bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tobacco specific nitrosamines and potential reduced exposure products for smokers: a preliminary evaluation of Advance™
Authors: Breland A B , Acosta M C , Eissenberg T 
Published: September 2003

Objective:To develop a method for evaluating the carcinogen delivery of potential reduced exposure products (PREPs) like Advance™, a PREP marketed to reduce smokers’ exposure to one tobacco specific nitrosamine (TSN), NNK, a potent lung carcinogen.Design, setting, and participants:Latin square ordered, three condition, outpatient, crossover design with 12 smokers of light or ultra-light cigarettes (15 or more cigarettes/day). In each five day condition, participants either smoked own brand, Advance™, or no cigarettes. Also, on the first and last day of each condition, participants smoked one cigarette in the laboratory.Main outcome measures:Subject rated measures of tobacco/nicotine withdrawal, expired air carbon monoxide, urine concentrations of cotinine and NNAL (one TSN biomarker), puff volume, duration, number, and interpuff interval.Results:Relative to own brand, Advance™ produced similar withdrawal suppression, slightly lower carbon monoxide, equivalent cotinine, and 51% lower NNAL concentrations. The lowest cotinine and NNAL concentrations were observed in the no cigarette condition. Participants took fewer puffs when smoking Advance™.Conclusions:Past experience with PREPs that failed to reduce smoking’s harm demonstrates the need for clinical methods in PREP evaluation. This study shows how assessing PREP induced changes in withdrawal and exposure to carbon monoxide, nicotine, and carcinogens may help predict PREP harm reduction potential. Adequate withdrawal suppression, slightly lower concentrations of carbon monoxide, and reduction of one TSN biomarker were observed for Advance™. In the future, clinical methods like those described here may be valuable for evaluating PREPs before they are marketed publicly.
Using Model Checking in a Parallelizing Compiler
Authors: Rus Teodor , van Wyk Eric 
Published: September 2003

In this paper we describe the usage of temporal logic model checking in a parallelizing compiler to analyze the structure of a source program and locate opportunities for optimization and parallelization. The source program is represented as a process graph in which the nodes are sequential processes and the edges are control and data dependence relationships between the computations at the nodes. By labeling the nodes and edges with descriptive atomic propositions and by specifying the conditions necessary for optimizations and parallelizations as temporal logic formulas, we can use a model checker to locate nodes of the process graph where particular optimizations can be made. To discover opportunities for new optimizations or modify existing ones in this parallelizing compiler, we need only specify their conditions as temporal logic formulas; we do not need to add to or modify the code of the compiler. This greatly simplifies the process of locating optimization and parallelization opportunities in the source program and makes it easier to experiment with complex optimizations. Hence, this methodology provides a convenient, concise, and formal framework in which to carry out program optimizations by compilers.
Specification of the Behavior of Memory Operations in Distributed Systems
Authors: Cholvi Vicent 
Published: September 2003

Shared memory is a mechanism used for inter-process communication in distributed systems which is considered a feasible alternative to the traditional communication model. However, most of the work on shared memory has not paid enough attention to the way memory operations behave, leading to some degree of confusion. In this paper, we describe a framework for specifying the behavior of memory operations. That framework has been used to formally specify some of the most significant memory models. In this framework, to characterize a memory model it is enough to specify the executions that it allows. We use a dual approach. First, we provide axiomatic definitions of those memory models; then, we provide operational ones. Whereas axiomatic definitions are simple and intuitive, operational definitions are more convenient for being used in correctness proofs. We show that both approaches are equivalent.
Towards Industrially Relevant Fault-Proneness Models
Authors: Denaro Giovanni , Pezzè Mauro , Morasca Sandro 
Published: September 2003

Estimating software fault-proneness early, i.e., predicting the probability of software modules to be faulty, can help in reducing costs and increasing effectiveness of software analysis and testing. The many available static metrics provide important information, but none of them can be deterministically related to software fault-proneness. Fault-proneness models seem to be an interesting alternative, but the work on these is still biased by lack of experimental validation. This paper discusses barriers and problems in using software fault-proneness in industrial environments, proposes a method for building software fault-proneness models based on logistic regression and cross-validation that meets industrial needs, and provides some experimental evidence of the validity of the proposed approach.
Trade-off Analysis for Requirements Selection
Authors: Ruhe Günther , Eberlein Armin , Pfahl Dietmar 
Published: September 2003

