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Combining classifiers for word sense disambiguation based on Dempster-Shafer theory and OWA operators

Cuong Le — 2008-05-12T02:03:21-00:00

Data & Knowledge Engineering, Vol. 63, No. 2. (November 2007), pp. 381-396.

In this paper, we discuss a framework for weighted combination of classifiers for word sense disambiguation (WSD). This framework is essentially based on Dempster-Shafer theory of evidence [G. Shafer, A Mathematical Theory of Evidence, Princeton University Press, Princeton, 1976] and ordered weighted averaging (OWA) operators [R.R. Yager, On ordered weighted averaging aggregation operators in multicriteria decision making, IEEE Transactions on Systems, Man, and Cybernetics 18 (1988) 183-190] We first determine various kinds of features which could provide complementarily linguistic information for the context, and then combine these sources of information based on Dempster's rule of combination and OWA operators for identifying the meaning of a polysemous word. We experimentally design a set of individual classifiers, each of which corresponds to a distinct representation type of context considered in the WSD literature, and then the discussed combination strategies are tested and compared on English lexical samples of Senseval-2 and Senseval-3.

The Task Force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: full text (update 2005).

H Krum — 2008-05-12T02:00:20-00:00

European heart journal, Vol. 26, No. 22. (November 2005)

Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology.

K Swedberg — 2008-05-12T02:00:27-00:00

European heart journal, Vol. 26, No. 11. (June 2005), pp. 1115-1140.

Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology.

MS Nieminen — 2005-03-03T12:46:37-00:00

Eur Heart J, Vol. 26, No. 4. (February 2005), pp. 384-416.

ACC/AHA/ASE 2003 Guideline Update for the Clinical Application of Echocardiography: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography).

MD Cheitlin — 2008-05-12T01:58:40-00:00

Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, Vol. 16, No. 10. (October 2003), pp. 1091-1110.

Semi-supervised learning integrated with classifier combination for word sense disambiguation

Anh-Cuong Le — 2008-05-12T01:57:49-00:00

Computer Speech & Language, Vol. 22, No. 4. (October 2008), pp. 330-345.

Word sense disambiguation (WSD) is the problem of determining the right sense of a polysemous word in a certain context. This paper investigates the use of unlabeled data for WSD within a framework of semi-supervised learning, in which labeled data is iteratively extended from unlabeled data. Focusing on this approach, we first explicitly identify and analyze three problems inherently occurred piecemeal in the general bootstrapping algorithm; namely the imbalance of training data, the confidence of new labeled examples, and the final classifier generation; all of which will be considered integratedly within a common framework of bootstrapping. We then propose solutions for these problems with the help of classifier combination strategies. This results in several new variants of the general bootstrapping algorithm. Experiments conducted on the English lexical samples of Senseval-2 and Senseval-3 show that the proposed solutions are effective in comparison with previous studies, and significantly improve supervised WSD.

ACC/AHA Guidelines for the Clinical Application of Echocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography). Developed in collaboration with the American Society of Echocardiography.

MD Cheitlin — 2008-05-12T01:53:49-00:00

Circulation, Vol. 95, No. 6. (18 March 1997), pp. 1686-1744.

Prediction of Mode of Death in Heart Failure: The Seattle Heart Failure Model

Dariush Mozaffarian — 2008-05-12T01:53:32-00:00

Circulation, Vol. 116, No. 4. (24 July 2007), pp. 392-398.

Background-- Prognosis and mode of death in heart failure patients are highly variable in that some patients die suddenly (often from ventricular arrhythmia) and others die of progressive failure of cardiac function (pump failure). Prediction of mode of death may facilitate decisions about specific medications or devices. Methods and Results-- We used the Seattle Heart Failure Model (SHFM), a validated prediction model for total mortality in heart failure, to assess the mode of death in 10 538 ambulatory patients with New York Heart Association class II to IV heart failure and predominantly systolic dysfunction enrolled in 6 randomized trials or registries. During 16 735 person-years of follow-up, 2014 deaths occurred, which included 1014 sudden deaths and 684 pump-failure deaths. Compared with a SHFM score of 0, patients with a score of 1 had a 50% higher risk of sudden death, patients with a score of 2 had a nearly 3-fold higher risk, and patients with a score of 3 or 4 had a nearly 7-fold higher risk (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.68). Stratification of risk of pump-failure death was even more pronounced, with a 4-fold higher risk with a score of 1, a 15-fold higher risk with a score of 2, a 38-fold higher risk with a score of 3, and an 88-fold higher risk with a score of 4 (P<0.001 for all comparisons; 1-year area under the receiver operating curve, 0.85). The proportion of deaths caused by sudden death versus pump-failure death decreased from a ratio of 7:1 with a SHFM score of 0 to a ratio of 1:2 with a SHFM score of 4 (P trend <0.001). Conclusions-- The SHFM score provides information about the likely mode of death among ambulatory heart failure patients. Investigation is warranted to determine whether such information might predict responses to or cost-effectiveness of specific medications or devices in heart failure patients. 10.1161/CIRCULATIONAHA.106.687103

Clinical features and prognosis of heart failure in women. A 5-year prospective study.

Dan Rusinaru — 2008-05-12T01:45:06-00:00

International journal of cardiology (3 May 2008)

BACKGROUND: Although heart failure (HF) is frequent and causes significant morbidity and mortality in women, data on the prognosis of women hospitalized for a first episode of HF are scarce. This study was designed to describe the clinical characteristics and treatment of HF in women and to assess the effect of gender on long-term survival. METHODS: We prospectively included consecutive patients admitted for a first episode of HF in all healthcare establishments of the Somme department (France) during the year 2000. Baseline characteristics and long-term prognosis were evaluated and compared according to gender. RESULTS: 799 patients were included (389 women and 410 men). Women were older, had a higher prevalence of hypertension and renal insufficiency, and a lower prevalence of coronary artery disease. Prescription of HF medication at discharge was not significantly different between women and men. The prevalence of HF with preserved ejection fraction was higher in women. Five-year overall survival rates were not significantly different between women and men (39% vs. 41%, p=0.58). Cardiovascular mortality in women with HF was comparable with that observed in men. The 5-year survival in women was dramatically lower than the expected 5-year survival of the age-matched general population of women. On multivariable analysis, older age, cancer, stroke, diabetes, renal insufficiency, and lower natraemia were independent predictors of 5-year mortality in women. CONCLUSIONS: The prognosis after a first episode of HF in women is severe, comparable to that observed in men, with a 5-year survival rate of 39% and a dramatic excess mortality compared to the general population of women.

Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction. A prospective 5-year study.

