bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of introducing a cationic system into a thiol‐ene photopolymerizable formulation
Authors: Ortiz Ricardo Acosta , Urbina Bertha A. Puente , Valdez Liliana V. Cabello , Duarte Lydia Berlanga , Santos Ramiro Guerrero , Valdez Aída E. García , Soucek Mark D.
Published: September 2007

Hybrid materials derived from a thiol‐ene and cationic polymerization were obtained from concomitant polymerization. The hybrid materials were cured by both photopolymerization and thermally induced polymerization. The kinetics of the photopolymerization were measured using time resolved‐IR and optical pyrometry. The nucleophilic character of the polysulfide obtained initially in the thiol‐ene polymerization inhibited the development of the cationic photoinitiated polymerization of epoxy monomers. Besides, the epoxide groups underwent a proton catalyzed addition reaction with the thiols to form new sulfides groups in the reaction mixture. It is proposed that the formed sulfides can terminate the growing polyether chains forming dormant species like trialkylsulfonium salts. These salts promote the thermal polymerization of the epoxy monomer in a post treatment, producing hard and transparent materials. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4829–4843, 2007
Copper binding sites in the C‐terminal domain of mouse prion protein: A hybrid (QM/MM) molecular dynamics study
Authors: Colombo Maria Carola , VandeVondele Joost , Van Doorslaer Sabine , Laio Alessandro , Guidoni Leonardo , Rothlisberger Ursula
Published: September 2007

We present a hybrid QM/MM Car–Parrinello molecular dynamics study of the copper‐loaded C‐terminal domain of the mouse prion protein. By means of a statistical analysis of copper coordination in known protein structures, we localized the protein regions with the highest propensity for copper ion binding. The identified candidate structures were subsequently refined via QM/MM simulations. Their EPR characteristics were computed to make contact with the experimental data and to probe the sensitivity to structural and chemical changes. Overall best agreement with the experimental EPR data (Van Doorslaer et al., J Phys Chem B 2001; 105: 1631–1639) and the information currently available in the literature is observed for a binding site involving H187. Moreover, a reinterpretation of the experimental proton hyperfine couplings was possible in the light of the present computational findings. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Predicting experimental properties of integral membrane proteins by a naive Bayes approach
Authors: Martin‐Galiano Antonio J. , Smialowski Pawel , Frishman Dmitrij
Published: September 2007

Integral membrane proteins (iMPs) are challenging targets for structure determination because of the substantial experimental difficulties involved in their sample preparation. Accordingly, success rates of large‐scale structural genomics consortia are much lower for this class of molecules compared to globular targets, underscoring the pressing need for predictive strategies to identify iMPs that are more likely to overcome laboratory bottlenecks. On the basis of the target status information available in the TargetDB repository, we describe the first large‐scale analysis of experimental behavior of iMPs. Using information on recalcitrant and propagating iMP targets as negative and positive sets, respectively, we present naive Bayes classifiers capable of predicting, from sequence alone, those proteins that are more amenable to cloning, expression, and solubilization studies. Protein sequences are represented in the space of 72 features, including amino acid composition, occurrence of amino acid groups, ratios between residue groups, and hydrophobicity measures. Taking into account unequal representation of main taxonomic groups in the TargetDB, sequence database had a beneficial effect on the prediction results. The classifiers achieve accuracies of 70%, 63–70%, and 61% in predicting the amenability of iMPs for cloning, expression, and solubilization, respectively, thus making them useful tools in target selection for structure determination. Our assessment of prediction results clearly demonstrates that classifiers based on single features do not possess acceptable discriminative power and that the experimental behavior of iMPs is imprinted in their primary sequence through relationships between a restricted set of key properties. In most cases, sets of 10–20 protein features were found actually relevant, most notably, the content of isoleucine, valine, and positively‐charged residues. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Thermostable variants of the recombinant xylanase a from Bacillus subtilis produced by directed evolution show reduced heat capacity changes
Authors: Ruller Roberto , Deliberto Laila , Ferreira Tatiana Lopes , Ward Richard J.
Published: September 2007

Directed evolution techniques have been used to improve the thermal stability of the xylanase A from Bacillus subtilis (XylA). Two generations of random mutant libraries generated by error prone PCR coupled with a single generation of DNA shuffling produced a series of mutant proteins with increasing thermostability. The most Thermostable XylA variant from the third generation contained four mutations Q7H, G13R, S22P, and S179C that showed an increase in melting temperature of 20°C. The thermodynamic properties of a representative subset of nine XylA variants showing a range of thermostabilities were measured by thermal denaturation as monitored by the change in the far ultraviolet circular dichroism signal. Analysis of the data from these thermostable variants demonstrated a correlation between the decrease in the heat capacity change (ΔCp) with an increase in the midpoint of the transition temperature (Tm) on transition from the native to the unfolded state. This result could not be interpreted within the context of the changes in accessible surface area of the protein on transition from the native to unfolded states. Since all the mutations are located at the surface of the protein, these results suggest that an explanation of the decrease in ΔCp should include effects arising from the protein/solvent interface. Proteins 2008. © 2007 Wiley‐Liss, Inc.
More compact protein globules exhibit slower folding rates
Authors: Galzitskaya Oxana V. , Reifsnyder Danielle C. , Bogatyreva Natalya S. , Ivankov Dmitry N. , Garbuzynskiy Sergiy O.
Published: September 2007

