bluuebunny/crossref_metadata_2025 huggingface dataset:
A sensor histidine kinase co‐ordinates cell wall architecture with cell division in Bacillus subtilis
Authors: Fukushima Tatsuya , Szurmant Hendrik , Kim Eun‐Ja , Perego Marta , Hoch James A.
Published: June 2008

The concerted interconnection between processes driving DNA synthesis, division septum formation and cell wall synthesis and remodelling in rapidly growing bacteria requires precise co‐ordination by signalling mechanisms that are, for the most part, unknown. The YycG (sensor histidine kinase)–YycF (response regulator/transcription factor) two‐component system of Bacillus subtilis controls the synthesis of enzymes and their inhibitors that function in cell wall remodelling and cell separation. Here it is shown that the YycG sensor histidine kinase is a component of the division septum in growing cells. RT‐PCR quantification of YycF∼PO4‐regulated gene transcription, in wild type and FtsZ‐depleted, septum‐less cells, indicated that YycG kinase activity on YycF is dependent on YycG localization to a division septum. The data support a model in which the YycG sensor kinase perceives information at the division septum and regulates the reciprocal synthesis of autolysins and autolysin inhibitors to co‐ordinate growth and division with cell wall restructuring.
Targeted mutagenesis of the ring‐exported protein‐1 of Plasmodium falciparum disrupts the architecture of Maurer's cleft organelles
Authors: Hanssen Eric , Hawthorne Paula , Dixon Matthew W. A. , Trenholme Katharine R. , McMillan Paul J. , Spielmann Tobias , Gardiner Donald L. , Tilley Leann
Published: June 2008

Mature red blood cells have no internal trafficking machinery, so the intraerythrocytic malaria parasite, Plasmodium falciparum, establishes its own transport system to export virulence factors to the red blood cell surface. Maurer's clefts are parasite‐derived membranous structures that form an important component of this exported secretory system. A protein with sequence similarity to a Golgi tethering protein, referred to as ring‐exported protein‐1 (REX1), is associated with Maurer's clefts. A REX1–GFP chimera is trafficked to the Maurer's clefts and preferentially associates with the edges of these structures, as well as with vesicle‐like structures and with stalk‐like extensions that are involved in tethering the Maurer's clefts to other membranes. We have generated transfected P. falciparum expressing REX1 truncations or deletion. Electron microscopy reveals that the Maurer's clefts of REX1 truncation mutants have stacked cisternae, while the 3D7 parent line has unstacked Maurer's clefts. D10 parasites, which have lost the right end of chromosome 9, including the rex1 gene, also display Maurer's clefts with stacked cisternae. Expression of full‐length REX1–GFP in D10 parasites restores the 3D7‐type unstacked Maurer's cleft phenotype. These studies reveal the importance of the REX1 protein in determining the ultrastructure of the Maurer's cleft system.
Deletion of the Mycoplasma genitalium MG_217 gene modifies cell gliding behaviour by altering terminal organelle curvature
Authors: Burgos Raul , Pich Oscar Q. , Querol Enrique , Piñol Jaume
Published: June 2008

Motility is often a virulence factor of pathogenic bacteria. Although recent works have identified genes involved in gliding motility of mycoplasmas, little is known about the mechanisms governing the cell gliding behaviour. Here, we report that Mycoplasma genitalium MG217 is a novel protein involved in the gliding apparatus of this organism and it is, at least, one of the genes that are directing cells to move in narrow circles when they glide. In the absence of MG_217 gene, cells are still able to glide but they mainly move drawing erratic or wide circular paths. This change in the gliding behaviour correlates with a rearrangement in the terminal organelle disposition, suggesting that the terminal organelle operates as a guide to steer the mycoplasma cell in a specific direction. Immunogold labelling reveals that MG217 protein is located intracellular at the distal end of the terminal organelle, between the cell membrane and the terminal button. Such location is consistent with the idea that MG217 could act as a modulator of the terminal organelle curvature, allowing cells to move in specific directions.
Recurrent nodule on the nasal columella: a good reason to re‐biopsy
Authors: Vujevich Justin J. , Goldberg Leonard H. , Kimyai‐Asadi Arash , Law Robert
Published: June 2008

Background  A 15‐year‐old Caucasian male presented with 9‐month history of a recurrent nodule on the nasal columella. The previous biopsy was reported as a neurofibroma.

Methods  Frozen sections revealed a spindle cell neoplasm. Permanent section immunohistochemistry sections stained positive for vimentin and smooth muscle actin and negative for S100 and CD34, confirming the diagnosis of leiomyosarcoma.

Results  The tumor was removed using Mohs micrographic surgery. Radiological work‐up revealed no distant metastasis. There has been no local recurrence to date.

