bluuebunny/crossref_metadata_2025 huggingface dataset:
On the probability that a novel variant is a disease-causing mutation
Authors: Mitchell Adele A. , Chakravarti Aravinda , Cutler David J.
Published: June 2005

When a novel variant is found in a patient and not in a group of controls, it becomes a candidate for the disease-causing mutation in that patient. At present, no sampling theory exists for assessing the probability that the novel SNP might actually be a neutral variant. We have developed a population genetics-based method for calculating a P-value for a mutation-detection effort. Our method can be applied to a heterozygous patient, a homozygous patient, with or without inbreeding, or to a patient who is a compound heterozygote. Additionally, the method can be used to calculate the probability of finding a neutral variant at frequencies that differ between a group of patients and a group of controls, given some length of sequence examined. This method accounts for the multiple testing that is inherent in identification of variants through sequencing, to be used in subsequent case-control analyses. We show, for example, that for complete resequencing of 10 kb, the probability of finding a neutral variant in a patient and not in 50 controls is about 15%. Thus, discovery of a variant in a patient and not in a group of controls is, on its own, very weak evidence of involvement with disease.
Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity
Authors: Stone Eric A. , Sidow Arend
Published: June 2005

We find that the degree of impairment of protein function by missense variants is predictable by comparative sequence analysis alone. The applicable range of impairment is not confined to binary predictions that distinguish normal from deleterious variants, but extends continuously from mild to severe effects. The accuracy of predictions is strongly dependent on sequence variation and is highest when diverse orthologs are available. High predictive accuracy is achieved by quantification of the physicochemical characteristics in each position of the protein, based on observed evolutionary variation. The strong relationship between physicochemical characteristics of a missense variant and impairment of protein function extends to human disease. By using four diverse proteins for which sufficient comparative sequence data are available, we show that grades of disease, or likelihood of developing cancer, correlate strongly with physicochemical constraint violation by causative amino acid variants.
The Maize Root Transcriptome by Serial Analysis of Gene Expression
Authors: Poroyko V. , Hejlek L.G. , Spollen W.G. , Springer G.K. , Nguyen H.T. , Sharp R.E. , Bohnert H.J.
Published: June 2005

Serial Analysis of Gene Expression was used to define number and relative abundance of transcripts in the root tip of well-watered maize seedlings (Zea mays cv FR697). In total, 161,320 tags represented a minimum of 14,850 genes, based on at least two tags detected per transcript. The root transcriptome has been sampled to an estimated copy number of approximately five transcripts per cell. An extrapolation from the data and testing of single-tag identifiers by reverse transcription-PCR indicated that the maize root transcriptome should amount to at least 22,000 expressed genes. Frequency ranged from low copy number (2–5, 68.8%) to highly abundant transcripts (100→1,200; 1%). Quantitative reverse transcription-PCR for selected transcripts indicated high correlation with tag frequency. Computational analysis compared this set with known maize transcripts and other root transcriptome models. Among the 14,850 tags, 7,010 (47%) were found for which no maize cDNA or gene model existed. Comparing the maize root transcriptome with that in other plants indicated that highly expressed transcripts differed substantially; less than 5% of the most abundant transcripts were shared between maize and Arabidopsis (Arabidopsis thaliana). Transcript categories highlight functions of the maize root tip. Significant variation in abundance characterizes transcripts derived from isoforms of individual enzymes in biochemical pathways.
Localized Hormone Fluxes and Early Haustorium Development in the Hemiparasitic PlantTriphysaria versicolor
Authors: Tomilov Alexey A. , Tomilova Natalia B. , Abdallah Ibrahim , Yoder John I.
Published: June 2005

Perhaps the most obvious phenotypes associated with chemical signaling between plants are manifested by parasitic species of Orobanchaceae. The development of haustoria, invasive root structures that allow hemiparasitic plants to transition from autotrophic to heterotrophic growth, is rapid, highly synchronous, and readily observed in vitro. Haustorium development is initiated in aseptic roots of the facultative parasite Triphysaria versicolor when exposed to phenolic molecules associated with host root exudates and rhizosphere bioactivity. Morphological features of early haustorium ontogeny include rapid cessation of root elongation, expansion, and differentiation of epidermal cells into haustorial hairs, and cortical cell expansion. These developmental processes were stimulated in aseptic T. versicolor seedlings by the application of exogenous phytohormones and inhibited by the application of hormone antagonists. Surgically dissected root tips formed haustoria if the root was exposed to haustorial-inducing factors prior to dissection. In contrast, root tips that were dissected prior to inducing-factor treatment were unable to form haustoria unless supplemented with indole-3-acetic acid. A transient transformation assay demonstrated that auxin and ethylene-responsive promoters were up-regulated when T. versicolor was exposed to either exogenous hormones or purified haustoria-inducing factors. These experiments demonstrate that localized auxin and ethylene accumulation are early events in haustorium development and that parasitic plants recruit established plant developmental mechanisms to realize parasite-specific functions.
Auxin Dynamics after Decapitation Are Not Correlated with the Initial Growth of Axillary Buds
Authors: Morris Suzanne E. , Cox Marjolein C.H. , Ross John J. , Krisantini Santi , Beveridge Christine A.
Published: June 2005

