bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and environmental sources of continuity and change in teacher‐rated aggression during early adolescence
Authors: Vierikko Elina , Pulkkinen Lea , Kaprio Jaakko , Rose Richard J.
Published: June 2006

Genetic and environmental sources of continuity and change in aggression were studied in a sample of 1,041 twin pairs (364 monozygotic; 348 same‐sex dizygotic; and 329 opposite‐sex dizygotic) as part of an ongoing, population‐based Finnish twin‐family study. At ages 12 and 14, the twins' aggression was assessed by their classroom teachers, using a rating form of the Multidimensional Peer Nomination Inventory. Genetic and environmental sources of continuity and change were studied by fitting a longitudinal bivariate Cholesky decomposition model. Longitudinal model‐fitting results indicated that both genetic and environmental factors influenced continuity in aggression during this 2‐year period, but the age‐to‐age correlation of these factors differed by sex. Continuity in boys' aggression was mediated by genes and common environmental factors; in girls, in contrast, continuity was due primarily to common environmental, and to a lesser degree, unique environmental factors. Genes and unique environments contributed to change in aggression in both sexes. Aggr. Behav. 31:1–13, 2006. © 2006 Wiley‐Liss, Inc.
Transient displacement of Newtonian liquids by gas in periodically constricted tubes
Authors: Dimakopoulos Yannis , Tsamopoulos John
Published: June 2006

The displacement of viscous liquids by pressurized gas from harmonically undulated tubes of finite length is examined. This unsteady process gives rise to a long open bubble of varying radius, increasing length and surrounded by the liquid. In general, the thickness of the liquid film that remains on the tube wall is nonuniform. Under creeping flow conditions, it varies periodically, but with a phase difference from the tube radius. The liquid fraction remaining in each periodic segment of the tube increases as the ratio between the minimum and maximum of the tube radius S decreases, whereas it tends to the well‐known asymptotic value for straight tubes as S → 1, or as the wavelength of the tube undulation increases, although here the flow is accelerating. At high‐values of the Reynolds number, the film thickness increases with the axial distance, and the periodicity of the flow field ahead of the bubble tip, which exists under creeping flow conditions, is broken. At even higher Reynolds numbers, recirculating vortices develop inside each tube expansion and when S also decreases significantly, nearly isolated bubbles are formed in each tube segment. The location of the bubble tip can be monitored by examining the time variation of the pressure at the tube wall. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Stratification based on language‐related endophenotypes in autism: Attempt to replicate reported linkage
Authors: Spence Sarah J. , Cantor Rita M. , Chung Lien , Kim Sharon , Geschwind Daniel H. , Alarcón Maricela
Published: June 2006

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism‐related susceptibility regions. To further explore the utility of using language‐related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non‐parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome‐wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples. © 2006 Wiley‐Liss, Inc.
When it's over before it's completed: The finality of interim awards
Authors: Widman Stuart M.
Published: June 2006

How final is final? In the first of two parts, Stuart M. Widman, of Chicago, examines the state of the law on when and why arbitration awards are considered final and, therefore, when they may be confirmed by a court.
Research backs survey results: Achieving rapport is the key to getting mediation parties to reach a settlement
Authors: Goldberg Stephen B.
Published: June 2006

In the conclusion of his two‐part article on mediators' view of their own successes, Stephen B. Goldberg, of Chicago, examines academic research that expands upon some of his survey impressions
A novel 4‐methylene‐3‐borahomoadamantane: 1,1‐organoboration of an alkyn‐1‐ylsilane using 1‐boraadamantane
Authors: Wrackmeyer Bernd , Tok Oleg L. , Milius Wolfgang
Published: June 2006

1,1‐Dibromo‐2,2‐bis(trimethylsilylethynyl)ethene (2) reacts with two equivalents of 1‐boraadamantane (1) by 1,1‐organoboration of both trimethylsilylethynyl groups to give a triene 3 bearing two 4‐methylene‐3‐borahomoadamantane moieties in terminal positions. The triene was characterized by one‐ and two‐dimensional 1H, 11B, 13C and 29Si NMR spectroscopy in solution and X‐ray structural analysis in the solid state. The planes of the C double bond are strongly twisted against each other as a result of the bulky substituents, and the surroundings of the boron atoms deviate from the ideal trigonal planar geometry owing to the tension in the tricyclic frameworks. Copyright © 2006 John Wiley & Sons, Ltd.
Ground‐penetrating radar mapping in clay: success from South Carolina, USA
Authors: Weaver Wendy
Published: June 2006

A ground‐penetrating radar (GPR) survey conducted in a clay‐rich floodplain of the Savannah River, South Carolina, produced what were very difficult to interpret reflection profiles caused by energy coupling changes. These changes were caused by deep hardened plow furrows at the ground surface that caused antenna movement to be irregular, and energy to be transmitted into the ground at various angles, and with different properties. A dense clay layer also attenuated much of the radar energy at about 50 cm, further obscuring the profiles. Despite these ambiguous data, amplitude mapping at slices below the clay layer yielded images of distinct circular and linear features, which proved to be palisade walls dating from about the late Mississippian to Early Contact period (AD1400‐1740). This survey illustrates that it is possible to obtain good GPR results even when energy passes through dense clay and when reflection profiles are obscured by attenuation and coupling changes. Copyright © 2006 John Wiley & Sons, Ltd.
Resolution of ground‐penetrating radar reflections at differing frequencies
Authors: Grealy Michael
Published: June 2006