Conclusions  Leiomyosarcoma is a difficult diagnosis to make clinically and requires histological confirmation. Re‐biopsy of a “benign” growth may be necessary if clinicopathological correlation does not match with the clinical behavior of the tumor in question. Finally, Mohs micrographic surgery is a useful treatment modality for leiomyosarcomas, particularly those located in cosmetically‐sensitive regions of the body such as the nose.
Dermoscopy: basic concepts
Authors: Campos‐do‐Carmo Gabriella , Ramos‐e‐Silva Marcia
Published: June 2008

Dermoscopy is a very useful technique for the analysis of pigmented skin lesions. It represents a link between clinical and histological views, permitting an earlier diagnosis of skin melanoma. It also helps in the diagnosis of many other pigmented skin lesions, such as seborrheic keratosis, pigmented basal cell carcinoma, hemangioma, blue nevus, atypical nevus, and mole, which can often clinically simulate melanoma. In this article, dermoscopy is reviewed from its history to the basic concepts of the interpretation of dermoscopic images. The goal is to introduce this subject to those not yet familiar with it, in order to instigate and encourage the training and practice of this technique of growing importance for everyday usage.
Granular parakeratosis
Authors: Martín José M. , Pinazo Isabel , Molina Inmaculada , Monteagudo Carlos , Villalón Guillermo , Jordá Esperanza
Published: June 2008

A healthy 62‐year‐old woman was referred to our dermatology department with a 1‐month history of a pruritic axillary eruption.

 On examination, multiple erythematous and brownish hyperkeratotic papules were seen in both axillae. Some of these lesions coalesced into plaques, with small areas of sparing, and a background erythematous color was also found in the axillary vaults (Fig. 1).

Multiple erythematous and brownish hyperkeratotic papules in the axillary vaults

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 There was no involvement of other intertriginous sites and there were no associated systemic symptoms. The patient was not obese.

 The patient had removed the hair from her axillae with wax 3 weeks before the development of the eruption. Moreover, she had changed her antiperspirant 1 week before the onset of the lesions.

 A cutaneous biopsy for histologic analysis was performed. Histologically, the stratum corneum was thickened, with persistent nuclei together with countless small basophilic granules. The granular layer was preserved and, in some areas, hypergranulosis was found (Fig. 2). These findings were characteristic of granular parakeratosis.

Countless small basophilic granules in a thickened stratum corneum (hematoxylin and eosin; original magnification, ×400)

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 The cutaneous lesions resolved completely after 1 week of treatment with topical betamethasone dipropionate and gentamicin sulfate (twice daily). The patient was urged to discontinue her use of deodorants.
Lichen striatus in adults and pimecrolimus: open, off‐label clinical study
Authors: Campanati Anna , Brandozzi Giuliano , Giangiacomi Mirella , Simonetti Oriana , Marconi Barbara , Offidani Anna Maria
Published: June 2008

Background  Lichen striatus is a well‐known, acquired, self‐healing, linear inflammatory dermatosis. Lichen striatus occurring in adults tends to be more extensive and itchy than in children, sometimes requiring symptomatic treatment. The therapeutic approach usually adopted is topical steroids, even though prolonged use may lead to several side‐effects, particularly cutaneous atrophy.

Objective  To report the results of an open, off‐label study on the use of pimecrolimus 1% in the treatment of diffuse, nonresponsive forms of lichen striatus.

Methods  Three adult patients suffering from relapsing or disseminated and itchy lichen striatus received topical application of pimecrolimus 1% cream (Elidel®, Novartis Pharma, Basle, Switzerland) twice daily for 6 weeks, or until complete disappearance of the cutaneous lesions.

Results  All patients experienced rapid healing of the dermatosis, without any recurrence for at least 14 months.

Conclusion  Our preliminary results show that pimecrolimus may represent a useful therapeutic alternative for lichen striatus, although further studies on a larger number of cases are needed to confirm its safety and efficacy in the treatment of this condition.
Prevention and treatment of glucocorticoid‐induced osteoporosis in daily dermatologic practice
Authors: Vermaat Hester , Kirtschig Gudula
Published: June 2008

Background  Systemic glucocorticoids (GCs) are often needed to treat dermatologic patients. The long‐term use of GCs, however, is associated with potentially severe side‐effects. GC‐induced osteoporosis (GIO) is one of the most serious complications, but the risk of the occurrence of GIO seems to be generally underestimated.

Aim  To provide an update of the recent advances in the prevention of GIO in dermatologic practice.

Methods  Review of the literature and several European and US guidelines up to August 2007.

Results  Data regarding the prevention and treatment of GIO are limited and guidelines for the prevention of GIO are not fully consistent.

Conclusion  The prophylaxis of osteoporosis needs to be started early during treatment with GCs. Calcium and vitamin D supplements in all patients on systemic GCs and bisphosphonates in patients who take GCs for more than 3 months are practical and effective measures.
Clinical significance of dermoscopy in alopecia areata: analysis of 300 cases
Authors: Inui Shigeki , Nakajima Takeshi , Nakagawa Koichi , Itami Satoshi
Published: June 2008

Objective  To determine dermoscopic findings of alopecia areata (AA) from a large‐scale study that can be used as clinical indicators of disease.

Methods  Dermoscopic examination of areas of hair loss on the scalp of 300 Asian patients with AA was performed using a DermLite® II pro, which can block light reflection from the skin surface without immersion gels. Using the Spearman rank‐order correlation coefficient by rank test, correlations between the incidence of each dermoscopic finding and the severity of disease and disease activity were examined. The sensitivity and specificity of the findings as diagnostic clues for AA were evaluated.