One of the first and most enduring roles identified for the plant hormone auxin is the mediation of apical dominance. Many reports have claimed that reduced stem indole-3-acetic acid (IAA) levels and/or reduced basipetal IAA transport directly or indirectly initiate bud growth in decapitated plants. We have tested whether auxin inhibits the initial stage of bud release, or subsequent stages, in garden pea (Pisum sativum) by providing a rigorous examination of the dynamics of auxin level, auxin transport, and axillary bud growth. We demonstrate that after decapitation, initial bud growth occurs prior to changes in IAA level or transport in surrounding stem tissue and is not prevented by an acropetal supply of exogenous auxin. We also show that auxin transport inhibitors cause a similar auxin depletion as decapitation, but do not stimulate bud growth within our experimental time-frame. These results indicate that decapitation may trigger initial bud growth via an auxin-independent mechanism. We propose that auxin operates after this initial stage, mediating apical dominance via autoregulation of buds that are already in transition toward sustained growth.
The Histidine Kinase Hik34 Is Involved in Thermotolerance by Regulating the Expression of Heat Shock Genes in Synechocystis
Authors: Suzuki Iwane , Kanesaki Yu , Hayashi Hidenori , Hall John J. , Simon William J. , Slabas Antoni R. , Murata Norio
Published: June 2005

Histidine kinases (Hiks) in Synechocystis sp. PCC 6803 are involved in the transduction of signals associated with various kinds of environmental stress. To examine the potential role in thermotolerance of Hiks, we used genome microarray analysis to screen a Hik knockout library for mutations that affected the expression of genes for heat shock proteins. Mutation of the hik34 gene enhanced the levels of transcripts of a number of heat shock genes, including htpG and groESL1. Overexpression of the hik34 gene repressed the expression of these heat shock genes. In addition, the cells with a mutant gene for Hik34 (ΔHik34 cells) survived incubation at 48°C for 3 h, while wild-type cells and cells with mutations in other Hiks were killed. However, mutation of the hik34 gene had only an insignificant effect on the global expression of genes upon incubation of the mutant cells at 44°C for 20 min. Quantitative two-dimensional gel electrophoresis revealed that levels of GroES and HspA were elevated in ΔHik34 cells after incubation of cells at 42°C for 60 min. We overexpressed recombinant Hik34 protein in Escherichia coli and purified it. We found that the protein was autophosphorylated in vitro at physiological temperatures, but not at elevated temperatures, such as 44°C. These results suggest that Hik34 might negatively regulate the expression of certain heat shock genes that might be related to thermotolerance in Synechocystis.
Surrogate Splicing for Functional Analysis of Sesquiterpene Synthase Genes
Authors: Wu Shuiqin , Schoenbeck Mark A. , Greenhagen Bryan T. , Takahashi Shunji , Lee Sungbeom , Coates Robert M. , Chappell Joseph
Published: June 2005

A method for the recovery of full-length cDNAs from predicted terpene synthase genes containing introns is described. The approach utilizes Agrobacterium-mediated transient expression coupled with a reverse transcription-polydeoxyribonucleotide chain reaction assay to facilitate expression cloning of processed transcripts. Subsequent expression of intronless cDNAs in a suitable prokaryotic host provides for direct functional testing of the encoded gene product. The method was optimized by examining the expression of an intron-containing β-glucuronidase gene agroinfiltrated into petunia (Petunia hybrida) leaves, and its utility was demonstrated by defining the function of two previously uncharacterized terpene synthases. A tobacco (Nicotiana tabacum) terpene synthase-like gene containing six predicted introns was characterized as having 5-epi-aristolochene synthase activity, while an Arabidopsis (Arabidopsis thaliana) gene previously annotated as a terpene synthase was shown to possess a novel sesquiterpene synthase activity for α-barbatene, thujopsene, and β-chamigrene biosynthesis.
Atypical Regulation of a Green Lineage-Specific B-Type Cyclin-Dependent Kinase
Authors: Corellou Florence , Camasses Alain , Ligat Laetitia , Peaucellier Gérard , Bouget François-Yves
Published: June 2005

Cyclin-dependent kinases (CDKs) are the main regulators of cell cycle progression in eukaryotes. The role and regulation of canonical CDKs, such as the yeast (Saccharomyces cerevisiae) Cdc2 or plant CDKA, have been extensively characterized. However, the function of the plant-specific CDKB is not as well understood. Besides being involved in cell cycle control, Arabidopsis (Arabidopsis thaliana) CDKB would integrate developmental processes to cell cycle progression. We investigated the role of CDKB in Ostreococcus (Ostreococcus tauri), a unicellular green algae with a minimal set of cell cycle genes. In this primitive alga, at the basis of the green lineage, CDKB has integrated two levels of regulations: It is regulated by Tyr phosphorylation like cdc2/CDKA and at the level of synthesis-like B-type CDKs. Furthermore, Ostreococcus CDKB/cyclin B accounts for the main peak of mitotic activity, and CDKB is able to rescue a yeast cdc28ts mutant. By contrast, Ostreococcus CDKA is not regulated by Tyr phosphorylation, and it exhibits a low and steady-state activity from DNA replication to exit of mitosis. This suggests that from a major role in the control of mitosis in green algae, CDKB has evolved in higher plants to assume other functions outside the cell cycle.
Phytic Acid Synthesis and Vacuolar Accumulation in Suspension-Cultured Cells of Catharanthus roseus Induced by High Concentration of Inorganic Phosphate and Cations
Authors: Mitsuhashi Naoto , Ohnishi Miwa , Sekiguchi Yoko , Kwon Yong-Uk , Chang Young-Tae , Chung Sung-Kee , Inoue Yoshinori , Reid Robert J. , Yagisawa Hitoshi , Mimura Tetsuro
Published: June 2005