Ground‐Penetrating Radar (GPR) data that are frequency filtered will produce a variety of data sets, each with a differing subsurface resolution. At the site of Petra, Jordan, filtered reflection data were processed to produce discrete categories of low (200–350 MHz), middle (500–650 MHz), and high (650–800 MHz) frequency wave amplitudes. The high frequency reflections were especially effective in identifying construction techniques from a buried Nabataean age wall. The results suggest that post‐acquisition GPR data frequency filtering may be helpful in identifying some differences in construction techniques and building materials in otherwise difficult to interpret subtle buried features. Copyright © 2006 John Wiley & Sons, Ltd.
Correcting for topography and the tilt of ground‐penetrating radar antennae
Authors: Goodman Dean , Nishimura Yasushi , Hongo Hiromichi , Higashi Noriaki
Published: June 2006

Static corrections of radargrams can account for the tilt that the GPR antenna encounters on sites with topography. Radargrams that are topography‐tilt corrected, show that changes in the imaged locations of subsurface structures can be significant. The results of these corrections indicate that tilt corrections are necessary to improve the accuracy in imaging subsurface structures on sites with significant topographic changes. Copyright © 2006 John Wiley & Sons, Ltd.
Imaging in the ground‐penetrating radar near‐field zone: a case study from New Mexico, USA
Authors: Ernenwein Eileen G.
Published: June 2006

It has long been suggested that the near field zone in GPR data contains no usable information, and should be ignored. This paper shows that there can be usable information in the near‐field zone when accurate time‐zero is chosen, and near‐surface reflections are processed. Reflection data from a Pueblo site in New Mexico were filtered and then re‐gained to reveal floors within the upper 3 nanoseconds, and their presence was confirmed by excavation. Copyright © 2006 John Wiley & Sons, Ltd.
Competitive adsorption of labeled and native protein in confocal laser scanning microscopy
Authors: Teske Christopher A. , Lieres Eric von , Schröder Magnus , Ladiwala Asif , Cramer Steven M. , Hubbuch Jürgen J.
Published: June 2006

Confocal laser scanning microscopy has been previously applied to the study of protein uptake in porous chromatography resins. This method requires labeling the protein with a fluorescent probe. The labeled protein is then diluted with a large quantity of native protein so that the fluorescence intensity is a linear function of the labeled protein concentration. Ideally, the attachment of a fluorescent probe should not affect the affinity of the protein for the stationary phase; however, recent experimental work has shown that this assumption is difficult to satisfy. In the present study, we present a mathematical model of protein diffusion and adsorption in a single adsorbent particle. The differences in adsorption behavior of labeled and native protein are accounted for by treating the system as a two‐component system (labeled and native protein) described by the steric mass action isotherm (SMA). SMA parameters are regressed from experimental linear gradient elution data for lysozyme and lysozyme‐dye conjugates (for the fluorescent dyes Cy3, Cy5, Bodipy FL, and Atto635). When the regressed parameters are employed in the model, an overshoot in the labeled lysozyme concentration is predicted for Cy5‐ and Bodipy‐labeled lysozyme, but not for Atto635‐labeled lysozyme. The model predictions agree qualitatively well with recent work showing the dependence of the concentration overshoot on the identity of the attached dye and provide further evidence that the overshoot is likely caused by the change of binding characteristics due to the fluorescent label. © 2006 Wiley Periodicals, Inc.
Coherent anti‐stokes Raman scattering microscopy: A biological review
Authors: Rodriguez Luis G. , Lockett Stephen J. , Holtom Gary R.
Published: June 2006

Microscopic imaging of cells and tissues are generated by the interaction of light with either the sample itself or contrast agents that label the sample. Most contrast agents, however, alter the cell in order to introduce molecular labels, complicating live cell imaging. The interaction of light from multiple laser sources has given rise to microscopy, based on Raman scattering or vibrational resonance, which demonstrates selectivity to specific chemical bonds while imaging unmodified live cells. Here, we discuss the nonlinear optical technique of coherent anti‐Stokes Raman scattering (CARS) microscopy, its instrumentation, and its status in live cell imaging. © 2006 International Society for Analytical Cytology
Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes
Authors: Rinta‐Valkama Johanna , Aaltonen Petri , Lassila Markus , Palmén Tuula , Tossavainen Päivi , Knip Mikael , Holthöfer Harry
Published: June 2006

Background and aim

The development of autoantibodies against antigens of the pancreatic islet cells is a typical phenomenon in patients with type 1 diabetes. The expression of densin, recently shown to be present in kidney podocytes, was explored in the pancreas. Additionally, we studied whether densin and filtrin, another molecule shared between the kidney podocytes and pancreatic islet cells, can act as autoantigens and whether autoantibodies against these can be detected in patients with type 1 diabetes.

Methods

Expression of pancreatic densin was studied with reverse transcription polymerase chain reaction (RT–PCR) and immunofluorescence. Children and adolescents (n = 66) with type 1 diabetes and control subjects were analysed for densin autoantibodies (DAA) and filtrin autoantibodies (FAA) using radioimmunoprecipitation assay. The serum samples were obtained at the time of diagnosis and after a duration of 2, 5 and 10 years.

