bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of psychosocial factors in African‐American and white breast cancer patients
Authors: Soler‐Vila Hosanna , Kasl Stanislav V. , Jones Beth A. 
Published: September 2003

AbstractBACKGROUNDIt has been suggested that psychosocial factors, such as coping and emotional support, influence cancer survival, but results have been inconclusive. Given the scarce data from racially/ethnically diverse populations, the authors investigated the prognostic significance of selected psychosocial variables in a cohort of African‐American women and white women with breast cancer.METHODSThe authors examined the effects of coping styles, perceived emotional support, fatalism, and health locus of control on survival for a population‐based cohort of 145 African‐American women and 177 white women who were diagnosed with breast cancer in Connecticut between January 1987 and March 1989 and were followed for survival for approximately 10 years. Cox proportional hazards models were adjusted for sociodemographic factors, biomedical factors (American Joint Committee on Cancer stage at diagnosis, histologic grade, comorbidity, obesity, menopausal status, and treatment), and lifestyle factors.RESULTSFully adjusted models showed that lower perceived emotional support (disagreeing with the statement, “cancer is a topic I can talk about freely with my friends/relatives”) at diagnosis was associated with a higher risk of death from any cause (hazard ratio, 1.39; 95% confidence interval, 1.09–1.79). Adjustment for additional tumor characteristics (nuclear grade, estrogen and progesterone receptor status) and genetic alterations (p53, HER‐2) did not alter the findings. No other psychosocial factors significantly predicted survival in patients with breast cancer.CONCLUSIONSHigher levels of perceived emotional support showed a moderate but significant association with increased survival in African‐American and white women with breast cancer who were followed for 10 years after diagnosis when adjusting for known prognostic factors. Survival was not related to coping styles, fatalism, or health locus of control. Cancer 2003;98:1299–308. © 2003 American Cancer Society.DOI 10.1002/cncr.11670
Optimal call admission control under packet and call level QoS constraints and effect of buffering
Authors: Spitler Stephen L. , Lee Daniel C. 
Published: September 2003

AbstractFor a single network switch allocating link bandwidth to connections of a single class, an optimal call admission control (CAC) policy is found by the solution of a linear programming (LP) problem. Our optimization differs from previous work in that we include the effect of an output buffer in the switch for the temporary storage of packets bound for transmittal across the link. We find a policy that is optimal in the sense of minimizing call blocking subject to a packet level quality of service (QoS) requirement that limits the packet loss ratio. Such a policy's call blocking probability, if it is small enough to satisfy a call level QoS requirement, then establishes the feasibility of satisfying both the packet and call level QoS requirements for a given call request rate. We show with a previously described example that the addition of even a small output buffer can significantly increase the range of call request rates for which there exists a feasible policy, i.e. one that satisfies both QoS requirements. Also presented is an upper bound, valid for any fixed buffer size, on the range of call request rates for which there exists a feasible CAC policy. Copyright © 2003 John Wiley & Sons, Ltd.
The end‐user application toolkit: a QoS portal for the next generation Internet
Authors: Tsetsekas Charilaos A. , Maniatis Sotirios I. , Venieris Iakovos S. 
Published: September 2003

AbstractThe support of quality of service (QoS) in the Internet has become one of the most important topics within the Internet community. The introduction of the Integrated Services (IntServ) and the Differentiated Services (DiffServ) architectures was a major breakthrough in this direction. Enhanced by the Bandwidth Broker concept, DiffServ aims to provide QoS in the Internet through the prioritization of some IP flows over others. However, up to now the DiffServ architecture lacks a standard mechanism for the interaction between users/applications and the Bandwidth Brokers (BB), so that end‐to‐end QoS can be achieved.In this paper we present a distributed middleware architecture for the transparent support of QoS in the Internet. The paper focuses on bridging the gap that currently exists between applications and the network and presents the end‐user application toolkit (EAT). The EAT middleware provides a framework for the presentation of network services to users, the description and selection of QoS parameters, the forwarding of reservation requests and the verification of the accredited QoS level. Through the concept of application profiles, it aims to support QoS for legacy applications, that is, commercial applications that cannot be modified to support QoS. Copyright © 2003 John Wiley & Sons, Ltd.
Waiting time distribution of an ATM switch routing two‐class traffic with two service rates
Authors: Nassar Hamed , Ali Ahmed Mohamed 
Published: September 2003