We have established a new system for studying phytic acid, myo-inositol hexakisphosphate (InsP6) synthesis in suspension-cultured cells of Catharanthus. InsP6 and other intermediates of myo-inositol (Ins) phosphate metabolism were measured using an ion chromatography method. The detection limit for InsP6 was less than 50 nm, which was sufficient to analyze Ins phosphates in living cells. Synthesis of Ins phosphates was induced by incubation in high inorganic phosphate medium. InsP6 was mainly accumulated in vacuoles and was enhanced when cells were grown in high concentration of inorganic phosphates with the cations K+, Ca2+, or Zn2+. However, there was a strong tendency for InsP6 to accumulate in the vacuole in the presence of Ca2+ and in nonvacuolar compartments when supplied with Zn2+, possibly due to precipitation of InsP6 with Zn2+ in the cytosol. A vesicle transport inhibitor, brefeldin A, stimulated InsP6 accumulation. The amounts of both Ins(3)P1myo-inositol monophosphate synthase, a key enzyme for InsP6 synthesis, and Ins(1,4,5)P3 kinase were unrelated to the level of accumulation of InsP6. The mechanisms for InsP6 synthesis and localization into vacuoles in plant cells are discussed.
Tocopherols Protect Synechocystis sp. Strain PCC 6803 from Lipid Peroxidation
Authors: Maeda Hiroshi , Sakuragi Yumiko , Bryant Donald A. , DellaPenna Dean
Published: June 2005

Tocopherols (vitamin E) are lipid-soluble antioxidants synthesized only by photosynthetic eukaryotes and some cyanobacteria, and have been assumed to play important roles in protecting photosynthetic membranes from oxidative stress. To test this hypothesis, tocopherol-deficient mutants of Synechocystis sp. strain PCC 6803 (slr1736 and slr1737 mutants) were challenged with a series of reactive oxygen species-generating and lipid peroxidation-inducing chemicals in combination with high-light (HL) intensity stress. The tocopherol-deficient mutants and wild type were indistinguishable in their growth responses to HL in the presence and absence of superoxide and singlet oxygen-generating chemicals. However, the mutants showed enhanced sensitivity to linoleic or linolenic acid treatments in combination with HL, consistent with tocopherols playing a crucial role in protecting Synechocystis sp. strain PCC 6803 cells from lipid peroxidation. The tocopherol-deficient mutants were also more susceptible to HL treatment in the presence of sublethal levels of norflurazon, an inhibitor of carotenoid synthesis, suggesting carotenoids and tocopherols functionally interact or have complementary or overlapping roles in protecting Synechocystis sp. strain PCC 6803 from lipid peroxidation and HL stress.
Profile and Analysis of Gene Expression Changes during Early Development in Germinating Spores ofCeratopteris richardii
Authors: Salmi Mari L. , Bushart Thomas J. , Stout Stephen C. , Roux Stanley J.
Published: June 2005

Analysis of an expressed sequence tag library with more than 5,000 sequences from spores of the fern Ceratopteris richardii reveals that more than 3,900 of them represent distinct genes, and almost 70% of these have significant similarity to Arabidopsis (Arabidopsis thaliana) genes. Eight genes are common between three very different dormant plant systems, Ceratopteris spores, Arabidopsis seeds, and Arabidopsis pollen. We evaluated the pattern of mRNA abundance over the first 48 h of spore development using a microarray of cDNAs representing 3,207 distinct genes of C. richardii and determined the relative levels of RNA abundance for 3,143 of these genes using a Bayesian method of statistical analysis. More than 900 of them (29%) show a significant change between any of the five time points analyzed, and these have been annotated based on their sequence similarity with the Arabidopsis proteome. Novel data arising from these analyses identify genes likely to be critical for the germination and subsequent early development of diverse cells and tissues emerging from dormancy.
Raising awareness of the benefits of diversity at ING
Authors: Dawson Michael
Published: June 2005

Purpose

Explains how ING, the global financial‐services group, called in drama‐based training specialist Steps Drama to help it to raise awareness of the business benefits of diversity – and the possible legal implications of non‐inclusive behaviour – for all 1,000 staff in its UK wholesale‐banking operation.

Design/methodology/approach

Presents information on the training garnered from an interview with the human‐resource manager at ING UK.

Findings

Demonstrates that Steps designed a three‐hour workshop combining professional role‐plays with ING company information and employment law input. The result was an entertaining and memorable experience, which provided a foundation in diversity.

Practical implications

Demonstrates that while for many organizations, diversity is simply a means of complying with employment law and anti‐discriminatory practices, ING Group believes that diversity management and an inclusive culture can contribute to long‐term profitability as well.

Originality/value

Highlights the benefits of combining role‐plays with company information and lawyer input, to get employees of all grades interested in, and discussing, diversity issues.
Why HR outsourcing continues to expand
Authors: Davidson Glenn
Published: June 2005

Purpose

To highlight that human‐resource outsourcing (HRO) arrangements have proved to be strategic partnerships that help to put people matters at the top of corporate strategic decision‐making.