Results  Characteristic dermoscopic findings of AA included black dots, tapering hairs, broken hairs, yellow dots, and clustered short vellus hairs (shorter than 10 mm) in the areas of hair loss. Black dots, yellow dots, and short vellus hairs correlated with the severity of disease, and black dots, tapering hairs, broken hairs, and short vellus hairs correlated with disease activity. For diagnosis, yellow dots and short vellus hairs were the most sensitive markers, and black dots, tapering hairs, and broken hairs were the most specific markers.

Conclusion  Dermoscopic characteristics, such as black dots, tapering hairs, broken hairs, yellow dots, and clustered short vellus hairs, are useful clinical indicators for AA.
Chilling stress response of postemergent cotton seedlings
Authors: DeRidder Benjamin P. , Crafts‐Brandner Steven J.
Published: June 2008

Early season development of cotton is often impaired by sudden episodes of chilling temperature. We determined the chilling response specific to postemergent 13‐day‐old cotton (Gossypium hirsutum L. cv. Coker 100A‐glandless) seedlings. Seedlings were gradually chilled during the dark period and rewarmed during the night‐to‐day transition. For some chilled plants, the soil temperature was maintained at control level. Plant growth, water relations and net photosynthesis (Pn) were analyzed after one or three chilling cycles and after 3 days of recovery. Three chilling cycles led to lower relative growth rate (RGR) compared with controls during the recovery period, especially for plants with chilled shoots and roots. Treatment differences in RGR were associated with net assimilation rate rather than specific leaf area. Both chilling treatments led to loss of leaf turgor during the night‐to‐day transition; this effect was greater for plants with chilled compared with warm roots. Chilling‐induced water stress was associated with accumulation of the osmolyte glycine betaine to the same extent for both chilling treatments. Inhibition of Pn during chilling was related to both stomatal and non‐stomatal effects. Pn fully recovered after seedlings were returned to control conditions for 3 days. We conclude that leaf expansion during the night‐to‐day transition was a significant factor determining the magnitude of the chilling response of postemergent cotton seedlings.
Use of the Perceive, Recall, Plan and Perform System of Task Analysis for persons with schizophrenia: A preliminary study
Authors: Aubin Ginette , Chapparo Christine , Gélinas Isabelle , Stip Emmanuel , Rainville Constant
Published: June 2008

Background/aim:  Task analysis that targets information processing skills is an essential tool to understanding difficulties encountered by people with schizophrenia in their daily activities. The purpose of this preliminary study was to explore the use of the Perceive, Recall, Plan and Perform (PRPP) System of Task Analysis for this clientele. The specific objectives were to describe information processing difficulties as measured by the PRPP and to examine preliminary evidence of construct validity and interrater reliability.

Methods:  In the first part of this study, 10 participants with schizophrenia living in the community were assessed using the PRPP during both a simple and a complex meal preparation task. Community functioning was measured using the Independent Living Skills Survey. In the second part, interrater reliability was appraised using three trained raters, who scored 15 participants preparing the complex meal preparation task.

Results:  Analysis of performance demonstrates that people with schizophrenia have difficulties especially in the Perceive and Plan quadrants of the PRPP and are more challenged in the complex task. The PRPP total score for the complex task is strongly related to the community functioning score. Results indicate good interrater reliability for the PRPP total score and moderate interrater reliability for the quadrant scores.

Conclusion:  Despite the small sample size, results from this preliminary study support the use of the PRPP System of Task Analysis to further explore the impact cognitive deficits have on daily task performance and thus on community functioning in people with schizophrenia.
Transanal endoscopic microsurgery in 143 consecutive patients with rectal adenocarcinoma: results from a Danish multicenter study
Authors: Baatrup G. , Breum B. , Qvist N. , Wille‐Jørgensen P. , Elbrønd H. , Møller P. , Hesselfeldt P.
Published: June 2008

Objective  The long‐term results are presented on total survival, cancer‐specific survival and recurrence in 143 consecutive patients treated with transanal endoscopic microsurgery (TEM) for adenocarcinoma of the rectum.

Method  Four Danish centres established in 1995 a database for registration of all TEM procedures. Data were supplemented from pathology reports and death certificates were checked in the Danish patient registry. Data were analysed with multivariance regression and survival analysis.

Results  The T stage was as follows: T1 50%, T2 33%, T3 14%, and stage unknown 3%. TEM was performed with curative intent in 43%, for compromise in 52% and for palliation in 5%. Five‐year total survival was 66% and 5‐year cancer‐specific survival 87%. Cancer‐specific survival for T1 was 94%. The significant predictors for total survival were age and tumour size. For cancer‐specific survival T stage, radical resection, tumour size and recurrence were significant predictors. Eighteen per cent had recurrence and 15% had immediate reoperation.

