bluuebunny/crossref_metadata_2025 huggingface dataset:
Free radical biology and medicine: it's a gas, man!
Authors: Pryor William A. , Houk Kendall N. , Foote Christopher S. , Fukuto Jon M. , Ignarro Louis J. , Squadrito Giuseppe L. , Davies Kelvin J. A.
Published: April 2006

We review gases that can affect oxidative stress and that themselves may be radicals. We discuss O2toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen (3O2), and the more energetic, reactive singlet oxygen (1O2). Nitric oxide (·NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant,·NO and related species have other functions. Other endogenously produced gases include carbon monoxide (CO), carbon dioxide (CO2), and hydrogen sulfide (H2S). Like·NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (CO3·−) react selectively at moderate rates with nonradicals, but react fast with a second radical. These reactions establish “cross talk” between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitrolipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance.
Attenuation of homeostatic responses to hypotension and glucoprivation after destruction of catecholaminergic rostral ventrolateral medulla neurons
Authors: Madden Christopher J. , Stocker Sean D. , Sved Alan F.
Published: April 2006

This study determined the effect of destruction of rostral ventrolateral medulla (RVLM)-C1 cells on integrated sympathetic and hormonal responses to hypotension or glucoprivation. Injection of anti-dopamine β-hydroxylase-saporin into the RVLM resulted in 29–99% depletion of RVLM-C1 neurons and ∼60% reduction in the number of A5 neurons. As in our previous study in unanesthetized rats, resting mean arterial pressure (MAP) was reduced by ∼10 mmHg in rats with >80% depletion of RVLM-C1 cells compared with control rats, although resting heart rate (HR) did not differ significantly. In the present study, resting plasma levels of norepinephrine (NE) did not differ significantly between control rats and rats with >80% depletion of RVLM-C1 cells, although there was a tendency for RVLM-C1 lesioned rats to have lower levels. Also consistent with our previous study, hydralazine (HDZ)-evoked hypotension resulted in smaller increases in HR and plasma levels of NE in rats with >80% depletion of RVLM-C1 cells compared with control rats. Furthermore, the elevated plasma levels of posterior pituitary hormones vasopressin and oxytocin evoked by HDZ were blunted in RVLM-C1 lesioned rats compared with control rats, even though MAP fell to lower levels in the lesioned rats. Plasma renin activity, plasma osmolality, and plasma protein concentrations did not differ between control rats and rats with >80% depletion of RVLM-C1 neurons. In response to systemic administration of 2-deoxyglucose, the circulating level of epinephrine and the resulting hyperglycemia were attenuated in rats with >80% depletion of RVLM-C1 cells compared with control rats. These results demonstrate that RVLM-C1 cells, in addition to playing a role in acute cardiovascular reflexes, play an important role in integrated sympathetic and hormonal responses to homeostatic challenges such as hypotension and glucoprivation.
Wide-pulse-width, high-frequency neuromuscular stimulation: implications for functional electrical stimulation
Authors: Baldwin Evan R. L. , Klakowicz Piotr M. , Collins David F.
Published: April 2006

Electrical stimulation (1-ms pulses, 100 Hz) produces more torque than expected from motor axon activation (extra contractions). This experiment investigates the most effective method of delivering this stimulation for neuromuscular electrical stimulation. Surface stimulation (1-ms pulses; 20 Hz for 2 s, 100 Hz for 2 s, 20 Hz for 3 s) was delivered to triceps surae and wrist flexors (muscle stimulation) and to median and tibial nerves (nerve stimulation) at two intensities. Contractions were evaluated for amplitude, consistency, and stability. Surface electromyograph was collected to assess how H-reflexes and M-waves contribute. In the triceps surae, muscle stimulation produced the largest absolute contractions (23% maximal voluntary contraction), evoked the largest extra contractions as torque increased by 412% after the 100-Hz stimulation, and was more consistent and stable compared with tibial nerve stimulation. Absolute and extra contraction amplitude, consistency, and stability of evoked wrist flexor torques were similar between stimulation types: torques reached 11% maximal voluntary contraction, and extra contractions increased torque by 161%. Extra contractions were 10 times larger in plantar flexors compared with wrist flexors with muscle stimulation but were similar with nerve stimulation. For triceps surae, H reflexes were 3.4 times larger than M waves during nerve stimulation, yet M waves were 15 times larger than H reflexes during muscle stimulation. M waves in the wrist flexors were larger than H reflexes during nerve (8.5 times) and muscle (18.5 times) stimulation. This is an initial step toward utilizing extra contractions for neuromuscular electrical stimulation and the first to demonstrate their presence in the wrist flexors.
Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigs
Authors: Gatti Raffaele , Andre Eunice , Amadesi Silvia , Dinh Thai Q. , Fischer Axel , Bunnett Nigel W. , Harrison Selena , Geppetti Pierangelo , Trevisani Marcello
Published: April 2006