Results

Densin expression was observed in the pancreas, localising to the beta cells. DAA were detected in 33% of the patients and the positivity was typically seen already at diagnosis. FAA were observed in 11% of the patients. The proportion of islet cell antibody (ICA) positive, GADA positive and protein tyrosine phosphatase‐related islet antigen 2 antibody (IA‐2A)‐positive patients decreased during the follow‐up period, and a similar trend was seen for DAA but not for FAA. Among the 14 patients with signs of renal injury, four tested positive for DAA and two for FAA.

Conclusions

Densin is a novel molecule shared by the kidney glomerular podocytes and pancreatic islet cells. Densin and filtrin can act as autoantigens, and autoantibodies against these can be detected in patients with type 1 diabetes. Copyright © 2006 John Wiley & Sons, Ltd.
Vibration perception threshold—a valuable assessment of neural dysfunction in people with diabetes
Authors: Garrow Adam P. , Boulton Andrew J. M.
Published: June 2006

Diabetic peripheral neuropathy (DPN) has been identified as a key element in the causal pathway to foot ulceration and other lower‐extremity complications, impaired quality of life and increased mortality. Early detection is essential to optimise effective risk management, including adequate foot care, patient education, and future pharmacological therapy. However, data suggest that screening has been mostly sub‐optimal, and many physicians remain unfamiliar with non‐invasive screening tests. There is evidence in the literature to suggest that vibration perception threshold (VPT) measures can be used to easily and accurately identify at‐risk diabetic patients, including those with early neuropathic deficits. These measures have been used in population‐based studies and are associated with an increased risk of severe and expensive outcomes, such as ulcers and amputations. Incorporating VPT testing into clinical practice has the potential to significantly improve the outcomes in patients with DPN, thereby substantially reducing the socio‐economic burden of this common and challenging disease. Copyright © 2006 John Wiley & Sons, Ltd.
Synthesis and characterization of macroporous poly(ethylene glycol)‐based hydrogels for tissue engineering application
Authors: Sannino A. , Netti P. A. , Madaghiele M. , Coccoli V. , Luciani A. , Maffezzoli A. , Nicolais L.
Published: June 2006

Peptide activated poly(ethylene glycol) (PEG)‐based hydrogels have received wide attention as material for tissue engineering application. However, the close structure of these materials may pose severe barriers to tissue invasion and nutrient transport. The aim of this work was to synthesize highly interconnected macroporous PEG hydrogels, suitable for use as tissue engineering scaffolds, by combining the photocrosslinking reaction with a foaming process. In particular, various porous samples, differing for both the polymer molecular weight and concentration in the starting precursor solution, have been prepared and characterized by means of scanning electron microscopy and mercury porosimetry. Moreover, water swelling properties have been evaluated and compared with those of the conventional nonporous ones, by performing both equilibrium and kinetic swelling measurements in distilled water. Results indicated that foamed hydrogels display a well‐interconnected porous network, suitable for tissue invasion and free molecular trafficking within them. Pores dimension as well as swelling rate can be modulated by polymer concentrations and bubbling agent composition in the precursor solution. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Bone cell transfection in tissue culture using hydroxyapatite microparticles
Authors: Frayssinet Patrick , Rouquet Nicole , Mathon Didier
Published: June 2006

Coprecipitates of calcium phosphate and DNA have been used in vitro for several decades for cell transfection. We evaluated the efficiency of calcium phosphate ceramics associated to plasmid DNA in the transfection of bone cells in vitro when they are grown in tissue culture. Newborn rat calvariae and tibia epiphyses were grown on an agar surface for a period of 48 h to 30 days. The hydroxyapatite (HA)‐particles were loaded with a plasmid bearing a galactosidase reporter gene by incubation of the plasmid solution in PBS with the particles. One milligram of HA‐particles was then placed in contact with the bone explants for 8 and 30 days. Histological sections were then performed and the galactosidase activity was revealed using an X‐gal solution. At eight days, very few cells expressing the galactosidase activity were detected. By 30 days, however, the explants appeared uniformly stained blue. The staining of sections showed that the osteoblasts, chondroblasts, perichondroblasts, and perisoteal cells all expressed the lacZ gene while the number of cells stained in the control was negligible. The time dependence of the transfection suggests that transfection using ceramics is linked to the degradation of the ceramic by the cells. Furthermore, the cells are stained remote from the particles suggesting that the particles induce a coprecipitate of DNA in the explant. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Ab initio protein fold prediction using evolutionary algorithms: Influence of design and control parameters on performance
Authors: Djurdjevic Dusan P. , Biggs Mark J.
Published: June 2006