Conclusion  The TEM provides good long‐term results for pT1 cancers. In old patients and patients with co‐morbidity TEM may provide acceptable long‐term results for T2 cancers. Tumours larger than 3 cm should not be treated with TEM for cure.
DISTANT FRIENDS ONLINE? RURAL AND URBAN ADOLESCENTS’ COMMUNICATION ON THE INTERNET
Authors: DOORIS JOHN , SOTIRELI THOMAI , VAN HOOF SJEF
Published: June 2008

This study explores how rural and urban adolescents use the Internet as a tool for communication in their social environment. It aims to analyse the differences in the use of the Internet to overcome environmental constraints between urban and rural adolescents. In this paper, environmental constraints are defined in two ways: (1) The lack of contacts that a person may have in his/her local environment and (2) The distance between the contacts that prevents him/her from having face‐to‐face social interaction. The empirical part of the research is a questionnaire‐based survey of two samples of pre‐university high school pupils in Den Bosch and Winterswijk in the Netherlands. The outcomes of the research show that pupils in the urban area find more emotional support in their physical environment than pupils from the rural area and that they also receive more emotional support via the Internet than their rural counterparts.
Morphological plasticity in scleractinian corals
Authors: Todd Peter A.
Published: June 2008

When describing coral shape and form the term phenotypic plasticity, i.e. environment‐induced changes in morphology, is often used synonymously with intraspecific variation. Variation, however, may simply be due to genetic differentiation (polymorphism). Of the 1314 extant scleractinian coral species, less than 20 have been tested for plastic responses. Morphological plasticity has important implications for coral identification, as skeletal features used in coral systematics are directly affected by environment. Furthermore, plastic changes can indicate how corals acclimatise to environmental change. The studies that have examined phenotypic plasticity in corals experimentally can be divided into two groups, i.e. ‘non‐clonal’—those that have transplanted whole colonies or fragments of colonies (but not treated the fragments as clones) to new environments, and ‘clonal’—those that have transplanted colony fragments and used them as clone‐mates. The use of clone‐mates is preferable as it facilitates the identification of among‐genotype variation for plasticity. The heterogeneous nature of the reef environment makes identifying the parameters that affect coral morphology difficult in the field, but there are also many problems conducting suitable aquarium experiments. Nevertheless, evidence to date suggests light and water movement are the most important variables inducing change. As these factors are known to be axiomatic to coral growth, it is possible that associated plastic changes in corals are adaptive; however, this hypothesis is yet to be tested rigorously.
Mineral Status of COPD Patients under Long‐Term Inhaled Corticosteroid Therapy
Authors: Buyukkaplan U. Sebnem , Akkaya Ahmet , Yildiz Mustafa , Bircan Ahmet , Aksoy Dogan Alev , Ozturk Onder
Published: June 2008

Purpose: The aim of this study was to determine the mineral status of mandibles, femurs, and spines in chronic obstructive pulmonary disease (COPD) patients under long‐term inhaled corticosteroid therapy.

Materials and Methods: Pulmanory function tests were conducted on patients (n = 30) with COPD under inhaled corticosteroid therapy for at least 1 year. The results were compared to sex‐ and age‐matched controls (n = 30). Analyses of blood gases were also carried out relative to COPD, and bone mineral densities (BMD) of the mandible, lumbar spine, femoral neck, trochanter, and Ward's triangle were also measured by dual‐energy X‐ray absorptiometry (DEXA). Levels of serum osteocalcin, alkaline phosphatase, calcium, phosphorus, and cortisol were also assessed.

Results: In accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria, 8 of the COPD patients had moderate, 11 patients had severe, and 11 patients had very severe forms of the disease. All BMD measurements were lower in the COPD patients than in the control group. The serum osteocalcin levels in COPD patients were significantly lower than those in the control group (p < 0.0001). Serum calcium (p < 0.004) and cortisol levels (p < 0.026) in the COPD patients were also significantly lower than those in the control subjects. Although serum alkaline phosphatase level was higher and the phosphorus level was lower in the treatment group than in the control group, the differences were not statistically significant.

Conclusion: Regular evaluation of the biochemical markers of bone metabolism and BMD would be helpful for detecting any detrimental changes of bone in COPD patients under long‐term inhaled corticosteroid therapy. In this study, mandibular BMD was observed to be lower in COPD patients under long‐term inhaled corticosteroid therapy than in healthy subjects. Thus, dental implant treatment may require preventive measures in COPD patients under long‐term inhaled corticosteroid therapy.
Regularized Estimation for the Accelerated Failure Time Model
Authors: Cai T. , Huang J. , Tian L.
Published: June 2008

SummaryIn the presence of high‐dimensional predictors, it is challenging to develop reliable regression models that can be used to accurately predict future outcomes. Further complications arise when the outcome of interest is an event time, which is often not fully observed due to censoring. In this article, we develop robust prediction models for event time outcomes by regularizing the Gehan's estimator for the accelerated failure time (AFT) model (Tsiatis, 1996,Annals of Statistics18, 305–328) with least absolute shrinkage and selection operator (LASSO) penalty. Unlike existing methods based on the inverse probability weighting and the Buckley and James estimator (Buckley and James, 1979,Biometrika66, 429–436), the proposed approach does not require additional assumptions about the censoring and always yields a solution that is convergent. Furthermore, the proposed estimator leads to a stable regression model for prediction even if the AFT model fails to hold. To facilitate the adaptive selection of the tuning parameter, we detail an efficient numerical algorithm for obtaining the entire regularization path. The proposed procedures are applied to a breast cancer dataset to derive a reliable regression model for predicting patient survival based on a set of clinical prognostic factors and gene signatures. Finite sample performances of the procedures are evaluated through a simulation study.
Expanded donor natural killer cell and IL‐2, IL‐15 treatment efficacy in allogeneic hematopoietic stem cell transplantation
Authors: Chen Guanghua , Wu Depei , Wang Yi , Cen Jiannong , Feng Yufeng , Sun Aining , Tang Xiaowen , Chang Huirong , Zhu Ziling
Published: June 2008