AbstractIn this article we analyse the waiting time of an arbitrary packet in an output buffered space division switch routing two‐class traffic, e.g. in a multimedia environment. For the purpose of the analysis, the switch is modelled as a priority, discrete time, batch arrival queueing system, with a single server having two service rates. The results of the analysis are verified in various ways, including obtaining previously published results as special cases.The fundamental contribution of this article is the assumption of two service rates, one for each class, rather than the typical assumption of one service rate for both classes. This assumption is useful in that it accounts for the different quality of service (QoS) needs of each class. Another contribution is the introduction of a new approach to analyse the waiting time—an approach not based on the system occupancy as is typical in the published literature. Copyright © 2003 John Wiley & Sons, Ltd.
Performance analysis of an improved multi‐carrier CDMA system under frequency‐selective Rayleigh fading channels
Authors: Chen Hsiao‐Hwa 
Published: September 2003

AbstractIn this article, an analytical method is proposed to study an improved orthogonal multi‐carrier DS/CDMA system, which uses QPSK for both spreading and carrier modulations without redundant sub‐carriers and time interleavers in each sub‐channel. The article concerns in particular such a system and its performance under frequency‐selective Rayleigh fading channels with various delay‐power profiles. The bit error probabilities under varying multipath‐diversity orders (using maximal ratio combing RAKE reception) and different numbers of resolvable multipaths are derived. It has been shown that the system, despite of its structural simplicity, performs well in mitigating frequency‐selective fading. The performance is also evaluated taking into account various other parameter sets, such as numbers of users and sub‐carriers, lengths of PN codes and the number of fingers in an RAKE receiver, etc. Copyright © 2003 John Wiley & Sons, Ltd.
Proteinase‐activated receptors (PARs): An evolving hormonal system
Authors: Hollenberg Morley D. 
Published: September 2003

AbstractAn overview of the articles presented in this two‐part special issue of Drug Development Research is provided here. This two‐part series focuses on the discovery, molecular pharmacology, and physiology of the Proteinase‐activated Receptor (PAR) family. This recently discovered G‐protein‐coupled receptor family mediates the signaling properties of a number of serine proteinases, including thrombin. PARs are responsible for a variety of physiological roles that proteinases may now be seen to play in their capacity as “signaling molecules.” It is the aim of the Special Issue articles to illustrate PARs' unique pharmacological properties and to alert the scientific community to the widespread physiological roles this receptor family can play in a variety of settings. Drug Dev. Res. 59:334–335, 2003. © 2003 Wiley‐Liss, Inc.
Proteinase‐activated receptors: Tethered ligands and receptor‐activating peptides
Authors: Hollenberg Morley D. 
Published: September 2003

AbstractProteinase‐activated receptors (PARs), newly‐discovered members of the G‐protein‐coupled receptor superfamily, comprising four cloned family members (PARs 1 to 4), are activated by the proteolytic unmasking of a “tethered ligand” sequence situated in the N‐terminal extracellular receptor domain. Furthermore, synthetic peptides with sequences based on the revealed tethered ligands can, in the absence of proteolysis, trigger receptor signaling. This report reviews the data supporting the tethered ligand mechanism of receptor activation, outlines the utility of the receptor‐activating peptides (so‐called PAR‐APs) for exploring the potential physiological roles of the PARs, and discusses the potential differences between the activation of the receptors via their tethered ligands as opposed to activation by the soluble peptides having the same amino acid sequences. Drug Dev. Res. 59:336–343, 2003. © 2003 Wiley‐Liss, Inc.
Proteinase‐activated receptor domains and signaling
Authors: Hollenberg Morley D. , Compton Steven J. 
Published: September 2003