We have demonstrated that, among proteins of the same size, α/β proteins have on the average a greater number of contacts per residue due to their more compact (more “spherical”) structure, rather than due to tighter packing. We have examined the relationship between the average number of contacts per residue and folding rates in globular proteins according to general protein structural class (all‐α, all‐β, α/β, α+β). Our analysis demonstrates that α/β proteins have both the greatest number of contacts and the slowest folding rates in comparison to proteins from the other structural classes. Because α/β proteins are also known to be the oldest proteins, it can be suggested that proteins have evolved to pack more quickly and into looser structures. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Computational analysis of folding and mutation properties of C5 domain of myosin binding protein C
Authors: Guardiani Carlo , Cecconi Fabio , Livi Roberto
Published: September 2007

Thermal folding molecular dynamics simulations of the domain C5 of Myosin binding protein C were performed using a native‐centric model to study the role of three mutations related to Familial Hypertrophic Cardiomyopathy. Mutation of Asn755 causes the largest shift of the folding temperature, and the residue is located in the CFGA′ β‐sheet featuring the highest Φ‐values. The mutation thus appears to reduce the thermodynamic stability in agreement with experimental data. The mutations on Arg654 and Arg668, conversely, cause little change in the folding temperature and they reside in the low Φ‐value BDE β‐sheet, so that their pathological role cannot be related to impairment of the folding process but possibly to the binding with target molecules. As the typical signature of Domain C5 is the presence of a longer and destibilizing CD‐loop with respect to the other Ig‐like domains, we completed the work with a bioinformatic analysis of this loop showing a high density of negative charge and low hydrophobicity. This indicates the CD‐loop as a natively unfolded sequence with a likely coupling between folding and ligand binding. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Sampling of near‐native protein conformations during protein structure refinement using a coarse‐grained model, normal modes, and molecular dynamics simulations
Authors: Stumpff‐Kane Andrew W. , Maksimiak Katarzyna , Lee Michael S. , Feig Michael
Published: September 2007

Protein structure refinement from comparative models with the goal of predicting structures at near‐experimental accuracy remains an unsolved problem. Structure refinement might be achieved with an iterative protocol where the most native‐like structure from a set of decoys generated from an initial model in one cycle is used as the starting structure for the next cycle. Conformational sampling based on the coarse‐grained SICHO model, atomic level of detail molecular dynamics simulations, and normal‐mode analysis is compared in the context of such a protocol. All of the sampling methods can achieve significant refinement close to experimental structures, although the distribution of structures and the ability to reach native‐like structures differs greatly. Implications for the practical application of such sampling methods and the requirements for scoring functions in an iterative refinement protocol are analyzed in the context of theoretical predictions for the distribution of protein‐like conformations with a random sampling protocol. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Recognizing in situ oxygen analyzers as ignition sources in fired equipment
Authors: Van Geffen Sheila , Corripio Bernardo , Weber Andy
Published: September 2007

Most modern ethylene cracking furnaces use close‐coupled extractive or in situ oxygen analyzers based on a zirconium oxide sensor in the stack area to provide fast and reliable measurement of the oxygen content of the flue gas exiting the firebox. This allows for precise control of the excess combustion air in the firebox, resulting in higher energy efficiency for the furnace than is typical using conventional extractive sample‐based analyzer systems where the analyzer might be several hundred feet away from the sample point. These analyzers use a zirconium oxide sensing element that operates at 700°C, which is well above the auto‐ignition temperature of many flammable hydrocarbon mixtures. Although flame arrestors can be installed on these analyzers to prevent flame propagation from the probe element into the firebox there are still situations that can exist that the analyzer can pose as an ignition source. This paper will discuss the two typical zirconium oxide oxygen analyzer designs and how the analyzer can be a source of ignition, and review an incident in a Dow cracking furnace, which resulted from an in situ oxygen analyzer igniting a flammable mixture in a furnace. Corrective actions are included in this paper. © 2007 American Institute of Chemical Engineers Process Saf Prog, 2007
Quantitative Structure‐Properties Relationship in Stilbene‐Triazine Optical Brightener Design
Authors: Wilkowska Ewa , Konopski Leszek
Published: September 2007

The Quantitative Structure‐Property Relationship (QSPR) has been studied in a group of bis(s‐triazin‐2‐yl)‐4,4′‐diamino‐2,2′‐disulphostilbene Fluorescent Brightening Agents (FBAs). The degree of whiteness, tint and Yellowness Index (YI) were studied as parameters determining the brightening properties using surface‐size press method on neutral printing papers, and the degree of whiteness W was chosen as the most appropriate for QSPR studies. The effectiveness of brightening depended on the substituent R in positions 4‐(sulphophenylamino, disulphophenylamino or methoxy groups), and especially at position 6 of the triazine ring (disubstituted amino group NYZ). The best results were obtained when an amino acid moiety was built in the 6‐substituent. Hammett electron constants and Taft induction constants were used as substituent descriptors. A quantitative correlation was found using simple and multiple regression analysis. The constructed model allowed to design two new brighteners containing R=2,5‐disulphoaniline group, Y=H and Z=appropriately taurine and N‐cyanoethyltaurine. To validate the model, the high values of whiteness predicted by the regression equation were confirmed by synthesis. The Taft σ*‐constant values for CH(CH3)COOH and CH(CH2COOH)COOH substituents were calculated using the developed equation.
Theoretical Modeling of PrkCc, Serine–Threonine Protein Kinase Intracellular Domain, Complexed with ATP Derivatives
Authors: Gruszczyński Paweł , Kaźmierkiewicz Rajmund , Obuchowski Michał , Lammek Bernard
Published: September 2007

