bluuebunny/crossref_metadata_2025 huggingface dataset:
HRAS and the Costello syndrome
Authors: Rauen KA
Published: January 2007

Costello syndrome (CS) is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies and a predisposition to develop neoplasia, both benign and malignant. CS is caused by activating germline mutations in HRAS and belongs to an exciting class of genetic syndromes that are caused by perturbation of function through the Ras pathway. Some of these other syndromes include Noonan syndrome, LEOPARD syndrome, neurofibromatosis 1 and cardio‐facio‐cutaneous syndrome. Ras is a critical signaling hub in the cell and is activated by receptor tyrosine kinases, G‐protein‐coupled receptors, cytokine receptors and extracellular matrix receptors. The downstream effectors of Ras are many and control vital cellular functions including cell cycle progression, cell survival, motility, transcription, translation and membrane trafficking. Understanding the genetic etiology of CS is the first step in gaining insight to the role Ras plays in human development, cellular signaling and cancer pathogenesis.
A possible bichromatid mutation in a male gamete giving rise to a female mosaic for two different mutations in the X‐linked gene WAS
Authors: Dobbs AK , Yang T , Farmer DM , Howard V , Conley ME
Published: January 2007

In genetic disorders caused by point mutations or small frameshift mutations, affected members of the same family are expected to have the same mutation in the causative gene. We have recently evaluated a family in which this was not the case. Maternal cousins with Wiskott–Aldrich syndrome (WAS; MIM 301000) had two different but contiguous single base pair deletions in WAS. The proband had an A deletion in codon 242 in exon 7 of WAS; his two cousins had a C deletion in codon 241. The mother of the proband was heterozygous for the A deletion allele, but her three sisters, including the mother of the affected cousins, were heterozygous for the C deletion. Both deletions occurred on the haplotype from the unaffected maternal great‐grandfather. The maternal grandmother, who was a carrier of WAS, based on a non‐random pattern of X chromosome inactivation in T cells, was mosaic for both deletions. These findings are most consistent with the mutations originating in a male gamete with different mutations on the two strands of DNA, a bichromatid mutation.
Gene discovery in craniofacial development and disease – cashing in your chips
Authors: Handrigan GR , Buchtová M , Richman JM
Published: January 2007

An unbiased, polygenic approach is needed to unravel the complex molecular bases of craniofacial development and disease. DNA microarrays, the current paradigm of genome‐wide analysis, permit the simultaneous study of many thousands of genes, the ready identification of candidate molecules and pathways, and the compilation of gene expression profiles for whole systems – pathologic and embryonic alike. We survey the existing literature applying microarrays to craniofacial biology and highlight the value of animal models, particularly mice and chickens, to understanding molecular regulation in the craniofacial complex. We also emphasize the importance of functional studies and high‐throughput assays to extracting useful data from microarray output. It is our goal to help put researchers and clinicians on the same page as microarray technology moves into the forefront of craniofacial biology.
Comparative evaluation of 2D time‐of‐flight and 3D elliptic centric contrast‐enhanced MR venography in patients with presumptive cerebral venous and sinus thrombosis
Authors: Klingebiel R. , Bauknecht H.C. , Bohner G. , Kirsch R. , Berger J. , Masuhr F.
Published: January 2007

We retrospectively evaluated an elliptic centric ordered 3D (ec 3D) magnetic resonance venography (MRV) technique in comparison to 2D time‐of‐flight (2D TOF) MRV in patients with presumptive cerebral venous sinus thrombosis (CVST). Twenty‐five patients (mean age 40.6 ± 16.5 years) with presumptive CVST underwent cerebral MRI including 2D TOF and ec 3D MRV. Radiologic findings and clinical outcome were correlated. MRV studies were evaluated by two neuroradiologists in a blinded manner for image quality, assessment of various sinus, internal cerebral veins (ICV), vein of Labbé and Galen (VL/VG) as well as for additional imaging procedures required. Sensitivity/specificity of ec 3D MRV amounted to 85.7%/97.2% as compared with 2D TOF 71.4%/55.6 %. Ec 3D MRV performed superior in terms of image quality as well as assessment of all sinus and veins except for the straight sinus. Additional imaging procedures were less often required in ec 3D MRV studies (28% vs. 66% for 2D TOF MRV; P < 0.001). Interobserver agreement was significantly increased by using ec 3D MRV (93.1% vs. 70.9% of readings). The results of our study provide additional evidence for the superiority of ec 3D compared with 2D TOF MR venography for the diagnosis or exclusion of acute CVST in daily clinical practice.
Association of rural life setting and poorer quality of life in Parkinson's disease patients: a cross‐sectional study in Croatia
Authors: Klepac N. , Pikija S. , Kraljić T. , Relja M. , Trkulja V. , Juren S. , Pavliček I. , Babić T.
Published: January 2007

Assessment of quality of life (QoL) has become an important measure in Parkinson's disease (PD) healthcare as a part of the efforts to evaluate the ‘total burden’ of the illness, and not only the motor disabilities. By analogy with some other diseases, we aimed to investigate potential urban–rural disparities in QoL in PD patients. A total of 111 consecutive PD patients were assessed for QoL using a specific 39‐item version of PD quality of life questionnaire (PDQ‐39) in a cross‐sectional study involving two centers in Croatia. Rural life setting (adjustment for center, age, sex, levodopa dose, disease duration and severity, education, employment status and number of household co‐members) was an independent negative predictor of QoL: rural patients had significantly (P < 0.05) worse PDQ‐39 Summary Index Score and most of the PDQ‐39 subscale scores (cognition, social support, stigma, emotional wellbeing and mobility score, and communication and activity of daily living scores with borderline significance) than their urban counterparts. Socioeconomic background should be considered in attempts to achieve the best management of PD patients’ needs.
Combination of low‐dose mirtazapine and ibuprofen for prophylaxis of chronic tension‐type headache
Authors: Bendtsen L. , Buchgreitz L. , Ashina S. , Jensen R.
Published: January 2007