True ab initio prediction of protein 3D structure requires only the protein primary structure, a physicochemical free energy model, and a search method for identifying the free energy global minimum. Various characteristics of evolutionary algorithms (EAs) mean they are in principle well suited to the latter. Studies to date have been less than encouraging, however. This is because of the limited consideration given to EA design and control parameter issues. A comprehensive study of these issues was, therefore, undertaken for ab initio protein fold prediction using a full atomistic protein model. The performance and optimal control parameter settings of twelve EA designs where first established using a 15‐residue polyalanine molecule—design aspects varied include the encoding alphabet, crossover operator, and replacement strategy. It can be concluded that real encoding and multipoint crossover are superior, while both generational and steady‐state replacement strategies have merits. The scaling between the optimal control parameter settings and polyalanine size was also identified for both generational and steady‐state designs based on real encoding and multipoint crossover. Application of the steady‐state design to met‐enkephalin indicated that these scalings are potentially transferable to real proteins. Comparison of the performance of the steady state design for met‐enkephalin with other ab initio methods indicates that EAs can be competitive provided the correct design and control parameter values are used. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1177–1195, 2006
Efficient transduction of monocyte‐ and CD34+‐ derived Langerhans cells with lentiviral vectors in the absence of phenotypic and functional maturation
Authors: Veron P. , Boutin S. , Bernard J. , Danos O. , Davoust J. , Masurier C.
Published: June 2006

Background

Gene delivery in dendritic cells (DC) has raised considerable interest to modulate DC functions and induce therapeutic immunity or tolerance in an antigen‐specific fashion. Among immature DC, Langerhans cells (LC) are attractive candidates for antigen delivery using lentiviral vectors (LV).

Methods

LC derived from monocytes (Mo‐LC), or derived from CD34+ cells (CD34‐LC) in the presence of cytokine cocktail, were transduced with LV expressing enhanced green fluorescent protein (E‐GFP) under the control of the ubiquitous phosphoglycerate kinase (PGK) promoter at a multiplicity of infection of 18, at days 0 to 3 for Mo‐LC, or at days 0 to 12 for CD34‐LC. We assessed gene transfer levels from the percentage of E‐GFP+ cells in the final cultures, and examined the morphology, immunophenotype, state of differentiation and function of transduced LC.

Results

Day 0 transduction of monocytes or CD34+ progenitors before cytokine pre‐activation and LC differentiation resulted in stable gene expression in 7.8% of Mo‐LC and 24% of CD34‐LC. Monocyte‐derived DC (Mo‐DC) differentiated in serum‐free medium were also efficiently transduced up to 13.2%. Interestingly, Mo‐LC cells committed towards LC phenotype were permissive for transduction up to day 3. Transduction levels of CD34‐LC peaked at day 6 to 44% and decreased thereafter. LV transduction did not perturb viability, phenotype and function of E‐GFP‐expressing LC.

Conclusions

LC generated ex vivo can serve as vaccine vehicles in humans through efficient transduction by LV. These LC will be helpful to assess in vitro the immunogenicity of gene therapy vectors, from the characterization of their phenotypic and functional maturation. Copyright © 2006 John Wiley & Sons, Ltd.
Vertex partitions of chordal graphs
Authors: Wood David R.
Published: June 2006

A k‐tree is a chordal graph with no (k + 2)‐clique. An ℓ‐tree‐partition of a graph G is a vertex partition of G into ‘bags,’ such that contracting each bag to a single vertex gives an ℓ‐tree (after deleting loops and replacing parallel edges by a single edge). We prove that for all k ≥ ℓ ≥ 0, every k‐tree has an ℓ‐tree‐partition in which each bag induces a connected ${\lfloor k} /(\ell+1) \rfloor$‐tree. An analogous result is proved for oriented k‐trees. © 2006 Wiley Periodicals, Inc. J Graph Theory 53: 167–172, 2006
Maximal and maximum independent sets in graphs with at most r cycles
Authors: Sagan Bruce E. , Vatter Vincent R.
Published: June 2006

Let m(G) denote the number of maximal independent sets of vertices in a graph G and let c(n,r) be the maximum value of m(G) over all connected graphs with n vertices and at most r cycles. A theorem of Griggs, Grinstead, and Guichard gives a formula for c(n,r) when r is large relative to n, while a theorem of Goh, Koh, Sagan, and Vatter does the same when r is small relative to n. We complete the determination of c(n,r) for all n and r and characterize the extremal graphs. Problems for maximum independent sets are also completely resolved. © 2006 Wiley Periodicals, Inc. J Graph Theory 53: 283–314, 2006
Inpatient management of diabetes and hyperglycemia among general medicine patients at a large teaching hospital
Authors: Schnipper Jeffrey L. , Barsky Emily E. , Shaykevich Shimon , Fitzmaurice Garrett , Pendergrass Merri L.
Published: June 2006

BACKGROUND

Because of the relationship between inpatient hyperglycemia and adverse patient outcomes, current guidelines recommend glucose levels less than 180 mg/dL in the non‐ICU inpatient setting and the use of effective insulin protocols for appropriate patients.

OBJECTIVE

To determine the current state of glucose management on an academic hospitalist service and the relationship between insulin‐ordering practices and glycemic control.

DESIGN

Prospective cohort study.

SETTING

Hospitalist‐run general medicine service of an academic teaching hospital.

PATIENTS

107 consecutive patients with diabetes mellitus or inpatient hyperglycemia.

MEASUREMENTS

We collected data on up to 4 bedside glucose measurements per day, detailed clinical information, and all orders related to glucose management. The primary outcomes were rate of hyperglycemia (glucose > 180 mg/dL) per patient and mean glucose level per patient‐day.

