bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐injury: A research review for the practitioner
Authors: Klonsky E. David , Muehlenkamp Jennifer J.
Published: October 2007

Non‐suicidal self‐injury is the intentional destruction of body tissue without suicidal intent and for purposes not socially sanctioned. In this practice‐friendly review, the authors summarize the empirical research on who self‐injures, why people self‐injure, and what treatments have demonstrated effectiveness. Self‐injury is more common in adolescents and young adults as compared to adults. Common forms include cutting, severe scratching, burning, and banging or hitting; most individuals who self‐injure have used more than one method. Although diagnostically heterogeneous, self‐injurers typically exhibit two prominent characteristics: negative emotionality and self‐derogation. Self‐injury is most often performed to temporarily alleviate intense negative emotions, but may also serve to express self‐directed anger or disgust, influence or seek help from others, end periods of dissociation or depersonalization, and help resist suicidal thoughts. Psychotherapies that emphasize emotion regulation, functional assessment, and problem solving appear to be most effective in treating self‐injury. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 1045–1056, 2007.
Clinical assessment of self‐injury: A practical guide
Authors: Walsh Barent
Published: October 2007

In this article, the author provides a practice‐friendly guide to the psychological assessment of self‐injury, such as self‐inflicted cutting, burning, hitting, and excoriation of wounds. The crucial distinction between self‐injury and suicide is emphasized. The author presents a structure for the assessment of self‐injury that focuses first on the therapeutic relationship, and thereafter on the history and specifics of the behavior, its intrapersonal and interpersonal functions, and its antecedents and consequences. Types of self‐injury that are atypical, and especially alarming, are identified. A case example illustrates both the style and content of a thorough assessment. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 1057–1068, 2007.
Developing and maintaining the therapeutic alliance with self‐injuring patients
Authors: Nafisi Nira , Stanley Barbara
Published: October 2007

In this article, the authors outline methods of strengthening the therapist–patient bond with individuals who self‐injure. Self‐injuring patients present with a host of challenges that differ from other patient populations and therefore certain approaches may be more effective than others. Among the strategies described are validation, checking in, working collaboratively toward goals, providing support, and repairing a ruptured alliance. Potential pitfalls (e.g., reinforcing maladaptive behavior, negative judging, and the fundamental attribution error) to which psychotherapists often fall prey are discussed as well. Self‐injury is explained as functional rather than manipulative behavior and detailed clinical guidelines and examples are provided to better illustrate approaches that will improve the therapeutic alliance. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 1069–1079, 2007.
Psychological treatment of self‐injury among adolescents
Authors: Nock Matthew K. , Teper Romi , Hollander Michael
Published: October 2007

Self‐injury is a dangerous and pervasive behavior problem among adolescents. Clinical trials testing the effectiveness of psychological treatments for this behavior problem among adolescents are lacking; however, several treatments have shown promise, such as those focused on teaching emotion regulation, distress tolerance, and interpersonal skills. The authors provide a case illustration of the use of dialectical behavior therapy, which is one of the most promising treatments for adolescent self‐injury. They then discuss several important considerations in the treatment of self‐injury, such as the use of strategies to increase treatment participation and the assessment of self‐injury and related target behaviors over the course of treatment to determine its effectiveness and to manage risk of self‐injury. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 1081–1089, 2007.
Feminist therapy with people who self‐inflict violence
Authors: Brown Laura S. , Bryan Tracy C.
Published: October 2007

In this article, the authors describe how a feminist therapist approaches work with clients who practice self‐inflicted violence (SIV). They begin by discussing feminist therapy, with its focus on empowerment of clients and the use of noncoercive strategies. The feminist perspective on understanding SIV behaviors is described, with SIV being defined as a coping strategy used by survivors of complex trauma as a means of self‐care. Feminist therapy is illustrated with a case example of a woman who used SIV, and the challenges to a therapist wishing to promote client safety while empowering the client. Practice recommendations and cautions are advanced. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 1121–1133, 2007.
Heterochromatin endoreduplication prior to gametogenesis and chromatin diminution during early embryogenesis in Mesocyclops edax (Copepoda: Crustacea)
Authors: Rasch Ellen M. , Wyngaard Grace A. , Connelly Barbara A.
Published: October 2007

The segregation of progenitor somatic cells from those of the primordial germ cells that sequester and retain elevated levels of DNA during subsequent developmental events, poses an interesting, alternative pathway of chromosome behavior during the reproductive cycle of certain species of cyclopoid copepods and several other organisms. Separation of maternal and paternal chromosome sets during very early cleavages (gonomery) is often a feature following marked elevations of DNA levels in germ cells for some of these species. Here, we report on the accumulation of large amounts of DNA in germ line nuclei of both female and male juveniles and adults of a freshwater copepod, Mesocyclops edax (Forbes, 1890). We also report the robust uptake of 3H‐thymidine by germ cells prior to gametogenesis in this species. By using cytophotometric analysis of the DNA levels in both germ line cells and somatic cells from the same specimens we demonstrate that germ cell nuclei accumulate high levels of DNA prior to the onset of gametogenesis. These elevated amounts coincide with the levels of heterochromatic DNA discarded during chromatin diminution. A new model is proposed of major cytological events accompanying the process of chromatin diminution in M. edax. J. Morphol., 2008. © 2007 Wiley‐Liss, Inc.
Evaporative climate change in the British Isles
Authors: Stanhill Gerald , Möller Markus
Published: October 2007