Chronic headaches are difficult to treat and represent the biggest challenge in headache centres. Mirtazapine has a prophylactic and ibuprofen an acute effect in tension‐type headache. Combination therapy may increase efficacy and lower side effects. We aimed to evaluate the prophylactic effect of a combination of low‐dose mirtazapine and ibuprofen in chronic tension‐type headache. Ninety‐three patients were included in the double‐blind, placebo‐controlled, parallel trial. Following a 4‐week run‐in period they were randomized to four groups for treatment with a combination of mirtazapine 4.5 mg and ibuprofen 400 mg, placebo, mirtazapine 4.5 mg or ibuprofen 400 mg daily for 8 weeks. Eighty‐four patients completed the study. The primary efficacy parameter, change in area under the headache curve from run‐in to the last 4 weeks of treatment, did not differ between combination therapy (190) and placebo (219), P = 0.85. Explanatory analyses revealed worsening of headache already in the third week of treatment with ibuprofen alone. In conclusion, the combination of low‐dose mirtazapine and ibuprofen is not effective for the treatment of chronic tension‐type headache. Moreover, the study suggests that daily intake of ibuprofen worsens headache already after few weeks in chronic tension‐type headache.
Neuro‐Behçet's disease in Caucasians: a study of 22 patients
Authors: Joseph F. G. , Scolding N. J.
Published: January 2007

Several analyses of the neurological features of Behçet's disease (BD) have concluded that there are significant racial differences in its clinical expression. Other series, however, failed to elicit such differences. We aimed to describe in this retrospective survey the frequency, nature and relationship to systemic disease of the neurological features in a cohort of BD patients of Caucasian origin. We searched hospital records from nine District General or Regional Centre hospitals in south‐west Great Britain and identified 22 individuals of Caucasian ethnic origin with neuro‐BD, with a mean of 10 years follow‐up per patient – the largest ‘western’ case series with the longest period of follow‐up reported. We found that presentation with neurological features was commoner in our patients (23%) than Middle Eastern series (3–10%). Seizures (27%) were likewise commoner (0–5%), as was optic neuritis (9% compared with 1–2%). Two patients developed movement disorders (chorea and parkinsonism), which have only been rarely reported. Of further clinical significance, we noted that non‐neuropsychiatric features: oral ulceration, intraocular inflammation and skin lesions – were virtually always present or exacerbated during neurological complications. Ethnicity – or conceivably environment – may play a significant role in the manifestation of neurological BD.
CB1‐independent inhibition of dopamine transporter activity by cannabinoids in mouse dorsal striatum
Authors: Price David A. , Owens William A. , Gould Georgianna G. , Frazer Alan , Roberts James L. , Daws Lynette C. , Giuffrida Andrea
Published: January 2007

Cannabinoid drugs are known to affect dopaminergic neurotransmission in the basal ganglia circuitry. In this study, we usedin vitroandin vivotechniques to investigate whether cannabinoid agonists and antagonist could affect dopaminergic transmission in the striatum by acting at the dopamine transporter. Incubation of striatal synaptosomes with the cannabinoid agonists WIN55,212‐2 or methanandamide decreased dopamine uptake (IC50 = 2.0 μmol/L and 3.1 μmol/L, respectively). A similar inhibitory effect was observed after application of the inactive WIN55,212‐2 isomer, S(−)WIN55,212‐3. The CB1antagonist AM251 did not reverse WIN55,212‐2 effect but rather mimicked it. WIN55,212‐2 and AM251 partially displaced the binding of the cocaine analog [3H]WIN35,428, thus acting as dopamine transporter pseudo‐substrates in the high micromolar range. High‐speed chronoamperometry measurements showed that WIN55,212‐2 (4 mg/kg, i.p.) caused significant release of endogenous dopamineviaactivation of CB1receptors, followed by a reduction of dopamine clearance. This reduction was CB1‐independent, as it was mimicked by S(−)WIN55,212‐3. Administration of AM251 (1 and 4 mg/kg, i.p.) increased the signal amplitude and reduced the clearance of dopamine pressure ejected into the striatum. These results indicate that both cannabinoid agonists and antagonists inhibit dopamine transporter activityviamolecular targets other than CB1receptors.
Characterization of 12 new microsatellite loci in Aenictus and Neivamyrmex army ants
Authors: KRONAUER DANIEL J. C. , GADAU JÜRGEN , BOOMSMA JACOBUS J.
Published: January 2007

Here we describe 12 polymorphic microsatellite loci that were cloned and characterized for three species of army ants: the North American Neivamyrmex nigrescens, and the Asian Aenictus laeviceps and Aenictus dentatus. Observed and expected heterozygosities ranged from 0.37 to 0.97 (mean 0.70), and from 0.48 to 0.95 (mean 0.72), respectively. We observed 2–30 (mean 12) alleles per locus. These new genetic markers will be useful for studies of overall population structure and the complex pedigrees in colonies of army ants.
Thrombin peptide Chrysalin® stimulates healing of diabetic foot ulcers in a placebo‐controlled phase I/II study
Authors: Fife Caroline , Mader Jon T. , Stone Jeffery , Brill Leon , Satterfield Kathleen , Norfleet Andrea , Zwernemann Amber , Ryaby James T. , Carney Darrell H.
Published: January 2007