RESULTS

The mean rate of hyperglycemia was 31% of measurements per patient. Basal insulin was ordered for 43% of patients, and scheduled rapid‐ or short‐acting insulin was ordered for 4% of patients. Sixty‐five percent of patients who had at least 1 episode of hyper‐ or hypoglycemia had no change made to any insulin order during the first 5 days of the hospitalization. When adjusted for clinical factors, the use of sliding‐scale insulin by itself was associated with a 20 mg/dL higher mean glucose level per patient‐day.

CONCLUSIONS

Management of diabetes and hyperglycemia on a general medicine service showed several deficiencies in process and outcome. Possible targets for improvement include increased use of basal and nutritional insulin and daily insulin adjustment in response to hyperglycemia. Journal of Hospital Medicine 2006;3:145–150. © 2006 Society of Hospital Medicine.
Expression of protein 4.1G in Schwann cells of the peripheral nervous system
Authors: Ohno Nobuhiko , Terada Nobuo , Yamakawa Hisashi , Komada Masayuki , Ohara Osamu , Trapp Bruce D. , Ohno Shinichi
Published: June 2006

The membrane‐associated cytoskeletal proteins, including protein 4.1 family, play important roles in membrane integrity, protein targeting, and signal transduction. Although protein 4.1G (4.1G) is expressed ubiquitously in mammalian tissues, it can have very discrete distributions within cells. The present study investigated the expression and distributions of 4.1G in rodent sciatic nerve. Northern and Western blot analysis detected abundant 4.1G mRNA and protein in rat sciatic nerve extracts. Immunohistochemical staining with a 4.1G‐specific antibody and double immunolabeling with E‐cadherin, βIV spectrin, and connexin 32 detected 4.1G in paranodal loops, Schmidt‐Lanterman incisures, and periaxonal, mesaxonal, and abaxonal membranes of rodent sciatic nerve. Immunoelectron microscopy confirmed the immunodistribution of 4.1G in Schwann cells. In developing mouse sciatic nerves, 4.1G was diffusely distributed in immature Schwann cells and gradually localized at paranodes, incisures, and periaxonal and mesaxonal membranes during their maturation. These data support the concept that 4.1G plays an important role in the membrane expansion and specialization that occurs during formation and maintenance of myelin internodes in the peripheral nervous system. © 2006 Wiley‐Liss, Inc.
Dynamic domain threading
Authors: Taylor William R. , Lin Kuang , Klose Daniel , Fraternali Franca , Jonassen Inge
Published: June 2006

A modeling method is described that avoids the need to consider the domain structure of the template used for modeling, and automatically extracts compact fragments of structure that would be of a suitable size to build the model. This aids automation as the size or nature of the template structure can be ignored and does not have to be broken into domain (or multi‐domain) units beforehand. The approach leads to the generation of a large number of models each based on slightly differing domain definitions and this variation was further increased by considering alternative secondary structure predictions. Each model, of which there may be thousands, takes the form of a complete alpha‐carbon trace and some methods (including residue burial) were investigated for their power to discriminate good models from bad models using decoys. The method is also compared to an earlier retroviral capsid modeling problem for which the X‐ray structure is now known. Some potential extensions of the approach to more distant modeling problems are discussed. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Free energy calculations show that acidic P1 variants undergo large pKa shifts upon binding to trypsin
Authors: Brandsdal Bjørn O. , Smalås Arne O. , Åqvist Johan
Published: June 2006

Serine proteinases and their protein inhibitors belong to one of the most comprehensively studied models of protein–protein interactions. It is well established that the narrow trypsin specificity is caused by the presence of a negatively charged aspartate at the specificity pocket. X‐ray crystallography as well as association measurements revealed, surprisingly, that BPTI with glutamatic acid as the primary binding (P1) residue was able to bind to trypsin. Previous free energy calculations showed that there was a substantially unfavorable binding free energy associated with accommodation of ionized P1 Glu at the S1‐site of trypsin. In this study, the binding of P1 Glu to trypsin has been systematically investigated in terms of the protonation states of P1 Glu and Asp189, the orientation of Gln192, as well as the possible presence of counterions using the linear interaction energy (LIE) approach and the free energy perturbation (FEP) method. Twenty‐four conceivable binding arrangements were evaluated and quantitative agreement with experiments is obtained when the P1 Glu binds in its protonated from. The results suggest that P1 Glu is one of the variants of BPTI that inhibit trypsin strongest at low pH, contrary to the specificity profile of trypsin, suggesting a new regulation mechanism of trypsin‐like enzymes. Proteins 2006. © 2006 Wiley‐Liss, Inc.
The planar conformation of a strained proline ring: A QM/MM study
Authors: Donnini Serena , Groenhof Gerrit , Wierenga Rik K. , Juffer André H.
Published: June 2006