Evaluation, prioritization and selection of candidate requirements are of tremendous importance and impact for subsequent software development. Effort, time as well as quality constraints have to be taken into account. Typically, different stakeholders have conflicting priorities and the requirements of all these stakeholders have to be balanced in an appropriate way to ensure maximum value of the final set of requirements. Trade-off analysis is needed to proactively explore the impact of certain decisions in terms of all the criteria and constraints. The proposed method called Quantitative WinWin uses an evolutionary approach to provide support for requirements negotiations. The novelty of the presented idea is four-fold. Firstly, it iteratively uses the Analytical Hierarchy Process (AHP) for a stepwise analysis with the aim to balance the stakeholders' preferences related to different classes of requirements. Secondly, requirements selection is based on predicting and rebalancing its impact on effort, time and quality. Both prediction and rebalancing uses the simulation model prototype GENSIM. Thirdly, alternative solution sets offered for decision-making are developed incrementally based on thresholds for the degree of importance of requirements and heuristics to find a best fit to constraints. Finally, trade-off analysis is used to determine non-dominated extensions of the maximum value that is achievable under resource and quality constraints. As a main result, quantitative WinWin proposes a small number of possible sets of requirements from which the actual decision-maker can finally select the most appropriate solution.
Self-Consistent Pushing and Cranking Corrections to the Meson Fields of the Chiral Quark-Loop Soliton
Authors: Schleif M. , Wünsch R. , Maissner T. 
Published: September 2003

We study translational and spin-isospin symmetry restoration for the two-flavor chiral quark-loop soliton. Instead of a static soliton at rest we consider a boosted and rotating hedgehog soliton. Corrected classical meson fields are obtained by minimizing a corrected energy functional which has been derived by semi-classical methods (variation after projection). We evaluate corrected meson fields in the region 300 MeV ≤ M≤ 600 MeV of constituent quark masses M and compare them with the uncorrected fields. We study the effect of the corrections on various expectation values of nuclear observables such as the root-mean square radius, the axial-vector coupling constant, magnetic moments and the delta-nucleon mass splitting.
Salvage Radiotherapy in Patients with Persisting Prostate-Specific Antigen after Radical Prostatectomy for Prostate Cancer
Authors: Bottke Dirk , Wiegel Thomas , Höcht Stefan , Müller Markus , Schostak Martin , Hinkelbein Wolfgang 
Published: September 2003

Salvage radiotherapy in patients with persisting prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer offers an approach to reduce local recurrence rates and to improve the rate of biochemical freedom from relapse. 30–70% of these patients experience a decrease in their PSA to an undetectable range; in about 40–50% of these patients, PSA remains stable after 5 years. Therefore, radiation therapy offers these patients an ultimate chance of cure. The pre-irradiation PSA value is of particular importance. The PSA level should not exceed 2 ng/ml because otherwise the rate of distant metastases increases significantly. Serious side effects are apparently low, thus confirming the suitability of this therapeutic approach.
Venous thromboembolism among patients with advanced lung cancer randomized to prinomastat or placebo, plus chemotherapy
Authors: Ruiz Rolando , Behrendt Carolyn 
Published: September 2003