Thrombin and thrombin peptides play a role in initiating tissue repair. The potential safety and efficacy of TP508 (Chrysalin®) treatment of diabetic foot ulcers was evaluated in a 60‐subject, prospective, randomized, double‐blind, placebo‐controlled phase I/II clinical trial. Chrysalin® in saline or saline alone was applied topically, twice weekly, to diabetic ulcers with standardized care and offloading. A dose‐dependent effect was seen in the per‐protocol population where 1 and 10 μg Chrysalin® treatment resulted in 45 and 72% more subjects with complete healing than placebo treatment. Chrysalin® treatment of foot ulcers more than doubled the incidence of complete healing (p<0.05), increased mean closure rate ∼80% (p<0.05), and decreased the median time to 100% closure by ∼40% (p<0.05). Chrysalin® treatment of heel ulcers within this population resulted in mean closure rates 165% higher than placebos (p<0.02) and complete healing in 86% (6/7) of ulcers compared with 0% (0/5) of placebo ulcers (p<0.03). Local wound reactions and adverse events (AEs) were equal between groups with no reported drug‐related changes in laboratory tests or serious AEs. These results indicate the potential safety and efficacy of Chrysalin® for treatment of diabetic foot ulcers.
Collagenase‐2 (MMP‐8) and matrilysin‐2 (MMP‐26) expression in human wounds of different etiologies
Authors: Pirilä Emma , Korpi Jarkko T , Korkiamäki Timo , Jahkola Tiina , Gutierrez‐Fernandez Ana , Lopez‐Otin Carlos , Saarialho‐Kere Ulpu , Salo Tuula , Sorsa Timo
Published: January 2007

Wound healing involves highly controlled events including reepithelialization, neoangiogenesis, and reformation of the stromal compartment. Matrix metalloproteinases (MMPs) are a family of neutral zinc‐dependent endopeptidases known to be essential for the wound‐healing process. MMP‐8 (collagenase‐2) is a neutrophil‐derived highly effective type I collagenase, recently indicated to be important for acute wound healing. MMP‐26 is a more recent and less well‐studied member of the MMP family. Our aim was to study the expression of MMP‐8 and MMP‐26 in human cutaneous wound repair and chronic wounds using histological methods and cell culture. MMP‐8 expression was associated with epithelial cells, neutrophils, and other inflammatory cells in chronic human wounds. MMP‐26 was prominently expressed in the extracellular compartment of most chronic wounds in close vicinity to the basement membrane area. MMP‐26 was also expressed in acute day 1 wounds with declining expression thereafter. In vitro wound experiments showed that both MMP‐8 and MMP‐26 were expressed by migrating human mucosal keratinocytes. Inhibiting MMP‐26 resulted in aberrant keratinocyte migration and proliferation. We conclude that MMP‐8 and MMP‐26 are differentially expressed in acute and chronic wounds.
A comparative study of the cytotoxicity of silver‐based dressings in monolayer cell, tissue explant, and animal models
Authors: Burd Andrew , Kwok Chi H , Hung Siu C , Chan Hui S , Gu Hua , Lam Wai K , Huang Lin
Published: January 2007

Over the past decade, a variety of advanced silver‐based dressings have been developed. There are considerable variations in the structure, composition, and silver content of these new preparations. In the present study, we examined five commercially available silver‐based dressings (Acticoat™, Aquacel® Ag, Contreet® Foam, PolyMem® Silver, Urgotul®SSD). We assessed their cytotoxicity in a monolayer cell culture, a tissue explant culture model, and a mouse excisional wound model. The results showed that Acticoat™, Aquacel® Ag, and Contreet® Foam, when pretreated with specific solutes, were likely to produce the most significant cytotoxic effects on both cultured keratinocytes and fibroblasts, while PolyMem® Silver and Urgotul®SSD demonstrated the least cytotoxicity. The cytotoxicity correlated with the silver released from the dressings as measured by silver concentration in the culture medium. In the tissue explant culture model, in which the epidermal cell proliferation was evaluated, all silver dressings resulted in a significant delay of reepithelialization. In the mouse excisional wound model, Acticoat™ and Contreet® Foam indicated a strong inhibition of wound reepithelialization on the postwounding‐day 7. These findings may, in part, explain the clinical observations of delayed wound healing or inhibition of wound epithelialization after the use of certain topical silver dressings. Caution should be exercised in using silver‐based dressings in clean superficial wounds such as donor sites and superficial burns and also when cultured cells are being applied to wounds.
Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)‐β1–induced collagen synthesis
Authors: Sandulache Vlad C. , Parekh Aron , Li‐Korotky HaSheng , Dohar Joseph E. , Hebda Patricia A.
Published: January 2007