Christophe Tribouilloy — 2008-05-12T01:43:29-00:00

Heart (British Cardiac Society) (20 January 2008)

Objective To evaluate the prognostic impact of diabetes mellitus (DM) in patients with heart failure and preserved ejection fraction (HFPEF) Design A 5-year prospective observational study Setting Population of 386 consecutive patients from 11 healthcare establishments Patients All patients hospitalised for a first episode of HFPEF in 2000 in the Somme department (France) Interventions Diagnosis of heart failure (HF) was validated during the index hospitalisation by two independent cardiologists. Diabetic and non-diabetic groups were compared. After discharge, patients were managed by the general practitioner or referring cardiologist. Main outcome measures Overall and cardiovascular mortality Results The 96 diabetic patients (26%) were younger and had a higher prevalence of clinical coronary artery disease (CAD) than non-diabetic patients. Patients with DM had higher discharge prescription rates of ACE-inhibitors, calcium channel blockers, nitrates and statins. During the 5-year follow-up, 208 patients died (43.5%). DM was a potent independent predictor of 5-year overall mortality (HR 1.77, 95%CI 1.27-2.48, p=0.001). Compared to the expected survival of the age- and gender-matched general population, the 5-year survival of patients with DM was dramatically lower (32% vs. 79%). The 5-year relative survival (observed/expected survival) of diabetic patients was lower than that of the non-diabetic group (41% vs. 68%). Cardiovascular causes were responsible for >60% of deaths in the DM group. DM was associated with an increased risk of death in patients with clinical CAD (HR 1.82, 95%CI 1.02-3.25, p=0.04), as well as in patients without clinical CAD (HR 1.85, 95%CI 1.22-2.82, p=0.004). Conclusion In patients with HFPEF, DM is a strong predictor of poorer long-term survival.

Prognosis of heart failure with preserved ejection fraction: a 5 year prospective population-based study.

C Tribouilloy — 2008-05-12T01:42:30-00:00

European heart journal, Vol. 29, No. 3. (February 2008), pp. 339-347.

AIMS: This study was designed to identify the characteristics and long-term prognosis of heart failure with preserved ejection fraction (HFPEF) in patients hospitalized for a first episode of HF. METHODS AND RESULTS: Consecutive patients (n = 799) hospitalized for a first episode of HF during 2000 in the Somme department (France) were recruited. EF was available in 662 (83%) patients, representing the study population. Patients with HFPEF (55.6% of cases) were significantly older, with a high proportion of women. During the 5 year follow-up, 370 patients (56%) died. Patients with HFPEF had a significantly lower 5 year survival than the age- and sex-matched general population (43 vs. 72%). Five year survival rates were not significantly different in patients with preserved and reduced EF (43 vs. 46%; P = 0.95). Both groups had similar relative 5 year survival rates compared with the general population. Multivariable analysis identified age, stroke, chronic obstructive pulmonary disease, cancer, diabetes, low glomerular filtration rate, and hyponatraemia as independent predictors of 5 year mortality in patients with HFPEF. CONCLUSIONS: Heart failure with preserved ejection fraction has a poor prognosis, comparable with that of HF with reduced EF, with a 5 year survival rate after a first episode of 43% and a high excess mortality compared with the general population.

Effect of atrial fibrillation on long-term survival in patients hospitalised for heart failure with preserved ejection fraction.

Dan Rusinaru — 2008-05-12T01:40:59-00:00

European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology (3 May 2008)

BACKGROUND: The prognostic importance of atrial fibrillation (AF) in heart failure (HF) is not clearly established. Studies conducted in systolic HF have led to discordant results. AIMS: To evaluate the relation between AF and long-term survival in patients with heart failure and preserved ejection fraction (HFPEF). METHODS AND RESULTS: We prospectively included 368 consecutive patients hospitalised for a first episode of HFPEF during 2000 and compared the 5-year outcome of patients according to the presence or absence of AF on the baseline electrocardiogram. Propensity scores were used to reduce imbalance in baseline characteristics. Baseline AF was observed in 36% (n=132) of the study population. Patients with AF were older and more often had hypertensive heart disease. On univariate analysis, baseline AF was associated with an increased risk of 5-year overall mortality (HR=1.36; 95%CI 1.03-1.79; p=0.03). After adjustment for covariates, baseline AF was no longer a predictor of reduced survival. The risk of adjusted cardiovascular death in patients with and without AF was comparable. In the propensity-matched patients, AF was not related to a poorer outcome (HR=1.08; 95%CI 0.78-1.51; p=0.63). CONCLUSION: In patients hospitalised for HFPEF, AF is frequent and associated with an excess mortality mainly related to the advanced age of these patients. After adjustment for covariates, baseline AF is not an independent predictor of long-term mortality.

Heart failure with preserved ejection fraction and systolic dysfunction in the community.

MA Moutinho — 2008-05-12T01:40:21-00:00

Arquivos brasileiros de cardiologia, Vol. 90, No. 2. (February 2008), pp. 132-137.

BACKGROUND: In developed countries, heart failure with preserved ejection fraction (HFpEF) is more prevalent than heart failure with reduced ejection fraction (HFrEF) in the community. However, it has not been completely established if this fact is also observed within our community. OBJECTIVE: To determine the most prevalent form of heart failure (HFpEF or HFrEF) and whether the prevalence of HFpEF is higher in the community. METHODS: This is a cross-sectional study conducted with patients clinically diagnosed with HF who were seen in community-based health care centers from January to December 2005. Echodopplercardiograms were performed for all patients. The form of HF was stratified according to the presence of abnormalities and the shortening fraction observed on the echodopplercardiogram. RESULTS: The study evaluated 170 patients (61.0 +/- 13.3 years of age), most of them women and elderly. HFpEF was the more prevalent form of HF (64.2%, p<0.001), affecting mostly elderly women (62%, p = 0.07), whereas the opposite condition, HFrEF, was observed mostly in elderly men (63.6%, p = 0.07). Patients with no HF represented one-third of the cases (27.6%). HFrEF patients had more lower-limb edema, coronary disease, diabetes, chronic renal failure, higher Boston scores and hospital readmissions. Use of alcoholic beverages and smoking were also more common among HFrEF patients. CONCLUSION: HFpEF is the most prevalent form of HF in the community especially among elderly women, whereas HFrEF affects mostly elderly men and is associated with greater clinical severity, main risk factors and no changes in lifestyle. Despite the signs and symptoms of HF, this condition was not confirmed for one-third of the cases.

Hypertension, RAS, and gender: what is the role of aminopeptidases?

MJ Ramírez-Expósito — 2008-05-12T01:35:45-00:00

Heart failure reviews, Vol. 13, No. 3. (September 2008), pp. 355-365.

Hypertension is the major risk factor for coronary heart disease, stroke, and renal disease. Also, it is probably the most important risk factor for peripheral vascular disease and vascular dementia. Although hypertension occurs in both men and women, gender differences have been observed. However, whether sex hormones are responsible for the observed gender-associated differences in arterial blood pressure, and which is their mechanism of action, remains unclear. Local and circulating renin-angiotensin systems (RAS) are examples of systems that may be involved in the pathogenesis of hypertension. Classically, angiotensin II (Ang II) has been considered as the effector peptide of the RAS, but Ang II is not the only active peptide. Several of its degradation products, including angiotensin III (Ang III) and angiotensin IV (Ang IV) also possess biological functions. These peptides are formed via the activity of several aminopeptidases. This review will briefly summarize what is known about gender differences in RAS-regulating aminopeptidase activities, their relationship with sex hormones, and their potential role in controlling blood pressure acting through local and circulating RAS.

Interaction between two spherical particles in a nematic liquid crystal

Jun-Ichi Fukuda — 2008-05-12T01:29:04-00:00

Physical Review E, Vol. 69, No. 4. (30 April 2004), 041706.