Graft‐versus‐host disease (GVHD), leukemia relapse, and immune deficiency remain the major limitations of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Donor natural killer cells (NK) and cytokines have good potential in GVHD prevention and immune reconstitution enhancement. Improved survival after allo‐HSCT therefore requires effective prophylaxis to reduce GVHD and strategy to mediate graft‐versus‐leukemia (GVL) effect. We studied the administration of expanded donor NK cell infusion and interleukin‐2 (IL‐2) and IL‐15 mixture treatment in a murine allo‐HSCT model for its effects on GVHD, immune reconstitution and leukemia relapse. In the GVHD model, recipient mice were reconstituted with bone marrow (BM) cells and splenocytes via vein. In the leukemia model, recipient mice were inoculated with EL9611 leukemia cells via vein 8 d prior to transplant. NK cell infusion mice group had lower clinical GVHD scores and suffered less severe GVHD‐associated weight loss than control mice group. 90% of control mice died of leukemia relapse within 52 d post‐transplant. NK cell infusion and IL‐2 and IL‐15 treatment recipient mice had improved survival compared with control mice. NK cell infusion and IL‐2 and IL‐15 treatment recipient mice had also accelerated lymphoid immune reconstitution compared with control mice group. Expanded donor NK cell infusion and IL‐2 and IL‐15 treatment could promote lymphoid immune reconstitution, mitigate GVHD, and reduce leukemia relapse in allo‐HSCT recipients. The findings may have important significance for complication prevention in clinical allo‐HSCT.
Characterization of eight polymorphic microsatellite loci for the giant grouper (Epinephelus lanceolatus Bloch)
Authors: ZENG HUA‐SONG , DING SHAO‐XIONG , WANG JUN , SU YONG‐QUAN
Published: June 2008

Eight polymorphic microsatellite loci were isolated and characterized using a small insert genomic DNA library for the giant grouper (Epinephelus lanceolatus Bloch, 1790), a commercially valuable marine fish in tropical waters. They showed polymorphism information content ranging from 0.177 to 0.775, allele numbers ranging from two to 10, effective allele numbers ranging from 1.227 to 5.012, and observed and expected heterozygosities from 0.2 to 0.733 and from 0.185 to 0.801, respectively, which we anticipate will be useful for population genetic studies of the giant grouper.
Microsatellite markers for the endangered Roanoke logperch, Percina rex (Percidae) and their potential utility for other darter species
Authors: DUTTON DANIEL J. , ROBERTS JAMES H. , ANGERMEIER PAUL L. , HALLERMAN ERIC M.
Published: June 2008

The Roanoke logperch (Percina rex Jordan and Evermann), an endangered fish, occurs in only six watersheds in the Roanoke and Chowan river drainages of Virginia, USA. The species’ population genetic structure is poorly known. We developed 16 microsatellite markers that were reliably scorable and polymorphic P. rex. Markers were also screened in seven other darter species of the genus Percina. Most markers exhibited successful amplification and polymorphism in several species. These markers may therefore prove useful for population genetic studies in other darters, a diverse but highly imperiled group.
Isolation and characterization of polymorphic microsatellite loci from Tetratheca ericifolia (Elaeocarpaceae)
Authors: MCPHERSON HANNAH , PORTER CAROLYN , RYMER PAUL D. , CRAYN DARREN M. , ROSSETTO MAURIZIO
Published: June 2008

We identified 11 informative microsatellite loci in Tetratheca ericifolia from an (AG)n‐enriched library. Using these loci on 32 individuals from two populations (16 individuals from each), we detected an average of 11.3 alleles per locus (range of five to 21, average expected heterozygosity of 0.728), of which 56% were unique to one population or the other. All loci were amplifiable in seven to 12 of a further 12 species of Tetratheca under the same reaction conditions. The markers will be useful tools for evolutionary studies of this Australian endemic group.
A novel transport and delivery mechanism underpins the effectiveness of prolyl‐m‐sarcolysyl‐p‐fluorophenylalanine (PSF) in a human melanoma xenograft nude‐mouse model
Authors: Dierickx Karen ME , Morandini Renato , Nguyen Thi Hien , Salès François , Kauffmann Jean‐Michel , Ghanem Ghanem E
Published: June 2008

The alkylating peptide PSF shows very promising results in vitro on different cancer cells but its efficacy in animals has not been assessed. Here we evaluate the efficacy of PSF in human melanoma‐bearing nude mice and examine the underlying mechanism. In melanoma‐bearing nude mice, escalating doses of PSF showed dose‐dependent responses and reached tumor regression with an optimal dose of 20 mg/kg for 1 month. A comparison of PSF with its free moiety m‐sarcolysin and melphalan showed a highly significant advantage of PSF. Furthermore, dose fractionation yielded an even better control of tumor regrowth. In vitro studies unraveled an original delivery mechanism based on the rapid binding of PSF mainly due to red blood cells to form a pro‐drug complex and the subsequent release of active metabolites by tumor‐associated proteolytic enzymes. Blood kinetics showed one major metabolite partially released over time, while in the presence of melanoma cells three additional metabolites are generated. Interestingly, tumor‐shed proteases also induce the production of these metabolites and varying combinations of enzyme inhibitors indicate the involvement of metallo‐ and other families of proteases in the delivery process. This particular transport and delivery of such an alkylating agent may have several benefits, mainly lowering the drug‐free moiety in plasma and at the same time increasing its concentration in protease rich areas such as tumors.
CC family chemokines directly regulate myoblast responses to skeletal muscle injury
Authors: Yahiaoui Linda , Gvozdic Dusanka , Danialou Gawiyou , Mack Matthias , Petrof Basil J.
Published: June 2008