Design/methodology/approach

On the basis of a survey by The Conference Board, produced in partnership with Accenture HR Services, the article demonstrates the key motivating factors in the decision to outsource. The article presents a case study of a mid‐size American chemical producer that, because of human resource outsourcing (HRO), can now more effectively perform financial analyses because of better HR reporting. Additionally, the company now pays 99 percent of employee claims within two weeks and manages every service request within 48 hours.

Findings

The article demonstrates that HRO is about the best use of company resources, not a means for cost savings or job cutting. By fully understanding the economics and opportunities of HRO, executives can help their companies to achieve new heights of performance.

Practical implications

The article demonstrates that the key advantages of HRO include lower costs, better insights, greater control over the HR function and improved customer services.

Originality/value

The article contains plenty to interest top managers who are considering outsourcing their HR functions.
HR outsourcing in operation: critical success factors
Authors: Hindle John
Published: June 2005

Purpose

Examine the critical success factors for human resources (HR) outsourcing.

Design/methodology/approach

Success factors have been identified following work with many clients and in‐depth industry knowledge of best practice in HR outsourcing.

Findings

Article outlines the critical success factors that companies should employ when implementing HR outsourcing to ensure they maximize return on investment. It also highlights the expected benefits of HR outsourcing.

Practical implications

Practical ideas are given for improving the client vendor relationship and management of the outsourcing partnership.

Originality/value

The article is of value to all HR professionals who are embarking on outsourcing any of their HR functions, as it outlines likely benefits and best practice in HR outsourcing.
Don't sit idly by if you want your staff to stay
Authors: Lewis Justin
Published: June 2005

Purpose

Advises bosses of firms large and small about how to prevent their talented staff leaving mid‐career now that employees are increasingly reluctant to work long hours.

Design/methodology/approach

Discusses changing employee attitudes and how HR managers should react to these changes.

Findings

Urges organizations to put in structures that ensure all staff are working efficiently and fairly. Suggests that, with the right structure, regular monitoring and “policing”, enormous amounts of time will be liberated, enabling staff to reduce their working hours and take longer holidays. Argues that there is a balance to be struck in giving employees the right amount of responsibility: they should have enough, so that their judgment and intelligence are fully used, but not so much that they feel overburdened and are unable to relax after work. Contends that holiday cover should be provided so that employees do not return to a mountainous in‐tray.

Practical implications

Stresses the key role of HR managers in ensuring that employees do not become overburdened with work and opt to leave the organization.

Originality/value

Provides a viewpoint from the front line – the chief executive of City of London stockbroking firm Corporate Synergy, who has had to confront the issues about which he writes.
High retention rates bring customer benefits at SITEL Direct
Authors: Cordray Kevin
Published: June 2005

Purpose

Explains SITEL Direct's approach to staff retention and how successful strategies to empower, encourage and promote employees provide business benefits to its clients and their customers.

Design/methodology/approach

Highlights the main benefits available to agents working in SITEL's bureau and fulfillment programs: varied work, flexible hours, good training and personal development opportunities, and the chance to work in one of England's prettiest towns. Emphasizes the importance of having a settled team.

Findings

Shows that SITEL has established a monthly retention target of 95 percent for its bureau agents, but in 2004, there was an average monthly retention rate of 97.2 percent in quarter one, 95.9 percent in quarter two and 94.3 percent in quarter three. Fulfillment has achieved even higher retention rates. With a similar target of 95 percent monthly retention, the program in 2004 achieved an average monthly retention rate of 100 percent in quarter one, 97.2 percent in quarter two and 97.8 percent in quarter three.

Practical implications

Demonstrates that high staff turnover need not, in all cases, characterize the call‐centre industry.

Originality/value

Emphasizes that the agents working in SITEL's bureau and fulfillment programs are critical to the success of a client's campaign, as they are the first people that consumers interact with either directly or indirectly.
Part I. General practitioner–specialist relationship
Authors: Piterman L. , Koritsas S.
Published: June 2005

Abstract

This article is the first of a two‐part series that seeks to explore the relationship and interaction between general practitioners (GPs) and medical specialists. A historical account of the medical profession is given, beginning from the tripartite division (i.e. the physicians, surgeons or barbers and the apothecaries), the Apothecaries Act of 1815, and the Medical Act of 1858. An account is also given of factors that exacerbated the division and friction between GPs and specialists, and how general practice developed in Australia. The role of the GP is stated as the provision of primary care, preventive care, patient‐centred care, continuing care, comprehensive care, and community‐based care to individuals and their families. The role of the specialists on the other hand is that of a consultant to advise GPs who carry on the management after the patient leaves the specialist. The dynamics of the GP–specialist relationship are discussed in relation to power, interdependence, morale, public image, education and training, and support from the Colleges, and we conclude by discussing the importance of collaboration between professions. (Intern Med J 2005; 35: 430–434)
Robot‐assisted vs pure laparoscopic radical prostatectomy: are there any differences?
Authors: Joseph Jean V. , Vicente Ivelisse , Madeb Ralph , Erturk Erdal , Patel Hitendra R.H.
Published: June 2005

OBJECTIVE

To compare our experience of pure laparoscopic radical prostatectomy (LRP) with robot‐assisted radical prostatectomy (RAP).