Enhanced Production of Trichoderma reesei Endoglucanases and Use of the New Cellulase Preparations in Producing the Stonewashed Effect on Denim Fabric

Arja Miettinen-Oinonen — 2008-05-12T01:30:38-00:00

Appl. Environ. Microbiol., Vol. 68, No. 8. (1 August 2002), pp. 3956-3964.

Trichoderma reesei strains were constructed for production of elevated amounts of endoglucanase II (EGII) with or without cellobiohydrolase I (CBHI). The endoglucanase activity produced by the EGII transformants correlated with the copy number of the egl2 expression cassette. One copy of the egl2 expression cassette in which the egl2 was under the cbh1 promoter increased production of endoglucanase activity 2.3-fold, and two copies increased production about 3-fold above that of the parent strain. When the enzyme with elevated EGII content was used, an improved stonewashing effect on denim fabric was achieved. A T. reesei strain producing high amounts of EGI and -II activities without CBHI and -II was constructed by replacing the cbh2 locus with the coding region of the egl2 gene in the EGI-overproducing CBHI-negative strain. Production of endoglucanase activity by the EG-transformant strain was increased fourfold above that of the host strain. The filter paper-degrading activity of the endoglucanase-overproducing strain was lowered to below detection, presumably because of the lack of cellobiohydrolases. 10.1128/AEM.68.8.3956-3964.2002

Long-term prevention of diabetic nephropathy: an audit.

KJ Schjoedt — 2008-05-12T01:23:40-00:00

Diabetologia, Vol. 51, No. 6. (June 2008), pp. 956-961.

AIMS/HYPOTHESIS: In type 1 diabetic patients with microalbuminuria not receiving antihypertensive treatment, an increase in urinary AER (UAER) of 6-14%/year and a risk of developing diabetic nephropathy (DN) of 3-30%/year have been reported. We audited the long-term effect of blocking the renin-angiotensin-aldosterone system (RAAS) with an ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in microalbuminuric type 1 diabetic patients on progression of microalbuminuria and development of DN. METHODS: All patients with type 1 diabetes and persistent microalbuminuria (30-300 mg/24 h) were identified (n = 227) in 1995 at Steno Diabetes Center and followed for 11 years. Development of DN was defined as a UAER of >300 mg/24 h in two of three consecutive urine samples. RESULTS: Age and duration of diabetes at baseline (mean +/- SD) were 46 +/- 15 and 28 +/- 13 years, respectively. During follow-up 14 patients emigrated and 58 (26%) died. Over the same period 79% were treated with an ACEI or ARB. There was a mean decline in UAER of 4%/year. Sixty-five patients (29%) progressed to overt DN, corresponding to 3.1%/year. However, 29 of them regressed to normo- or microalbuminuria on intensified antihypertensive treatment. Glycaemic control and blood pressure remained nearly unchanged. CONCLUSIONS/INTERPRETATION: In our outpatient clinic, the implementation of RAAS-blocking treatment in type 1 diabetic patients with microalbuminuria successfully reduced long-term progression to overt DN to a rate similar to those previously reported in randomised, double-blind intervention trials of shorter duration using RAAS blockade.

Genetics of the human renin angiotensin system.

X Jeunemaitre — 2008-05-12T01:29:59-00:00

Journal of molecular medicine (Berlin, Germany), Vol. 86, No. 6. (June 2008), pp. 637-641.

The genes coding for the renin angiotensin system have been extensively studied. During the last 15 years, informative markers and functional polymorphisms have been identified, and numerous linkage and association studies have been performed in cardiovascular diseases, especially human hypertension. This mini-review aims to summarize the main findings observed for each component of this enzymatic cascade taken alone or in combination, with an emphasis on the most recent or innovative studies.

Are we poised to target ACE2 for the next generation of antihypertensives?

AJ Ferreira — 2008-05-12T01:29:45-00:00

Journal of molecular medicine (Berlin, Germany), Vol. 86, No. 6. (June 2008), pp. 685-690.

Antihypertensive drugs based on the blockade of the renin-angiotensin system (RAS) target classical components of this system, i.e., angiotensin-converting enzyme (ACE) and angiotensin (Ang) II type 1 receptor. These antihypertensives are well-recognized and successful, if prescribed properly, in reducing high blood pressure, but much less effective in preventing and reverting end-organ damage induced by cardiovascular disease (CVD) and hypertension. Thus, new strategies and new drug targets that are more effective must be discovered. Recent identification of a counterregulatory axis of the RAS [ACE2, Ang-(1-7), and Mas receptor] that is potentially important in promoting vasoprotective effects offers a novel target for CVD therapeutics. In this brief review, we will highlight the functional characteristics of this axis with special emphasis on ACE2 and its possible involvement in the pathophysiology of the CVD. In addition, we will present our views on the potential of ACE2 as a new target for the development of innovative antihypertensives by highlighting the development and functional findings obtained with small molecules ACE2 activators.

Role of the vasodilator peptide angiotensin-(1-7) in cardiovascular drug therapy.

C Schindler — 2008-05-12T01:28:20-00:00

Vascular health and risk management, Vol. 3, No. 1. (2007), pp. 125-137.

The renin-angiotensin-system (RAS) is a cascade of enzymatic reactions resulting ultimately in the formation of angiotensin II. Recent research has expanded the knowledge about the RAS by adding new components to the pathways: angiotensin-(1-5) [Ang-1-5], angiotensin-(1-7) [Ang-(1-7)], angiotensin-(1-9) [Ang-(1-9)], an ACE homologous enzyme, ACE2, and the G-protein-coupled receptor mas as a molecular receptor for Ang-(1-7). Although previous studies provided some conflicting evidence about the relevance of Ang-(1-7) in the regulation of vascular and renal function, data now demonstrate that Ang-(1-7) contributes to the cardiovascular effects of ACE-inhibitors (ACE-1) and AT1-receptor-blockers (ARBs) both in experimental conditions and in humans. This review summarizes and critically discusses the currently available experimental and clinical study evidence for the role of Ang-(1-7) as a vasodilator and anti-trophic peptide in cardiovascular drug therapy. In addition, the potential therapeutic impact of currently available RAS blocking agents (ACE-1 and ARBs) and new agents still under development (renin-inhibitors) on the RAS-effector peptides is highlighted.

New angiotensins.

J Varagic — 2008-05-12T01:27:37-00:00

Journal of molecular medicine (Berlin, Germany), Vol. 86, No. 6. (June 2008), pp. 663-671.

Accumulation of a large body of evidence during the past two decades testifies to the complexity of the renin-angiotensin system (RAS). The incorporation of novel enzymatic pathways, resulting peptides, and their corresponding receptors into the biochemical cascade of the RAS provides a better understanding of its role in the regulation of cardiovascular and renal function. Hence, in recent years, it became apparent that the balance between the two opposing effector peptides, angiotensin II and angiotensin-(1-7), may have a pivotal role in determining different cardiovascular pathophysiologies. Furthermore, our recent studies provide evidence for the functional relevance of a newly discovered rat peptide, containing two additional amino acid residues compared to angiotensin I, first defined as proangiotensin-12 [angiotensin-(1-12)]. This review focuses on angiotensin-(1-7) and its important contribution to cardiovascular function and growth, while introducing angiotensin-(1-12) as a potential novel angiotensin precursor.