QM and QM/MM energy calculations have been carried out on an atomic resolution structure of liganded triosephosphate isomerase (TIM) that has an active site proline (Pro168) in a planar conformation. The origin of the planarity of this proline has been identified. Steric interactions between the atoms of the proline ring and a tyrosine ring (Tyr166) on one side of the proline prevent the ring from adopting the up pucker (χ1 is approximately −30°), while the side chain of a nearby alanine (Ala171) forbids the down pucker (χ1 is approximately +30°). To obtain a proline conformation that is in agreement with the experimentally observed planar state, a quantum system of sufficient size is required and should at least include the nearby side chains of Tyr166, Ala171, and Glu129 to provide enough stabilization. It is argued that the current force fields for structure optimization do not describe strained protein fragments correctly. The proline is part of a catalytic loop that closes upon ligand binding. Comparison of the proline conformation in different TIM X‐ray structures, indicates that in the closed conformation of TIM the proline is planar or nearly planar, while in the open conformation it is down puckered. This suggests that the planarity possibly plays a role in the overall catalytic cycle of TIM, presumable acting as a reservoir of energy that becomes available upon loop opening. Proteins 2006. © 2006 Wiley‐Liss, Inc.
Soil application of azadirachtin and 3‐tigloyl‐azadirachtol to control western flower thrips, Frankliniella occidentalis (Thysanoptera: Thripidae): translocation and persistence in bean plants
Authors: Thoeming Gunda , Draeger Gerald , Poehling Hans‐Michael
Published: June 2006

To study the systemic effects of active neem ingredients, the substrate of bean plants was treated with a 170 g kg−1 azadirachtin (NeemAzal‐U; Trifolio‐M GmbH, Lahnau, Germany, registration pending). This product was used at a dose rate of 10 mg AZA (azadirachtin a) and 1.2 mg 3‐tigloyl‐azadirachtol (azadirachtin b) per treated bean plant. Afterwards, the translocation and persistence of AZA and 3‐tigloyl‐azadirachtol and the effects on western flower thrips, Frankliniella occidentalis (Pergande), were studied. Residues of AZA and 3‐tigloyl‐azadirachtol from substrates with different contents of organic matter [pure culture substrate (CS), CS–sand mixture] and from various plant parts were quantified by high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS). The dissipation trends of AZA and 3‐tigloyl‐azadirachtol were similar within the same substrates. A slower decline of both active ingredients was measured with CS than with CS–sand mixture. Residue analysis of the bean plants showed that only small proportions of the initial amounts of AZA and 3‐tigloyl‐azadirachtol applied to the substrate were present in the plant (0.3‐8.1%). Variable amounts of residues of the active components in relation to plant parts and time of analysis indicated a different translocation pattern for the two active ingredients. Higher residues of the active ingredients were found in roots and stems after neem application using CS, whereas higher residues were found in leaves after CS–sand mixture treatments. Mortality of F. occidentalis after NeemAzal‐U soil applications reached up to 95% on CS–sand mixture, compared with 86% in CS. Copyright © 2006 Society of Chemical Industry
Pycnogenol® protects against Ionizing radiation as shown in the intestinal mucosa of rats exposed to X‐rays
Authors: de Moraes Ramos Flávia Maria , Schönlau Frank , Novaes Pedro Duarte , Manzi Flávio Ricardo , Bóscolo Frab Norberto , de Almeida Solange Maria
Published: June 2006

X‐rays and gamma radiation delivered to the abdominal region for cancer treatment encompasses severe damage to the intestinal mucosa, which significantly impairs a patient's quality of life. To a great extent the deleterious effects of x‐radiation originate from radiolysis‐induced reactive oxygen species. The well‐researched powerful antioxidant Pycnogenol® was administered orally to rats prior to x‐irradiation with 15 Gy. Histological sections of the intestines showed a dramatically better condition of the mucosal layers compared with the irradiated control animals administered water without Pycnogenol®. Pycnogenol® treatment significantly preserved the height and number of villi as well as the glandular layer and a diminished number of congested vases were present. No intestinal alterations were seen in control animals receiving Pycnogenol® in the absence of radiation. It is concluded that Pycnogenol® provides significant protection from ionizing radiation damage. Copyright © 2006 John Wiley & Sons, Ltd.
Improving upon the ZORA Hamiltonian
Authors: Sadlej Andrzej J.
Published: June 2006

The metric perturbation method is used to derive what is called the normalized zeroth‐order regular approximation (ZORA) Hamiltonian. This Hamiltonian, although derived in a different way, turns out to be equivalent to the infinite‐order regular approximation (IORA) operator of Dyall and van Lenthe. The normalized ZORA Hamiltonian is analyzed in terms of its expansion with respect to the leading order of the fine structure constant. Through the leading second‐order in the fine structure constant, the normalized ZORA Hamiltonian recovers all terms of what is known as the first‐order regular approximation (FORA). The relation of the regular approximation to methods based on the Douglas–Kroll transformation is discussed. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006
Effect of moderate ethanol dose on dopamine uptake in rat nucleus accumbens in vivo
Authors: Jones Sara R. , Mathews Tiffany A. , Budygin Evgeny A.
Published: June 2006

The present study was designed to evaluate the effects of a moderate dose of ethanol (1 g/kg) on dopamine (DA) dynamics in rat nucleus accumbens (NAc) using fast‐scan cyclic voltammetry. Voltammetric recordings were made every 100 ms at a carbon fiber microelectrode, positioned in the NAc core. Acute ethanol did not significantly alter DA uptake parameters (KmandVmax), but amplitudes of the DA signals were decreased after the drug in both freely moving and anesthetized rats. Therefore, the present in vivo voltammetry results suggest that DA uptake changes are not involved in ethanol‐induced increases in extracellular DA concentrations. Synapse 60:251–255, 2006. © 2006 Wiley‐Liss, Inc.
Enhanced locomotor activity in adult rats with neonatal administration of N‐omega‐nitro‐L‐arginine
Authors: Mejorada Alejandro , Aguilar‐Alonso Patricia , León‐Chavez Bertha Alicia , Flores Gonzalo
Published: June 2006