PATIENTS AND METHODS

The two techniques were compared retrospectively in 100 patients with localized prostate cancer who had LRP or RAP (50 each). Both groups were similar in age, serum prostate‐specific antigen level, Gleason score and clinical stage. Their charts were reviewed, collating intraoperative data and early functional outcome.

RESULTS

The mean surgical time for LRP and RAP was 235 and 202 min (P > 0.05) and mean (95% confidence interval) blood loss 299 (40) and 206 (63) mL (P = 0.014), with no transfusions in either group. The positive margin rate did not differ significantly (14% LRP and 12% RAP) and there was no biochemical recurrence in either group. Early functional outcomes were similar.

CONCLUSIONS

Both LRP and RAP are technically demanding, but feasible, with the patient clearly benefiting. There were no major surgical differences between the techniques, but RAP is more costly.
Phosphatidylinositol 3‐kinase and ERK1/2 are not involved in adenosine A1, A2A or A3 receptor‐mediated preconditioning in rat ventricle strips
Authors: Button Laura , Mireylees Stewart E. , Germack Renee , Dickenson John M.
Published: June 2005

Mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase 1 and 2 (ERK1/2) and phosphatidylinositol 3‐kinase (PI3‐kinase)/protein kinase B (PKB; also known as Akt) are important antiapoptotic signalling pathways which have recently been implicated in cardioprotection. However, at present the involvement of ERK1/2 and PI3‐kinase/PKB in adenosine receptor‐mediated cardioprotection is poorly understood. In this study we used isolated rat right ventricular strips, contracted by electrical‐field stimulation, in order to investigate the role of ERK1/2 and PI3‐kinase/PKB in adenosine receptor‐induced cardioprotection. Ventricle strips were pretreated for 2 min with the agonists adenosine (non‐selective), CPA (A1 selective), CGS 21680 (A2A selective) and Cl‐IB‐MECA (A3 selective) before 30 min hypoxia followed by 30 min reoxygenation. Each agonist significantly improved posthypoxic percentage contraction recovery compared to control strips. Similarly hypoxic preconditioning (10 min hypoxia followed by 20 min reoxygenation) significantly improved posthypoxic percentage contraction recovery compared to non‐preconditioned strips. The selective adenosine receptor antagonists DPCPX (A1), ZM 241385 (A2A) and MRS 1220 (A3) attenuated cardioprotection induced by CPA, CGS 21680 and Cl‐IB‐MECA, respectively. Pre‐incubation (30 min) of ventricle strips with the MEK1 inhibitor PD 98059 (50 μm) or the PI3‐kinase inhibitor wortmannin (100 nm) significantly reduced posthypoxic percentage contraction recovery induced by hypoxic preconditioning. In contrast, PD 98059 and wortmannin had no significant effect on cardioprotection induced by CPA, Cl‐IB‐MECA or CGS 21680. Overall these data indicate that although selective A1, A2A and A3 adenosine receptor agonists induce preconditioning in rat right ventricular strips the effects are independent of ERK1/2‐ and PI3‐kinase‐dependent pathways. In contrast ERK1/2 and PI3‐kinase‐dependent pathways do appear to be involved in early hypoxic preconditioning.
Vanquishing the Terror of Poliomyelitis
Authors: Pallansch Mark
Published: June 2005

Polio
. An American Story.
By David M. Oshinsky
. Oxford University Press, New York, 2005. 340 pp. $30, £18.99. ISBN 0-19-515294-8.

Splendid Solution
. Jonas Salk and the Conquest of Polio.
By Jeffrey Kluger
. Putnam, New York, 2004. 381 pp. $25.95, C$38. ISBN 0-399-15216-4.

Living with Polio
. The Epidemic and Its Survivors.
By Daniel J. Wilson
. University of Chicago Press, Chicago, 2005. 300 pp. $29, £20.50. ISBN 0-226-90103-3.

The authors offer three perspectives on polio in the United States: Oshinsky gives a broad view of the efforts to eradicate the disease, Kluger focuses on the work of Salk, and Wilson highlights the stories of people who were struck by the virus or lived with its consequences.
PLANE REAL ALGEBRAIC CURVES OF ODD DEGREE WITH A DEEP NEST
Authors: OREVKOV STEPAN YU.
Published: June 2005

We apply the Murasugi–Tristram inequality to real algebraic curves of odd degree in RP2 with a deep nest, i.e. a nest of the depth k - 1 where 2k + 1 is the degree. For such curves, the ingredients of the Murasugi–Tristram inequality can be computed (or estimated) inductively using the computations for iterated torus links due to Eisenbud and Neumann as the base case of the induction and Conway's skein relation as the induction step. As an example of applications, we prove that some isotopy types are not realizable by M-curves of degree 9. In Appendix B, we give some generalization of the skein relation for Conway polynomial.
Digital Image Reconstruction: Deblurring and Denoising
Authors: Puetter R.C. , Gosnell T.R. , Yahil Amos
Published: June 2005