Prevention of type 2 diabetes mellitus with angiotensin-converting-enzyme inhibitors.

LV Solski — 2008-05-12T01:26:39-00:00

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, Vol. 65, No. 10. (15 May 2008), pp. 935-940.

PURPOSE: The physiological and clinical data for using angiotensin-converting- enzyme (ACE) inhibitors to prevent new-onset type 2 diabetes mellitus are reviewed. SUMMARY: ACE inhibitors have established their role in hypertension, primary and secondary prevention of cardiovascular events, and prevention of progression to and worsening of renal function. However, their ability to preserve pancreatic function and prevent new-onset diabetes is also coming to the forefront. Secondary analyses of large-scale clinical trials, such as the Captopril Prevention Project, the Heart Outcomes Prevention Evaluation, and the Studies of Left Ventricular Dysfunction trial, are revealing the potential benefits of these agents in diabetes prevention. However, the results of such studies have limited application because they are secondary analyses and, in some cases, were conducted 10 or more years after the original study. Enrollees were evaluated using different diagnostic guidelines for diabetes or not formally evaluated at all. Even in the most recent of the trials, the validity of the results is questionable because researchers coadministered a disease-modifying drug with the ACE inhibitor, potentially blunting the results. While intense lifestyle modifications are still superior in the prevention of new-onset diabetes, patients and providers will continue to investigate new options for preventing the progression of impaired fasting glucose to diabetes, though this delay does not correlate with a decrease in morbidity and mortality. CONCLUSION: ACE inhibitors may preserve pancreatic function and prevent new-onset diabetes, especially for patients who are hypertensive with impaired glucose tolerance. Large studies investigating the effect of ACE inhibitors on the prevention of diabetes as a primary outcome are needed to determine the use for this indication.

Angiotensin-(1-7): Pharmacological properties and pharmacotherapeutic perspectives.

D Iusuf — 2008-05-12T01:24:43-00:00

European journal of pharmacology, Vol. 585, No. 2-3. (13 May 2008), pp. 303-312.

Therapeutic modulation of the renin-angiotensin system is not complete without taking into consideration the beneficial effects of angiotensin-(1-7) in cardiovascular pathology. Various pharmacological pathways are already exploited to involve this heptapeptide in therapy as both inhibitors of angiotensin-converting enzyme and angiotensin II type 1 receptor blockers increase its levels. These drugs and administered angiotensin-(1-7) elicit various common effects, and some effects of the drugs are partially mediated by angiotensin-(1-7). The pharmacodynamic profile of angiotensin-(1-7) is rather complex, and in vitro and in vivo studies demonstrated a wide palette of effects for angiotensin-(1-7), some of them potentially beneficial for cardiovascular disease. Using various animal models to study cardiovascular physiology and disease it was shown that angiotensin-(1-7) has antihypertensive, antihypertrophic, antifibrotic and antithrombotic properties, all properties that may prove beneficial in a clinical setting. We also observed a novel action of angiotensin-(1-7), namely its capacity to stimulate the proliferation of endothelial progenitor cells. Access of angiotensin-(1-7) to the clinic, however, is restricted due to its unfavorable pharmacokinetic properties. In order to benefit of the therapeutic potential of angiotensin-(1-7) it is crucial to increase its half-life, either by using more stable analogues, which are now under development, or specific delivery methods. We here review the pharmacological characteristics and therapeutic potential of angiotensin-(1-7), implementing the experimental strategies taken to exploit the pharmacological mechanism of this heptapeptide in a clinical setting, and present our contribution to this field of research.

Computation in finitary stochastic and quantum processes

Karoline Wiesner — 2008-05-11T13:48:14-00:00

Physica D: Nonlinear Phenomena, Vol. In Press, Corrected Proof

We introduce stochastic and quantum finite-state transducers as computation-theoretic models of classical stochastic and quantum finitary processes. Formal process languages, representing the distribution over a process' behaviors, are recognized and generated by suitable specializations. We characterize and compare deterministic and nondeterministic versions, summarizing their relative computational power in a hierarchy of finitary process languages. Quantum finite-state transducers and generators are a first step toward a computation-theoretic analysis of individual, repeatedly measured quantum dynamical systems. They are explored via several physical systems, including an iterated-beam-splitter, an atom in a magnetic field, and atoms in an ion trap--a special case of which implements the Deutsch quantum algorithm. We show that these systems' behaviors, and so their information processing capacity, depends sensitively on the measurement protocol.

Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit.

E Lipsic — 2008-05-12T01:25:50-00:00

European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology, Vol. 10, No. 1. (January 2008), pp. 22-29.

BACKGROUND: Erythropoietin (EPO) may improve cardiac function and induce neovascularisation in experimental models of chronic heart failure (CHF). However, the increased haematocrit associated with EPO treatment might exert concomitant deleterious effects. AIM: To investigate the haematocrit independent effects of EPO on cardiac function. METHODS AND RESULTS: Rats underwent permanent coronary artery ligation to induce myocardial infarction (MI) or sham surgery. Three weeks after MI, rats were randomly allocated to treatment with vehicle (MI) or the long-acting EPO analogue darbepoetin alfa administered in a high (40 microg/kg/3 weeks, MI-EPO-high) or a low-dose (0.4 microg/kg/3 weeks, MI-EPO-low). After 9 weeks, haemodynamic parameters, myocardial histology and Myosin Heavy Chain (MHC) isoforms were determined. High-dose EPO resulted in a significant increase in haematocrit (p<0.01) while low-dose EPO had no effect on haematocrit levels. EPO significantly improved cardiac function in both EPO groups, reflected by increased left ventricular (LV)-developed pressure and improved contractility (dP/dt(max)) and relaxation (dP/dt(min)) indices of the LV at 9-weeks (all p<0.05 compared to MI). The improved cardiac function was associated with increased capillary growth (38% in MI-EPO-high (p<0.01) and 27% in MI-EPO-low (p<0.05)) and an attenuated switch to slow beta-MHC isoforms in both EPO groups. CONCLUSIONS: EPO improves cardiac function and induces neovascularisation at a dose that does not increase haematocrit, thereby circumventing the possible deleterious effects of increased erythropoiesis.

Erythropoietin in cardiac disease: New features of an old drug.

WP Ruifrok — 2008-05-12T01:25:30-00:00

European journal of pharmacology, Vol. 585, No. 2-3. (13 May 2008), pp. 270-277.

Erythropoietin is a haematopoietic hormone with extensive non-haematopoietic effects. The discovery of an erythropoietin receptor outside the haematopoietic system has fuelled the research into the beneficial effects of erythropoietin for various conditions, predominantly in cardiovascular disease. Experimental evidence has revealed the cytoprotective and angiogenic properties of erythropoietin and it seems that the erythropoietin-erythropoietin receptor system provides a powerful backbone against acute and chronic myocardial ischemia, each gaining from the different properties of erythropoietin. Clinical trials in which erythropoietin was titrated to achieve certain haematocrit levels have generated equivocal results. It has been suggested that a (too) high haematocrit is undesirable in cardiovascular disease. We have shown that intermittent (low-dose) erythropoietin administration, that does not increase haematocrit substantially, suffices to activate the beneficial downstream pathways of erythropoietin. We postulate that intermittent administration or a lower than conventional dose of erythropoietin, not only aimed at increasing haemoglobin at high levels, will provide powerful cellular protection and will improve cardiac outcome, without the side effects of erythropoietin associated with increased haematocrit.

Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10).

R Wilcox — 2008-05-12T01:20:25-00:00

American heart journal, Vol. 155, No. 4. (April 2008), pp. 712-717.

BACKGROUND: Composite end points of major adverse cardiovascular events (MACEs) are standard measures for comparing treatment in large cardiovascular outcome studies. This analysis from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive) evaluated the effects of pioglitazone on the prespecified MACE end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE1) and on 6 post hoc MACE composites (various combinations of all-cause, cardiovascular, or cardiac mortality; plus nonfatal myocardial infarction; plus nonfatal stroke; and/or acute coronary syndrome) in patients with type 2 diabetes. METHODS: PROactive was a cardiovascular outcome study that randomized patients with type 2 diabetes to pioglitazone (n = 2605) or placebo (n = 2633), in addition to existing glucose-lowering and cardiovascular medications. Pioglitazone was titrated from 15 to 45 mg/d based upon tolerability. Mean follow-up was 34.5 months. RESULTS: At final visit, 257 (9.9%) pioglitazone-treated and 313 (11.9%) placebo-treated patients had a first event that contributed to the MACE1 end point (hazard ratio 0.82, 95% CI 0.70-0.97, P = .0201). There were statistically significant differences in favor of pioglitazone in 5 of the other MACE end points (P < .05) and a trend to benefit in the sixth (P = .052), with hazard ratios of 0.79 to 0.83. CONCLUSIONS: In patients with advanced type 2 diabetes at high risk for cardiovascular events, pioglitazone treatment resulted in significant risk reductions in MACE composite end points to 3 years.

Quasi-Newton Methods, Motivation and Theory

Jr — 2008-05-12T01:18:41-00:00

SIAM Review, Vol. 19, No. 1. (1977), pp. 46-89.

This paper is an attempt to motivate and justify quasi-Newton methods as useful modifications of Newton's method for general and gradient nonlinear systems of equations. References are given to ample numerical justification; here we give an overview of many of the important theoretical results and each is accompanied by sufficient discussion to make the results and hence the methods plausible.

Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension.

T Philipp — 2008-05-12T01:18:49-00:00

Clinical therapeutics, Vol. 29, No. 4. (April 2007), pp. 563-580.

BACKGROUND: Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. OBJECTIVES: Two studies were conducted to compare the efficacy of various combinations of amlodipine and valsartan administered once daily with their individual components and placebo in patients with mild to moderate essential hypertension (mean sitting diastolic blood pressure [MSDBP] >/=95 and < 110 mm Hg). A secondary objective was to evaluate safety and tolerability. METHODS: The 2 studies were multinational, multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group trials. In study 1, patients were randomized to receive amlodipine 2.5 or 5 mg once daily, valsartan 40 to 320 mg once daily, the combination of amlodipine 2.5 or 5 mg with valsartan 40 to 320 mg once daily, or placebo. In study 2, patients were randomized to receive amlodipine 10 mg once daily, valsartan 160 or 320 mg once daily, the combination of amlodipine 10 mg with valsartan 160 or 320 mg once daily, or placebo. The primary efficacy variable in both studies was change from baseline in MSDBP at the end of the study. Secondary variables included the change in mean sitting systolic blood pressure (MSSBP), response rate (the proportion of patients achieving an MSDBP <90 mm Hg or a >/= 10-mm Hg decrease from baseline), and control rate (the proportion of patients achieving an MSDBP <90 mm Hg). Safety was assessed in terms of adverse events (spontaneously reported or elicited by questioning), vital signs, and laboratory values. RESULTS: A total of 1911 patients were randomized to treatment in study 1 (1022 amlodipine + valsartan; 507 valsartan; 254 amlodipine; 128 placebo); 1250 were randomized to treatment in study 2 (419, 415, 207, and 209, respectively). In all treatment groups in both studies, the majority of patients were white (79.5% study 1, 79.4% study 2) and male (53.5% and 50.3%, respectively). The overall mean age was 54.4 years in study 1 and 56.9 years in study 2. The mean weight of patients in study 1 was higher than that in study 2 (88.8 vs 79.7 kg). The overall baseline mean sitting BP was 152.8/99.3 mm Hg in study 1 and 156.7/99.1 mm Hg in study 2. With the exception of a few combinations that included amlodipine 2.5 mg, the combination regimens in both studies were associated with significantly greater reductions in MSDBP and MSSBP compared with their individual components and placebo (P < 0.05). A positive dose response was observed for all combinations. The highest response rate in study 1 was associated with the highest dose of combination therapy (amlodipine 5 mg + valsartan 320 mg: 91.3%). Amlodipine 5 mg, valsartan 320 mg, and placebo were associated with response rates of 71.9%, 73.4%, and 40.9%, respectively. In study 2, the 2 doses of combination therapy were associated with similar response rates (amlodipine 10 mg + valsartan 160 mg: 88.5%; amlodipine 10 mg + valsartan 320 mg: 87.5%). Amlodipine 10 mg was associated with a response rate of 86.9%; valsartan 160 and 20 mg were associated with response rates of 74.9% and 72.0%, respectively; and placebo was associated with a response rate of 49.3%. Control rates followed a similar pattern. The incidence of peripheral edema with combination therapy was significantly lower compared with amlodipine monotherapy (5.4% vs 8.7%, respectively; P = 0.014), was significantly higher compared with valsartan monotherapy (2.1%; P < 0.001), and did not differ significantly from placebo (3.0%). CONCLUSIONS: In these adult patients with mild to moderate hypertension, the combination of amlodipine + valsartan was associated with significantly greater blood pressure reductions from baseline compared with amlodipine or valsartan monotherapy or placebo. The incidence of peripheral edema was significantly lower with combination therapy than with amlodipine monotherapy.

DNA sequence of the excision sites of a mitochondrial plasmid from senescent Podospora anserina.

DJ Cummings — 2008-05-12T01:10:53-00:00

Nucleic acids research, Vol. 11, No. 7. (11 April 1983), pp. 2111-2119.

During senescence in Podospora anserina, specific gene regions of the mitochondrial genome are excised and amplified. The most prevalent, termed alpha-event senDNA, is a 2600 bp circular molecule which is excised from the contiguous Hae III fragments 23,14 region of the mitochondrial DNA restriction map. We have cloned alpha-DNA plasmid from races s+ and A+ as well as the genomic fragments Hae III 23,14 and have sequenced those regions which constitute the alpha-junction sites. We have found that one excision site (J1) is located 24 bp from the proximal Hae III 23 restriction site and the other (J2) 172 bp from the distal Hae III 14 site. Flanking the alpha-DNA sequences on the mitochondrial genome, there are 10 bp palindromic sequences: CAATATATTG, ending 3 bases from the J1 site, and ATTATATAAT which starts 8 bases from the J2 site. Neither of these 10 bp palindromes are present on the alpha-DNA plasmid. Abutting the J1 site on the alpha-DNA there is a 5 bp sequence (GTGCT) which is repeated 8 bp downstream. In joining the two distal J1 and J2 sites, a 7 bp repeat (ACGTGCG) is produced. These results are discussed within the context of site-specific recombination.