With the advent of the Molecular Dynamics (MD) methods two complexes of PrkC catalytic domain with N6‐methoxy‐ATP and N6‐pyrrolidino‐ATP analogues were studied. Structures of the intracellular domain of the enzyme and the ATP derivatives were modeled theoretically. We report here the spatial arrangement of the PrkC kinase and its two complexes as well as their behavior during the MD simulations.
Development and Evaluation of a QSPR Model for the Prediction of Diamagnetic Susceptibility
Authors: Afantitis Antreas , Melagraki Georgia , Sarimveis Haralambos , Koutentis Panayiotis A. , Markopoulos John , Igglessi‐Markopoulou Olga
Published: September 2007

A novel QSPR model is developed and evaluated for the prediction of diamagnetic susceptibility. The model was produced using the Multiple Linear Regression (MLR) technique on a database that consists of 406 organic compounds involving a diverse set of chemical structures. The accuracy of the QSPR model (R2=0.88) is illustrated using various evaluation techniques, such as leave‐one‐out procedure (Q2=0.87) and validation through an external test set (R$\rm{ {_{pred}^{2}}}$=0.89). The study leads to the conclusion that three physical–topological descriptors affect significantly the diamagnetic susceptibility: Polar Surface Area (PSAr), Principal Moment of Inertia X (PMIX), and Diameter (Diam).
Adaptive Dunnett tests for treatment selection
Authors: Koenig Franz , Brannath Werner , Bretz Frank , Posch Martin
Published: September 2007

Clinical trials incorporating treatment selection at pre‐specified interim analyses allow to integrate two clinical studies into a single, confirmatory study. In an adaptive interim analysis, treatment arms are selected based on interim data as well as external information. The specific selection rule does not need to be pre‐specified in advance in order to control the multiple type I error rate. We propose an adaptive Dunnett test procedure based on the conditional error rate of the single‐stage Dunnett test. The adaptive procedure uniformly improves the classical Dunnett test, which is shown to be strictly conservative if treatments are dropped at interim. The adaptive Dunnett test is compared in a simulation with the classical Dunnett test as well as with adaptive combination tests based on the closure principle. The method is illustrated with a real‐data example. Copyright © 2007 John Wiley & Sons, Ltd.
Markovian power curves for wind turbines
Authors: Anahua E. , Barth St. , Peinke J.
Published: September 2007

This paper shows a novel method to characterize wind turbine power performance directly from high‐frequency fluctuating measurements. In particular, we show how to evaluate the dynamic response of the wind turbine system on fluctuating wind speed in the range of seconds. The method is based on the stochastic differential equations known as the Langevin equations of diffusive Markov processes. Thus, the fluctuating wind turbine power output is decomposed into two functions: (i) the relaxation, which describes the deterministic dynamic response of the wind turbine to its desired operation state, and (ii) the stochastic force (noise), which is an intrinsic feature of the system of wind power conversion. As a main result, we show that independently of the turbulence intensity of the wind, the characteristic of the wind turbine power performance is properly reconstructed. This characteristic is given by their fixed points (steady states) from the deterministic dynamic relaxation conditioned for given wind speed values. The method to estimate these coefficients directly from the data is presented and applied to numerical model data, as well as to real‐world measured power output data. The method is universal and is not only more accurate than the current standard procedure of ensemble averaging (IEC‐61400‐12) but it also allows a faster and robust estimation of wind turbines' power curves. Copyright © 2007 John Wiley & Sons, Ltd.
Combination of enzyme analysis, allele‐specific PCR and sequencing to detect mutations in the GALT gene
Authors: Calderon F. R. O. , Nelson L. , Dobrowolski P. , Sinitsyna I. , Phansalkar A. , Longo N. , Pasquali M. , Mao R.
Published: September 2007

Newborn screening can identify patients with classical galactosaemia, and their diagnosis needs to be confirmed with assay of the activity of galactose‐1‐phosphate uridyltransferase (GALT). Unfortunately, in many cases the results can be ambiguous and further testing is required. Here we report a combination of biochemical analysis of GALT enzyme activity and mutation analysis of the most common mutations in the corresponding gene. Samples (n=43) submitted for confirmatory testing for classical galactosaemia were analysed simultaneously for GALT enzyme activity and allele‐specific PCR/fragment analysis for seven mutations and two polymorphisms in the GALT gene (mutations IVS2‐2A>G, p.S135L, p.T138M, p.L195P, p.K285N, p.Q188R, p.Y209C; polymorphisms p.N314D, p.L218L). Mutation detection accorded with biochemical analysis in 93% of samples. Subsequently, a total of 34 samples with either discordant results between the above methods or low enzyme activity were fully sequenced, identifying previously reported pathogenic mutations and seven novel variations (p.P185H, p.R201C, p.E220K, p.R223S, p.I278N, p.L289F and p.L218X) in the GALT gene. This approach further increased concordance between genetic and biochemical analysis to 99% of all alleles tested. Our results indicate that DNA testing can help to verify biochemical enzymatic data and improve distinction of borderline enzyme activities where a patient may still benefit from treatment.
Acid sphingomyelinase‐deficient Niemann–Pick disease: Novel findings in a Greek child
Authors: Fotoulaki M. , Schuchman E. H. , Simonaro C. M. , Augoustides‐Savvopoulou P. , Michelakakis H. , Panagopoulou P. , Varlamis G. , Nousia‐Arvanitakis S.
Published: September 2007