Evaporation measurements made at 16 sites in the British Isles were analysed for evidence of long‐term changes. Half of the series were from sites in Ireland measured with Class A evaporation pans between 1963 and 2005 and half in England and Scotland measured with the British Meteorological Office (MO) sunken evaporation tank between 1885 and 1968. Four of the Irish series showed significant linear trends, three of increasing and one of decreasing evaporation. These significant changes ranged between − 0.1 and + 0.1 mm year−1 equivalent to annual changes between − 0.22 and + 0.15%. Five of the UK series showed statistically significant linear trends, three of them decrease and two increase: These ranged in size between − 3.7 and + 2.1 mm year−1, equivalent to annual changes of − 1.05 to + 0.40% of the mean. Curvilinear time trends accounted for twice the amount of inter‐annual variation in evaporation as did the linear trends. Differences in sunshine duration (SD), used as a proxy for global radiation, were found to be the major factor explaining spatial as well as temporal changes in evaporation in the British Isles.

The pooled Irish data, expressed as normalized anomalies, showed a small and significant linear increase in evaporation over the last 40 years. Similarly parameterized the UK measurements showed no significant trend up till 1968; the one UK series that did extend till 2004 indicated a marked increase during the last 20 years. The long‐term changes found in annual evaporation were similar to those in air temperatures both in Ireland and England. The relevance of these findings to the hypothesis of an acceleration in the hydrological cycle is discussed. Copyright © 2007 Royal Meteorological Society
Predicting realizations of daily weather data for climate forecasts using the non‐parametric nearest‐neighbour re‐sampling technique
Authors: Bannayan Mohammad , Hoogenboom Gerrit
Published: October 2007

Weather is one of the primary driving variables that prominently impacts agricultural production and associated disciplines, such as resource management. Lack of daily weather data for many locations along with many prognosis requirements for weather for various applications has resulted in continuous efforts to determine the best possible approach for weather sequence prediction. The goal of this study was to verify thek‐nearest neighbours (k‐NN) approach for the prediction of daily weather sequences. This method can be employed on the assumption that the weather during the target year is analogous to the weather recorded in the past. We used the nearest‐neighbour re‐sampling method for the simultaneous prediction of daily radiation, maximum and minimum temperature, and precipitation for multiple locations. A vector of weather variables, including precipitation, radiation, maximum and minimum temperature, on day (t+ 1) is re‐sampled from historical data by conditioning on the vector of the same variables for the preceding day (t). Observed historical weather data for ten different sites located in Georgia were used for evaluation. The selected sites represent different climatic conditions and the number of daily records varied from 46 to 97 years. The predicted daily and monthly data were compared with both the observed daily and monthly average historical weather data and the target year of 2005 for all ten study sites. The statistical analysis included summary statistics, mean square difference (MSD) and its components, and the Kolmogorov‐Smirnov (KS) test. The results showed that thek‐NN approach was able to reproduce a similar pattern of the target year 2005 from the observed historical weather data. For all weather variables, both the lower and upper quartiles (Q1 and Q3) showed a very good agreement with the data of the observed target year. The cumulative distribution functions (CDFs) for the observed and predicted data were not significantly (P> 0.05) different across all sites for precipitation, except for the minimum temperature of seven study sites, radiation for five study sites, and maximum temperature for one study site. Our investigation to determine the minimum number of historical observed weather data required for obtaining reliable prediction revealed that 25 years of data were sufficient to find similar patterns compared to when all available weather data were used across all sites. It can be concluded from this study that thek‐NN approach on the basis of pattern recognition can be considered as a reliable method to predict daily weather sequences based on historical weather data. Copyright © 2007 Royal Meteorological Society
Late Quaternary terrestrial tephrochronology of Iceland—frequency of explosive eruptions, type and volume of tephra deposits
Authors: Larsen Gudrún , Eiríksson Jón
Published: October 2007

Close to 100 silicic tephra layers have been identified in Icelandic terrestrial soils of Holocene age. The majority of these tephras were erupted at the Hekla, Torfajökull, Öræfajökull, Askja, Snæfellsjökull, Eyjafjallajökull and Katla central volcanoes. By far the most active is Hekla with close to 50 identified silicic tephra layers in ∼8000 years, showing an inverse relationship between eruption frequency and volume of erupted tephra. Volumes of uncompacted silicic tephra layers range from <0.01 km3 to >10 km3, with nearly 50% of known tephra volumes lying between 0.1 and 0.5 km3. Seven closely spaced Hekla eruptions in the period 950–550 BC with identical major element composition illustrate the need of stratigraphic control in short and long distance correlations. A 2600 year old tephra geochemically indistinguishable from the Borrobol tephra is a reminder that no tephra is geochemically unique. The major producers of basaltic tephra are the volcanic systems that are partly covered by ice, or partly lying within areas of high groundwater or extending offshore, i.e. the Grímsvötn, Katla, Veidivötn‐Bárdarbunga, Reykjanes, Kverkfjöll and Vestmannaeyjar volcanic systems. The best known eruption record is that of the Katla system with over 170 identified basaltic tephra layers and more than 300 estimated in 8400 years. The Grímsvötn system is currently the most active volcanic system with over 70 eruptions during the last 1100 years. Volumes of uncompacted basaltic tephra layers range from <0.01 km3 to >20 km3, the majority of known tephra volumes lying between 0.1 and 1 km3. The most voluminous basaltic tephra deposit, the ∼10 200 yr old Saksunarvatn tephra, may however represent more than one eruption on the Grímsvötn system. Deposition of approximately 800 basaltic tephra layers during the last 9000 14C years is estimated but many of those erupted from volcanoes within ice caps have not been preserved. Copyright © 2007 John Wiley & Sons, Ltd.
Stable minimal hypersurfaces in locally symmetric spaces
Authors: Yun Gabjin
Published: October 2007