Nitric oxide (NO) is a neuronal messenger molecule that plays important roles in the development, maintenance, and functional modifications of brain circuits. We investigated whether the NO levels at different postnatal day (P) periods of the brain develop interference with the locomotion in a novel environment during the postpuberal age (P60). First, using the determination of the nitrite accumulation, we evaluated whether treatment with the NO‐synthase inhibitor N‐nitro‐L‐arginine (L‐NNA) during different neonatal ages (P1 to P3, P4 to P6, and P7 to P9) affected the levels of NO activity in different regions in the neonatal brain of the rat. We then evaluated whether the locomotor activity in the adult rat (P60) is affected by the blocking of the neonatal NO‐activity during a specific period of the development of the nervous system. Neonatal rats with L‐NNA administration at P4 to P6 and P7 to P9 show a significant decrease in the levels of NO activity in all the brain regions. However, the blocking of NO synthesis during the neonatal period between P4 to P6 produced an increase in the locomotion after puberty. These data suggest that during a specific step in the development of the brain, the NO levels may play a critical role in the structures that control the spontaneous locomotion in a novel environment after puberty. Synapse 60:264–270, 2006. © 2006 Wiley‐Liss, Inc.
Bilateral chylothorax following left-sided radical neck dissection
Authors: Srikumar S , Newton J R , Westin T A B
Published: June 2006

Chylothorax is an extremely rare but potentially life-threatening complication of radical neck dissection. Its rarity makes surgeons unfamiliar with its management. We report the case of a bilateral chylothorax occurring after a left radical neck dissection and discuss its management. A multi-disciplinary approach is advocated, involving surgical, respiratory and dietetic input, and this led to a favourable outcome for our patient.
Surgical management of retraction pockets of the pars tensa with cartilage and perichondrial grafts
Authors: Spielmann P , Mills R
Published: June 2006

Stable, self-cleansing retraction pockets of the pars tensa are common incidental findings and require no treatment. In other cases, recurrent discharge occurs and there may also be associated conductive hearing loss. In a minority of cases, cholesteatoma may develop.

This paper presents the results of surgery using a graft composed of cartilage and perichondrium for retraction pockets involving the posterior half of the tympanic membrane, as well as early results using a larger graft designed to manage retraction of the entire tympanic membrane. Data on 51 patients with posterior retraction pockets are presented. Forty-two (82 per cent) patients had no aural discharge one year following surgery and the tympanic membrane was not retracted in 43 (84 per cent). The larger ‘Mercedes-Benz’ graft was used in four patients and the results obtained suggested that it may prove a successful technique for extensive retraction pockets.
Emergency cardiopulmonary bypass for impassable airway
Authors: Tyagi I , Goyal A , Syal R , Agarwal S K , Tewari P
Published: June 2006

Introduction: Some medical emergencies need compromised airway management as the first measure. Most of these cases are first seen by an ENT surgeon, whose proper evaluation and timely intervention can prove decisive. Knowledge of alternatives for airway management can prove life-saving, although these may require the active involvement of other specialities.

Case reports: Two patients, a 27-year-old man and a 31-year-old woman, presented in respiratory distress with cyanosis. Each had a pedunculated mass in the lower trachea above the carina, with about 90 per cent tracheal lumen obstruction. They were managed successfully with femorofemoral cardiopulmonary bypass and restoration of airway.

Conclusion: Femorofemoral cardiopulmonary bypass can be a relatively safe option which gains time for airway management in such conditions. Knowledge of this procedure among ENT surgeons can lead to timely intervention, in properly selected cases, which can save valuable time.
Compound odontoma causing airway obstruction of the newborn: a case report
Authors: Tam D , Francis L , Perry C , Thirwall A
Published: June 2006

A newborn presented with acute airway obstruction secondary to a compound odontoma of the hard palate/nasal floor. This is the first case recorded in the literature. We review the pathology of compound odontomas and discuss the management of this rare and interesting case.
Molecular characterization of a family of metalloendopeptidases from the intestinal brush border of Haemonchus contortus
Authors: NEWLANDS G. F. J. , SKUCE P. J. , NISBET A. J. , REDMOND D. L. , SMITH S. K. , PETTIT D. , SMITH W. D.
Published: June 2006