A lowered threshold to the cough response frequently accompanies chronic airway inflammatory conditions. However, the mechanism(s) that from chronic inflammation results in a lowered cough threshold is poorly understood. Irritant agents, including capsaicin, resiniferatoxin, and citric acid, elicit cough in humans and in experimental animals through the activation of the transient receptor potential vanilloid 1 (TRPV1). Protease-activated receptor-2 (PAR2) activation plays a role in inflammation and sensitizes TRPV1 in cultured sensory neurons by a PKC-dependent pathway. Here, we have investigated whether PAR2 activation exaggerates TRPV1-dependent cough in guinea pigs and whether protein kinases are involved in the PAR2-induced cough modulation. Aerosolized PAR2 agonists (PAR2-activating peptide and trypsin) did not produce any cough per se. However, they potentiated citric acid- and resiniferatoxin-induced cough, an effect that was completely prevented by the TRPV1 receptor antagonist capsazepine. In contrast, cough induced by hypertonic saline, a stimulus that provokes cough in a TRPV1-independent manner, was not modified by aerosolized PAR2 agonists. The PKC inhibitor GF-109203X, the PKA inhibitor H-89, and the cyclooxygenase inhibitor indomethacin did not affect cough induced by TRPV1 agonists, but abated the exaggeration of this response produced by PAR2 agonists. In conclusion, PAR2 stimulation exaggerates TRPV1-dependent cough by activation of diverse mechanism(s), including PKC, PKA, and prostanoid release. PAR2 activation, by sensitizing TRPV1 in primary sensory neurons, may play a role in the exaggerated cough observed in certain airways inflammatory diseases such as asthma and chronic obstructive pulmonary disease.
Third Ventricular Colloid Cysts in Children
Authors: Maqsood Ahmed A.R. , Devi Indira B. , Mohanty A. , Chandramouli B.A. , Sastry Kolluri V.R.
Published: April 2006

Introduction: Colloid cysts of the 3rd ventricle are relatively rare intracranial tumours, more so in children. They are benign tumours with excellent prognosis if diagnosed and treated early. Methods: A retrospective analysis of 18 cases of colloid cysts in children below 18 years, operated in our institution between September 1998 and November 2003 (5 years) was made. Clinical presentation, radiological findings, surgical approaches and outcome were analysed. Results: Age ranged from 7 to 18 years. The male-to-female ratio was 12:6. Headache and vomiting were the most common symptoms. Papilloedema was the most common clinical sign. Pre-operative CT showed a hyperdense non-enhancing lesion in the majority. Twelve patients underwent a transcallosal, 2 a transcortical and 4 an endoscopic approach. Ventriculoperitoneal shunts were done in 5 patients. Postoperatively 2 patients developed epidural haemorrhage which required evacuation. One patient was re-explored for symptomatic residue. A mean follow-up of 10.2 months was available in 9 patients; the majority were asymptomatic. Conclusion: Colloid cysts though rare are increasingly detected in children. Their early recognition and treatment give excellent results.
CSF Shunt Failure with Stable Normal Ventricular Size
Authors: Winston Ken R. , Lopez John A. , Freeman Jane
Published: April 2006

Objective: The purpose of this study was to review the clinical features of a group of patients in whom ventricular enlargement was not a manifestation of prolonged CSF shunt obstruction. Results: Twelve patients who had prolonged symptoms consistent with CSF shunt failure and stable normal ventricular size were demonstrated at the time of surgery to have obstruction of their CSF shunts. Conclusion: Ventricular enlargement is a common but not sine qua non indicator of CSF shunt failure, even after weeks or months of elevated intracranial pressure, and therefore cannot be relied upon for the diagnosis of CSF shunt failure. Although an increase in ventricular size is usually seen relatively early in the course of shunt malfunction, stable normal ventricular size in patients with symptoms and signs that are consistent with shunt failure can delay the diagnosis with potentially serious adverse consequences.
Residual or Recurrent Cerebellar Low-Grade Glioma in Children after Tumor Resection: Is Re-Treatment Needed? A Single Center Experience from 1983 to 2003
Authors: Benesch Martin , Eder Hans-Georg , Sovinz Petra , Raith Johann , Lackner Herwig , Moser Andrea , Urban Christian
Published: April 2006

Purpose:The aim of this study was to report on children with cerebellar low-grade glioma (LGG), who were found to have progressive or nonprogresssive residual tumors or tumor recurrence after tumor resection. Patients and Methods: Medical records and magnetic resonance imaging (MRI) studies of children (<16 years) with cerebellar LGG were retrospectively analyzed. Results: Of 289 patients with CNS tumors referred between 1983 and 2003, 28 (9.7%) (15 male, 13 female; median age at diagnosis: 71 months) had cerebellar LGG (pilocytic astrocytoma grade I: n = 21; fibrillary astrocytoma grade II: n = 5; mixed hamartoma/pilocytic astrocytoma: n = 1; radiographic diagnosis: n = 1). Total resection was initially performed in 16 patients (57.1%), near total resection in 4 (14.3%), and partial resection in 6 patients (21.4%). One patient underwent biopsy. At a median follow-up of 112 months, 25 patients (89.3%) were alive, 18 of them being in complete remission. Three patients died, 2 due to symptoms related to brain stem compression/infiltration and 1 patient due to postoperative cerebral edema. Presently 5 patients have nonprogressive residual tumors and 2 patients developed nonprogressive recurrences 10 years and 20 months after initial total resection, respectively. None of them required second surgery and none received additional nonsurgical therapies. Only 1 additional patient had to undergo second surgery due to disease progression. Conclusions: A ‘wait and see’ strategy is justified in patients with nonprogressive recurrent or residual cerebellar LGG after primary tumor resection. However, long-term follow-up with repeated MRI is mandatory in these patients to detect disease progression. Second surgery is indicated only in patients with unequivocal disease progression, as documented by MRI.
Frontal Bone Agenesis in a Patient of Spinal Dysraphism
Authors: Nayak P.K. , Mahapatra A.K.
Published: April 2006