LetM be a complete non‐compact stable minimal hypersurface in a locally symmetric space N of nonnegative Ricci curvature. We prove that if the integral of square norm of the second fundamental form is finite, i.e., ∫M |A |2 dv < ∞, then M must be totally geodesic. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Abstract K and J spaces and measure of non‐compactness
Authors: Cobos Fernando , Fernández–Cabrera Luz M. , Martínez Antón
Published: October 2007

We establish a formula for the measure of non‐compactness of an operator interpolated by the general real method generated by a sequence lattice Γ. The formula is given in terms of the norms of the shift operators in Γ. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Gene profiling approaches help to define the specific functions of retinoblastoma family in epidermis
Authors: Lara M. Fernanda , García‐Escudero Ramón , Ruiz Sergio , Santos Mirentxu , Moral Marta , Martínez‐Cruz Ana B. , Segrelles Carmen , Lorz Corina , Paramio Jesús M.
Published: October 2007

The epidermal‐specific ablation of Rb gene leads to increased proliferation, aberrant differentiation, and the disengagement of these processes in vivo and in vitro. These differences in phenotype are more severe with the loss of p107, demonstrating the functional compensation between pRb and p107. As p107 and p130 also exert overlapping functions in epidermis, we have generated RbF19/F19K14cre;Rbl2−/− (pRb−;p130−) mice to analyze possible functional redundancies between pRb and p130. The epidermal phenotype was very similar between pRb− and pRb−;p130− mice, suggesting that pRb and p130 activities are not redundant in epidermis. Importantly, we can correlate the proliferation differences with specific changes in gene expression between pRb−, pRb−;p107− and pRb−;p130− primary keratinocytes using microarray analysis, and explain the phenotypes in the context of altered E2F expression and functionality. Our findings support a model in which the distinct retinoblastoma family members, in conjunction with E2F members, play a central role in regulating epidermal homeostasis through specific or overlapping activities. © 2007 Wiley‐Liss, Inc.
Anti‐diol epoxide of benzo[a]pyrene induces transient Mdm2 and p53 Ser15 phosphorylation, while anti‐diol epoxide of dibenzo[a,l]pyrene induces a nontransient p53 Ser15 phosphorylation
Authors: Pääjärvi Gerd , Jernström Bengt , Seidel Albrecht , Stenius Ulla
Published: October 2007

The polycyclic aromatic hydrocarbons (PAHs) dibenzo[a,l]pyrene (DBP) and benzo[a]pyrene (BP) are environmental contaminants and potent carcinogens. DBP is several orders of magnitude more mutagenic/carcinogenic than BP. This can be ascribed to differences in DNA binding efficiency of their ultimate carcinogenic bay‐ and fjord‐region diol epoxide (DE) intermediates, differences in structural features of the DNA adducts and differences in DNA adduct recognition and the subsequent downstream signaling. In this study, we have characterized the effect of the ultimate carcinogenic DEs, (+)‐anti‐BPDE and (−)‐anti‐DBPDE following short exposure times, on Mdm2 and p53 pathway in A549 human lung epithelial carcinoma cells. In contrast to (−)‐anti‐DBPDE, (+)‐anti‐BPDE induces stabilization of phosphorylated Mdm2. (+)‐anti‐BPDE‐induced effects on Mdm2 were transient and correlated with transient p53 Ser15 phosphorylation. DNA adducts of (−)‐anti‐DBPDE are more refractory to removal by nucleotide excision repair (NER) than adducts of (+)‐anti‐BPDE and do not induce Mdm2 phosphorylation. This suggests a role of phosphorylated Mdm2 in the repair process. In addition, (−)‐anti‐DBPDE, in contrast to (+)‐anti‐BPDE, induced prolonged p53 Ser15 phosphorylation as well as phosphorylation of p53 at Ser46, a phosphorylation site associated with apoptosis. It is also concluded that p53 Ser15 phosphorylation and antibody 2A10‐site specific Mdm2 alterations are induced by nonidentical signaling pathways by the bay‐ and fjord‐region DE. These differences may reflect the different carcinogenic potential of these compounds. © 2007 Wiley‐Liss, Inc.
Control of peripheral benzodiazepine receptor‐mediated breast cancer in rats by soy protein
Authors: Mukhopadhyay Sutapa , Rajaratnam Veera , Mukherjee Shyamali , Das Salil K.
Published: October 2007