AbstractGiven that the proteinase‐activated receptors (PARs) are activated by a “tethered ligand mechanism,” an important question to answer is: Which other extracellular domains of the receptors are involved in this novel signaling mechanism? Further, as for other G‐protein‐coupled receptors (GPCRs), it is of importance to know about the intracellular receptor domains that are involved in coupling receptor activation to signal transduction. Studies summarized in this article have singled out the importance of extracellular loop‐2 of PAR1 and PAR2 for tethered‐ligand signaling. In human PAR1, but not in PAR2, a short sequence in the extracellular N‐terminal domain (Q83 to G94) is also important for receptor activation. As for other GPCRs, intracellular loops 2 and 3 mediate receptor‐G‐protein coupling, and the C‐terminal sequence, with a putative “palmitoylation” site and target residues for kinase C phosphorylation, plays a role in receptor signaling and desensitization. This article provides an overview of the experiments leading to the current understanding of the PAR domains involved in signal transduction. Drug Dev. Res. 59:344–349, 2003. © 2003 Wiley‐Liss, Inc.
Glycosylation and proteinase‐activated receptor function
Authors: Compton Steven J. 
Published: September 2003

AbstractN‐linked glycosylation is a post‐translational modification that enables the cell to regulate protein function without recourse to the genome. The Proteinase‐Activated Receptors (PAR) each possesses a number of N‐linked glycosylation sites on their extracellular domains. However, little is currently known about the relative glycosylation status of each family member and about the influence that glycosylation may confer on receptor function. Interestingly, each PAR possesses an N‐linked glycosylation site in close proximity to the cleavage/activation site on the receptor N‐terminus. Recent studies focusing on PAR2 have pointed out a role for glycosylation on the N‐terminus in influencing receptor activation. Consequently, shifts in tissue and/or cell glycosylation patterns in health and disease could play an important role in regulating PAR function. Drug Dev. Res. 59:350–354, 2003. © 2003 Wiley‐Liss, Inc.
Design and evaluation of potent peptide‐mimetic PAR1 antagonists
Authors: Derian Claudia K. , Maryanoff Bruce E. , Andrade‐Gordon Patricia , Zhang Han‐Cheng 
Published: September 2003

AbstractThe serine protease α‐thrombin is a powerful mediator of cellular responses, not only playing a key regulatory role in the maintenance of normal hemostasis, but also contributing more broadly to a range of physiological and potentially pathological conditions. Most of the cellular actions attributed to α‐thrombin have been linked to the activation of a family of seven‐transmembrane G‐protein‐coupled protease‐activated receptors, termed PARs. Of the four family members identified, PAR1 has received recognition as the most significant receptor for mediating thrombin's cellular actions. Thus, the development of a potent, selective antagonist of PAR1 would be an important and essential tool to probe the physiological and potential pathological roles of PAR1. In this review, we provide a synopsis of our de novo design approach to the discovery of selective PAR1 antagonists, exemplified by RWJ‐58259, along with the in vitro and in vivo studies performed to demonstrate the important role of this receptor in thrombosis and vascular injury. RWJ‐58259 demonstrated antithrombotic activity in a model of vascular injury‐induced thrombosis in cynomolgus monkeys and prevented neointimal proliferation in a rat balloon angioplasty model. These seminal studies clearly lay the groundwork for more detailed preclinical in vivo studies and ultimately, advancing PAR1 antagonists into human clinical studies. Expanded chemical synthetic efforts and other novel technologies targeted to PAR1 and its intracellular signaling pathways are already on the horizon in an effort to further modulate thrombin's biological actions. Drug Dev. Res. 59:355–366, 2003. © 2003 Wiley‐Liss, Inc.
Intracellular signalling by the G‐protein coupled proteinase‐activated receptor (PAR) family
Authors: Macfarlane Scott R. , Plevin Robin 
Published: September 2003

AbstractThe proteinase‐activated receptor (PAR) family are novel members of the G‐protein coupled receptor superfamily that are activated by a mechanism involving specific proteolytic cleavage of their N‐terminal. Activation of intracellular signalling pathways by the PAR family has received relatively little attention compared with the other aspects of their function. Along with activation of intracellular calcium, diacylglycerol, and inositol 1,4,5‐trisphosphate, PARs have been reported to activate signalling pathways closely linked to both cell proliferation and inflammation. Here we attempt to describe these signalling pathways and the G‐proteins involved in coupling the receptors to these intracellular events. Drug Dev. Res. 59:367–374, 2003. © 2003 Wiley‐Liss, Inc.
The inflammatory response
Authors: Vergnolle Nathalie 
Published: September 2003