SummaryTwo clinical trials have suggested that the combination of vascular endothelial growth factor inhibitor with chemotherapy is associated with venous thromboembolism (VTE). This retrospective cohort study investigates whether a similar association exists when matrix metalloproteinase inhibitor (prinomastat) is combined with chemotherapy.Patients (n=1,023) with stage IIIB, IV, or recurrent non-small cell lung cancer (NSCLC) were followed during 2 randomized, double-blind trials of prinomastat versus placebo orally bid, plus gemcitabine/cisplatin (GC) or paclitaxel/carboplatin (PC). VTE included deep venous thrombosis (DVT) or pulmonary embolism (PE) confirmed by imaging or autopsy. Risks identified in univariate analysis (incidence densities compared by t test) were confirmed in multivariate analysis (proportional hazards model).During 7,500.3 patient-months, 58 VTE (31 PE, 27 isolated DVT) were confirmed in 54 patients. On univariate analysis, VTE was associated with central venous catheter placed within 3 months,15 mg prinomastat plus GC, and to a lesser extent, 15 mg prinomastat plus PC, baseline performance status, and histologic type. VTE incidence was not increased by 15 mg prinomastat alone (post-discontinuation of chemotherapy), by chemotherapy plus placebo, or by 5 or 10 mg prinomastat plus chemotherapy. On multivariate analysis, VTE hazards (95% confidence interval) were 5.69 (2.61, 12.40) with recently placed central catheter, 2.78 (1.42, 5.43) with 15 mg prinomastat plus GC, and 2.06 (0.98, 4.31) with 15 mg prinomastat plus PC; performance status and histology were nonsignificant.We can conclude that combined treatment with 15 mg prinomastat plus chemotherapy approximately doubles the hazard of VTE among patients with advanced NSCLC.Research support: Pfizer Inc
Mechanisms of the priming effect of low doses of lipopolysaccharides on leukocyte-dependent platelet aggregation in whole blood
Authors: Montrucchio Giuseppe , Bosco Ornella , Sorbo Lorenzo , Pecetto Paolo , Lupia Enrico , Goffi Alberto , Omedè Paola , Emanuelli Giorgio , Camussi Giovanni 
Published: September 2003

SummarySeveral studies focused on the ability of bacterial lipopolysaccharides (LPS) in triggering platelet and/or leukocyte activation. The aim of this study was to investigate the molecular mechanisms involved in the aggregation of platelets and in their interaction with leukocytes in whole blood after stimulation with low doses of LPS.LPS did not directly induce platelet aggregation in whole blood, but they primed the aggregation of platelets induced by epinephrine, adenosine diphosphate and arachidonic acid. As shown by cytofluorimetry, platelets neither bind FITC-LPS, nor express the LPS-receptors CD14 and toll-like receptor 4 (TLR4). On the contrary, LPS primed monocytes and to a lesser extent polymorphonuclear neutrophils to adhere to platelets. Both platelet-leukocyte interaction and platelet aggregation in whole blood were inhibited by blockade of CD14 and TLR4. Moreover, the interaction between platelets and leukocytes was inhibited by P-selectin, and by blockade of PAF and reactive oxygen species, suggesting a role of P-selectin and of leukocyte-derived mediators.In conclusion, these results elucidate the mechanisms leading to platelet activation and interaction with leukocytes triggered by LPS. They suggest that the activation of platelets by LPS is mainly dependent on leukocytes and especially monocytes as a result of CD14 and TLR4 engagement. Moreover, we found that leukocyte-platelet interaction was triggered by the synthesis of PAF and the generation of oxygen radicals that induced upregulation of surface expression of P-selectin.
Studies of α-granule proteins in cultured human megakaryocytes
Authors: Veljkovic Dragoslava , Cramer Elisabeth , Alimardani Gulie , Fichelson Serge , Massé Jean-Marc , Hayward Catherine 
Published: September 2003

Summaryα-Granule protein storage is important for producing platelets with normal haemostatic function. The low to undetectable levels of several megakaryocyte-synthesized α-granule proteins in normal plasma suggest megakaryocytes are important to sequester these proteins in vivo. α-Granule protein storage in vitrohas been studied using other cell types, with differences observed in how some proteins are processed compared to platelets. Human megakaryocytes, cultured from cord blood CD34+cells and grown in serum-free media containing thrombopoietin, were investigated to determine if they could be used as a model for studying normal α-granule protein processing and storage. ELISA indicated that cultured megakaryocytes contained the α-granule proteins multimerin, von Willebrand factor, thrombospondin-1, β-thromboglobulin and platelet factor 4, but no detectable fibrinogen and factor V. A significant proportion of the α-granule protein in megakaryocyte cultures was contained within the cells (averages: 41 – 71 %), consistent with storage. Detailed analyses of multimerin and von Willebrand factor confirmed that α-granule proteins were processed to mature forms and were predominantly located in the α-granules of cultured megakaryocytes. Thrombopoietin-stimulated cultured megakaryocytes provide a useful model for studying α-granule protein processing and storage.
Plasminogen activator inhibitor-1 and outcome after femoropopliteal angioplasty: analysis of genotype and plasma levels
Authors: Schillinger Martin , Exner Markus , Sabeti Schila , Mannhalter Christine , Minar Erich , Wagner Oswald , Mlekusch Wolfgang 
Published: September 2003