Soy protein is known to have breast tumor suppressing activity. The expression of peripheral benzodiazepine receptors (PBRs), currently renamed as translocator protein (TSPO) and their associated functions, such as nuclear cholesterol uptake and content also have been shown to be increased in breast cancer. Here we investigated whether the breast tumor suppressing effects of soy protein is mediated by down‐regulation of PBR expression and function. Breast tumors were induced by gavage administration of a single dose (80 mg/kg) of dimethylbenz[a]anthracene (DMBA) into 50‐d old female Sprague Dawley rats, maintained on a standard AIN‐76A diet containing either casein or soy protein. Approximately 120 d following DMBA administration, the animals were sacrificed. All tumors were detected by palpation and at autopsy biopsy specimens were taken for histological grading. The ligand binding capacity, expression, and protein levels of PBRs, their nuclear localization and function, such as nuclear cholesterol uptake and content, were significantly increased in the tumors. However, replacement of casein by soy protein in the diet caused a significant decrease in all of these parameters. These data suggest that soy protein inhibits breast tumor development by decreasing the expression of the tumor‐promoting gene, which encodes PBRs. © 2007 Wiley‐Liss, Inc.
DLC‐1 suppresses non‐small cell lung cancer growth and invasion by RhoGAP‐dependent and independent mechanisms
Authors: Healy Kevin D. , Hodgson Louis , Kim Tai‐Young , Shutes Adam , Maddileti Savitri , Juliano Rudolph L. , Hahn Klaus M. , Harden T. Kendall , Bang Yung‐Jue , Der Channing J.
Published: October 2007

Expression of the tumor suppressor deleted in liver cancer‐1 (DLC‐1) is lost in non‐small cell lung (NSCLC) and other human carcinomas, and ectopic DLC‐1 expression dramatically reduces proliferation and tumorigenicity. DLC‐1 is a multi‐domain protein that includes a Rho GTPase activating protein (RhoGAP) domain which has been hypothesized to be the basis of its tumor suppressive actions. To address the importance of the RhoGAP function of DLC‐1 in tumor suppression, we performed biochemical and biological studies evaluating DLC‐1 in NSCLC. Full‐length DLC‐1 exhibited strong GAP activity for RhoA as well as RhoB and RhoC, but only very limited activity for Cdc42 in vitro. In contrast, the isolated RhoGAP domain showed 5‐ to 20‐fold enhanced activity for RhoA, RhoB, RhoC, and Cdc42. DLC‐1 protein expression was absent in six of nine NSCLC cell lines. Restoration of DLC‐1 expression in DLC‐1‐deficient NSCLC cell lines reduced RhoA activity, and experiments with a RhoA biosensor demonstrated that DLC‐1 dramatically reduces RhoA activity at the leading edge of cellular protrusions. Furthermore, DLC‐1 expression in NSCLC cell lines impaired both anchorage‐dependent and ‐independent growth, as well as invasion in vitro. Surprisingly, we found that the anti‐tumor activity of DLC‐1 was due to both RhoGAP‐dependent and ‐independent activities. Unlike the rat homologue p122RhoGAP, DLC‐1 was not capable of activating the phospholipid hydrolysis activity of phospholipase C‐δ1. Combined, these studies provide information on the mechanism of DLC‐1 function and regulation, and further support the role of DLC‐1 tumor suppression in NSCLC. © 2007 Wiley‐Liss, Inc.
Chemoprevention of familial adenomatous polyposis in ApcMin/+ mice by phenethyl isothiocyanate (PEITC)
Authors: Khor Tin Oo , Cheung William Ka Lung , Prawan Auemduan , Reddy Bandaru S. , Kong Ah‐Ng Tony
Published: October 2007

Phenethyl isothiocyanate (PEITC) is an isothiocyanate which is a major constituent of watercress and other cruciferous vegetables. Its chemopreventive potential has been previously shown in various rodent models of cancer. In this study, we investigated the chemopreventive efficacy of PEITC in the ApcMin/+ mouse model. ApcMin/+ mice were fed with diet supplemented with 0.05% of PEITC for 3‐wk. Our results clearly demonstrated that ApcMin/+ mice fed with PEITC supplemented diet developed significantly less (31.7% reduction) and smaller polyps in comparison to mice fed with the standard AIN‐76A diet. Subsequent mechanistic study using Western blotting shows that inhibition of growth of adenomas by PEITC is associated with increase of apoptosis (cleaved‐caspase‐3, ‐caspase‐7, and PARP). Treatments also led to the inhibition of cell cycle‐related biomarkers such as the cyclins (D1, A, and E) and activation of p21. However, PEITC has no effect on the expression of p‐Erk, p‐JNK or p‐p38. In conclusion, our results demonstrate that PEITC is a potent natural dietary compound for chemoprevention of gastrointestinal cancers. Its mechanism of actions may include induction of apoptosis and cell cycle arrest. © 2007 Wiley‐Liss, Inc.
Precancerous carcinogenesis of human breast epithelial cells by chronic exposure to benzo[a]pyrene
Authors: Siriwardhana Nalin , Wang Hwa‐Chain Robert
Published: October 2007