Chemokines have been implicated in the promotion of leucocyte trafficking to diseased muscle. The purpose of this study was to determine whether a subset of inflammatory chemokines are able to directly drive myoblast proliferation, an essential early component of muscle regeneration, in a manner which is entirely independent of leucocytes. Cultured myoblasts (C2C12) were exposed to monocyte chemoattractant protein‐1 (MCP‐1; CCL2), macrophage inflammatory protein‐1α(MIP‐1α; CCL3) or MIP‐1β (CCL4). All chemokines induced phosphorylation of extracellular signal‐regulated kinase (ERK)1/2 mitogen‐activated protein kinase (MAPK) and greatly increased myoblast proliferative responses. Chemokine‐induced myoblast proliferation was abolished by pertussis toxin and the MEK1/2 inhibitor U0126, implicating both Gαi‐coupled receptors and ERK1/2‐dependent signalling. Myoblasts expressed receptors for all of the chemokines tested, and mitogenic responses were specifically inhibited by antibodies directed against CC family chemokine receptors 2 and 5 (CCR2 and CCR5). Within an in vitro myogenic wound healing assay devoid of leucocytes, all chemokines significantly accelerated the time course of myoblast wound closure after mechanical injury. Injections of MCP‐1 into cardiotoxin‐injured skeletal muscles in vivo also suppressed expression of the differentiation marker myogenin, consistent with a mitogenic effect. Taken together, our results indicate that CC chemokines have potent and direct effects on myoblast behaviour, thus indicating a novel role in muscle repair beyond leucocyte chemoattraction. Therefore, interventions aimed at modulating the balance between myoblast and leucocyte effects of CC chemokines in injured muscle could represent a novel strategy for the treatment of destructive muscle pathologies.
Altered synaptic and non‐synaptic properties of CA1 pyramidal neurons in Kv4.2 knockout mice
Authors: Andrásfalvy B. K. , Makara J. K. , Johnston D. , Magee J. C.
Published: June 2008

Back‐propagating action potentials (bAPs) travelling from the soma to the dendrites of neurons are involved in various aspects of synaptic plasticity. The distance‐dependent increase in Kv4.2‐mediated A‐type K+ current along the apical dendrites of CA1 pyramidal cells (CA1 PCs) is responsible for the attenuation of bAP amplitude with distance from the soma. Genetic deletion of Kv4.2 reduced dendritic A‐type K+ current and increased the bAP amplitude in distal dendrites. Our previous studies revealed that the amplitude of unitary Schaffer collateral inputs increases with distance from the soma along the apical dendrites of CA1 PCs. We tested the hypothesis that the weight of distal synapses is dependent on dendritic Kv4.2 channels. We compared the amplitude and kinetics of mEPSCs at different locations on the main apical trunk of CA1 PCs from wild‐type (WT) and Kv4.2 knockout (KO) mice. While wild‐type mice showed normal distance‐dependent scaling, it was missing in the Kv4.2 KO mice. We also tested whether there was an increase in inhibition in the Kv4.2 knockout, induced in an attempt to compensate for a non‐specific increase in neuronal excitability (after‐polarization duration and burst firing probability were increased in KO). Indeed, we found that the magnitude of the tonic GABA current increased in Kv4.2 KO mice by 53% and the amplitude of mIPSCs increased by 25%, as recorded at the soma. Our results suggest important roles for the dendritic K+ channels in distance‐dependent adjustment of synaptic strength as well as a primary role for tonic inhibition in the regulation of global synaptic strength and membrane excitability.
The Slc26a4 transporter functions as an electroneutral Cl−/I−/HCO3− exchanger: role of Slc26a4 and Slc26a6 in I− and HCO3− secretion and in regulation of CFTR in the parotid duct
Authors: Shcheynikov Nikolay , Yang Dongki , Wang Youxue , Zeng Weizong , Karniski Lawrence P. , So Insuk , Wall Susan M. , Muallem Shmuel
Published: June 2008