Keloid formation has been linked to aberrant fibroblast activity, exacerbated by growth factors and inflammatory mediators. Prostaglandin E2 (PGE2), synthesized from arachidonic acid by cyclooxygenases (COX) and synthases (PGES), acts as both an inflammatory mediator and fibroblast modulator. Although PGE2 has known antifibrotic effects in the lower airway, its role in dermal fibrosis in general, and keloid formation in particular, remains unclear. This study focused on: (1) the effects of PGE2 on keloid fibroblast migration, contraction, and collagen synthesis and (2) endogenous PGE2 synthesis in response interleukin‐1β. PGE2 decreased keloid fibroblast migration and contraction via an EP2/EP4–cAMP mechanism that disrupted actin cytoskeletal dynamics and reversed transforming growth factor‐β1–induced collagen I and III synthesis. Impaired fibroblast PGE2 production has been linked to lower airway fibrosis and recently to keloid formation. Here, we showed that interleukin‐1β stimulation leads to nuclear factor‐κB translocation to the nucleus, resulting in up‐regulation of COX‐2 and microsomal PGE2 synthase 1. Up‐regulation of COX‐2 in, and secretion of PGE2 by keloid fibroblasts are diminished compared with their normal fibroblast counterparts. We suggest that the antifibrotic effects of PGE2 during keloid formation are potentially diminished due to aberrant paracrine fibroblast signaling. Exogenous PGE2 may supplement decreased endogenous levels and inhibit keloid formation or progression.
In Heavy Drinkers, Fatty Acid Ethyl Esters Remain Elevated for Up to 99 Hours
Authors: Borucki K. , Dierkes J. , Wartberg J. , Westphal S. , Genz A. , Luley C.
Published: January 2007

Background: Both medical and forensic needs require reliable detection of earlier ethanol intake after the disappearance of ethanol from blood. The esters of ethanol with free fatty acids (FAEEs) are candidate markers of this kind. However, it is unknown whether FAEEs can serve as a marker for a single prior ethanol intake. In addition, the period for which FAEEs are elevated is unknown. Therefore, we measured FAEEs in heavy drinkers admitted to detoxification, and in healthy subjects after a drinking experiment.

Methods: Blood from 30 heavy drinkers was obtained for up to 5 days during a detoxification period in a psychiatric hospital. In addition, 17 healthy subjects who participated in a drinking experiment and who were abstinent thereafter gave blood during a similar time period for analysis of FAEEs. Fatty acid ethyl esters were measured by gas chromatography–mass spectroscopy.

Results: Heavy drinkers had much higher ethanol and FAEEs concentrations than healthy subjects; however, in both groups, FAEEs decreased rapidly during the first day. Only in heavy drinkers, elevated concentrations of FAEEs were observed at days 2 to 4. Concentrations of FAEEs were not associated with serum triglycerides or patients' body mass index.

Conclusions: It is concluded that kinetics of FAEEs are different in heavy drinkers compared with healthy subjects and that FAEEs are of limited value for the detection of prior single ethanol intake.
Alcohol Screening Scores and Risk of Hospitalizations for GI Conditions in Men
Authors: Au David H. , Kivlahan Daniel R. , Bryson Chris L. , Blough David , Bradley Katharine A.
Published: January 2007

Background: Alcohol misuse is a common cause of liver disease, upper gastrointestinal (GI) bleeding, and pancreatitis, but it is not known whether alcohol screening questionnaires can identify patients at increased risk for hospitalizations due to these conditions.

Objective: To evaluate the association of alcohol screening scores with the risk of subsequent hospitalization for alcohol‐related GI conditions.

Design: Retrospective cohort study.

Participants: Male general medicine outpatients from 7 Veterans Affairs (VA) medical centers who returned mailed questionnaires.

Measurements: The CAGE questionnaire (0–4 points) and the Alcohol Use Disorders Identification Test‐Consumption questions (AUDIT‐C; 0–12 points) were included on mailed surveys. The main outcome, “GI hospitalization,” was a primary VA or Medicare discharge diagnosis indicating liver disease, upper GI bleeding, or pancreatitis.

Results: Among 31,311 patients followed, a median of 3.75 years, patients with CAGE scores ≥2 points or AUDIT‐C scores ≥6 points were at a significantly increased risk for GI hospitalizations. Adjusted hazard ratios (HRadj) ranged from 1.6 (95% CI 1.2–2.0) for CAGE score 2, to 1.7 (1.4–2.2) for CAGE 4, and from 1.4 (1.01–2.0) for AUDIT‐C scores from 6 to 7, to 2.7 (1.9–3.8) for AUDIT‐C scores from 10 to 12. Secondary analyses demonstrated that the association was the strongest among patients less than 50 years of age who reported drinking in the past year.

Conclusions: Brief alcohol screening questionnaires predict subsequent hospitalizations for alcohol‐related GI conditions.
A Joint Frailty Model for Survival and Gap Times Between Recurrent Events
Authors: Huang Xuelin , Liu Lei
Published: January 2007

SummaryTherapy for patients with a recurrent disease focuses on delaying disease recurrence and prolonging survival. A common analysis approach for such data is to estimate the distribution of disease‐free survival, that is, the time to the first disease recurrence or death, whichever happens first. However, treating death similarly as disease recurrence may give misleading results. Also considering only the first recurrence and ignoring subsequent ones can result in loss of statistical power. We use a joint frailty model to simultaneously analyze disease recurrences and survival. Separate parameters for disease recurrence and survival are used in the joint model to distinguish treatment effects on these two types of events. The correlation between disease recurrences and survival is taken into account by a shared frailty. The effect of disease recurrence on survival can also be estimated by this model. The EM algorithm is used to fit the model, with Markov chain Monte Carlo simulations in the E‐steps. The method is evaluated by simulation studies and illustrated through a study of patients with heart failure. Sensitivity analysis for the parametric assumption of the frailty distribution is assessed by simulations.
On Models for Binomial Data with Random Numbers of Trials
Authors: Comulada W. Scott , Weiss Robert E.
Published: January 2007