To understand carcinogenesis of human breast epithelial cells induced by chronic exposure to environmental pollutants, we studied biological and molecular changes in progression of cellular carcinogenesis induced by accumulated exposures to the potent environmental carcinogen benzo[a]pyrene (B[a]P). Increasing exposures of human breast epithelial MCF10A cells to B[a]P at picomolar concentrations resulted in cellular transformation from a noncancerous stage to precancerous substages, in which cells acquired the cancerous abilities of a reduced dependence on growth factors, anchorage‐independent growth, and disruption in acini formation on reconstituted basement membranes. Using cDNA microarrays, we detected seven upregulated genes related to human cancers in B[a]P‐transformed MCF10A cells. Using this model, we verified that green tea catechin significantly (P < 0.05) suppressed B[a]P‐induced carcinogenesis. Our studies indicate that this cellular model may serve as a cost‐efficient, in vitro system, mimicking the chronic carcinogenesis of breast cells that likely occurs in early stages of carcinogenesis in vivo, to identify agents that inhibit cellular carcinogenesis. © 2007 Wiley‐Liss, Inc.
A non‐coaxial constitutive model for sand deformation under rotation of principal stress axes
Authors: Lashkari Ali , Latifi Manouchehr
Published: October 2007

A constitutive model for the simulation of non‐coaxiality, an aspect of anisotropic behavior of sand subjected to the rotation of the principal stress axes, is presented in this paper. Experimental studies have shown that non‐coaxiality or non‐coincidence of principal plastic strain increments with principal stress axes under loadings involving the rotation of principal stress axes may be considerable. Besides, the rotation of the principal stress axes results in dramatic effects on stiffness and dilatant behavior of sand. Therefore, the consequences of principal stress axes rotation on deformational behavior, dilatancy and soil stiffness must be taken into account in theoretical and practical problems.

To this aim, the following steps are taken: (1) A general relationship for flow direction with respect to possibility of non‐coaxial flow is developed. Moreover, special circumstances linking non‐coaxiality to instantaneous interaction between loading and soil fabric are proposed. (2) Proposing novel expressions for plastic modulus and dilatancy function, the model is enforced to provide realistic simulations when sand is subjected to the rotation of the principal stress axes.

Finally, with numerous examples and comparisons, the model capabilities are shown under various stress paths and drainage conditions. Copyright © 2007 John Wiley & Sons, Ltd.
Voiding urges perceived by patients with interstitial cystitis/painful bladder syndrome
Authors: Greenberg Patty , Brown Jessica , Yates Teresa , Brown Vivian , Langenberg Patricia , Warren John W.
Published: October 2007

Aims

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a symptom‐based diagnosis. We studied the IC/PBS symptom commonly referred to as “urgency” and its relationship to IC/PBS pain in a group of women with recent onset of the disease.

Methods

As part of a case control study to identify risk factors for IC, cases completed a questionnaire including two statements regarding the perceived cause of their urge to void. One was related to fear of incontinence and the other was linked with relief of pain. A Likert scale indicating level of agreement/disagreement comprised the response options.

Results

Most respondents (65%) agreed with the statement linking urge with pain relief. A minority (21%) concurred with the fear of incontinence statement. Disagreement for both was found in 19%. A substantial proportion (46%) agreed with pain relief but also disagreed that urge is related to fear of incontinence. Those who reported urge to relieve pain were significantly more likely to report worsened pain with bladder filling and/or improved pain with voiding. There were no such associations with urge to prevent incontinence. Overactive bladder or diabetes prior to IC onset did not confound these results.

Conclusions

At least two distinct experiences of urge to urinate are evident in this population. For most, urge is linked with pain relief and is associated with bladder filling/emptying. About 1/5 reported urge to prevent incontinence. A similar portion did not agree with either urge, indicating that they may experience something altogether different, which requires further inquiry. Neurourol. Urodynam. 27:287–290, 2008. © 2007 Wiley‐Liss, Inc.
An isostatic assumed stress triangular element for the Reissner–Mindlin plate‐bending problem
Authors: Brasile Sandro
Published: October 2007

The paper describes a new assumed stress triangular element for Reissner–Mindlin plates, called TIP3, with three nodes and three degrees of freedom per node. The kinematics is constructed by means of the so‐called linked interpolation ruled by technically significant degrees of freedom (i.e. one transversal displacement and two rotations per node) without using additional bubble modes. The static representation starts from a moment–shear uncoupled polynomial approximation and is constrained to satisfy some equilibrium conditions in order to reduce the stress parameters to a minimum number. The resulting element is locking free, presents correct rank and passes the bending patch test even for very thin plates. The good performances of the element are demonstrated by several comparisons with other triangular plate elements available in the literature. Copyright © 2007 John Wiley & Sons, Ltd.
A regularized XFEM model for the transition from continuous to discontinuous displacements
Authors: Benvenuti E. , Tralli A. , Ventura G.
Published: October 2007