SummaryPlasminogen activator inhibitor-1 (PAI-1) is suggested to be involved in the pathophysiology of early thrombosis and late restenosis after percutaneous transluminal angioplasty (PTA). The role of the PAI-1 promoter genotype in this context is indeterminate. We investigated the association of the (4G/5G) polymorphism at nucleotide position (–675) in the PAI-1 gene promoter, PAI-1 plasma levels, and postangioplasty outcome after femoropopliteal PTA.We studied 251 consecutive patients who underwent femoropopliteal PTA. In a subgroup of 86 patients PAI-1 plasma levels at baseline,8,24 and 48 hours postintervention were measured and correlated to the genotype. Patients were followed for early thrombosis and the late restenosis (≥50%) within 12 months. Multivariate Cox proportional hazards analysis was performed to assess the association between the PAI-1 genotype and PTA failure.Results show that the PAI-1 genotype was neither associated with PAI-1 plasma levels (p=0.40) nor the change of PAI-1 from baseline to 8 (p=0.39), 24 (p=0.86) and 48 hours (p=0.89). Three out of 35 homozygous (4G/4G) patients (9%) had early thrombotic reocclusions, compared to two out of 153 heterozygous (4G/5G) patients (1%) and none of the 63 homozygous (5G/5G) patients (p=0.007). Restenosis after median 5 months (interquartile range 3 to 9) was found in 117 patients (42%), without significant association between the PAI-1 genotype and late postangioplasty failure (Log Rank p=0.95).We can conclude that carriers of the 4G allele exhibited a higher frequency of early thrombotic reocclusions after percutaneous angioplasty. However, the PAI-1 gene promoter polymorphism (4G/5G) was not associated with PAI-1 plasma levels or late postangioplasty restenosis.
The ACE D/D genotype is protective against the development of idiopathic deep vein thrombosis and pulmonary embolism
Authors: Rodger Marc , Forgie Melissa , Langlois Nicole , Armstrong Linlea , Carson Nancy , Jaffey James , Wells Philip 
Published: September 2003

SummaryThe deletion/deletion (D/D) genotype of the angiotensin converting enzyme (ACE) has been purported to be a risk for postoperative thrombosis. This D/D genotype has not been evaluated as a risk factor for idiopathic venous thromboembolism (VTE).The primary objective of the present study was to determine whether the D/D genotype of ACE is independently associated with the occurrence of idiopathic venous thromboembolic disease.We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic VTE. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. Patients were tested for the ACE I/D polymorphism in addition to factor V Leiden, prothrombin G20210A, and factor VIII levels.Three hundred cases and 300 controls were enrolled; 97% were Caucasian. There were 148 females and 152 males in each group with a mean age of 56.21 years (SD=15.33). The ACE D/D genotype was present in 25.3% of cases and 32.4% of controls for an adjusted odds ratio of 0.66 (95% CI = 0.433 to 0.997). We can conclude that the ACE D/D genotype is protective against idiopathic venous thromboembolism.
Thrombophilic mutations in high-risk atrial fibrillation patients: high prevalence of prothrombin gene G20210A polymorphism and lack of correlation with thromboembolism
Authors: Poli Daniela , Antonucci Emilia , Cecchi Emanuele , Betti Irene , Valdrè Lelia , Mugnaini Cristina , Alterini Bruno , Morettini Alessandro , Nozzoli Carlo , Abbate Rosanna , Franco Gensini Gian , Prisco Domenico 
Published: September 2003