▪ Abstract  Digital image reconstruction is a robust means by which the underlying images hidden in blurry and noisy data can be revealed. The main challenge is sensitivity to measurement noise in the input data, which can be magnified strongly, resulting in large artifacts in the reconstructed image. The cure is to restrict the permitted images. This review summarizes image reconstruction methods in current use. Progressively more sophisticated image restrictions have been developed, including (a) filtering the input data, (b) regularization by global penalty functions, and (c) spatially adaptive methods that impose a variable degree of restriction across the image. The most reliable reconstruction is the most conservative one, which seeks the simplest underlying image consistent with the input data. Simplicity is context-dependent, but for most imaging applications, the simplest reconstructed image is the smoothest one. Imposing the maximum, spatially adaptive smoothing permitted by the data results in the best image reconstruction.
ECONOMIC THEORIES OF SETTLEMENT BARGAINING
Authors: Daughety Andrew F. , Reinganum Jennifer F.
Published: June 2005

▪ Abstract  We briefly review two basic models of settlement bargaining based on concepts from information economics and game theory. We then discuss how these models have been generalized to address issues that arise when there are more than two litigants with related cases. Linkages between cases can arise because of exogenous factors such as correlated culpability or damages, or they can be generated by discretionary choices on the part of the litigants themselves or by legal doctrine and rules of procedure.
TRANSNATIONAL HUMAN RIGHTS: Exploring the Persistence and Globalization of Human Rights
Authors: Klug Heinz
Published: June 2005

▪ Abstract  This review considers how a socio-legal approach may be used to explore the relationship between human rights and law in the new century. Drawing on the classic traditions of law and society research, including gap studies, rights consciousness, public interest lawyering, and legal resource mobilization, as well as more recent approaches to legal globalization and epistemic communities or nongovernment networks, this paper begins to define a field of transnational human rights. The review traces the idea of transnational human rights to the struggles between social movements, in national and international fora, and the impact these struggles have had on the relationship between state power or sovereignty and the quest for legitimate and effective forms of governance. A key element of this endeavor, the paper concludes, is the need to integrate and understand the interaction between three traditionally separate domains of rights: international human rights, humanitarian law, and constitutional rights. It is this focus that defines the emerging field of transnational human rights.
LAW AND CORPORATE GOVERNANCE
Authors: Fligstein Neil , Choo Jennifer
Published: June 2005

▪ Abstract  Corporate governance concerns three sets of issues: property rights, relationships between firms and financial markets, and labor relations. Our literature review shows that the system of corporate governance that emerges within a particular country reflects the outcome of political, social, and economic struggles in that country and that it does not reflect efficiency considerations focused on managing agency relations between owners and managers. Despite these facts, much research has been done in recent years attempting to analyze whether a superior matrix of institutional arrangements or a set of best practices of corporate governance exists to produce greater economic growth. Our review shows that there does not appear to be a single set of best practices, but rather that what is important are stable institutions that are legitimate and prevent extreme rent seeking on the part of governments and capitalists.
The influence of body size on measurements of overall cardiac function
Authors: Chantler Paul D. , Clements R. E. , Sharp L. , George K. P. , Tan L.-B. , Goldspink D. F.
Published: June 2005

The purpose of this study was to determine the best scaling method to account for the effects of body size on measurements of overall cardiac function and subsequently the interpretation of data based on cardiac power output (CPO). CPO was measured at rest (CPOrest) and at maximal exercise (CPOmax) on 88 and 103 healthy but untrained men and women, respectively, over the age range of 20–70 yr. Cardiac reserve (CR) was calculated as CPOmax− CPOrest. CPOrest, CPOmax, and CR were all significantly related to body mass (BM), body surface area (BSA), and lean body mass (LBM). The linear regression model failed to completely normalize these measurements. In contrast, the allometric model produced size-independent values of CPO. Furthermore, all the assumptions associated with the allometric model were achieved. For CPOrest, mean body size exponents were BM0.33, BSA0.60, and LBM0.47. For CPOmax, the exponents were BM0.41, BSA0.81, and LBM0.71. For CR, mean body size exponents were BM0.44, BSA0.87, and LBM0.79. LBM was identified (from the root-mean-squares errors of the separate regression models) as the best physiological variable (based on its high metabolic activity) to be scaled in the allometric model. Scaling of CPO to LBMb(where b is the scaling exponent) dramatically reduced the between-gender differences with only a 7% difference in CPOrestand CPOmaxvalues. In addition, the gender difference in CR was completely removed. To avoid erroneous interpretations and conclusions being made when comparing data between men and women of different ages, the allometric scaling of CPO to LBMbwould seem crucial.
Electrophysiological effects of O2−· on the plasma membrane in vascular endothelial cells
Authors: Brzezinska Anna K. , Lohr Nicole , Chilian William M.
Published: June 2005