This work focuses on the modelling through the extended finite element method of structural problems characterized by discontinuous displacement. As a model problem, an elastic isotropic domain characterized by a displacement discontinuity across a surface is studied. A regularization of the displacement field is introduced depending on a scalar parameter. The regularized solution is defined in a layer. The emerging strain and stress fields are independently modelled using specific constitutive assumptions. In particular, it is shown that the mechanical work spent within the regularization layer can be interpreted as an interface work provided that a spring‐like constitutive law is adopted. The accuracy of the integration procedures adopted for the stiffness matrix is assessed, as highly non‐linear terms appear. Standard Gauss quadrature is compared with adaptive quadrature and with a new technique, based on an equivalent polynomial approach. One‐ and two‐dimensional results are reported for varying discretization size, regularization parameter, and constitutive parameters. Copyright © 2007 John Wiley & Sons, Ltd.
Simulating deformation of objects with multi‐materials using boundary element method
Authors: Zhou Aifang , Hui Kinchuen , Lai Yuenhoo
Published: October 2007

In this paper, an algorithm for simulating the elastostatic deformation of multiple objects with different material properties using boundary element method is introduced. By tessellating the surface of a geometric model into elements and classifying all the element nodes into different groups with different attributes, and partitioning the stiffness matrix into several sub‐matrices according to these attributes, a compact expression for the unknown variables is obtained. Comparing with the direct matrix inversion method, the dimension of the system matrix in the expression has been effectively reduced. Besides, this expression shows that the deformation of a multi‐component object can be simulated in a way similar to that of a single‐component object. The capacitance method is adopted for evaluating the deformation of the object. Experimental results illustrate that the proposed method is practical and efficient. Copyright © 2007 John Wiley & Sons, Ltd.
Antibiotics in Dutch general practice: nationwide electronic GP database and national reimbursement rates
Authors: Akkerman Annemiek E. , Kuyvenhoven Marijke M. , Verheij Theo J.M. , van Dijk Liset
Published: October 2007

Purpose

In order to assess whether different databases generate information which can be reliable compared with each other, this study aimed to assess to which degree prescribing rates for systemic antibiotics from a nationwide electronic general practitioner (GP) database correspond with national reimbursement rates, and to investigate for which indications antibiotics are prescribed.

Methods

Nationwide GP prescribing data were collected from the Second Dutch National Survey of General Practice (DNSGP‐2) based on 90 general practices serving 358 008 patients in 2001. Dutch national reimbursement rates for GPs were derived from claims data of the Dutch Drug Information System/Health Care Insurance Board (GIP/CVZ) from 2001. We calculated antibiotic prescribing rates per 1000 patients/inhabitants for each database, and these rates were compared for the total rates and according to antibiotic subgroups. Indications for which GPs prescribed antibiotics were described.

Results

In national reimbursement data, 339 antibiotic prescriptions per 1000 inhabitants were prescribed by GPs, while the nationwide GP database showed 255 prescriptions per 1000 patients (75% coverage with reimbursement rates). The nationwide GP database showed high volumes of sulphonamides & trimethoprim, and small volumes of macrolides and quinolones. Half of the prescriptions (48%) were prescribed for respiratory diseases, a quarter (26%) for urinary diseases and 7% for ear diseases.

Conclusions

GPs voluntarily participating in a research network prescribe less antibiotics than Dutch GPs in general, and are cautious in prescribing newer and more broad‐spectrum antibiotics. This point has to be taken into account when databases will be compared with each other. Copyright © 2007 John Wiley & Sons, Ltd.
Neuroproteomics and its applications in research on nicotine and other drugs of abuse
Authors: Li Ming D. , Wang Ju
Published: October 2007

The rapidly growing field of neuroproteomics is able to track changes in protein expression and protein modifications underlying various physiological conditions, including the neural diseases related to drug addiction. Thus, it presents great promise in characterizing protein function, biochemical pathways, and networks to understand the mechanisms underlying drug dependence. In this article, we first provide an overview of proteomics technologies and bioinformatics tools available to analyze proteomics data. Then we summarize the recent applications of proteomics to profile the protein expression pattern in animal or human brain tissues after the administration of nicotine, alcohol, amphetamine, butorphanol, cocaine, and morphine. By comparing the protein expression profiles in response to chronic nicotine exposure with those appearing in response to treatment with other drugs of abuse, we identified three biological processes that appears to be regulated by multiple drugs of abuse: energy metabolism, oxidative stress response, and protein degradation and modification. Such similarity indicates that despite the obvious differences among their chemical properties and the receptors with which they interact, different substances of abuse may cause some similar changes in cellular activities and biological processes in neurons.
Clinical proteomics in neurodegenerative diseases
Authors: Zhou Jian‐Ying , Hanfelt John , Peng Junmin
Published: October 2007

Investigation of the human specimens is an essential element for understanding the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. The studies hold promise for identifying biomarkers for diagnosis and prognosis, elucidating disease mechanisms, and accelerating the development of new strategies for therapeutic intervention. Here, we review proteomics studies of human brain samples in light of recent advances of mass spectrometry, focusing on the general strategies for experimental design and analysis (e.g., sample pooling and replication, selection of proteomics platforms, and false discovery rate in data processing), because quantitative analysis of clinical samples is confounded by a number of variables, including genetic differences, antemortem and postmortem factors, and experimental errors. Diverse proteomics platforms are also discussed with respect to sensitivity, throughput, and accuracy. Regarding the enormous complexity of the human brain and the limitation of current proteomics technologies, it may be more practical to analyze a subset of proteome in a functional context, in order to facilitate the identification of important disease‐related proteins in the substantial noise reflecting biological and technical variances.
Predicting the order in which contacts are broken during single molecule protein stretching experiments
Authors: Sułkowska Joanna I. , Kloczkowski Andrzej , Sen Taner Z. , Cieplak Marek , Jernigan Robert L.
Published: October 2007

