answers to questions
Authors: Foxx R. M. , McMorrow Martin J. , Faw Gerald D. , Kyle Martha S. , Bittle Ron G.
Published: June 2007

This study assessed the applicability of Cues‐Pause‐Point language training procedures in teaching students to obtain information from the statements of others. Two mentally retarded subjects, one of whom was echolalic, received training on one set of stimuli but not on another. During training the subjects were encouraged to remain quiet before, during, and briefly after the presentation of statements and then verbalize (i.e., answer a question) using the verbal cue(s) that had been presented in the statement. Correct responding reached 100% to the trained stimuli and both subjects' responding improved to the untrained stimuli. Posttests revealed that subjects used the trainer's statements to answer novel questions. The results suggest that Cues‐Pause‐Point procedures may be useful in teaching severely retarded individuals the functional use of observing and listening to others' verbal behavior.
Effects of phenobarbitol on aggressive behaviors in a program of required relaxation: A case study
Authors: Seekins Tom , Swenson Richard P.
Published: June 2007

A naturally occurring experiment of the effects of two dosage levels of phenobarbitol on aggressive behaviors in a program of required relaxation is described. A required relaxation program was initiated as a consequence for throwing and hitting by a 13‐year‐old developmentally disabled male resident of an institutional cottage. The resident had been receiving 50 mg of phenobarbitol twice per day to control seizure activity for two years prior to the introduction of this program. Aggressive behavior decreased from an average of 7.2 incidents a day during baseline to 1.7 per day after six weeks of the required relaxation program. Following several reported seizures, medical staff increased phenobarbitol dosage to 100 mg twice per day and hitting behavior increased beyond baseline levels. After five weeks at this dosage, medication was returned to 50 mg twice a day and hitting behavior returned quickly to the lower intervention levels, while seizure activity remained stable. All observations of behavior were collected during unstructured and regularly occurring events of the individual's daily life. These data suggested that changes in medication influenced observed changes in behavior.
Behavior disorder teams: An efficient institutional strategy
Authors: Dura Jason R. , Mulick James A.
Published: June 2007

Recent trends toward deinstitutionalization have lead to an increased prevalence of behavioral and physical handicaps within institutional populations. At the same time, funding allocations have remained constant or have reduced creating an ever increasing need for the most efficient and cost‐effective delivery of services. The present article traces the evolution of a program designed to create in‐house panels of experts in an intermediate care facility for nonambulatory, severely and profoundly retarded children. The model is proposed as a means of improving quality of care and staff expertise and reducing the need for outside consultation.
The influence of anxiety and mental status on social isolation among the elderly in nursing homes
Authors: Carstensen Laura L. , Fremouw William J.
Published: June 2007

Social isolation is a pervasive problem for older adults and interventions designed to reduce it have met with only limited success. The current research was designed to identify observable behaviors and qualitative aspects of emotional distress that differentiate socially active from socially isolated elderly nursing home residents. The investigation consisted of two parts: The first involved direct observation of subjects (n = 51) and the second involved a structured interview with a subsample of subjects (n = 23), including an assessment of social anxiety, social competence and depression. Results of a multiple regression analysis suggest that staff views of social isolation are related to rates of specific social behaviors, social anxiety, and mental status. Implications for treatment are discussed.
Promoting unsupervised activities with low‐functioning blind persons: Evaluation of a computer‐aided program
Authors: Lancioni Giulio E. , Oliva Doretta , Adorni Adolfo , Guzzini Francesco , Locatelli Marco , Spinaci Patrizia
Published: June 2007

The present study assessed a computer‐aided system devised to promote unsupervised (household and occupational) activities requiring locomotion and orientation with four low‐functioning blind persons. The computer system controlled the presentation of object‐signals (i.e., prompts) and the opening‐closing of little gates leading to the areas where the activities had to be executed. To assess the effects of the computer‐aided program, subjects were also exposed to a control program in which no computer was used. The results indicated that the computer‐aided program was successful in promoting the performance of scheduled activities with all subjects. Their performance was maintained and also improved over time. The control program was unsuccessful with three of the subjects, whereas it showed moderately positive effects with the fourth one. The findings are discussed in terms of program components as well as in terms of cost and benefits.
Fire evacuation skills training for institutionalized mentally retarded adults
Authors: Rowe Mary , Kedesdy Jurgen H.
Published: June 2007

Thirty‐seven institutionalized mentally retarded clients were given time‐limited intensive group training in fire evacuation skills. Clients were trained to independently exit their residence within 2.5 minutes of the onset of a fire alarm in drills conducted during both day and night and with one of multiple exits blocked or unblocked. Three weeks of training produced a substantial increase in the percentage of clients passing training drills, and clients continued to improve at three and six month follow‐up periods. Six months after training, 18 of these clients had been independently certified capable of self‐preservation. A post‐hoc analysis of variables related to training outcome suggests that client choice of monetary reinforcers strongly predicted performance, while level of mental retardation, psychiatric diagnosis, and use of psychotropic medication did not.