Encyclopedia of Rhetoric and Composition: Communication from Ancient Times to the Information Age (Garland Reference Library of the Humanities)

Theresa Enos — 2008-05-12T00:50:28-00:00

(01 January 1996)

Modern rhetoric is a vital tool Rhetoric, the strategic presentation of ideas and choice of language, informs all writing, speaking, thinking, and learning. It provides the guiding principles and practical framework for effective written and spoken communication. Modern rhetoric can help fight the current literacy crisis in our schools--it is a vital tool for teaching students to write logically and persuasively. Alphabetically arranged This alphabetically-arranged reference guide surveys the field, covering rhetoric's principles, concepts, applications, practical tools, and major thinkers. Rhetoric is increasingly studied in the context of other disciplines, such as anthropology, linguistics, philosophy, psychology, and pedagogy, because its well-established rules and time-honored methods are useful for developing modern communications and writing skills. Draws on expertise of 288 contributors Drawing on the scholarship and expertise of 288 contributors, the Encyclopediapresents a long-needed overview of rhetoric and its role in contemporary education and communications, discusses rhetoric's contributions to various fields, surveys the applications of this versatile discipline to the teaching of English and language arts, and illustrates its usefulness in all kinds of discourse, argument, and exchange of ideas. The coverage has been tailored to meet the needs of American teachers and students. Each entry followed by a bibliographyFollowing each entry is a bibliography of key texts and recommended reading. Cross-references, a comprehensive index, and a list of entries and contributors make this unique reference work easy to use. The Encyclopedia's 467 entries take four forms: brief identification of figure, term, or concept (Hugh Blair, commonplaces, kairos) * elaborate notes (exposition, hermeneutics, Nietzsche) * essays that explore a subject in depth (Aristotle, ethos, feminist rhetoric) * extended articles that illuminate rhetoric's art and methodology (argument, composition studies, invention) Distinguished Advisory Board: Carroll C. Arnold, Emeritus, Pennsylvania State University * Patricia Bizzell, Department of English, College of the Holy Cross * Ernest G. Bormann, Department of Speech-Communication, University of Minnesota * Stuart C. Brown, Department of English, New Mexico State University * Edward P.J. Corbett, Emeritus, Department of English, Ohio State University * Frank J. D'Angelo, Department of English, Arizona State University * Richard Leo Enos, Department of English, Texas Christian University * Bruce E. Gronbeck, Department of Communication Studies, University of Iowa * Bruce Herzberg, Department of English, Bentley College * Winifred Bryan Horner, Emerita, Department of English, Texas Christian University * Richard L. Johannesen, Department of Communication Studies, Northern Illinois University * Henry W. Johnstone, Jr., Department of Philosophy, Pennsylvania State University * James Kinneavy, Department of English, University of Texas at Austin * Janice M. Lauer, Department of English, Purdue University * Andrea A. Lunsford, Department of English, Ohio State University * James J. Murphy, Department of Rhetoric, University of California, Davis * Muriel Saville-Troike, Department of English, University of Arizona * Robert L. Scott, Department of Speech-Communication, University of Minnesota * Kathleen E. Welch, Department of English, University of Oklahoma * W. Ross Winterowd, Department of Rhetoric, Linguistics, and Literature, University of Southern California * Richard Young, Department of English, Carnegie Mellon University

Density-dependent warning coloration

Gregory Sword — 2008-05-12T00:51:07-00:00

Nature, Vol. 397, No. 6716. (21 January 1999), pp. 217-217.

A role for phenotypic plasticity in the evolution of aposematism.

GA Sword — 2008-05-12T00:48:16-00:00

Proceedings. Biological sciences / The Royal Society, Vol. 269, No. 1501. (22 August 2002), pp. 1639-1644.

The evolution of warning coloration (aposematism) has been difficult to explain because rare conspicuous mutants should suffer a higher cost of discovery by predators relative to the cryptic majority, while at frequencies too low to facilitate predator aversion learning. Traditional models for the evolution of aposematism have assumed conspicuous prey phenotypes to be genetically determined and constitutive. By contrast, we have recently come to understand that warning coloration can be environmentally determined and mediated by local prey density, thereby reducing the initial costs of conspicuousness. The expression of density-dependent colour polyphenism is widespread among the insects and may provide an alternative pathway for the evolution of constitutive aposematic phenotypes in unpalatable prey by providing a protected intermediate stage. If density-dependent aposematism can function as an adaptive intermediate stage for the evolution of constitutive aposematic phenotypes, differential reaction norm evolution is predicted among related palatable and unpalatable prey populations. Here, I present empirical evidence that indicates that (i) the expression of density-dependent colour polyphenism has differentially evolved between palatable and unpalatable populations of the grasshopper Schistocerca emarginata (= lineata) (Orthoptera: Acrididae), and (ii) variation in plasticity between these populations is commensurate with the expected costs of conspicuousness.

RNA loop-loop interactions as dynamic functional motifs

Christine Brunel — 2006-04-13T20:54:36-00:00

Biochimie, Vol. 84, No. 9. (September 2002), pp. 925-944.

RNA loop-loop interactions are frequently used to trigger initial recognition between two RNA molecules. In this review, we present selected well-documented cases that illustrate the diversity of biological processes using RNA loop-loop recognition properties. The first one is related to natural antisense RNAs that play a variety of regulatory functions in bacteria and their extra-chromosomal elements. The second one concerns the dimerization of HIV-1 genomic RNA, which is responsible for the encapsidation of a diploid RNA genome. The third one concerns RNA interactions involving double-loop interactions. These are used by the bicoid mRNA to form dimers, a property that appears to be important for mRNA localization in drosophila embryo, and by bacteriophage phi29 pRNA which forms hexamers that participate in the translocation of the DNA genome through the portal vertex of the capsid. Despite the high diversity of systems and mechanisms, some common features can be highlighted. (1) Efficient recognition requires rapid bi-molecular binding rates, regardless of the RNA pairing scheme. (2) The initial recognition is favored by particular conformations of the loops enabling a proper presentation of nucleotides (generally a restricted number) that initiate the recognition process. (3) The fate of the initial reversible loop-loop complex is dictated by both functional and structural constraints. RNA structures have evolved either to “freeze” the initial complex, or to convert it into a more stable one, which involves propagation of intermolecular interactions along topologically feasible pathways. Stabilization of the initial complex may also be assisted by proteins and/or formation of additional contacts.