We combine two methods to enable the prediction of the order in which contacts are broken under external stretching forces in single molecule experiments. These two methods are Gō‐like models and elastic network models. The Gō‐like models have shown remarkable success in representing many aspects of protein behavior, including the reproduction of experimental data obtained from atomic force microscopy. The simple elastic network models are often used successfully to predict the fluctuations of residues around their mean positions, comparing favorably with the experimentally measured crystallographic B‐factors. The behavior of biomolecules under external forces has been demonstrated to depend principally on their elastic properties and the overall shape of their structure. We have studied in detail the muscle protein titin and green fluorescent protein and tested for ten other proteins. First, we stretch the proteins computationally by performing stochastic dynamics simulations with the Gō‐like model. We obtain the force–displacement curves and unfolding scenarios of possible mechanical unfolding. We then use the elastic network model to calculate temperature factors (B‐factors) and compare the slowest modes of motion for the stretched proteins and compare them with the predicted order of breaking contacts between residues in the Gō‐like model. Our results show that a simple Gaussian network model is able to predict contacts that break in the next time stage of stretching. Additionally, we have found that the contact disruption is strictly correlated with the highest force exerted by the backbone on these residues. Our prediction of bond‐breaking agrees well with the unfolding scenario obtained with the Gō‐like model. We anticipate that this method will be a useful new tool for interpreting stretching experiments. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Assessing secondary structure assignment of protein structures by using pairwise sequence‐alignment benchmarks
Authors: Zhang Wei , Dunker A. Keith , Zhou Yaoqi
Published: October 2007

How to make an objective assignment of secondary structures based on a protein structure is an unsolved problem. Defining the boundaries between helix, sheet, and coil structures is arbitrary, and commonly accepted standard assignments do not exist. Here, we propose a criterion that assesses secondary structure assignment based on the similarity of the secondary structures assigned to pairwise sequence‐alignment benchmarks, where these benchmarks are determined by prior structural alignments of the protein pairs. This criterion is used to rank six secondary structure assignment methods: STRIDE, DSSP, SECSTR, KAKSI, P‐SEA, and SEGNO with three established sequence‐alignment benchmarks (PREFAB, SABmark, and SALIGN). STRIDE and KAKSI achieve comparable success rates in assigning the same secondary structure elements to structurally aligned residues in the three benchmarks. Their success rates are between 1–4% higher than those of the other four methods. The consensus of STRIDE, KAKSI, SECSTR, and P‐SEA, called SKSP, improves assignments over the best single method in each benchmark by an additional 1%. These results support the usefulness of the sequence‐alignment benchmarks as a means to evaluate secondary structure assignment. The SKSP server and the benchmarks can be accessed at http://sparks.informatics.iupui.edu Proteins 2008. © 2007 Wiley‐Liss, Inc.
Common occurrence of internal repeat symmetry in membrane proteins
Authors: Choi Sungwon , Jeon Jouhyun , Yang Jae‐Seong , Kim Sanguk
Published: October 2007

Symmetry plays significant roles in protein structure and function. Particularly, symmetric interfaces are known to act as switches for two‐state conformational change. Membrane proteins often undergo two‐state conformational change during the transport process of ion channels or the active/inactive transitions in receptors. Here, we provide the first comprehensive analyses of internal repeat symmetry in membrane proteins. We examined the known membrane protein structures and found that, remarkably, nearly half of them have internal repeat symmetry. Moreover, we found that the conserved cores of these internal repeats are positioned at the interface of symmetric units when they are mapped on structures. Because of the large sequence divergence that occurs between internal repeats, the inherent symmetry present in protein sequences often has only been detected after structure determination. We therefore developed a sensitive procedure to predict the internal repeat symmetry from sequence information and identified 4653 proteins that are likely to have internal repeat symmetry. Proteins 2008. © 2007 Wiley‐Liss, Inc.
In silico local structure approach: A case study on Outer Membrane Proteins
Authors: Martin Juliette , de Brevern Alexandre G. , Camproux Anne‐Claude
Published: October 2007

The detection of Outer Membrane Proteins (OMP) in whole genomes is an actual question, their sequence characteristics have thus been intensively studied. This class of protein displays a common β‐barrel architecture, formed by adjacent antiparallel strands. However, due to the lack of available structures, few structural studies have been made on this class of proteins. Here we propose a novel OMP local structure investigation, based on a structural alphabet approach, i.e., the decomposition of 3D structures using a library of four‐residue protein fragments. The optimal decomposition of structures using hidden Markov model results in a specific structural alphabet of 20 fragments, six of them dedicated to the decomposition of β‐strands. This optimal alphabet, called SA20‐OMP, is analyzed in details, in terms of local structures and transitions between fragments. It highlights a particular and strong organization of β‐strands as series of regular canonical structural fragments. The comparison with alphabets learned on globular structures indicates that the internal organization of OMP structures is more constrained than in globular structures. The analysis of OMP structures using SA20‐OMP reveals some recurrent structural patterns. The preferred location of fragments in the distinct regions of the membrane is investigated. The study of pairwise specificity of fragments reveals that some contacts between structural fragments in β‐sheets are clearly favored whereas others are avoided. This contact specificity is stronger in OMP than in globular structures. Moreover, SA20‐OMP also captured sequential information. This can be integrated in a scoring function for structural model ranking with very promising results. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Shark IgNAR antibody mimotopes target a murine immunoglobulin through extended CDR3 loop structures
Authors: Simmons David P. , Streltsov Victor A. , Dolezal Olan , Hudson Peter J. , Coley Andrew M. , Foley Michael , Proll David F. , Nuttall Stewart D.
Published: October 2007