Associated cranial abnormalities with spinal dysraphism are not uncommon. We came across an unusual case of a 1-year-old male child with spinal dysraphism having lumbar meningomyelocele, who also had split cord malformation (hemicord with intervening bony spur) with lipoma of one of the hemicord and filum terminale. The patient also had communicating hydrocephalus without Chiari malformation and also near-total frontal bone agenesis. Single photon emission computed tomography scanning of brain revealed normal perfusion. In the first stage of repair, the patient had postoperative CSF leak for which ventriculo-peritoneal shunt was performed. This constitutes a rare anomaly associated with spinal dysraphism.
Atheroprotective Effects of Neuronal Nitric Oxide Synthase in Apolipoprotein E Knockout Mice
Authors: Kuhlencordt Peter J. , Hötten Stefanie , Schödel Johannes , Rützel Sebastian , Hu Kai , Widder Julian , Marx Alexander , Huang Paul L. , Ertl Georg
Published: April 2006

Objective—

All 3 isoforms of the nitric oxide synthase (NOS) are expressed in atherosclerotic lesions. To test whether neuronal NOS (nNOS) deficiency affects atherosclerosis, we studied apoE/nNOSα double knockout (DKO) and apolipoprotein E (apoE) knockout (KO) control mice.

Methods and Results—

Lesion area was significantly increased in male DKO (66%) mice after 14 weeks and in female DKO animals (31%) after 24 weeks of “western” diet. Moreover, mean arterial blood pressure was significantly reduced in female DKO animals. Immunohistochemistry revealed nNOS expression in the neointima of KO mice. In DKO animals, residual nNOS staining was caused by the presence of nNOS splice variants. Whereas nNOSα was present in vessels of KO and absent in DKO animals, nNOSγ was expressed in KO and DKO mice.

Conclusion—

nNOSα protects against atherosclerosis as nNOSα deletion leads to an increase in plaque formation in apoE/nNOSα DKO mice. Female DKO mice showed a significant reduction in mean arterial blood pressure. Additionally, we found expression of nNOS splice variants in vessels of apoE KO mice. Our data highlights nNOSα overexpression as a potential therapeutic strategy and naturally occurring splice variants that lack exon 2 of the nNOS gene as a potential risk factor for vascular disease.
Poststroke Rehabilitation
Authors: Deutsch Anne , Granger Carl V. , Heinemann Allen W. , Fiedler Roger C. , DeJong Gerben , Kane Robert L. , Ottenbacher Kenneth J. , Naughton John P. , Trevisan Maurizio
Published: April 2006

Background and Purpose—

To assess whether poststroke rehabilitation outcomes and reimbursement for Medicare beneficiaries differ across inpatient rehabilitation facilities (IRFs) and skilled nursing facility (SNF) subacute rehabilitation programs.

Methods—

Clinical data were linked with Medicare claims for 58 724 Medicare beneficiaries with a recent stroke who completed treatment in 1996 or 1997 in IRFs and subacute rehabilitation SNFs that subscribed to the Uniform Data System for Medical Rehabilitation. Outcome measures were discharge destination, discharge FIM ratings and Medicare Part A reimbursement during the institutional stay.

Results—

IRF patients that were more likely to have a community-based discharge, compared with rehabilitation SNF patients, were patients with mild motor disabilities and FIM cognitive ratings of 23 or greater (adjusted odds ratio [AOR]=2.19; 95% CI: 1.52 to 3.14), patients with moderate motor disabilities (AOR=1.98; 95% CI: 1.49 to 2.61), patients with significant motor disabilities (AOR=1.26; 95% CI: 1.01 to 1.57) and patients younger than 82 with severe motor disabilities (AOR=1.43; 95% CI: 1.25 to 1.64). IRF patients with significant and severe motor disabilities achieved greater motor function of 2 or more FIM units compared with rehabilitation SNF patients. Medicare Part A payments for IRFs were higher than rehabilitation SNF payments across all subgroups.