SummaryAtrial fibrillation (AF) is a common arrhythmia that results in a high risk of cerebral and peripheral embolism. Factor V Leiden and factor II G20210A variant are two leading conditions for venous thrombosis. The aim of our study was to find out whether these two common prothrombotic mutations play a role in the occurrence of embolic events in AF patients. We investigated 336 non-valvular AF patients and 336 healthy control subjects. Factor II G20210A variant was found in 24/336 patients (7.14%) and in 11/336 of control subjects (3.3%). At a multivariate analysis, factor II G20210A variant was independently associated to AF (OR 2.4 95% CI 1.1-5.2; p<0.05). No significant difference was observed in the prevalence of factor V Leiden in the two groups investigated [6/304 (2.0%) in patients vs 13/336 (3.9%) in controls (p=0.24)]. AF patients were separately analyzed in relation to the occurrence or absence of a cerebral or peripheral embolic event (200 with and 136 without embolic event). The prevalence of the two mutations among AF patients with and without an embolic event was similar [factor II G20210A polymorphism (7% and 7.3% respectively) and factor V Leiden (1.2% and 2.9%, respectively)]. No differences were found in relation to the type of embolic event. Our results suggest a possible relationship between the presence of prothrombin gene variant and AF per se.
Pharmacokinetics and anticoagulant properties of the factor VIIa-tissue factor inhibitor recombinant Nematode Anticoagulant Protein c2 following subcutaneous administration in man
Authors: Bradbury Annette , Lopez-Kinninger Lily , Colón Sonia , Bergum Peter , Maki Steven , Rote William , Vlasuk George 
Published: September 2003

SummaryRecombinant Nematode Anticoagulant Protein c2 (rNAPc2) is a potent (Ki=10 pM), inhibitor of the factor VIIa/tissue factor (fVIIa/TF) complex that requires the prerequisite binding to zymogen or activated factor X (fX). In two double blind, placebo-controlled, sequential dose-escalation phase I studies, rNAPc2 was found to be safe and well tolerated following single and repeat subcutaneous administrations in healthy human male volunteers at doses ranging from 0.3 to 5 µg/kg. There was a dose-dependent elevation of the prothrombin time reaching almost 4-fold above the baseline value in the highest dose group that directly correlated with rNAPc2 plasma concentration. In contrast, there was little or no effect on the activated partial thromboplastin time, thrombin time or template bleeding time. The pharmacokinetic behavior of rNAPc2 revealed a dose-independent and prolonged elimination half-life (t1/2β) with a mean of >50 hours. A high affinity interaction between rNAPc2 and plasma fX was shown to be essential for the prolonged t1/2β in man using crossed immunoelectrophoresis and was confirmed by exploiting the considerably weaker interaction between rNAPc2 and bovine fX which resulted in an attenuated t1/2β of ~1.5 hours in calves. The accumulated data suggests that rNAPc2 is safe and well tolerated following repeat subcutaneous administrations at doses up to 5 µg/kg in healthy volunteers. In addition, the in vivofate of rNAPc2 in man appears to be governed by its high affinity interaction with circulating fX. This data supports the continued development of this novel anticoagulant for the prevention and treatment of acute thrombotic disorders.
Accounting for Error: How Scientists Construct their Social World when they Account for Correct and Incorrect Belief
Authors: Mulkay Michael , Gilbert G. Nigel 
Published: September 2003

There is an asymmetry in the procedures used by natural scientists to account for `correct belief' and for `error'. Correct belief is treated as the normal state of affairs, as deriving unproblematically from experimental evidence, and as requiring no special explanation. Errors are seen as something to be explained away, as due to the intrusion of non-scientific influences. An elaborate repertoire of interpretative resources is employed in accounting for error. Asymmetrical accounting for error and for correct belief is a social device which reinforces the traditional conception of scientific rationality and which makes the community of scientists appear as the kind of community we, and they, recognize as scientific. These conclusions are based on a detailed analysis of interviews with researchers in an area of biochemistry.
On the Demise of Oligarchic Parliamentarism in the Semi-Periphery: A Balkan-Latin American Comparison
Authors: Mouzelis Nicos 
Published: September 2003

This paper focuses on peripheral capitalist societies which (a) acquired their political independence relatively early and had already in the 19th century adopted parliamentary forms of political representation; (b) experienced a considerable degree of capitalist industrialization during the inter-war and post-war periods. A fundamental dimension for understanding the structure and functioning of political institutions in the above societies has to do, not only with the mode of expansion and structure of industrial capitalism but also with its timing: with the fact that in all these formations the transition from oligarchic to broader forms of political representation precedes rather than follows their industrialization. Three distinct forms of transition are identified: urban populism from above (the Latin American Southern Cone pattern), peasant populism from below (the pattern in interwar Northern Balkan societies) and political inclusion through a transformation of clientelistic networks (the Greek pattern).