SummaryA binomial outcome is a countsof the number of successes out of the total number of independent trialsn=s+f, wherefis a count of the failures. Thenare random variables not fixed by design in many studies. Joint modeling of(s,f)can provide additional insight into the science and into the probability π of success that cannot be directly incorporated by the logistic regression model. Observations wheren= 0are excluded from the binomial analysis yet may be important to understanding how π is influenced by covariates. Correlation betweensandfmay exist and be of direct interest. We propose Bayesian multivariate Poisson models for the bivariate response(s,f), correlated through random effects. We extend our models to the analysis of longitudinal and multivariate longitudinal binomial outcomes. Our methodology was motivated by two disparate examples, one from teratology and one from an HIV tertiary intervention study.
Applications of Additive Semivarying Coefficient Models: Monthly Suicide Data from Hong Kong
Authors: Huggins Richard M. , Hall Peter , Yip Paul S. F. , Bui Quang M.
Published: January 2007

Summary A semivarying coefficient model for the monthly numbers of suicides in Hong Kong is developed and a new estimation procedure for estimating the parametric component is proposed. The estimators are examined in a small simulation study and fitted to monthly suicide data to estimate a nonparametric long‐term trend and parametric seasonal and socioeconomic effects. Fitting the model detected interpretable structure in the data that is consistent with that driving public health policy. While exploratory, the analysis motivates the collection of more detailed data and the development of more sophisticated models to help determine target groups and strategies to reduce the suicide rate in Hong Kong.
Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies
Authors: Maertens Johan
Published: January 2007

Objective: Patients with hematologic malignancies are at substantial risk of developing invasive fungal infections (IFI) that are associated with substantial morbidity and mortality. This article reviews the epidemiology, risk factors, and efficacy of antifungal prophylaxis in patients with hematologic malignancies. Methods: A PubMed search was conducted to identify relevant studies with special emphasis on meta‐analyses and direct comparisons between antifungal agents. Results: The epidemiology of IFI has changed substantially in recent years with Candida albicans becoming less common owing to the widespread prophylactic use of azole antifungals. Invasive aspergillosis, fusariosis, and zygomycosis have increased in frequency. This change is at least partly related to the use of broad‐spectrum antifungal agents, either as prophylaxis or as empirical treatment. Other risk factors for IFI include prior fungal exposure, immunosuppression, underlying disease, graft‐vs.‐host disease, and organ dysfunction. Inconsistent results have been reported in studies evaluating the efficacy of antifungal prophylaxis in patients at risk of IFI. Meta‐analyses found that antifungals, such as fluconazole and itraconazole, are effective in decreasing IFI and IFI‐related mortality, primarily owing to yeast infections in patients with more severe immunosuppression (i.e. patients undergoing bone marrow transplantation), but do not decrease the overall mortality. The European Conference on Infections in Leukemia (ECIL) guidelines currently recommend fluconazole (AI, ie. strongly recommended, based on at least 1 well‐executed, randomized trial) and itraconazole (BI, ie. generally recommended, based on at least 1 well‐executed, randomized trial) in allogeneic transplant recipients. Posaconazole, a triazole antifungal, has been recently shown to decrease IFI incidence and overall mortality in some high‐risk patients compared with standard azoles. Based on preliminary data, a provisional AI ECIL recommendation has been given. Conclusions: Because of the substantial morbidity and mortality associated with IFI, there is a need to accurately define patient groups at greatest risk of IFI and, when appropriate, to initiate effective antifungal prophylaxis.
Fracture Strength of Endodontically Treated Teeth with Flared Root Canals and Restored with Different Post Systems
Authors: Maccari Paulo César , Cosme Dúcia caldas , Oshima Hugo Mitsuo , Burnett Luiz Henrique , Shinkai Rosemary Sadami
Published: January 2007

Background:  Many post systems are available to clinicians, yet no consensus exists about which one is better in restoring endodontically treated teeth.

Purpose:  This study evaluated the fracture strength of teeth with flared canals and restored with two fiber‐reinforced resin systems (glass fiber: FRC Postec [Ivoclar Vivadent, Schaan, Liechtenstein]; quartz fiber: D.T. Light‐Post [Bisco Dental Products, Schaumburg, IL, USA]), and one custom cast base metal (Ni‐Cr) post and core system.

Methods:  Thirty anterior teeth had their crowns removed below the cemento‐enamel junction and were endodontically treated. The canals were prepared for post fixation, and the canal walls were flared using a taper diamond bur. The prepared roots were randomly divided into three groups according to the post system. All posts were cemented with an adhesive resin cement. For the fiber‐reinforced resin posts, cores were built up using microhybrid composite. Metallic crowns were luted using zinc phosphate cement. Specimens were loaded at 45 degrees in a universal testing machine at a crosshead speed of 0.5 mm/min until failure. The mode of failure was classified as repairable or nonrepairable.

Results:  Teeth restored with cast posts had fracture strength twice that of teeth restored with resin posts. Fiber‐reinforced resin posts failed at a compressive force comparable to clinical conditions, but all failures were repairable.

Conclusion:  Fracture strength and mode of failure in anterior teeth with flared canals varied according to the type of post used to support a crown.