Mimotopes mimic the three‐dimensional topology of an antigen epitope, and are frequently recognized by antibodies with affinities comparable to those obtained for the original antibody–antigen interaction. Peptides and anti‐idiotypic antibodies are two classes of protein mimotopes that mimic the topology (but not necessarily the sequence) of the parental antigen. In this study, we combine these two classes by selecting mimotopes based on single domain IgNAR antibodies, which display exceptionally long CDR3 loop regions (analogous to a constrained peptide library) presented in the context of an immunoglobulin framework with adjacent and supporting CDR1 loops. By screening an in vitro phage‐display library of IgNAR variable domains (VNARs) against the target antigen monoclonal antibody MAb5G8, we obtained four potential mimotopes. MAb5G8 targets a linear tripeptide epitope (AYP) in the flexible signal sequence of the Plasmodium falciparum Apical Membrane Antigen—1 (AMA1), and this or similar motifs were detected in the CDR loops of all four VNARs. The VNARs, 1‐A‐2, −7, −11, and −14, were demonstrated to bind specifically to this paratope by competition studies with an artificial peptide and all showed enhanced affinities (3–46 nM) compared to the parental antigen (175 nM). Crystallographic studies of recombinant proteins 1‐A‐7 and 1‐A‐11 showed that the SYP motifs on these VNARs presented at the tip of the exposed CDR3 loops, ideally positioned within bulge‐like structures to make contact with the MAb5G8 antibody. These loops, in particular in 1‐A‐11, were further stabilized by inter‐ and intra‐ loop disulphide bridges, hydrogen bonds, electrostatic interactions, and aromatic residue packing. We rationalize the higher affinity of the VNARs compared to the parental antigen by suggesting that adjacent CDR1 and framework residues contribute to binding affinity, through interactions with other CDR regions on the antibody, though of course definitive support of this hypothesis will rely on co‐crystallographic studies. Alternatively, the selection of mimotopes from a large (<4 × 108) constrained library may have allowed selection of variants with even more favorable epitope topologies than present in the original antigenic structure, illustrating the power of in vivo selection of mimotopes from phage‐displayed molecular libraries. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Molecular dynamics simulations of domain motions of substrate‐free S‐adenosyl‐ L‐homocysteine hydrolase in solution
Authors: Hu Chen , Fang Jianwen , Borchardt Ronald T. , Schowen Richard L. , Kuczera Krzysztof
Published: October 2007

S‐Adenosyl‐L‐homocysteine hydrolase (SAHH) is an enzyme regulating intracellular methylation reactions. The homotetrameric SAHH exists in an open conformation in absence of substrate, while enzyme:inhibitor complexes crystallize in the closed conformation, in which the ligands are engulfed by the protein due to an 18° domain reorientation within each of the four subunits. We present a microscopic description of the structure and dynamics of the substrate‐free, NAD+‐bound SAHH in solution, based on a 15‐ns molecular dynamics simulation in explicit solvent. In the trajectory, the four cofactor‐binding domains formed a relatively rigid core with structure very similar to the crystal conformation. The four substrate‐binding domains, located at the protein exterior, also retained internal structures similar to the crystal, while undergoing large amplitude rigid‐body reorientations. The trajectory domain motions exhibited two interesting properties. First, within each subunit the domains fluctuated between open and closed conformations, while at the tetramer level 80% of the domain motions were perpendicular to the direction of the open‐to‐closed structural transition. Second, the domain reorientations in solution could be represented as a sum of two components, faster, with 20–50 ps correlation time and 3–4° amplitude, and slower, with 8–23 ns correlation time and amplitude of 14–22°. The faster motion is similar to the 1.5 cm−1 frequency hinge‐bending vibrations found in our recent normal mode analysis (Wang et al., Biochemistry 2005;44:7228–7239). The slower motion agrees with fluorescence anisotropy decay measurements, which detected a 10–20 ns domain reorientation of ca. 26° amplitude in the substrate‐free enzyme (Wang et al., Biochemistry 2006;45:7778–7786). Our simulations are thus in excellent agreement with experimental data. The simulations allow us to assign the observed nanosecond fluorescence anisotropy signal to fluctuations in domain orientations, and indicate that the microscopic mechanism of the motion involves rotational diffusion within a cone of 10–20°. Overall, our simulation results complement the existing experimental data and provide important new insights into SAHH domain motions in solution, which play a crucial role in the catalytic mechanism of SAHH. Proteins 2008. © 2007 Wiley‐Liss, Inc.