Niemann–Pick Disease (NPD) is a heterogeneous group of autosomal recessive disorders characterized by progressive accumulation of sphingomyelin and cholesterol in lysosomes. Six types of NPD have been described based on clinical presentation and involved organs. The primary defect in NPD types A and B is a deficiency of lysosomal acid sphingomyelinase (ASM). We present a case of a 5‐year‐old boy with type B NPD who had severe clinical manifestations, including heart involvement. He was first admitted to the hospital at 2 months because of vomiting, refusal to feed, lethargy, hepatomegaly and mild transaminasaemia. Liver biopsy at 12 months showed lipid accumulation and fibrosis. Investigations for lysosomal storage disorders revealed increased plasma chitotriosidase (549 nmol/h per ml, normal value 0–150). At 18 months, no detectable ASM activity was observed in cultured fibroblasts (normal range 23–226 nmol/h per mg protein) confirming NPD B. Pulmonary involvement was detected with high‐resolution computerized tomography which revealed reticulonodular infiltrations and thickening of the interlobular septa. At 2 years growth retardation and kyphosis were noted. At 2.5 years he manifested neurodevelopment regression, indicating CNS involvement. Cardiac involvement (grade III mitral valve insufficiency) developed at 4 years and heart failure at 5 years. Genetic analysis revealed two mutations: a H421Y mutation that is common in Saudi Arabian and Turkish patients, and a W32X mutation, which has been found in other Mediterranean patients.
A severity scoring tool to assess the neurological features of neuronopathic Gaucher disease
Authors: Davies E. H. , Surtees R. , DeVile C. , Schoon I. , Vellodi A.
Published: September 2007

Type III Gaucher disease is one of the three recognized subtypes of Gaucher disease, an inherited deficiency of lysosomal glucocerebrosidase. Phenotypically there is a wide spectrum of visceral and neurological manifestations. Enzyme replacement is effective in managing the visceral disease; however, the neurological manifestations remain a more challenging obstacle. There is an unfulfilled need to reliably monitor neurological disease and its response to treatment. A severity scoring tool was developed through neurological domain identification, item generation and tool formation. Domain identification was established based on a retrospective single centre study (n=15) and a systematic review of publications. Forty‐seven patients with neuronopathic Gaucher disease were then assessed using the tool to establish the clinical and statistical reliability of each domain. Judgement quantification of the tool was established through a process of content validity involving five European experts. Content validity is considered to be most effective when undertaken systematically. Concurrent validity and feasibility of the tool was also highlighted. This process allowed a revised and validated version of the tool to be developed.
The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome)
Authors: Garcia A. R. , Pan J. , Lamsa J. C. , Muenzer J.
Published: September 2007

Mucopolysaccharidosis II (MPS II, Hunter syndrome in humans) is an X‐linked inherited lysosomal storage disease caused by a deficiency in the lysosomal enzyme iduronate‐2‐sulfatase (I2S). I2S catalyses a step in the catabolism of glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate, and when it is deficient or absent GAGs accumulate in tissues and organs. Male knockout mice (IdS‐KO), which lack the gene coding for I2S, exhibit many of the characteristics seen in the human disease. Compared to wild‐type control mice, urine GAG excretion was elevated at 4 weeks of age and remained high throughout the lifespan, and tissue GAG levels were elevated as early as 7 weeks of age. Liver, spleen and other organs were significantly larger in the IdS‐KO mice than in the wild‐type. Radiographic examination revealed sclerosis and enlargement of the skull at 4 weeks of age and appendicular bone enlargement at 10–13 weeks of age. Micro CT scans showed severe periosteal bone formation at the lateral aspect of the distal tibia and calcification of the calcaneus tendon. This model was used in the development of idursulfase for treatment of MPS II and may continue to be useful in the evaluation of treatment strategies of this chronic and progressive disorder.
Novel insights into L‐2‐hydroxyglutaric aciduria: Mass isotopomer studies reveal 2‐oxoglutaric acid as the metabolic precursor of L‐2‐hydroxyglutaric acid
Authors: Struys E. A. , Gibson K. M. , Jakobs C.
Published: September 2007