AbstractInflammation, which constitutes the body's response to injury, is characterized by a series of events where several different cell types are playing distinct roles. Proteinase‐activated receptors (PARs) are expressed in all the cell types that are involved in inflammatory processes. The expression of PARs is up‐regulated during inflammatory processes. Activation of PARs can lead to inflammation or, in some circumstances, can be protective against uncontrolled inflammatory reaction. Most recently, studies have shown that inflammatory responses were altered in PAR‐deficient mice. Thus, a crucial role for PARs seems to emerge from the most recent literature and presents PARs as novel and interesting therapeutic targets for the treatment of inflammation. Drug Dev. Res. 59:375–381, 2003. © 2003 Wiley‐Liss, Inc.
Proteinase‐activated receptors and nociceptive pathways
Authors: Vergnolle Nathalie 
Published: September 2003

AbstractThe discovery of Proteinase‐Activated receptors (PARs) in the nervous system has led to new insights about the potential physiological role that these enzymes could play in relation to nerve functions. Here, we summarize evidence that proteinases, through the activation of PARs, interact with the nervous system, playing a role in pain perception and modulation of nociceptive pathways. New potential roles are suggested for the members of the PAR family, highlighting proteinases and their receptors as potential therapeutic targets for pain relief. Drug Dev. Res. 59:382–385, 2003. © 2003 Wiley‐Liss, Inc.
Intestinal epithelial secretory function: Role of proteinase‐activated receptors
Authors: Buresi Michelle C. , MacNaughton Wallace K. 
Published: September 2003

AbstractThe ability of enterocytes to secrete electrolytes and water into the intestinal lumen represents a critical feature of mucosal defense. During disease, this function may be altered and may initiate or exacerbate pathological conditions. Although many of the intracellular mechanisms linking stimulation to secretion have been elucidated, novel pathways continue to be revealed. These pathways provide potential for therapeutic manipulation of cellular function. In addition, the importance of the microenvironment surrounding enterocytes is increasingly being acknowledged, and the interactions between epithelial cells and their milieu are proving to be essential to the regulation of secretory function, both in health and disease. In this way, epithelial ion transport functions can be modulated by mediators released from neighboring nerves, inflammatory cells, and pathogens, or by endocrine factors. Much interest has recently been elicited by the discovery that proteinases can regulate cellular functions through the activation of proteinase‐activated receptors (PARs). Because of the abundance of proteases within the gastrointestinal tract, particularly in the setting of development, inflammation, and healing, it is likely that PARs have an important role to play in these processes. PARs have been localized to a variety of cell types in the gastrointestinal tract, and have been shown to influence epithelial secretory function on several levels. In this review, we discuss the mechanisms by which proteases and PARs regulate intestinal secretory function, and the manner in which these modulations might contribute to inflammatory processes. Drug Dev. Res. 59:386–394, 2003. © 2003 Wiley‐Liss, Inc.
Proteinase‐activated receptors (PARs), platelets and angiogenesis
Authors: Perini Rafael , Wallace John L. 
Published: September 2003

AbstractWith respect to the role of proteinase‐activated receptors (PARs), few cells have been as thoroughly studied as the platelet. PARs appear to act as the key receptors mediating the pro‐aggregatory and pro‐secretory effects of thrombin, but there is considerable variation from species to species in terms of which PARs are involved in these processes. In addition to contributing to hemostasis, platelets are increasingly being viewed as important contributors to healing and to tumor growth. This can be attributed to the many pro‐ and anti‐angiogenic factors that are stored within platelets and are released as sites of injury and new vessel growth. There is emerging evidence for an important role for PARs in regulating the release of growth factors from platelets, raising the specter that PARs may be a rational target for new therapies that will modulate repair processes and tumour growth. Drug Dev. Res. 59:395–399, 2003. © 2003 Wiley‐Liss, Inc.
Proteinase‐activated receptor activation by coagulation proteinases
Authors: Riewald Matthias , Ruf Wolfram 
Published: September 2003