Conclusions—

For most patients, poststroke rehabilitation in the more costly and intensive IRFs resulted in higher functional outcomes compared with care in a SNF-based rehabilitation program. IRF and SNF outcomes were similar for patients with minimal motor disabilities and patients with mild motor disabilities and significant cognitive disabilities. Cost-effectiveness analyses require considering the costs of the full episode of care.
Recommendations of the National Heart, Lung, and Blood Institute Working Group on Cerebrovascular Biology and Disease
Authors: Iadecola Costantino , Goldman Stephen S. , Harder David R. , Heistad Donald D. , Katusic Zvonimir S. , Moskowitz Michael A. , Simard J. Marc , Sloan Michael A. , Traystman Richard J. , Velletri Paul A.
Published: April 2006

The National Heart, Lung, and Blood Institute (NHLBI) convened a conference call working group, consisting of experts in stroke and cerebrovascular biology on January 28, 2005. The purpose of this working group was to develop a prioritized set of recommendations for NHLBI to establish a focused and comprehensive set of research activities in cerebrovascular biology and disease. Three thematic areas of research emerged: (1) molecular and cellular neurobiology of cerebral blood vessels, focusing on genomics and proteomics, neurovascular signaling and cerebrovascular embryogenesis, development and plasticity; (2) resource development, involving the development of new methodological approaches for normal and altered function of the neurovascular unit, collaborative research, and training in cerebrovascular pathobiology; and (3) cerebrovascular diseases and translational approaches, addressing vascular mechanisms of disease, the role of risk factors, importance of biomarkers with the ultimate goal of developing new treatments.
The Role of Antiplatelet Therapy in Carotid Stenting for Ischemic Stroke Prevention
Authors: Chaturvedi Seemant , Yadav Jay S.
Published: April 2006

Background and Purpose—

Carotid angioplasty and stenting (CAS) is a minimally invasive revascularization procedure that has become a popular and acceptable treatment option in the United States for high surgical risk patients with internal carotid artery atherosclerosis. It is effective and has an acceptable risk profile, but ischemic complications caused by distal embolization and underlying atherothrombosis persist.

Summary of Review—

Atherothrombosis is the pathological process that is frequently implicated as the underlying cause of stroke, transient ischemic attacks, and most other ischemic vascular disease. Critical steps in the development of occlusive episodes are the disruption of atherosclerotic plaque and subsequent formation of a platelet-rich mural thrombus. Vascular injury as a result of CAS or any other percutaneous intervention triggers platelet adhesion, activation, and aggregation, resulting in the formation of a mural thrombosis. This risk, in addition to the potential risk of embolization to distal sites, provides a rationale for early antiplatelet therapy with CAS. The risk of late stent (>30 days after stenting) thrombosis in some patients, particularly those receiving drug-eluting stents, provides a rationale for prolonged antiplatelet prophylaxis as well as for prophylaxis against late atherothrombotic events. Because of the systemic and progressive nature of atherothrombosis, protection against ischemic vascular events in other arterial beds expands the benefits of long-term antiplatelet therapy.

Conclusions—

As clinical experience with CAS increases, it is likely that it will be used more frequently for patients with occlusive carotid disease. In addition, adjunct antiplatelet therapy will play a key role in the continued development of CAS.
Classic Intermittent Claudication Is an Uncommon Manifestation of Lower Extremity Peripheral Arterial Disease in Hospitalized Patients with Coronary Artery Disease
Authors: Dieter Robert S. , Biring Timinder , Tomasson Jon , Gudjonsson Thorbjorn , Brown Roger L. , Vitcenda Mark , Einerson Jean , Tanke Timothy E. , McBride Patrick E.
Published: April 2006

Synchronous peripheral arterial disease (PAD) and coronary artery disease (CAD) is common. Standardized questionnaires such as the Rose/WHO questionnaire and later the Edinburgh modification of this questionnaire were developed to screen for PAD. Little data are available on the sensitivity of these questionnaires in hospitalized patients with CAD. The aim of this study was to determine the accuracy of these questionnaires and the prevalence of classic intermittent claudication in hospitalized patients with CAD. Medically stable patients with CAD were invited to participate before hospital discharge. The patients answered both the Rose/WHO and Edinburgh modification claudication questionnaires and had an ankle-brachial index (ABI) measured. An ABI less than or equal to 0.9 was considered to be indicative of significant PAD. Patients who had undergone previous lower extremity revascularization for PAD and had a corrected ABI greater than 0.9 were excluded. Ninety-five patients (66 men) were recruited. By measuring the ABI, 35 patients (25 men) were found to have significant PAD. An additional 3 patients who had an ABI corrected by lower extremity revascularization were excluded from the analysis. The Rose/WHO questionnaire had a sensitivity, specificity, and overall accuracy (95% CI) of 14.3% (2.7-25.9%), 96.7% (92.1-100%), and 66.3% (56.8-75.8%), respectively. The Edinburgh modification of the Rose/WHO questionnaire had a sensitivity, specificity, and overall accuracy (95% CI) of 28.6% (13.6-43.5%), 90.0% (82.4-97.6%), 67.4% (57.9-76.8%), respectively. Despite the high incidence of synchronous PAD in hospitalized patients with CAD, traditional claudication questionnaires are insensitive to PAD detection. Classic claudication is an uncommon manifestation of PAD in hospitalized patients with CAD.
Fibromuscular Dysplasia of Bilateral Brachial Arteries
Authors: Kolluri Raghu , Ansel Gary
Published: April 2006

Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic disease of the vascular system, that can affect intima, media, or adventitia. The dysplasia in these layers leads to decrease in the lumen and increased turbulence leading to diminished flow through the affected portion. The treatment of FMD thus far has been either surgical and/or interventional. The authors describe a patient who presented with painful digits and who was found to have bilateral brachial artery FMD and was treated with balloon angioplasty with complete resolution of symptoms.
Double-Orifice Mitral Valve Associated with Nonisolated Left Ventricular Noncompaction
Authors: Gorgulu Íevket , Celik Seden , Eksik Abdurrahman , Tezel Tuna
Published: April 2006

Double-orifice mitral valve is a rare congenital anomaly. Although it is more frequently associated with other cardiac abnormalities, it may occur as an isolated lesion. There are 2 forms of myocardial noncompaction: isolated and nonisolated myocardial noncompaction. Nonisolated myocardial noncompactions are occasionally reported postnatally in association with congenital heart anomalies such as ventricular septal defect, pulmonic stenosis, and atrial septal defect. To our knowledge, this is the first case presentation reporting a double-orifice mitral valve associated with nonisolated myocardial noncompaction.
An Explained Variation Measure for Ordinal Response Models With Comparisons to Other Ordinal R² Measures
Authors: Lacy Michael G.
Published: April 2006

No explained variation (R2) measure for ordinal response models enjoys wide use, and such measures have in fact received little specific attention or evaluation. To remedy this gap, the author presents and justifies R2O, an explained variation measure for ordinal response models, which is based on a recent ordinal dispersion measure. The use and function of R2O is illustrated, and the performance of it and other ordinal R2 measures is compared via a series of simulated sampling and variable selection experiments. The R2O and a bias-adjusted version of it perform well in the simulation experiments and have a number of other advantages that make them attractive as measures of fit for any ordinal response model.
On Measures of Gender Occupational Segregation: Statistical and Conceptual Considerations (a Response to Grusky and Levanon)
Authors: Jerby Iris , Semyonov Moshe , Lewin-Epstein Noah
Published: April 2006

In a recent article (2005), the authors proposed the first-order approximation (FOA) index for the measurement of gender occupational segregation across detailed occupational categories. The FOA index can remedy the two inherent limitations—sensitivity and singularity—associated with the ratio index and the association index, especially when applied to the measurement of micro-segregation. Grusky and Levanon (this issue), while acknowledging these limitations, view the FOA index as a misguided effort to remedy the shortcomings of the other indexes. When responding to Grusky and Levanon, the authors address two kinds of controversies. The first aims directly at the methodological reasoning put forward by Grusky and Levanon and centers on the statistical properties and statistical assumptions embodied in the various measures. The second revolves around different paradigmatic approaches to the study of occupational segregation and centers on different conceptual views of the gender segregation phenomenon.
Managing risk
Authors: Mcalinden Anne-Marie
Published: April 2006

In recent years the management of the dangerous, particularly sex offenders, has generated enormous concern. This concern has been reflected at a number of different levels—in media and popular responses to the risk posed by released sex offenders and in official discourses where an abundance of legislation and policy reforms have been enacted within a relatively short period. This analysis seeks to evaluate critically these developments within the context of contemporary criminal justice policy and practice in relation to the management of sex offenders in the community. The article analyses the contemporary focus on risk management or preventative governance which underpins the current regulatory framework and has been reflected in both the sentencing options and in control in the community initiatives for sex offenders. In this respect, the article highlights the gap between policy and practice in terms of the effective risk management of sex offenders. Given the failure of the traditional justice system with respect to these types of offences, it will be argued that the retributive framework could usefully be supplemented by the theory and practice of reintegrative or restorative community justice, in order to manage better the risk presented by sex offenders in the community.
Exploration of biological network centralities with CentiBiN
Authors: Junker Björn H , Koschützki Dirk , Schreiber Falk
Published: April 2006

Background

The elucidation of whole-cell regulatory, metabolic, interaction and other biological networks generates the need for a meaningful ranking of network elements. Centrality analysis ranks network elements according to their importance within the network structure and different centrality measures focus on different importance concepts. Central elements of biological networks have been found to be, for example, essential for viability.

Results

CentiBiN (Cent ralities i n Bi ological N etworks) is a tool for the computation and exploration of centralities in biological networks such as protein-protein interaction networks. It computes 17 different centralities for directed or undirected networks, ranging from local measures, that is, measures that only consider the direct neighbourhood of a network element, to global measures. CentiBiN supports the exploration of the centrality distribution by visualising central elements within the network and provides several layout mechanisms for the automatic generation of graphical representations of a network. It supports different input formats, especially for biological networks, and the export of the computed centralities to other tools.