Employing lymphoblasts derived from two non related patients with l‐2‐HG aciduria, we examined the origin of l‐2‐hydroxyglutaric acid (l‐2‐HG) through incubation with [13C6]glucose and [2H5]glutamic acid. Formation of labelled 2‐ketoglutaric acid (2‐KG), citric acid and l‐2‐HG was determined by GC‐MS. The quantitative and qualitative isotopomer pattern following incubation with [13C6]glucose was identical for all end‐products. Incubations with [2H5]glutamic acid as precursor revealed the formation of identical isotopomers for 2‐KG and l‐2‐HG. Our data indicate that 2‐KG is the metabolic precursor of l‐2‐HG, adding to previous studies which revealed that 2‐KG is the metabolic precursor of d‐2‐HG. These data suggest that 2‐KG has a pathophysiological role in combined d/l‐2‐HG aciduria.
High incidence of hypermethioninaemia in a single neonatal intensive care unit detected by a newly introduced neonatal screening programme
Authors: ten Hoedt A. E. , van Kempen A. A. , Boelen A. , Duran M. , Kemper‐Proper E. A. , Oey‐Spauwen M. J. W. , Wijburg F. A. , Bosch A. M.
Published: September 2007

From 1 January 2007 an expanded neonatal screening programme was initiated in the Netherlands, including homocystinuria with methionine as the primary marker. During the first 2 months hypermethioninaemia was detected in 14 newborns who, after proper evaluation, were demonstrated not to have classical homocystinuria. Remarkably, all these children were admitted to a single neonatal intensive care unit (Academic Medical Center, Amsterdam (AMC‐NICU)). We evaluated the possible causes for this finding. The cohort of newborns with hypermethioninaemia (group 1) was compared with the cohort of newborns with normal screening results admitted to the AMC‐NICU in the same time period (group 2). In addition, parenteral nutrition protocols from all NICUs in the Netherlands were compared. Mean birth weight and gestational age were significantly lower in group 1 than in group 2. All patients in group 1 received parenteral feeding (TPN) at the time of screening and received a higher mean amino acid intake per kilogram body weight than patients receiving TPN in group 2. Also, the AMC‐NICU uses a different amino acid mixture for TPN than the other Dutch NICUs, containing more than twice the amount of methionine per gram of amino acids compared with other mixtures. The high incidence of hypermethioninaemia in the AMC‐NICU is explained by a combination of low birth weight, low gestational age, and high protein intake supplied by a specific parenteral amino acid mixture containing large amounts of methionine. To prevent hypermethioninaemia, the use of high‐methionine containing solutions for TPN should be reconsidered.
Effect of ‘attenuated’ mutations in mucopolysaccharidosis IVA on molecular phenotypes of N‐acetylgalactosamine‐6‐sulfate sulfatase
Authors: Montaño A. M. , Sukegawa K. , Kato Z. , Carrozzo R. , Di Natale P. , Christensen E. , Orii K. O. , Orii T. , Kondo N. , Tomatsu S.
Published: September 2007

Mucopolysaccharidosis IVA is an autosomal recessive disease caused by the deficiency of N‐acetylgalactosamine‐6‐sulfate sulfatase (GALNS). Mutation screening of the GALNS gene was performed for seven MPS IVA patients with attenuated phenotypes from three unrelated families. Four of 5 missense mutations identified in this study (p.F167V, p.R253W, p.R380S, p.P484S) and two reported (p.F97V, p.N204K), associated with attenuated phenotypes, were characterized using in vitro stable expression experiments, enzyme kinetic study, protein processing and structural analysis. The stably expressed mutant enzymes defining the attenuated phenotype exhibited a considerable residual activity (1.2–36.7% of the wild‐type GALNS activity) except for p.R380S. Enzyme kinetic studies showed that p.F97V, p.F167V and p.N204K have lower affinity to the substrate compared with other mutants. The p.F97V enzyme was the most thermolabile at 55°C. Immunoblot analyses indicated a rapid degradation and/or an insufficiency in processing in the mutant proteins. Tertiary structure analysis revealed that although there was a tendency for ‘attenuated’ mutant residues to be located on the surface of GALNS, they have a different effect on the protein including modification of the hydrophobic core and salt‐bridge formation and different potential energy. This study demonstrates that ‘attenuated’ mutant enzymes are heterogeneous in molecular phenotypes, including biochemical properties and tertiary structure.
Retrospective Comparison of Percutaneous Fixation and Volar Internal Fixation of Distal Radius Fractures
Authors: Lozano-Calderón Santiago A. , Doornberg Job N. , Ring David
Published: September 2007

A change in the practice of a single surgeon provided an opportunity for retrospective comparison of comparable cohorts treated with percutaneous fixation (17 patients) or a volar plate and screws (23 patients) an average of 30 months after surgery. The final evaluation was performed according to the Gartland and Werley and Mayo rating systems and the DASH questionnaire. There were no significant differences on the average scores for the percutaneous and volar plating groups, respectively: Gartland and Werley, 4 vs 5; Mayo, 82 vs 83; and DASH score 13 for both cohorts. Motion, grip, and radiographical parameters were likewise comparable. Volar internal plate and screw fixation can achieve results comparable to percutaneous fixation techniques in the treatment of fractures of the distal radius.
Suicide ideation and social desirability among school‐aged young people
Authors: Miotto P. , Preti A.
Published: September 2007