CLINICAL SIGNIFICANCE

Under the conditions of this study, cast posts are preferable to restore endodontically treated teeth with flared canals and no ferrule.
A New Angelology: Mapping the Angel through Twentieth‐Century Literature
Authors: Hobson Suzanne
Published: January 2007

In ‘Professions for Women’, Virginia Woolf memorably calls on female writers to kill the ‘Angel in the House’. She implies that the angel, traditionally connoting feminine virtue and chastity, has no place in twentieth‐century literature. The literary texts and theoretical debates surveyed in this article suggest rather the opposite. They reveal that instead of being left behind at the end of the nineteenth century by a cultural imaginary which had outgrown religious orthodoxy and Victorian moral codes, the angel was reinvented, in a sense, modernised for the twentieth century. This article looks first at the importance of Walter Benjamin in carving out a politically charged space for this figure in contemporary literary criticism. It then turns to the angels in texts by Djuna Barnes, H.D., Carolyn Forché, Tony Kushner, D. H. Lawrence, Wyndham Lewis, Salman Rushdie and W. G. Sebald among others to show how the angel comes to figure the ‘new’– both the technologically advanced and the unexpectedly ‘avant‐garde’ as regards moral values and sexual propriety.
Women's Patronage‐Seeking as Familial Enterprise: Aemilia Lanyer, Esther Inglis, and Mary Wroth1
Authors: Kemp Theresa D.
Published: January 2007

Taking Aemilia Lanyer, Esther Inglis, and Mary Wroth as its primary examples, this article looks at how early modern women writers in Britain used the literary patronage system to promote not only personal ambitions but familial ones as well.
The C3–C4 propriospinal system in the cat and monkey: a spinal pre‐motoneuronal centre for voluntary motor control
Authors: Alstermark B. , Isa T. , Pettersson L.‐G. , Sasaki S.
Published: January 2007

This review deals with a spinal interneuronal system, denoted the C3–C4 propriospinal system, which is unique in the sense that it so far represents the only spinal interneuronal system for which it has been possible to demonstrate a command mediating role for voluntary movements. The C3–C4 propriospinal neurones govern target reaching and can update the descending cortical command when a fast correction is required of the movement trajectory and also integrate signals generated from the forelimb to control deceleration and termination of reaching.
The Rise of the Academies: Continuity or Change?
Authors: Tolley Kim
Published: January 2007

In his book, The Age of the Academies, Theodore R. Sizer argued that academies represented a significant break from the relatively narrow schooling that had been previously available to students in the early Latin grammar schools. In his view, the proliferation of academies heralded a new age in education, one more reflective of the Enlightenment values promoted by such Republican leaders as Benjamin Franklin, Thomas Jefferson, or Benjamin Rush. After thirty-five years of additional scholarship on academies, does Sizer's thesis still stand? This essay investigates the range of educational institutions that provided some form of advanced schooling to Americans just preceding and concurrent with the founding of the earliest academies. It examines the differences and similarities among a number of northern and southern early nineteenth-century schools in order to address the following question: to what extent did schools calling themselves academies represent a distinctly new turn in the history of American education? By clarifying the relations between the various types of institutions during the post-colonial period, I conclude that the historical significance of the early academy movement is broader than the intellectual or curricular reform discussed by Sizer.
Mission Matters: Mount Holyoke, Oberlin, and the Schooling of Southern Blacks, 1861–1917
Authors: Butchart Ronald E.
Published: January 2007

At the end of her spring term in 1862, Martha Hale Clary bade farewell to her classmates at Mount Holyoke Female Seminary one year before she was to graduate. She was a 24 year-old teacher, the daughter of a farming family from Conway, Massachusetts, who had graduated from Westfield State Normal School five years earlier. By the autumn of 1862, she was living in an abandoned plantation house in Beaufort, South Carolina, organizing a school for the Gullah people not many miles from Confederate lines, one of the earliest participants in the Sea Islands’ “Rehearsal for Reconstruction.” For the next eleven years she taught scores of the islands’ freed slaves in Beaufort and Hilton Head, one of the hundreds of teachers sponsored by the venerable American Missionary Association (AMA). By the early 1870s, young former slaves had themselves gained sufficient education to become their people's elementary teachers, so in 1873 Martha Clary accepted a position with the Presbyterian Committee on Missions to the Freedmen to teach in its academy for black students in North Carolina, Scotia Seminary. She would remain there for another fourteen years, finally retiring to her native state in 1887 after twenty-five years of service to southern African Americans.
Educating Youth in America's Wartime Detention Camps
Authors: Daniels Roger
Published: January 2007

Pupil for pupil, more has been written about Japanese American students than about those of any other ethnic group in America. They enter into our historical consciousness with the abortive attempt of the San Francisco School Board to segregate Japanese American students in 1906–07 which led to the Gentlemen's Agreement of 1907–08 between the United States and Japan. As Henry Yu has recently reminded us, scholars were fascinated by the achievements of “oriental” students in American schools in the 1920s. Sociologists and educational psychologists, especially at Stanford University and the University of Chicago and often in conjunction with the Institute of Pacific Relations and/or Robert E. Park's Survey of Race Relations, produced a substantial corpus of work that focused on second-generation Asian Americans and stressed such things as test scores and life course studies. Conceived as studies in Americanization they almost totally ignored the community-run language schools: the lack of sophisticated studies examining these schools remains one of major gaps in the historiography of ethnic education in America.
The Displacement of Black Educators Post-Brown: An Overview and Analysis
Authors: Fultz Michael
Published: January 2007