Conclusion

CentiBiN helps systems biology researchers to identify crucial elements of biological networks. CentiBiN including a user guide and example data sets is available free of charge at http://centibin.ipk-gatersleben.de/. CentiBiN is available in two different versions: a Java Web Start application and an installable Windows application.
Differential regulation of NF-κB activation and function by topoisomerase II inhibitors
Authors: Campbell Kirsteen J , O'Shea John M , Perkins Neil D
Published: April 2006

Background

While many common chemotherapeutic drugs and other inducers of DNA-damage result in both NF-κB nuclear translocation and DNA-binding, we have previously observed that, depending on the precise stimulus, there is great diversity of the function of NF-κB. In particular, we found that treatment of U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet (UV-C) light resulted in a form of NF-κB that repressed rather than induced NF-κB reporter plasmids and the expression of specific anti-apoptotic genes. Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting topoisomerase II, intercalating with DNA and undergoing redox cycling to produce oxygen free radicals. In this study we have investigated other anthracyclines, doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together with the topoisomerase II inhibitor ICRF-193, which all possess differing characteristics, to determine which of these features is specifically required to induce both NF-κB DNA-binding and transcriptional repression in U-2 OS cells.

Results

The use of mitoxantrone, which does not undergo redox cycling, and the reducing agent epigallocatechingallate (EGCG) demonstrated that oxygen free radical production is not required for induction of NF-κB DNA-binding and transcriptional repression by these agents and UV-C. In addition, the use of aclarubicin, which does not directly inhibit topoisomerase II and ICRF-193, which inhibits topoisomerase II but does not intercalate into DNA, demonstrated that topoisomerase II inhibition is not sufficient to induce the repressor form of NF-κB.

Conclusion

Induction of NF-κB DNA-binding and transcriptional repression by topoisomerase II inhibitors was found to correlate with an ability to intercalate into DNA. Although data from our and other laboratories indicates that topoisomerase II inhibition and oxygen free radicals do regulate NF-κB, they are not required for the particular ability of NF-κB to repress rather than activate transcription. Together with our previous data, these results demonstrate that the nature of the NF-κB response is context dependent. In a clinical setting such effects could profoundly influence the response to chemotherapy and suggest that new methods of analyzing NF-κB function could have both diagnostic and prognostic value.
Prevention of coronary heart disease in people with severe mental illnesses: a qualitative study of patient and professionals' preferences for care
Authors: Wright Christine A , Osborn David PJ , Nazareth Irwin , King Michael B
Published: April 2006

Background

People with severe mental illness (SMI) are at increased risk of developing coronary heart disease (CHD) and there is growing emphasis on the need to monitor their physical health. However, there is little consensus on how services for the primary prevention of CHD should be organised for this patient group. We explored the views of people with SMI and health professionals from primary care and community mental health teams (CMHTs) on how best to provide these services.

Methods

In-depth interviews were conducted with a purposive sample of patients with SMI (n = 31) and staff from primary care (n = 10) and community mental health teams (n = 25) in North Central London. Transcripts of the qualitative interviews were analysed using a 'framework' approach to identify the main themes in opinions regarding various service models.

Results

Cardiovascular risk factors in people with SMI were of concern to participants. However, there was some disagreement about the best way to deliver appropriate care. Although staff felt that primary care should take responsibility for risk factor screening and management, patients favoured CHD screening in their CMHT. Problems with both approaches were identified. These included a lack of familiarity in general practice with SMI and antipsychotic side effects and poor communication of physical health issues to the CMHT. Lack of knowledge regarding CHD risk factor screening and difficulties in interpreting screening results and implementing appropriate interventions exist in secondary care.

Conclusion

Management of physical health care for people with SMI requires complex solutions that cross the primary-secondary care interface. The views expressed by our participants suggest that neither primary nor secondary care services on their own can provide a comprehensive service for all patients. The increased risk of CHD associated with SMI and antipsychotic medications requires flexible solutions with clear lines of responsibility for assessing, communicating and managing CHD risks.
Recomposition and Retransition in Beethoven's String Quintet, op. 4
Authors: BURSTEIN L. POUNDIE
Published: April 2006

In revising his Wind Octet, op. 103, into his String Quintet, op. 4, Beethoven substantially altered the retransition to the main thematic return in each of the movements. The various retransitions of op. 4 are refashioned so as to become points of structural focus as well as of poetic expression. Throughout his career, Beethoven would continue to revisit strategies seen in op. 4's revised retransitions, including not only their specific aspects (such as the use of E♭/E♮ conflicts as a means of problematizing a return to the main key) but also more generally through his highlighting of the contrast between control and disruption at these critical formal junctures. Accordingly, the revised re-transitions of op. 4 suggest a new stage in the development not only of Beethoven's compositional technique but also of his artistic outlook.
Correct Logos and Truth in Gorgias' Encomium of Helen
Authors: Valiavitcharska Vessela
Published: April 2006

Abstract This paper argues against the tendency to interpret Gorgias' view of logos as a techne of persuasion which relies on opinion (doxa) and rests on deception either deliberately or incidentally in order to function. Rather, Gorgias appears to be making a connection between truthful speech (alethes logos) and correct speech (orthos logos). Gorgias' insistence on correctness of speech surfaces not only in the Encomium of Helen, but also in the Funeral Oration fragment and in Agathon's parody of Gorgianic rhetoric in Plato's Symposium. Correct speech goes beyond the effectiveness of language and into the domain of ethical correctness and responsibility.
“Be Fruitful and Multiply”: Genesis and Generation in Reformation Germany
Authors: Crowther-Heyck Kathleen
Published: April 2006