Enhanced quantum tunnelling induced by disorder

J Heinrichs — 2008-05-12T00:41:00-00:00

arXiv:0805.1347 (9 May 2008)

We reconsider the problem of the enhancement of tunnelling of a quantum particle induced by disorder of a one-dimensional tunnel barrier of length $L$, using two different approximate analytic solutions of the invariant imbedding equations of wave propagation for weak disorder. The two solutions are complementary for the detailed understanding of important aspects of numerical results on disorder-enhanced tunnelling obtained recently by Kim et al. (Phys. rev. B 77, 024203 (2008)). In particular, we derive analytically the scaled wavenumber $(kL)$-threshold where disorder-enhanced tunnelling of an incident electron first occurs, as well as the rate of variation of the transmittance in the limit of vanishing disorder. Both quantities are in good agreement with the numerical results of Kim et al. Our non-perturbative solution of the invariant imbedding equations allows us to show that the disorder enhances both the mean conductance and the mean resistance of the barrier.

Multi-objective Genetic Algorithm Based Clustering Approach and Its Application to Gene Expression Data

Tansel Özyer — 2008-05-12T00:37:43-00:00

Advances in Information Systems (2005), pp. 451-461.

Gene clustering is a common methodology for analyzing similar data based on expression trajectories. Clustering algorithms in general need the number of clusters as a priori, and this is mostly hard to estimate, even by domain experts. In this paper, we use Niched Pareto k-means Genetic Algorithm (GA) for clustering m-RNA data. After running the multi-objective GA, we get the pareto-optimal front that gives alternatives for the optimal number of clusters as a solution set. We analyze the clustering results under two cluster validity techniques commonly cited in the literature, namely DB index and SD index. This gives an idea about ranking the optimal numbers of clusters for each validity index. We tested the proposed clustering approach by conducting experiments using three data sets, namely figure2data, cancer (NCI60) and Leukaemia data. The obtained results are promising; they demonstrate the applicability and effectiveness of the proposed approach. Keywords: multi-objective genetic algorithm, clustering, validity analysis, gene expression data analysis.

Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists.

A Bernardo — 2008-05-12T00:36:12-00:00

PPAR research, Vol. 2008 (2008)

In the recent years, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders. PPAR-gamma agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Delta(12,14) prostaglandin J(2)), and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs) have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies. The pleiotropic effects of PPAR-gamma agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes), as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia. In the present article, we will review the recent findings supporting a major role for PPAR-gamma agonists in controlling neuroinflammation and neurodegeneration through their activities on glial cells, with a particular emphasis on microglial cells as major macrophage population of the brain parenchyma and main actors in brain inflammation.

A novel technique for isolating functional mast cells from the heart.

L Morgan — 2008-05-12T00:33:03-00:00

Inflammation research : official journal of the European Histamine Research Society ... [et al.] (9 May 2008)

OBJECTIVE AND DESIGN: The purpose of this study was to determine the feasibility of adapting peritoneal and pleural mast cell isolation techniques to recover cardiac mast cells that retain their functional response to the secretagogue, compound 48/80. METHODS: Using a novel protocol in rats, viable epicardial mast cells were recovered by aspiration of HBSS injected into the pericardial space. Functionality of these cells was determined by ELISA quantification of histamine release in response to compound 48/80, calcium ionophore A23187 and substance P. Mast cell phenotype was determined based on the presence of chymase and tryptase demonstrated by immunofluorescence, alcian blue-safranin staining, and Western blotting. RESULTS: Mast cells isolated in this manner have low basal rates of histamine release and are highly responsive to these secretagogues. These epicardial mast cells were of the connective tissue type, which is consistent with previous reports characterizing cardiac mast cells isolated from the heart by enzymatic dispersion techniques. CONCLUSIONS: This novel pericardial aspiration technique facilitates the straightforward characterization of isolated epicardial mast cell functionality in a controlled in vitro environment, furthering our understanding of their contribution to myocardial disease.

An in Vivo Map of the Yeast Protein Interactome

Kirill Tarassov — 2008-05-12T00:30:55-00:00

Science (8 May 2008), 1153878.

Protein interactions regulate the systems-level behavior of cells, thus, deciphering the structure and dynamics of protein interaction networks in their cellular context is a central goal in biology. We have performed a genome-wide in vivo screen for protein-protein interactions (PPIs) in Saccharomyces cerevisiae by means of a protein-fragment complementation assay (PCA). We identified 2,770 interactions among 1,124 endogenously expressed proteins. Comparison with previous studies confirms known interactions, but most are new, revealing a previously unknown sub-space of the yeast protein interactome. PCA detects structural and topological relationships between proteins, providing an 8-nanometer resolution map of dynamically interacting complexes in vivo and extended networks that provide insights into fundamental cellular processes, including cell polarization and autophagy, pathways that are evolutionarily conserved and central to both development and human health. 10.1126/science.1153878

D'orenone Blocks Polarized Tip-Growth of Root Hairs by Interfering with the PIN2-Mediated Auxin Transport Network in the Root Apex.

Markus Schlicht — 2008-05-12T00:29:22-00:00

The Plant journal : for cell and molecular biology (9 May 2008)

The C(18)-ketone ((5E,7E)-6-methyl-8-(2,6,6-trimethylcyclohex-1-enyl)octa-5,7-dien-2-one) (D'orenone) has been postulated to be an early cleavage product of beta-carotene en route to trisporic acids; these act as morphogenetic factors during the sexual reproduction of zygomycetes. Here we report that D'orenone blocks the highly polarized tip growth of root hairs at causing tip-growth to stop completely within a few minutes. Importantly, external auxin restores these effects of D'orenone on root hairs. Further analysis revealed that D'orenone lowers auxin concentration in trichoblasts via PIN2-mediated auxin efflux below critical levels essential for root hair growth. D'orenone increases specifically PIN2 protein abundance without affecting PIN2 transcripts, and that the PIN2 expression domain enlarges and shifts basipetally, resulting in more active auxin transport. Final evidence for PIN2 acting as the specific target of D'orenone is the observation that this compound does not interfere with the root hair growth in roots of null mutant lines.

COGNITIVE SCIENCE: Rethinking Folk Psychology

Erik Myin — 2008-05-12T00:29:01-00:00

Science, Vol. 320, No. 5876. (2 May 2008), 615.

10.1126/science.1157120

AUXIN RESPONSES IN MUTANTS OF THE ARABIDOPSIS COP9 SIGNALOSOME.

Esther Mirjam Natascha Dohmann — 2008-05-12T00:29:01-00:00

Plant physiology (8 May 2008)

The COP9 signalosome (CSN) is an evolutionarily conserved multiprotein complex that interacts with cullin-RING type E3 ubiquitin ligases (CRLs). CSN subunit 5 (CSN5), which when incorporated into CSN can deconjugate the NEDD8-modification from the cullin subunit of CRLs, is essential for CSN's role in controlling CRL activity. Whether the CSN5 monomer, which is maintained in csn mutants such as csn3 or csn4, has a functional role, remained to be established. We performed a comparative gene expression profiling experiment with Arabidopsis (Arabidopsis thaliana) csn3, csn4, and csn5 mutants, and we show here that these mutants cannot be distinguished at the transcriptional level. Furthermore, we show that csn3 csn5 mutants are morphologically indistinguishable from csn3 or csn5 mutants. Taken together these data suggest that the CSN5 monomer does not have a function that leads to transcriptional or morphological changes in the csn mutants. We further examined auxin responses in csn mutants. While CSN had previously been shown to be required for the auxin response-regulatory E3 complexes, specifically SCF(TIR1), the csn mutant phenotype suggests that CSN is not essential for auxin responses. We present physiological and genetic data, which indicate that auxin responses are indeed only partially impaired in csn mutants and that this is not the result of maternally contributed CSN. Finally, we discuss these findings in the context of the current understanding of the role of neddylation and CSN-mediated deneddylation for CRL activity.