AbstractCoagulation proteinases signal through proteinase activated receptors (PARs). Thrombin‐dependent PAR signaling on platelets is essential for hemostasis, but regulation of inflammation by PAR‐signaling is increasingly recognized as an important aspect of other pro‐ and anticoagulant pathways. In tissue factor (TF)‐dependent initiation of coagulation, factor Xa is the PAR1 or PAR2 activating proteinase while associated in the transient TF‐VIIa‐Xa complex. In the anticoagulant protein C (PC) pathway, the thrombin‐thrombomodulin complex activates PC bound to the endothelial PC receptor (EPCR) and EPCR functions as an essential co‐receptor for activated PC‐mediated signaling through endothelial cell PAR1. Thus, the pro‐ and anti‐inflammatory receptor cascades are mechanistically coupled to cell signaling that precedes systemic coagulant or anticoagulant effects. In contrast with the substrate‐like recognition of PARs by thrombin, TF, or EPCR targeted activation of PARs generates cell‐type specificity, PAR selectivity, and proteinase receptor co‐signaling with the G‐protein coupled PAR response. Cellular proteinase receptors are thus major determinants of the biological outcome of coagulation factor signaling on vascular cells. Drug Dev. Res. 59:400–407, 2003. © 2003 Wiley‐Liss, Inc.
Role of proteinase‐activated receptors in cutaneous biology and disease
Authors: Rattenholl Anke , Steinhoff Martin 
Published: September 2003

AbstractThe skin is the largest organ of the human body. It makes up of about 15% of the body weight. Proteinase‐activated receptor‐1 (PAR1) and PAR2 have been discovered in various constitutive or transient cells within the epidermis as well as the dermis. In fact, epidermal keratinocytes were among the first cells in which the presence of PAR2 was reported. Several observations advanced our knowledge of PARs as regulators of skin homeostasis and disease. For example, PARs are expressed by keratinocytes and regulate growth, differentiation, pigmentation, and release of growth factors and cytokines. Mast cells release tryptase, which activates PAR2 on keratinocytes and endothelial cells, thereby contributing to inflammation and probably allergic reactions. PAR2 is also involved in leukocyte/endothelial interactions within the skin by modulating the functions of both microvascular endothelial cells and neutrophils. Thus, PARs may be implicated in skin pathophysiology such as wound healing, cutaneous inflammation, pruritus, tumorigenesis (e.g. melanoma, squamous cell carcinoma) and bacterial infections. Functional PAR1 and PAR2 were recently demonstrated on primary afferent neurons in the skin, thereby regulating neurogenic inflammation. PAR2 agonists induce release of neuropeptides from cutaneous sensory nerves, leading to pain and itch. This review highlights the recent knowledge of PARs in cutaneous physiology and disease, and discusses the possibility of PAR agonists or antagonists as novel tools for the treatment of skin diseases. Drug Dev. Res. 59:408–416, 2003. © 2003 Wiley‐Liss, Inc.
Radiation toxicity and proteinase‐activated receptors
Authors: Wang Junru , Hauer‐Jensen Martin 
Published: September 2003

AbstractDespite recent technological advances, the cure rates that can be achieved with radiation therapy are limited by the risk of injury to the normal tissues that surround the tumor. This review summarizes current knowledge regarding proteinase‐activated receptors (PARs) and their possible role in the pathogenesis of normal tissue radiation injury. In particular, data are presented indicating that activation of PAR1 by thrombin, and PAR2 by trypsin and mast cell proteinases, may be involved both in acute radiation responses, as well as in the chronic fibroproliferative processes that lead to the development of radiation‐induced tissue fibrosis and clinical complications. If effective pharmacologic modulators of PAR1 or PAR2 were available, these compounds would be potentially useful as preventive or therapeutic agents in patients receiving radiation therapy, especially if blockade could be targeted to specific tissues or cellular compartments. Drug Dev. Res. 60:1–8, 2003. © 2003 Wiley‐Liss, Inc.
Modulation of gastric function by proteinase‐activated receptors
Authors: Nishikawa Hiroyuki , Kawabata Atsufumi 
Published: September 2003

AbstractProteinase‐activated receptor (PAR)1 and PAR2 are abundantly expressed in the gastric mucosa and smooth muscle. PAR2 modulates a variety of gastric functions, mediating secretion of mucus and pepsinogen, suppression of acid output, an increase in mucosal blood flow, and smooth muscle contraction/relaxation. PAR2 is considered primarily protective in the gastric mucosa. PARs other than PAR2 might also be involved in the modulation of gastric functions. PARs, especially PAR2, would thus appear to be novel targets for the development of drugs for treatment of gastric mucosal diseases. Drug Dev. Res. 60:9–13, 2003. © 2003 Wiley‐Liss, Inc.