Vascular dysfunction is a hallmark of many diseases, including coronary heart disease, stroke, and diabetes. The underlying mechanisms of these disorders are intimately associated with an increase in oxidative stress and excess generation of reactive oxygen species. Here, we report that the anionic free radical, superoxide (O2−·), directly affects the function of ion channels in vascular endothelial cells. Vascular endothelial cells were exposed to O2−· under physiological, symmetrical chloride and chloride-free conditions. Superoxide was generated from the reaction of xanthine (0.2 mM) and xanthine oxidase (0.1, 1, and 10 mU/ml) while its effects were determined with the whole cell mode of the patch-clamp technique. Inhibitors of K+and Cl−channels were used to determine the role of these ion channels in mediating the electrophysiological effects of superoxide. The addition of O2−· caused a dose-dependent depolarization of endothelial cells and activation of the whole cell current. Activation of superoxide-dependent current was observed in the presence of inhibitors of K+channels, Ba2+(100 μM) or iberiotoxin (100 nM), and was not affected by inhibitors of nonselective cation channels, La3+, or by inhibition of the Cl−/HCO3−transporter by bumetanide. The inhibitors of the Cl−channel, NPPB (0.1 mM) or DIDS (100 μM), partially prevented activation of superoxide-dependent current but were unable to reverse it. The effects of superoxide on the amplitude of whole cell current were prevented and reversed by superoxide dismutase. Taken together, these results suggest that superoxide directly affects the function of ion channels in vascular endothelium but the mechanisms of its modulatory effects remain unresolved.
Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome
Authors: Stewart Julian M. , Medow Marvin S. , Montgomery Leslie D. , Glover June L. , Millonas Mark M.
Published: June 2005

Prior work demonstrated dependence of the change in blood pressure during the Valsalva maneuver (VM) on the extent of thoracic hypovolemia and splanchnic hypervolemia. Thoracic hypovolemia and splanchnic hypervolemia characterize certain patients with postural tachycardia syndrome (POTS) during orthostatic stress. These patients also experience abnormal phase II hypotension and phase IV hypertension during VM. We hypothesize that reduced splanchnic arterial resistance explains aberrant VM results in these patients. We studied 17 POTS patients aged 15–23 yr with normal resting peripheral blood flow by strain gauge plethysmography and 10 comparably aged healthy volunteers. All had normal blood volumes by dye dilution. We assessed changes in estimated thoracic, splanchnic, pelvic-thigh, and lower leg blood volume and blood flow by impedance plethysmography throughout VM performed in the supine position. Baseline splanchnic blood flow was increased and calculated arterial resistance was decreased in POTS compared with control subjects. Splanchnic resistance decreased and flow increased in POTS subjects, whereas splanchnic resistance increased and flow decreased in control subjects during stage II of VM. This was associated with increased splanchnic blood volume, decreased thoracic blood volume, increased heart rate, and decreased blood pressure in POTS. Pelvic and leg resistances were increased above control and remained so during stage IV of VM, accounting for the increased blood pressure overshoot in POTS. Thus splanchnic hyperemia and hypervolemia are related to excessive phase II blood pressure reduction in POTS despite intense peripheral vasoconstriction. Factors other than autonomic dysfunction may play a role in POTS.
Electromechanics of paced left ventricle simulated by straightforward mathematical model: comparison with experiments
Authors: Kerckhoffs R. C. P. , Faris O. P. , Bovendeerd P. H. M. , Prinzen F. W. , Smits K. , McVeigh E. R. , Arts T.
Published: June 2005

Intraventricular synchrony of cardiac activation is important for efficient pump function. Ventricular pacing restores the beating frequency but induces more asynchronous depolarization and more inhomogeneous contraction than in the normal heart. We investigated whether the increased inhomogeneity in the left ventricle can be described by a relatively simple mathematical model of cardiac electromechanics, containing normal mechanical and impulse conduction properties. Simulations of a normal heartbeat and of pacing at the right ventricular apex (RVA) were performed. All properties in the two simulations were equal, except for the depolarization sequence. Simulation results of RVA pacing on local depolarization time and systolic midwall circumferential strain were compared with those measured in dogs, using an epicardial sock electrode and MRI tagging, respectively. We used the same methods for data processing for simulation and experiment. Model and experiment agreed in the following aspects. 1) Ventricular pacing decreased systolic pressure and ejection fraction relative to natural sinus rhythm. 2) Shortening during ejection and stroke work declined in early depolarized regions and increased in late depolarized regions. 3) The relation between epicardial depolarization time and systolic midwall circumferential strain was linear and similar for the simulation (slope = −3.80 ± 0.28 s−1, R2 = 0.87) and the experiments [slopes for 3 animals −2.62 ± 0.43 s−1 ( R2 = 0.59), −2.97 ± 0.38 s−1 ( R2 = 0.69), and −4.44 ± 0.51 s−1 ( R2 = 0.76)]. We conclude that our model of electromechanics is suitable to simulate ventricular pacing and that the apparently complex events observed during pacing are caused by well-known basic physiological processes.
Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE
Authors: Takeuchi Kazuhiko , Renic Marija , Bohman Quinn C. , Harder David R. , Miyata Noriyuki , Roman Richard J.
Published: June 2005