A mixed male–female sample of 950 school‐aged adolescents, corresponding to 10% of the young population aged 15–19 living in a rural district of Northeast Italy, was investigated with self‐reported questionnaires about the links between social desirability and suicide ideation. On the whole 30.6% of females and 23.9% of males reported suicidal ideation of some degree, with 5% in both genders reporting suicide ideation of a high degree (i.e. quite a lot/extremely often). Those who scored higher at the Marlowe–Crowne Social Desirability Scale (SDS) reported lower levels of psychiatric symptoms on the Symptom checklist 90R (SCL‐90R), with the “denial” subscale of the SDS resulting specifically associated to lower scores on SCL‐90R items measuring hopelessness, thoughts about death and suicide ideation. The personality traits measured by the Marlowe–Crowne SDS, such as defensiveness, denial and self‐deception, might be conceived as a protection against psychiatric disorders and suicide ideation.
Morphine‐6‐glucuronide (M6G) for postoperative pain relief
Authors: Dahan Albert , van Dorp Eveline , Smith Terry , Yassen Ashraf
Published: September 2007

Morphine‐6‐glucuronide (M6G) is morphine's active metabolite acting at the μ‐opioid receptor. Recent experimental human studies and 5 of 6 randomized clinical trials indicate that M6G causes adequate and long lasting pain relief comparable to morphine. There are various observations that M6G is associated with a reduction in the severity of side effects normally associated with opioid use, such as reduced postoperative nausea and vomiting (PONV) and reduced respiratory depression. The present drug profile provides a review of the pharmacological properties of M6G, the clinical evidence relating to its efficacy and safety, and discusses its future role in the treatment of postoperative pain.
Intradomain LexA rotation is a prerequisite for DNA binding specificity
Authors: Butala Matej , Hodošček Milan , Anderluh Gregor , Podlesek Zdravko , Žgur-Bertok Darja
Published: September 2007

In the absence of DNA damage the LexA protein represses the bacterial SOS system. We performed molecular dynamic simulations of two LexA dimers bound to operators. Our model predicted that rotation of the LexA DNA binding domain, with respect to the dimerised C‐terminal domain, is required for selective DNA binding. To confirm the model, double and quadruple cysteine LexA mutants were engineered. Electrophoretic mobility‐shift assay and surface plasmon resonance showed that disulfide bond formation between the introduced cysteine residues precluded LexA specific DNA binding due to blocked domain reorientation. Our model could provide the basis for novel drug design.
The C‐terminus of the yeast Lsm4p is required for the association to P‐bodies
Authors: Mazzoni Cristina , D'Addario Irene , Falcone Claudio
Published: September 2007

Here, we show that this truncated protein is dispersed in the cytoplasm and does not assemble to P‐bodies. As reported in decapping mutants, we observed an increase in the number of P‐bodies suggesting that the truncation of the protein impairs this process. The number of P‐bodies also increases after oxidative stress and is not dependent on the meta‐caspase gene YCA1, placing this phenomenon upstream to the onset of apoptosis.
Four members of the HSP101 gene family are differently regulated in Triticum durum Desf
Authors: Gullì Mariolina , Corradi Massimiliano , Rampino Patrizia , Marmiroli Nelson , Perrotta Carla
Published: September 2007

Heat shock proteins play an essential role in preventing deleterious effects of high temperatures. In many plants, HSP101 has a central role in heat stress survival. We report the isolation and characterization of four cDNAs corresponding to different members of the durum wheat HSP101 gene family. Expression analysis revealed differences in their induction. Accordingly, durum wheat HSP101 genes are differently regulated, therefore having distinct roles in stress response and thermotolerance acquisition. These findings are important for further dissection of the molecular mechanisms underlying the stress response and for understanding the functions of the HSP101 family members. This information could be important for the exploitation of specific alleles in marker assisted selection for abiotic stress resistance.
Urogenital and recto‐vaginal fistulas in southern Malawi: A report on 407 patients
Authors: Rijken Y. , Chilopora G.C.
Published: September 2007

This study from Southern Malawi reports on 407 patients with 408 vaginal fistulas (1 patient had 2 successive fistulas). There were 29 patients (7.6%) with a combined urogenital and recto‐vaginal fistula. Obstructed labor was the cause of 379 fistulas and the remaining 29 were not of obstetric origin. Although the actual incidence of vaginal fistulas is unknown, the incidence is probably much lower in Malawi than in other African countries. The rate of closure at first repair was 94.1% for urogenital fistulas but it reached 98.5% overall. For recto‐vaginal fistulas, closure at first repair was 78.8% but the overall rate of successful closure was 87.9%. Stress incontinence was seen in 16.2% of the patients immediately after repair and in 6.2% after 6 months. The latter rate is certainly too low, however, as 26 of 63 patients were lost to follow‐up. A national fistula task force has been set up in Malawi.
The classification of obstetric vesico‐vaginal fistulas
Authors: Arrowsmith S.D.
Published: September 2007