Transcellular Cl− and HCO3− transport is a vital function of secretory epithelia and exit across the luminal membrane is mediated by members of the SLC26 transporters in conjunction with cystic fibrosis transmembrane conductance regulator (CFTR) channel. Typically, secretory epithelia express several SLC26 transporters in the same tissue; however, how their specific function is determined in vivo is not known. In the present work we used the parotid gland duct which expressed Slc26a4 and Slc26a6 and the model systems of Slc26a4−/− and Slc26a6−/− mice to study the role and regulation of these SLC26 transporters. We examined the transport modes of SLC26A4 expressed in Xenopus oocytes and report that SLC26A4 functions as a coupled, electroneutral I−/Cl−, I−/HCO3− and Cl−/HCO3− exchanger with 1: 1 stoichiometry, with I− as the preferred anion. In the duct, Slc26a4 is expressed in the luminal membrane and mainly mediates I− secretion with minimal role in luminal HCO3− transport. By contrast, Slc26a6 mediates luminal Cl−/HCO3− exchange activity with minimal role in I− secretion. Furthermore, silencing of CFTR altered Cl−/HCO3− exchange by Slc26a6, but had no effect on I− secretion by Slc26a4. Accordingly, deletion of Slc26a6, but not deletion of Slc26a4, results in dysregulation of CFTR. These findings provide the first evidence for a selective role of the SLC26 transporters expressed in the same tissue in epithelial anion transport and suggest that transport specificity is achieved by both the properties of the transporters and the composition of the complexes they form.
Newborn granule cells in the ageing dentate gyrus
Authors: Morgenstern Nicolás A. , Lombardi Gabriela , Schinder Alejandro F.
Published: June 2008

The dentate gyrus of the hippocampus generates neurons throughout life, but adult neurogenesis exhibits a marked age‐dependent decline. Although the decrease in the rate of neurogenesis has been extensively documented in the ageing hippocampus, the specific characteristics of dentate granule cells born in such a continuously changing environment have received little attention. We have used retroviral labelling of neural progenitor cells of the adult mouse dentate gyrus to study morphological properties of neurons born at different ages. Dendritic spine density was measured to estimate glutamatergic afferent connectivity. Fully mature neurons born at the age of 2 months display ∼2.3 spines μm−1 and maintain their overall morphology and spine density in 1‐year‐old mice. Surprisingly, granule cells born in 10‐month‐old mice, at which time the rate of neurogenesis has decreased by ∼40‐fold, reach a density of dendritic spines similar to that of neurons born in young adulthood. Therefore, in spite of the sharp decline in cell proliferation, differentiation and overall neuronal number, the ageing hippocampus presents a suitable environment for new surviving neurons to reach a high level of complexity, comparable to that of all other dentate granule cells.
Effects of optic nerve injury, glaucoma, and neuroprotection on the survival, structure, and function of ganglion cells in the mammalian retina
Authors: Weber A. J. , Harman C. D. , Viswanathan S.
Published: June 2008

Glaucoma is an optic neuropathy that originates with pressure‐induced damage to the optic nerve. This results in the retrograde degeneration of ganglion cells in the retina, and a progressive loss of vision. Over the past several years, a number of studies have described the structural and functional changes that characterize ganglion cell degeneration in the glaucomatous eye, and following optic nerve injury. In addition, a variety of different strategies for providing neuroprotection to the injured retina have been proposed. Many of these are based on the use of brain‐derived neurotrophic factor (BDNF), a particularly potent neuroprotectant in the mammalian eye and the basis of our research in this area. Of particular importance is the fact that BDNF not only promotes ganglion cell survival following damage to the optic nerve, but also helps to preserve the structural integrity of the surviving neurons, which in turn results in enhanced visual function. The studies presented here describe these attributes, and serve as the foundation for ongoing work that suggests a need to think beyond the eye in the development of future treatment strategies.
Improving an Inverse Model of Sheet Metal Forming by Neural Network Based Regression
Authors: Frayman Y. , Rolfe B. F. , Webb G. I.
Published: June 2008

An inverse model for a sheet metal forming process aims to determine the initial parameter levels required to form the final formed shape. This is a difficult problem that is usually approached by traditional methods such as finite element analysis. Formulating the problem as a classification problem makes it possible to use well established classification algorithms, such as decision trees. Classification is, however, generally based on a winner-takes-all approach when associating the output value with the corresponding class. On the other hand, when formulating the problem as a regression task, all the output values are combined to produce the corresponding class value. For a multi-class problem, this may result in very different associations compared with classification between the output of the model and the corresponding class. Such formulation makes it possible to use well known regression algorithms, such as neural networks. In this paper, we develop a neural network based inverse model of a sheet forming process, and compare its performance with that of a linear model. Both models are used in two modes, classification mode and a function estimation mode, to investigate the advantage of re-formulating the problem as a function estimation. This results in large improvements in the recognition rate of set-up parameters of a sheet metal forming process for both models, with a neural network model achieving much more accurate parameter recognition than a linear model.
Towards a Hybrid Solver: Integration of a Genetic Algorithm Within “DSIDES”
Authors: Xie Shuiwei , Smith Warren F.
Published: June 2008