In 1951 three brief commentaries in the Journal of Negro Education drew public attention to the potentially tenuous job security of African-American educators in the South, Black professionals whose employment status was being called into question as southern educational institutions faced the prospect of desegregation. The specific incident which occasioned these commentaries was a December 1950 vote by the Board of Trustees of the University of Louisville to close the segregated, all-Black Louisville Municipal College, which it had administered since that college was founded in 1931, and to integrate the two institutions' student bodies. Fourteen African-American faculty and staff at Louisville Municipal College were informed that, despite tenure or contract status, they would be given two months' severance pay and summarily dismissed. With United States Supreme Court legal precedents from the 1938 Gaines case through the 1950 Sweatt and McLauren decisions already dramatically affecting the policy context of southern higher education, and with what would become known as the “Brown Decision” looming on the horizon, what might be the consequences for all Black educators throughout the South—if the high court overturned the 1896 Plessy v. Ferguson decision as National Association for the Advancement of Colored People (NAACP) lawyers urged?
Playground Physics: Determining the Moment of Inertia of a Merry-Go-Round
Authors: Van Hook Stephen , Lark Adam , Hodges Jeff , Celebrezze Eric , Channels Lindsey
Published: January 2007

A playground can provide a valuable physics education laboratory. For example, Taylor et al.1 describe bringing teachers in a workshop to a playground to examine the physics of a seesaw and slide, and briefly suggest experiments involving a merry-go-round. In this paper, we describe an experiment performed by students from a Society of Physics Students organization and their faculty advisor on a merry-go-round at a local park. The goal of the activity was for everyone to gain a greater understanding of the concepts of angular velocity, centripetal acceleration, moment of inertia, and conservation of angular momentum through their own personal experience—and to have fun, too.
An Oscillating System with Sliding Friction
Authors: Kamela Martin
Published: January 2007

Both harmonic oscillations and friction are the types of concepts in freshman physics that are readily applicable to the “real world” and as such, most students find these ideas interesting. Damped oscillations are usually presented with resistance proportional to velocity, which has the advantage of a relatively straightforward mathematical solution. This type of resistance occurs for very slow moving bodies in fluid, although a more common resistive force in fluid is proportional to velocity squared.1 Thus, mechanical oscillations with damping proportional to velocity may be more useful in the freshman course as an analogy for the future study of LRC circuits.2 Whereas an oscillator with damping proportional to velocity has an exponential decay in amplitude, a system with sliding friction results in amplitude that decays in a linear manner.3 In this paper I present a demonstration of an oscillator with sliding friction that exhibits very good agreement with a linear fall off in amplitude. The demonstration also confirms that sliding friction is proportional to the magnitude of the normal force.
Growth Inhibition of
Toxoplasma gondii
and
Plasmodium falciparum
by Nanomolar Concentrations of 1-Hydroxy-2-Dodecyl-4(1
H
)Quinolone, a High-Affinity Inhibitor of Alternative (Type II) NADH Dehydrogenases
Authors: Saleh Ahmad , Friesen Johannes , Baumeister Stefan , Gross Uwe , Bohne Wolfgang
Published: January 2007

Both apicomplexan parasites
Toxoplasma gondii
and
Plasmodium falciparum
lack type I NADH dehydrogenases (complex I) but instead carry alternative (type II) NADH dehydrogenases, which are absent in mammalian cells and are thus considered promising antimicrobial drug targets. The quinolone-like compound 1-hydroxy-2-dodecyl-4(1
H
)quinolone (HDQ) was recently described as a high-affinity inhibitor of fungal alternative NADH dehydrogenases in enzymatic assays, probably by interfering with the ubiquinol binding site of the enzyme. We describe here that HDQ effectively inhibits the replication rates of
P. falciparum
and
T. gondii
in tissue culture. The 50% inhibitory concentration (IC
50
) of HDQ for
T. gondii
was determined to be 2.4 ± 0.3 nM with a growth assay based on vacuole sizes and 3.7 ± 1.4 nM with a growth assay based on beta-galactosidase activity. Quantification of the
P. falciparum
replication rate using a fluorometric assay revealed an IC
50
of 14.0 ± 1.9 nM. An important feature of the HDQ structure is the length of the alkyl side chain at position 2. Derivatives with alkyl side chains of C
6
, C
8
, C
12
(HDQ), and C
14
all displayed excellent anti-
T. gondii
activity, while a C
5
derivative completely failed to inhibit parasite replication. A combined treatment of
T. gondii
-infected cells with HDQ and the antimalarial agent atovaquone, which blocks the ubiquinol oxidation site of cytochrome
b
in complex III, resulted in synergism, with a calculated fractional inhibitory concentration of 0.16 nM. Interference of the mitochondrial ubiquinone/ubiquinol cycle at two different locations thus appears to be a highly effective strategy for inhibiting parasite replication. HDQ and its derivatives, particularly in combination with atovaquone, represent promising compounds with a high potential for antimalarial and antitoxoplasmal therapy.
Metronidazole plus Rifampin Sterilizes Long-Term Dormant
Mycobacterium tuberculosis
Authors: Iona Elisabetta , Giannoni Federico , Pardini Manuela , Brunori Lara , Orefici Graziella , Fattorini Lanfranco
Published: January 2007

Long-term nonreplicating (dormant)
Mycobacterium tuberculosis
populations (26-day-old cells) were sterilized by metronidazole plus rifampin, but not by metronidazole or rifampin alone, after 7 and 11 days of exposure to the drugs. Lower or no drug activity was observed against 19- or 12-day-old dormant or 5-day-old actively replicating populations.
TRANSVERSE MOMENTUM DISTRIBUTION WITH RADIAL FLOW IN RELATIVISTIC DIFFUSION MODEL
Authors: SUZUKI N. , BIYAJIMA M.
Published: January 2007