This essay analyzes vernacular texts on reproduction from sixteenth-century Germany. It examines religious texts, including sermons and devotional treatises for pregnant women, as well as medical texts, such as midwifery manuals, books on the “secrets of nature,” and anatomical treatises. Vernacular authors, both medical and clerical, ascribed enormous spiritual and symbolic significance to human generation. Conception, pregnancy, and birth were linked to the biblical account of the creation and fall of mankind. In the creation of the child in the womb, sixteenthcentury Germans saw an echo of the original divine act of creation. And in the sufferings of a woman in labor they saw a reenactment of Christ's Passion. Discussions of reproduction thus served as a starting point for meditations on original sin, human mortality, and the relationship between body and soul.
Architecture and Music Reunited: A New Reading of Dufay's Nuper Rosarum Flores and the Cathedral of Florence
Authors: Trachtenberg Marvin
Published: April 2006

The proportions of the voices are harmonies for the ears; those of the measurements are harmonies for the eyes. Such harmonies usually please very much, without anyone knowing why, excepting the student of the causality of things.

—Palladio(1567)

The chiasmatic themes of architecture as frozen music and music as singing the architecture of the world run as leitmotifs through the histories of philosophy, music, and architecture. Rarely, however, can historical intersections of these practices he identified. This study proposes a transient nexus of architecture, sacred music, and theology in early modern Florence.
Reading Jerome in the Renaissance: Erasmus' Reception of the Adversus Jovinianum
Authors: Pabel Hilmar M.
Published: April 2006

Scholars are now devoting more attention to the reception of the Church Fathers during the Renaissance and Reformation. While Saint Jerome's function as icon and exemplar has been the subject of substantial study, his role as an author, read and edited during the Renaissance, still awaits thorough investigation. This essay examines how Erasmus of Rotterdam, the greatest Renaissance editor of Jerome, read the Church Fathers most elaborate polemic in favor of virginity's moral and spiritual superiority to marriage, theAdversus Jovinianum. An investigation of Erasmus’ editorial apparatus for this text, especially hisscholia, reveals a complex reading. Erasmus applauded Jerome's rhetorical skill but ventured cautious criticism of his scriptural exegesis without taking a firm position in the controversy over the relative merits of virginity and marriage.
The 2001 Josephine Waters Bennett Lecture: The Idea of Community in Renaissance Italy
Authors: Muir Edward
Published: April 2006

This essay is based upon the methodological assumption that by examining an exceptional event in an exceptional place one can unmask the hidden assumptions of the mundane and quotidian. The problem is to determine what the idea of community could have meant in north Italian towns and villages during the Renaissance. Depositions about a brawl in an otherwise insignificant small town provide an opportunity to examine how the idea of community was crystallized in three ways: community as social interaction in an institutional guise, community as a certain kind of space, and community as a process of social exclusion
Dutch Proverbs and Expressions in Erasmus' Adages, Colloquies, and Letters
Authors: Wesseling Ari
Published: April 2006

The impact of Dutch on Erasmus’ works is a neglected aspect of studies on the Netherlandish humanist. This article explores the presence of the Low Countries vernacular in the Colloquia, the letters, and the Adagiorum collectanea. It argues that Erasmus used proverbs of Dutch provenance in the same way as ancient adages, that is, as arguments and stylistic devices. Even though there are relatively few vernacular proverbs in his writings, the evidence gathered here demonstrates that, contrary to established opinion, he valued his native language and freely employed it in various works. To gain a better appreciation of his notion of proverbs and his” estimate of their worth, this essay starts with an analysis of his introduction to the Adagia.
A Permanent Tribunal of International Arbitration: Its Necessity and Value
Authors: Clarke R. Floyd
Published: April 2006

The average individual of these modern days views war with apprehension and alarm. To him it means loss, or risk, of life or limb, either for himself or for those dear to him, or loss of business opportunities and heavy taxes. The growth of socialistic and democratic doctrines has widely spread the historic truth that in the conflicts of the past, largely brought on by the selfish greed of the oligarchic few, the plain many, “the common herd,” Napoleon’s “food for powder,” have had their sufferings for their pains. And the heads of the aggregations of men we call “sovereign states”—the oligarchic few— softened by the spread of the civilizing influence of an industrial age, themselves begin to look on war askance, and to plan ways of avoiding it.
The Proposed International Prize Court and some of its Difficulties
Authors: Gregory Charles Noble
Published: April 2006

The twelfth convention adopted by the Hague Conference of 1907 provides for the establishment of an International Prize Court to which appeals may be carried in certain instances from the prize courts of the captors. The proposal for such a convention was presented very early in the proceedings of the conference.
The Most-Favored-Nation Clause
Authors: Hornbeck Stanley K.
Published: April 2006