CressExpress: A tool for large-scale mining of expression data from Arabidopsis thaliana.

Vinodh Srinivasasainagendra — 2008-05-12T00:28:45-00:00

Plant physiology (8 May 2008)

CressExpress is a user-friendly, on-line co-expression analysis tool for Arabidopsis microarray expression data that computes patterns of correlated expression between user-entered query genes and the rest of the genes in the genome. Unlike other co-expression tools, CressExpress allows characterization of tissue-specific co-expression networks through user-driven filtering of input data based on sample tissue type. CressExpress also performs Pathway-Level Co-expression (PLC) analysis on each set of query genes, identifying and ranking genes based on their common connections with two or more query genes. This allows identification of novel candidates for involvement in common processes and functions represented by the query group. Users launch experiments using an easy-to-use web-based interface and then receive the full complement of results, along with a record of tool settings and parameters, via an email link to the CressExpress Web site. Data sets featured in CressExpress are strictly versioned, and include expression data from MAS5, GCRMA, and RMA array processing algorithms. To demonstrate applications for CressExpress, we present co-expression analyses of cellulose synthase (CESA) genes, indolic glucosinolate biosynthesis, and flowering. We show that sub-selecting sample types produces a richer network for genes involved in flowering in Arabidopsis. CressExpress provides direct access to expression values via an easy-to-use URL-based web service, allowing users to determine quickly if their query genes are co-expressed with each other and likely to yield informative PLC results. The tool is available at http://www.cressexpress.org.

The AP2/ERF-domain transcription factor ORA59 integrates jasmonic acid and ethylene signals in plant defense.

Martial Pre — 2008-05-12T00:28:13-00:00

Plant physiology (8 May 2008)

Plant defense against pathogens depends on the action of several endogenously produced hormones, including jasmonic acid (JA) and ethylene. In certain defense responses, JA and ethylene signaling pathways synergize to activate a specific set of defense genes. Here we describe the role of the Arabidopsis thaliana AP2/ERF-domain transcription factor ORA59 in JA and ethylene signaling and in defense. JA- and ethylene-responsive expression of several defense genes, including the plant defensin gene PDF1.2, depended on ORA59. As a result, overexpression of ORA59 caused increased resistance against the fungus Botrytis cinerea, whereas ORA59-silenced plants were more susceptible. Several AP2/ERF-domain transcription factors have been suggested to be positive regulators of PDF1.2 gene expression based on overexpression in stably transformed plants. Using two different transient overexpression approaches we found that only ORA59 and ERF1 were able to activate PDF1.2 gene expression in contrast to the related proteins AtERF1 and AtERF2. Our results demonstrate that ORA59 is an essential integrator of the JA and ethylene signal transduction pathways, and thereby provide new insight in the nature of the molecular components involved in the crosstalk between these two hormones.

pBINPLUS/ARS: an improved plant transformation vector based on pBINPLUS.

W Belknap — 2008-05-12T00:27:19-00:00

BioTechniques, Vol. 44, No. 6. (May 2008), pp. 753-756.

Binary plant transformation vectors are widely used for introduction of transgenes into plants via Agrobacterium tumefaciens-mediated transformation. We report the construction of a binary plant vector pBINPLUS/ARS based on the pBINPLUS vector. Improvements introduced into pBINPLUS/ARS include the use of nonproprietary (ubiquitin-3 gene of Solanum tuberosum) promoter and terminator sequences for transcription of the NptII selectable marker and introduction of rare 8-bp restriction enzyme sites flanking both the NptII coding sequence (PmeI) and the entire selectable marker gene (FseI). This vector offers all of the advantages of its predecessor pBINPLUS and its helper plasmid pUCAP, which use the proprietary nopaline synthase promoter and terminator, while allowing for facile modification of selectable marker sequences in complex binary vector constructs. pBINPLUS/ARS has been used to introduce transgenes into potato and other crop species and is available to all researchers in academic, government, and industrial laboratories for proof-of-principle and commercial applications.

The topless plant developmental phenotype explained!

Karen Osmont — 2008-04-30T22:08:01-00:00

Genome Biology, Vol. 9 (30 April 2008), 219.

Classical Mechanics, 3rd ed.

Herbert Goldstein — 2007-05-04T12:50:15-00:00

American Journal of Physics, Vol. 70, No. 7. (2002), pp. 782-783.

doi:10.1119/1.1484149 PACS: 01.30.Vv, 01.50.-i, 45.00.00 Additional Information Full Text: [ HTML Sectioned HTML PDF (38 kB) GZipped PS

Speed kills? Speed, accuracy, encapsulations and causal understanding

Woods — 2006-09-22T21:55:36-00:00

Medical Education, Vol. 40, No. 10. (October 2006), pp. 973-979.

Should a colon cancer screening decision aid include the option of no testing? A comparative trial of two decision aids

Jennifer Griffith — 2008-03-06T05:30:43-00:00

BMC Medical Informatics and Decision Making, Vol. 8 (05 March 2008), 10.

Failure to Intensify Antihypertensive Treatment by Primary Care Providers: A Cohort Study in Adults with Diabetes Mellitus and Hypertension

Shari Bolen — 2008-05-12T00:09:47-00:00

Journal of General Internal Medicine, Vol. 23, No. 5. (23 May 2008), pp. 543-550.

Abstract Background Although tight blood pressure control is crucial in reducing vascular complications of diabetes, primary care providers often fail to appropriately intensify antihypertensive medications. Objective To identify novel visit-based factors associated with intensification of antihypertensive medications in adults with diabetes. Design Non-concurrent prospective cohort study. Patients A total of 254 patients with type 2 diabetes and hypertension enrolled in an academically affiliated managed care program. Over a 24-month interval (1999–2001), we identified 1,374 visits at which blood pressure was suboptimally controlled (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Measurements and Main Results Intensification of antihypertensive medications at each visit was the primary outcome. Primary care providers intensified antihypertensive treatment in only 176 (13%) of 1,374 visits at which blood pressure was elevated. As expected, higher mean systolic and mean diastolic blood pressures were important predictors of intensification. Treatment was also more likely to be intensified at visits that were “routine” odds ratio (OR) 2.08; 95% Confidence Interval [95% CI] 1.36–3.18), or that paired patients with their usual primary care provider (OR 1.84; 95% CI 1.11–3.06). In contrast, several factors were associated with failure to intensify treatment, including capillary glucose >150 mg/dL (OR 0.54; 95% CI 0.31–0.94) and the presence of coronary heart disease (OR 0.61; 95% CI 0.38–0.95). Co-management by a cardiologist accounted partly for this failure (OR 0.65; 95% CI 0.41–1.03). Conclusions Failure to appropriately intensify antihypertensive treatment is common in diabetes care. Clinical distractions and shortcomings in continuity and coordination of care are possible targets for improvement.