Classification systems for vesico‐vaginal fistulas (VVFs) are as old as fistula surgery itself. Many classification systems have been proposed over the past 150 years, and nearly all have been based on descriptions of the size and anatomic location of the defect. While useful in communicating the appearance of a given fistula, systems based on size and anatomy do not necessarily give information on the difficulty of repair or the prognosis for successful outcome. This article serves as a call for a classification system for VVFs based on outcome rather than anatomy. Developing a reliable system will require data resources that do not yet exist. Based on incomplete data from a Nigerian VVF center, a possible system is proposed for further study. Once available, an outcome‐based classification system could be vital in selecting fistula cases appropriate for training surgeons, and in improving communication with patients.
Obstetric fistulas: A clinical review
Authors: Creanga A.A. , Genadry R.R.
Published: September 2007

A high proportion of genitourinary fistulas have an obstetric origin. Obstetric fistulas are caused by prolonged obstructed labor coupled with a lack of medical attention. While successful management with prolonged bladder drainage has occasionally been reported, mature fistulas require formal operative repair, and it is crucial that the first repair is done properly. The literature reports 3 approaches to fistula repair: vaginal, abdominal, and combined vaginal and abdominal. Many authors report high success rates for the surgical closure of obstetric fistulas at the time of hospital discharge, without further evaluation of the repair's effect on urinary continence or subsequent quality of life. Data on obstetric fistulas are scarce, and thus many questions regarding fistula management remain unanswered. A standardized terminology and classification, as well as a data reporting system on the surgical management of obstetric fistulas and its outcomes, are critical steps that need to be taken immediately.
The role of delayed childbearing in the prevention of obstetric fistulas
Authors: Tsui A.O. , Creanga A.A. , Ahmed S.
Published: September 2007

Objective

To examine the role of delayed childbearing in the prevention of obstetric fistulas (OFs).

Methods

Data on 4798 deliveries in Niger (1995–1998), 3552 in Nigeria (1996–1999), and 6789 in Tanzania (1991–1996) were analyzed with logistic regression models.

Results

Young maternal age and primiparous status were identified as correlates of prolonged/obstructed labor. The annual incidence of OFs in Nigeria was found to be 2.11 per 1000 births, with 9817 cases developing each year, 28% in women and girls younger than 20 years. The predicted proportion of women experiencing prolonged/obstructed labor would be reduced by 11.2% in Niger, 11.4% in Nigeria, and 13.1% in Tanzania if the risks associated with young maternal age at first delivery and primiparity were eliminated.

Conclusions

Community programs to educate young, newly married women about delaying childbearing until they reach physical maturity should be implemented in countries with a high incidence of OFs.
A consolidated catalogue and graphical annotation of dbSNP polymorphisms in the human tissue kallikrein (KLK) locus
Authors: Goard Carolyn A. , Bromberg Irvin L. , Elliott Marc B. , Diamandis Eleftherios P.
Published: September 2007

The human tissue kallikreins, 15 secreted serine proteases, may play diverse roles in pathophysiology. The National Center for Biotechnology Information's dbSNP was mined for polymorphisms located within the kallikrein (KLK) locus using custom‐designed “ParSNPs” and “LocusAnnotator” software tools. Using “ParSNPs”, a filterable catalogue of 1856 KLK polymorphisms (1023 validated) was generated. “LocusAnnotator” was used to annotate the KLK locus sequence with gene and polymorphism features. A second locus was examined to validate the use of both programs on a non‐kallikrein locus. This report may assist in the informed selection of KLK polymorphisms for future association and biochemical studies in relation to disease. Furthermore, “ParSNPs” and “LocusAnnotator” are available at no cost from our website (www.acdcLab.org/annotations) to examine other loci.
New insights into the functional mechanisms and clinical applications of the kallikrein‐related peptidase family
Authors: Emami Nashmil , Diamandis Eleftherios P.
Published: September 2007

The Kallikrein‐related peptidase (KLK) family consists of fifteen conserved serine proteases that form the largest contiguous cluster of proteases in the human genome. While primarily recognized for their clinical utilities as potential disease biomarkers, new compelling evidence suggests that this family plays a significant role in various physiological processes, including skin desquamation, semen liquefaction, neural plasticity, and body fluid homeostasis. KLK activation is believed to be mediated through highly organized proteolytic cascades, regulated through a series of feedback loops, inhibitors, auto‐degradation and internal cleavages. Gene expression is mainly hormone‐dependent, even though transcriptional epigenetic regulation has also been reported. These regulatory mechanisms are integrated with various signaling pathways to mediate multiple functions. Dysregulation of these pathways has been implicated in a large number of neoplastic and non‐neoplastic pathological conditions. This review highlights our current knowledge of structural/phylogenetic features, functional role and regulatory/signaling mechanisms of this important family of enzymes.
Pollen evidence for variations in the southern margin of the westerly winds in SW patagonia over the last 12,600 years
Authors: Villa-Martínez Rodrigo , Moreno Patricio I.
Published: September 2007