Large transverse momentum distributions of identified particles observed at the Relativistic Heavy Ion Collider (RHIC) are analyzed by a relativistic stochastic model in the three dimensional (non-Euclidean) rapidity space. A distribution function obtained from the model is Gaussian-like in radial rapidity. It can well describe observed transverse momentum pT distributions. Estimation of radial flow is made from the analysis of pT distributions for [Formula: see text] in Au + Au Collisions. Temperatures are estimated from observed large pT distributions under the assumption that the distribution function approaches to the Maxwell–Boltzmann distribution in the lower momentum limit. The power-law behavior of large pT distribution is also derived from the model.
QUARK MODEL ESTIMATES OF THE STRUCTURE OF THE MESON-N-N*(1/2-) TRANSITION VERTICES
Authors: DILLIG M. , ROCHA S. S. , MARRANGHELLO G. F. , LÜTZ E. F. , VASCONCELLOS C. A. Z.
Published: January 2007

We address an actual problem of baryon-resonance dominated meson-exchange processes in the low GeV regime, i.e. the phase and the structure of meson-NN* transition vertices. Our starting point is a quark-diquark model for the baryons (obeying approximate covariance; the mesons are kept as elementary objects), together with the relative phases for the NN vertices, as determined from low energy NN scattering. From the explicit representation of the N and N* baryons, we exemplify the derivation of phases, coupling constants and form factors of the NN* (J = 1/2-) transition vertices for pseudo-scalar, scalar and vector mesons.
SOME COMPACTNESS RESULTS RELATED TO SCALAR CURVATURE DEFORMATION
Authors: YAN YU
Published: January 2007

Motivated by the prescribing scalar curvature problem, we study the equation [Formula: see text] on locally conformally flat manifolds (M,g) with R(g) ≡ 0. We prove that when K satisfies certain conditions and the dimension of M is 3 or 4, any positive solution u of this equation with bounded energy has uniform upper and lower bounds. Similar techniques can also be applied to prove that on four-dimensional locally conformally flat scalar positive manifolds the solutions of [Formula: see text] can only have simple blow-up points.
MatAlign: PRECISE PROTEIN STRUCTURE COMPARISON BY MATRIX ALIGNMENT
Authors: AUNG ZEYAR , TAN KIAN-LEE
Published: January 2007

We propose a detailed protein structure alignment method named "MatAlign". It is a two-step algorithm. Firstly, we represent 3D protein structures as 2D distance matrices, and align these matrices by means of dynamic programming in order to find the initially aligned residue pairs. Secondly, we refine the initial alignment iteratively into the optimal one according to an objective scoring function. We compare our method against DALI and CE, which are among the most accurate and the most widely used of the existing structural comparison tools. On the benchmark set of 68 protein structure pairs by Fischer et al., MatAlign provides better alignment results, according to four different criteria, than both DALI and CE in a majority of cases. MatAlign also performs as well in structural database search as DALI does, and much better than CE does. MatAlign is about two to three times faster than DALI, and has about the same speed as CE. The software and the supplementary information for this paper are available at . .
Clearance of Imidapril, an Angiotensin‐Converting Enzyme Inhibitor, During Hemodialysis in Hypertensive Renal Failure Patients: Comparison With Quinapril and Enalapril
Authors: Tsuruoka Shuichi , Kitoh Yasuhiko , Kawaguchi Atsuhiro , Sugimoto Koh‐ichi , Hayasaka Tokie , Saito Tetsuo , Fujimura Akio
Published: January 2007

The dialyzability of imidaprilat, an active metabolite of the angiotensin‐converting enzyme (ACE) inhibitor imidapril, was determined and compared with those of enalaprilat and quinaprilat in hypertensive patients on chronic hemodialysis. Imidapril (5 mg/d, n = 6), enalapril (2.5 mg/d, n = 6), or quinapril (2.5 mg/d, n = 6) was given for at least 8 weeks prior to the trial. During dialysis, enalaprilat, but not imidaprilat or quinaprilat, concentrations in both sides decreased significantly. Compared to enalaprilat, the dialyzabilities of imidaprilat and quinaprilat were significantly lower (dialyzer clearance [mL/min/m2]: enalaprilat, 41.8 ± 7.4; imidaprilat, 19.0 ± 7.8; quinaprilat, 8.9 ± 1.3). The dialyzabilities of the 3 drugs were negatively correlated with their respective protein‐binding rates. During hemodialysis, blood pressure did not change significantly in any group. These results suggest that imidapril provides good blood pressure control without a large fluctuation of drug concentration in hypertensive patients undergoing chronic hemodialysis.
NXY‐059 Does Not Affect Bleeding Time in Healthy Volunteers: A Randomized, Double‐Blind, Placebo‐Controlled, 3‐Period Crossover Phase I Study
Authors: Nilsson Dag , Wemer Johan , Cheng Yi‐Fang , Reinholdsson Ingalill , Englund Gunnar , Egberg Nils , Schulman Sam
Published: January 2007

NXY‐059 is a novel free radical–trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale. Any effect of NXY‐059 on hemostasis may be important when treating stroke patients. This phase I randomized, double‐blind, placebo‐controlled, 3‐period crossover study compared the effect of NXY‐059, desmopressin, and placebo on bleeding time, platelet aggregation, and adhesion in 30 healthy volunteers. NXY‐059 did not prolong bleeding time compared with placebo: mean (SD) time for NXY‐059, 369.5 seconds (125.0 seconds) versus placebo, 369.1 seconds (136.0 seconds). There were no significant effects on platelet aggregation or adhesion. At a mean unbound plasma concentration (Cuss) of 335 μmol/L, NXY‐059 was well tolerated, with no major safety concerns identified. In conclusion, NXY‐059 does not appear to affect primary hemostasis.