Probably no single treaty containing the most-favored-nation clause has caused more controversy than that made between the United States and Prussia, May 1, 1828. Certainly none has attracted more attention from individuals and bodies other than ministerial. This being the case, and since this controversy and its issue illustrate, in a variety of phases common to no other single instance, the necessity for careful application of certain of the principles and methods of interpretation indicated, it will be profitable to study the history of German-American most-favored-nation relations in some detail.
The International Opium Commission
Authors: Wright Hamilton
Published: April 2006

Following the issue of the Philippines Report, and as the diplomatic correspondence proceeded, which led to the International Commission, action after action was taken by the interested governments to control or stamp out the misuse of opium. The Chinese government was prompt, and her leaders and people enthusiastic. January, 1906, saw four of her great viceroys publish a manifesto on the subject. Part of it ran: “ As Great Britain is the friend of China, she will shortly be called to assist the Chinese government to stamp out the evil.” The Chinese government prohibited, without qualification, the use of opium in the Imperial colleges and schools, and in the recently created army.
Periodical Peace Conferences
Authors: Sillac M. Jarousse de
Published: April 2006

“ The law of nations is naturally based upon the principle that different nations in time of peace shall do each other the most good and in time of war the least evil possible.” — Montesquieu, Esprit des Lois, iii. I.

When Count Mouravieff, at the order of the Emperor of Russia, convoked the first peace conference by the circular of the 12th/24th August, 1898, hardly any one foresaw the importance which this first move was to take, which seemed then in the opinion of the writer Mommsen like “ a printer’s error in the history of the world.”

In order to realize the extent of the development to which coming periodical peace conferences are destined it is sufficient to examine the facts of yesterday and the road already traversed.

The object of the first Russian project was very limited; its purpose was to call together a certain number of Powers to study the possibility of “ putting a limit ” on armament for the purpose of diminishing the financial burdens of the states, but the exchanges of opinion which preceded the assembly of these “ disarmament conferences ” having shown that the chances of success were very feeble, a second circular by Mouravieff (January 11, 1899) extended the first program by attaching thereto particularly “the possibility of preventing armed conflicts by pacific means ” and the reduction of “ the laws and customs of war ” to a system of rules. These two new subjects changed the character of the assembly, the title of which even was modified. It was called thenceforth the “ Peace Conference.” And, in fact, the conference in obedience to the very force of things soon completed the transformation of accession to principle, subordinated the premature question of disarmament, and applied its efforts towards justifying its title by concentrating all its force on the matter of pacific adjustment of international conflicts.
Award Pronounced by His Majesty King George v As “ Amiable Compositeur ” Between the United States of America and the Republic of Chile in the Matter of the Alsop Claim
Authors: R. I. George
Published: April 2006

London, July 5, 1911.

Whereas by a Protocol dated the 1st day of December, 1909, the Government of the United States of America and the Government of the Republic of Chile resolved that, as they had not been able to agree as to the amount equitably due to the claimants in the Alsop case, they would submit the whole controversy to His late Majesty King Edward VII as an amiable compositeur to determine the amount equitably due to the said claimants; and

Whereas on account of his untimely death His late Majesty was not able to carry out the duty which he had undertaken; and

Whereas at the request of the two Governments We agreed to act in place of His late Majesty; and

Whereas We determined to designate a Commission to study the papers submitted to Us on either side, and submit a Report to Us for Our consideration as to the amount equitably due to the said claimants; and
The Work of the Second Hague Peace Conference
Authors: Scott James Brown
Published: April 2006

The Second International Peace Conference, like its predecessor of 1899, endeavored to humanize the hardships necessarily incident to war and to substitute for a resort to arms a pacific settlement of international grievances, which, if unsettled, might lead to war or make the maintenance of pacific relations difficult and problematical. The conference of 1907, no more than its immediate predecessor, satisfied the leaders of humanitarian thought. War was not abolished, nor was peace legislated into existence. Universal disarmament was as unacceptable in 1907 as in 1899, and some few nations were still unwilling to bind themselves to refer all international disputes not involving independence, vital interests, or national honor to a court of arbitration.
The Amelioration of the Rules of War on Land
Authors: Davis George B.
Published: April 2006

With a view to the systematic discussion of the questions inscribed upon its program, the membership of the conference was divided into four great committees, to each of which a related group of subjects was assigned for investigation with a view to the formulation of such stipulations as might be deemed worthy of insertion in a general convention.
Obligatory Arbitration and the Hague Conferences
Authors: Hull Wm. I.
Published: April 2006

The kinds or degrees of obligatory arbitration advocated in the two conferences were three in number, and may be called, respectively, universal, inclusive, and exclusive obligatory arbitration.
The Proposed Court of Arbitral Justice
Authors: Scott James Brown
Published: April 2006

Before undertaking a systematic and analytical exposition of the project relating to the establishment of an arbitral court of justice as approved by the Committee of Examination B and referred to the First Subcommission of the First Commission, it may be useful to devote a few lines, by way of introduction, to the Permanent Tribunal of Arbitration created in 1899 by the First Conference and alongside which it is proposed to establish an arbitral court of justice.