We report pollen and charcoal records from Vega Ñandú (∼ 51°0′S, 72°45′W), a small mire located near the modern forest-steppe ecotone in Torres del Paine National Park, southern Chile. The record shows an open landscape dominated by low shrubs and herbs between 12,600 and 10,800 cal yr BP, under cold and relatively humid conditions. Nothofagus experienced frequent, large-amplitude oscillations between 10,800 and 6800 cal yr BP, indicating recurrent transitions between shrubland/parkland environments, under warm and highly variable moisture conditions. A sustained increase in Nothofagus started at 6800 cal yr BP, punctuated by step-wise increases at 5100 and 2400 cal yr BP, implying further increases in precipitation. We interpret these results as indicative of variations in the amount of precipitation of westerly origin, with prominent increases at 6800, 5100, and 2400 cal yr BP. These pulses led to peak precipitation regimes during the last two millennia in this part of SW Patagonia. Our data suggest variations in the position and/or strength of the southern margin of the westerlies, most likely linked to variations in the extent and/or persistence of sea ice and sea-surface temperature anomalies in the Southern Ocean. Over the last two centuries the record shows a forest decline and expansion of Rumex acetosella, an exotic species indicative of European disturbance.
The difficult adolescents who are referred to a psychiatric unit—I. Classification
Authors: Place M. , Framrose R. , Willson C.
Published: September 2007

The first 206 cases referred to an adolescent psychiatry unit were coded on a clinical inventory. This inventory proved to have acceptable inter‐rater and test retest reliability, as well as quite a high degree of validity. Cluster analysis using Yule's similarity coefficient produced a series of near neighbours which, when combined with relevant history details produced four diagnostic groupings which seem to have clinical relevance to referrals to an adolescent psychiatric clinic. The importance of correct diagnosis in this age group is emphasized because of the part it plays in the search for more effective treatments of adolescent disorders.
An application of social learning methods in a residential programme for young offenders
Authors: Brown Barrie
Published: September 2007

The application of behavioural principles to working with young offenders has been extensive in the U.S.A. in recent years with the development of the Achievement Place family group home programme a significant feature. Developments in the United Kingdom have been more limited, with no published accounts other than very partial replications of the Achievement Place approach. This paper describes the development of a partial replication of the Achievement Place approach in Unit One, a community based residential programme for young offenders in South East London. The Unit One programme incorporates a token economy, a school programme, teaching interactions and self‐government. The paper describes successful outcomes for five out of eight of the delinquents first admitted to the programme, and identifies some of the factors associated with success. It also describes two process research projects evaluating effectiveness of training in social reinforcement for residential care staff, and in training teachers working with Unit One youth's to make effective demands for compliance. The paper concludes by highlighting problems in attempting a partial replication of the Achievement Place approach.
A follow‐up study of the first 70 admissions to a general purpose adolescent unit
Authors: Pyne Nicholas , Morrison Rosemary , Ainsworth Patricia
Published: September 2007

A follow‐up study of the first 70 admissions to a general purpose adolescent unit.

The adolescents and their families were given individual interviews. The outcome, which was assessed on the basis of these interviews, included psychiatric symptomatology and three basic areas of functioning: social, sexual and work adjustments. A global rating of the general level of function, relative to normality, was given for each adolescent. One third of the adolescents were functioning at a high level, one third were functioning at a moderate level and one third were severely handicapped in the most essential areas of functioning. The study group appeared to be disadvantaged socially and in the work situation.

Results suggested that the optimum length of stay was 5–25 weeks. The nature of discharge was important: those adolescents who completed treatment were more likely to have a better outcome than those discharged prematurely.
Preventative adolescent psychiatry? Practical problems in running social skills groups for the younger adolescent
Authors: Hardwick Peter J. , Pounds Alan B. , Brown Margaret
Published: September 2007

In order to develop autonomy an adolescent needs a satisfactory peer group experience. Poor peer relationships in children and adolescents are an important factor in the development of psychological disorder in adults. Family therapy and individual psychotherapy by themselves may not attend specifically to the issue of helping a child improve his peer relationships.

The first part of this article deals with theoretical considerations including the concept and development of social skills. The second part describes how we set up and run our social skills groups in both a Child Guidance Clinic and a school for the maladjusted. Issues such as selection of children, creating group cohesion, and techniques for intervention (including social learning games, modelling, role plays and cognitive strategies) are discussed. The third part portrays an attempt to evaluate outcome. Throughout we share practical difficulties we have encountered.
The age, fauna and palaeoenvironment of the Late Triassic fissure deposits of Tytherington, South Gloucestershire, UK
Authors: WHITESIDE D. I. , MARSHALL J. E. A.
Published: September 2007

Important vertebrate faunas occur in fissure deposits of Late Triassic–Jurassic age in SW Britain. Although the faunas are well described, their age and palaeoenvironment remain poorly understood. One such fissure system was documented in detail during quarrying operations at Tytherington and has yieldedin situpalynomorphs that add much information concerning its age and palaeoenvironment. Significantly, the Tytherington fauna is of the sauropsid type that has generally been dated as Norian or pre-Penarth Group transgression and was also regarded as representing a distinct upland fauna. The palynomorphs, which include a significant marine component, demonstrate that the Tytherington Triassic fissures are infilled with Late Triassic (Rhaetian) sediments that match specific levels in the Westbury Formation. In addition, many of the Tytherington solutional fissures probably formed during the Rhaetian and are consistent with a fluctuating saline to freshwater environment. There is noprima facieevidence of solutional formation and infilling of the reptile-bearing deposits before the Rhaetian trangression. The fissure reptile fauna, which includes the early dinosaurThecodontosaurus, inhabited a small fire-swept limestone island in the Rhaetian sea. The features of the herpetofauna are entirely consistent with this island model which has Quaternary analogues.