In contributing to the body of knowledge for decision-based design, the work reported in this paper has involved steps towards building a hybrid genetic algorithm to address systems design. Highlighted is a work in progress at the Australian Defence Force Academy (ADFA). A genetic algorithm (GA) is proposed to deal with discrete aspects of a design model (e.g., allocation of space to function) and a sequential linear programming (SLP) method for the continuous aspects (e.g., sizing). Our historical Decision Based Design (DBD) tool has been the code DSIDES (Decision Support In the Design of Engineering Systems). The original functionality of DSIDES was to solve linear and non-linear goal programming styled problems using linear programming (LP) and sequential (adaptive) linear programming (SLP/ALP). We seek to enhance DSIDES’s solver capability by the addition of genetic algorithms. We will also develop the appropriate tools to deal with the decomposition and synthesis implied. The foundational paradigm for DSIDES, which remains unchanged, is the Decision Support Problem Technique (DSPT). Through introducing genetic algorithms as solvers in DSIDES, the intention is to improve the likelihood of finding the global minimum (for the formulated model) as well as the ability of dealing more effectively with nonlinear problems which have discrete variables, undifferentiable objective functions or undifferentiable constraints. Using some numerical examples and a practical ship design case study, the proposed GA based method is demonstrated to be better in maintaining diversity of populations, preventing premature convergence, compared with other similar GAs. It also has similar effectiveness in finding the solutions as the original ALP DSIDES solver.
Real-Time Image Stabilization Using Fuzzy Logic
Authors: de Sam Lazaro Anthony , Tucker Joseph
Published: June 2008

The problem of video tele-operation of a moving vehicle is compounded by the fact that a camera mounted on such a vehicle moves rather violently and randomly depending on the terrain. This contributes to motion sickness of the operator who is controlling the vehicle from a stationary platform. In order to correct this problem, motion of the camera is counteracted by a stabilization routine that can account for all unwanted vibrations. A possibilistic model is described. The experimental set-up and preliminary results are presented.
Automatic Generation of Product Family Member CAD Models Supported by a Platform Using a Template Approach
Authors: Siddique Zahed , Zhou Yanjiang
Published: June 2008

Current global markets are volatile, where companies are striving to deliver greater quality, more customization, faster response, more innovative designs and lower prices. New models need to be introduced in the market more frequently, which has given momentum for designing family of products. Development of family of Products using a platform approach requires making decisions regarding platform selection and trade-off studies, which require analysis and evaluation of performance for the entire family instead of an individual products. One of the first steps in performing these activities require development of solid models for the entire family quickly and automatically as platform and family member configurations and size are changed. This paper presents an approach to automatically generate CAD models for a family of products. In the approach, a product family template that integrates configuration and parametric design information is presented. The template is implemented in the developed Product Family CAD (PF-CAD) module for Pro/E. A coffeemaker product family is used as a case study to automatically generate solid models of product family members from customer input.
Heat Pump Experiment With a Computer Interface for Control, Data Acquisition, and Analysis
Authors: Dini Said , Khosrowjerdi Mohammad , Aflaki James
Published: June 2008

This paper describes an effective, but simple, technique using a computer interface for control, data acquisition, and processing of a heat pump laboratory experiment. A water-to-air heat pump that allows comfort cooling and heating from a single source is used as an experiment and will be incorporated in a Mechanical Engineering Laboratory Course. Presently, the source is the city water. Plans are in place to use a ground source that provides a relatively constant temperature water supply, as low as 45°F. This well-instrumented laboratory teaching equipment allows students to measure temperatures, pressures, flow rate, and power input and then calculate the coefficient of performance of the system and the efficiency of the compressor both manually and automatically. A self-contained Windows-based data collection and analysis system has been developed for automating all the manual functions of a WPH-J Series Water-to-Air Heat Pump from Heat Controller, Inc. This system uses a data acquisition board to read the voltage signals corresponding to 9 T-type thermocouples, three pressure gauges, and compressor supplied power. The data acquisition and control software written in Visual Basic 6 uses 32-bit libraries to control the operation mode, read the thermocouples’ voltages, water flow rate, compressor’s input and output pressure, and supplied power.
Fan and Plate Apparatus for Illustrating Stability Concepts Using XPC Rapid-Prototyping Environment
Authors: Rahnamai Kourosh , Northrup Steve
Published: June 2008

In this study, a fan and plate apparatus is used to demonstrate the aerodynamic resonance phenomena and stability concepts. A series of controllers such as P, PD and PID are used to illustrate the aerodynamic behavior of this system. This laboratory apparatus can be used in an undergraduate or graduate controls course to illustrate and reinforce stability and controller design concepts. The xPC Rapid Prototyping Toolbox of MATLAB® is used for a fast and flexible method to implement a variety of controllers using a high-level programming language such as Simulink®.
Swirl Effects on Flow Dynamics and Fuel Spray Structure in Practical Combustors
Authors: Habibzadeh B. , Gupta A. K.
Published: June 2008

The effect of high shear in the flow on the spray flame characteristic has been examined. The shear was provided using different swirl combination in the inner and outer swirlers in the double concentric swirl burner. The burner allowed independent control of swirl and combustion airflow in the inner and outer annulus of the burner. Particle Image Velocimetry (PIV) and Phase Doppler Particle Analyzer (PDPA) laser diagnostic tools have been used to obtain comprehensive data related to droplet size, velocity, number density, vorticity in the flow for dispersed phase, and flow and strain rate in the axial direction in the carrier phase. A commercially available twin fluid nozzle has been used in this study. Results have been obtained for a swirl combination of 65° in inner swirler and 30° in outer swirler (referred to as 65°/30°). The results are compared with a swirl combination of 50°/30°. The results show secondary break-up of the droplets with high shear that was not present with low shear in the flow. They also show new way to obtain smaller size of droplets from a spray. Smaller size of droplets allows one to easily control the size, shape, stability and structure of the spray flames.