Substantial protection against the economically important parasitic nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of the worm (H-gal-GP). Previous studies showed that one of the major components of H-gal-GP is a family of at least 4 zinc metalloendopeptidases, designated MEPs 1–4. This paper describes aspects of the molecular architecture of this protease family, including the proteomic analysis of the MEP fraction of the H-gal-GP complex. These enzymes belong to the M13 zinc metalloendopeptidase family (EC 3.4.24.11), also known as neutral endopeptidases or neprilysins. The sequences of MEPs 1 and 3 suggested a typical Type II integral membrane protein structure, whilst MEPs 2 and 4 had putative cleavable signal peptides, typical of secreted proteins. Proteomic analysis of H-gal-GP indicated that the extracellular domain of all 4 MEPs had been cleaved close to the transmembrane region/signal peptide with additional cleavage sites mid-way along the polypeptide. MEP3 was present as a homo-dimer in H-gal-GP, whereas MEP1 or MEP2 formed hetero-dimers with MEP4. It was found that expression of MEP3 was confined to developing 4th-stage larvae and to adult worms, the stages of Haemonchus which feed on blood. MEP-like activity was detected in the H-gal-GP complex over a broad pH range (5–9). Since all 4 MEPs must share a similar microenvironment in the complex, this suggests that each might have a different substrate specificity.
Oesophagostomum dentatumandTrichuris suisinfections in pigs born and raised on contaminated paddocks
Authors: MEJER H. , ROEPSTORFF A.
Published: June 2006

Transmission ofOesophagostomum dentatumandTrichuris suiswas studied in outdoor reared pigs. Six farrowing paddocks were naturally contaminated in May to mid-June 2001 by experimentally infected seeder pigs. In early July 1 sow farrowed on each paddock and starting at week 3post-partum(p.p.) the offspring was slaughtered serially every 2 weeks for parasite recovery. Faeces were collected regularly for parasite egg counts and acid-insoluble ash (AIA) content as an indicator of geophagy. Weaning took place at week 7 p.p. by removing the sow. Paddock infection levels were estimated in mid-June (O. dentatum) and late November (O. dentatumandT. suis) using helminth-naïve tracer pigs. Soil and vegetation samples were collected regularly. Despite a high initial contamination by the seeder pigs,O. dentatumpaddock infectivity was negligible to low throughout the raising of the experimental piglets, which had a slow accumulation of nodular worms ending with a mean of 422 worms/pig at week 19 p.p. As only few eggs developed to infectivity overallT. suistransmission was minimal. The firstT. suiswere recovered at week 11 p.p. and the highest mean burden of 21 worms/pig was recorded at week 19 p.p. The experimental pigs initially had a high faecal level of AIA although it decreased over time. The results are discussed in relation to the biological characteristics of the 2 parasites and their occurrence in organic pig production.
Validation of influenza and pneumococcal vaccine status in adults based on self-report
Authors: MANGTANI P. , SHAH A. , ROBERTS J. A.
Published: June 2006

Self-report of polysaccharide pneumococcal vaccination is not thought reliable because of the increased risk of adverse events from inadvertent re-vaccination in elderly people. Some studies suggest a high sensitivity of self-report and hence a low risk of adverse events if vaccination is administered when medical records are unavailable. Self-report of pneumococcal and influenza vaccination in a sample of >64-year-olds in the United Kingdom was compared with information in their medical records. Self-report of pneumococcal vaccination, in contrast to some of the other studies had a low sensitivity. The findings here support the need for accurate knowledge of prior vaccine status before offering the polysaccharide pneumococcal vaccine. The study also confirms that self-report of influenza vaccination could be relied upon if rapid knowledge of uptake is required.
No increase in human cases of Mycobacterium bovis disease despite resurgence of infections in cattle in the United Kingdom
Authors: JALAVA K. , JONES J. A. , GOODCHILD T. , CLIFTON-HADLEY R. , MITCHELL A. , STORY A. , WATSON J. M.
Published: June 2006

A resurgence of Mycobacterium bovis infections in cattle in the United Kingdom since the 1980s has raised concern about risks to human health. Enhanced surveillance data for England, Wales and Northern Ireland between 1993 and 2003 of culture-positive human M. bovis cases identified 315 M. bovis infections; the mean annual number of cases was 28 (range 12–41). The most frequently reported exposures were consumption of unpasteurized dairy products 41/83 (49%) and exposure to cattle 45/123 (37%). Of all cases, 249 (83%) were born before 1960. Of 50 cases born after 1960, only 14 were born in the United Kingdom. Over the same time period the annual number of new herd infections increased from 332 to 1749 as derived from the UK State Veterinary Service database. In conclusion, despite a more than fivefold increase in cattle herd infections during the 1990s, there was no increase in reported human cases.
The use of randomization tests to assess the degree of similarity in PFGE patterns of E. coli O157 isolates from known outbreaks and statistical space–time clusters
Authors: PEARL D. L. , LOUIE M. , CHUI L. , DORÉ K. , GRIMSRUD K. M. , MARTIN S. W. , MICHEL P. , SVENSON L. W. , McEWEN S. A.
Published: June 2006

Using isolates from reported cases of Escherichia coli O157 from Alberta, Canada in 2002, we applied randomization tests to determine if cases associated with an outbreak or statistical space–time cluster had more similar pulsed-field gel electrophoresis patterns, based on Dice coefficients, than expected by chance alone. Within each outbreak and space–time cluster, we assessed the mean, median, 25th percentile, 75th percentile, standard deviation, coefficient of variation, and interquartile range of the Dice coefficients of each pairwise comparison among the isolates. To assess the statistical significance of measures of location (e.g. mean) and variation (e.g. standard deviation) we created randomization distributions using all isolates or only isolates from sporadic cases. We determined that randomization tests are an appropriate tool for evaluating the similarity among isolates from cases that have been linked epidemiologically or statistically. We found little difference between using all cases or only sporadic cases when creating our randomization distributions.