This study characterized the time course of changes in cerebral blood flow (CBF) and vascular diameter in a dual-hemorrhage model of subarachnoid hemorrhage (SAH) in rats and examined whether acute blockade of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) with N-(3-chloro-4-morpholin-4-yl)phenyl- N′-hydroxyimido formamide (TS-011) can reverse delayed vasospasm in this model. Rats received an intracisternal injection of blood (0.4 ml) on day 0 and a second injection 2 days later. CBF was sequentially measured using laser-Doppler flowmetry, and the diameters of the cerebral arteries were determined after filling the cerebral vasculature with a casting compound. CBF fell to 67% of control after the first intracisternal injection of blood but returned to a value near control 24 h later. CBF again fell to 63% of control after a second intracisternal injection of blood and remained 30% below control for 5 days. The fall in CBF after the second intracisternal injection of blood was associated with a sustained 30% reduction in the diameters of the middle cerebral, posterior communicating, and basilar arteries. Acute blockade of the synthesis of 20-HETE with TS-011 (0.1 mg/kg iv), 5 days after the second SAH, increased the diameters of the cerebral arteries, and CBF returned to control. These results indicate that the rats develop delayed vasospasm after induction of the dual-hemorrhage model of SAH and that blockade of the synthesis of 20-HETE fully reverses cerebral vasospasm in this model. They also implicate 20-HETE in the development and maintenance of delayed cerebral vasospasm.
Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell proliferative dysfunction
Authors: Varma Shubha , Lal Brajesh K. , Zheng Ruifang , Breslin Jerome W. , Saito Satoshi , Pappas Peter J. , Hobson Robert W. , Durán Walter N.
Published: June 2005

Diabetes mellitus is a major risk factor for the development of vascular complications. We hypothesized that hyperglycemia decreases endothelial cell (EC) proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathways. We cultured human umbilical vein ECs (HUVEC) in 5, 20, or 40 mM d-glucose. Cells grown in 5, 20, and 40 mM mannitol served as a control for osmotic effects. We measured EC proliferation for up to 15 days. We assessed apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt by Western blot analysis, and measured Akt kinase activity using a GSK fusion protein. HUVEC proliferation was also tested in the presence of pharmacological inhibitors of PI3k-Akt (wortmannin and LY294002) and after transfection with a constitutively active Akt mutant. ECs in media containing 5 mM d-glucose (control) exhibited log-phase growth on days 7–10. d-Glucose at 20 and 40 mM significantly decreased proliferation versus control ( P < 0.05 for both), whereas mannitol did not impair EC proliferation. Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. Pharmacological inhibition of PI3k-Akt resulted in a dose-dependent decrease in EC proliferation. Transfection with a constitutively active Akt mutant protected ECs by enhancing proliferation when grown in 20 and 40 mM d-glucose. We conclude that d-glucose regulates Akt signaling through threonine phosphorylation of Akt and that hyperglycemia-impaired PI3k-Akt signaling may promote EC proliferative dysfunction in diabetes.
Novel determinant of PKC-ε anchoring at cardiac Z-lines
Authors: Robia Seth L. , Kang Misuk , Walker Jeffery W.
Published: June 2005

The Z-line represents a critical link between the transverse tubule network and cytoskeleton of cardiac cells with a role in anchoring structural proteins, ion channels, and signaling molecules. Protein kinase C-ε (PKC-ε) regulates cardiac excitability, cardioprotection, and growth, possibly as a consequence of translocation to the Z-line/T tubule region. To investigate the mechanism of PKC-ε translocation, fragments of its NH2-terminal 144-amino acid variable domain, εV1, were fused with green fluorescent protein and evaluated by quantitative Fourier image analysis of decorated myocytes. Deletion of 23 amino acids from the NH2-terminus of εV1, including an EAVSLKPT motif important for binding to a receptor for activated C kinase (RACK2), reduced but did not abolish Z-line binding. Further deletions of up to 84 amino acids from the NH2-terminus of εV1 also did not prevent Z-line decoration. However, deletions of residues 85–144 from the COOH-terminus strongly reduced Z-line binding. COOH-terminal deletions caused 2.5-fold greater loss of binding energy (ΔΔG) than did NH2-terminal deletions. Synthetic peptides derived from these regions modulated εV1 binding and cardiac myocyte function, but also revealed considerable heterogeneity within populations of adult cardiac myocytes. The COOH-terminal subdomain important for Z-line anchoring maps to a surface in the εV1 crystal structure that complements the eight-amino acid RACK2 binding site and two previously identified membrane docking motifs. PKC-ε anchoring at the cardiac Z-line/T tubule appears to rely on multiple points of contact probably involving protein-lipid and protein-protein interactions.
Regulation of angiotensin-converting enzyme production by nicotine in human endothelial cells
Authors: Saijonmaa Outi , Nyman Tuulikki , Fyhrquist Frej
Published: June 2005

Nicotine, a component of cigarette smoke, has been implicated in the pathogenesis of cardiovascular disease. We examined whether nicotine regulates angiotensin-converting enzyme (ACE), an enzyme that plays an important role in the pathophysiology of atherosclerosis and hypertension. Human umbilical cord vein endothelial cells were treated with nicotine (0.1–1 μM) alone or in combination with vascular endothelial growth factor (VEGF; 0.5 nM) or GF-109203X (GFX; 2.5 μM). The amount of ACE in intact endothelial cells was measured by an inhibitor-binding assay method, and ACE mRNA levels were quantified using LightCycler technology. Phosphorylated PKC levels were measured by Western immunoblotting. Nicotine did not modulate basal ACE production but significantly potentiated VEGF-induced ACE upregulation. Treatment of endothelial cells with the PKC inhibitor GFX totally blocked VEGF- and nicotine-induced ACE upregulation. VEGF induced PKC phosphorylation, which was potentiated by cotreatment with nicotine. We conclude that nicotine significantly potentiated VEGF-induced ACE upregulation. This effect was probably mediated by PKC phosphorylation. The interaction of nicotine with VEGF in ACE induction may contribute to the pathogenesis of smoking-related cardiovascular disease.