bluuebunny/crossref_metadata_2025 huggingface dataset:
An approach to integrated office document processing and management
Authors: Mattos N. M. , Mitschang B. , Dengel A. , Bleisinger R.
Published: June 2007

We propose an approach towards an integrated document processing and management system that has the intention to capture essentially freely structured documents, like those typically used in the office domain. The document analysis system ANASTASIL is capable to reveal the structure as well as the contents of complex paper documents. Moreover, it facilitates the handling of the containing information. Analyzed documents are stored in the management system KRISYS that is connected to several different subsequent services. The described system can be considered as an ideal extension of the human clerk, making his tasks in information processing easier. The symbolic representation of the analysis results allow an easy transformation in a given international standard, e.g., ODA/ODIF or SGML, and to interchange it via global network.
LAN based real time audio-data systems
Authors: Soares L. F. G. , Martins S. L. , Bastos T. L. P. , Ribeiro N. R. , Cordeiro R. C. S.
Published: June 2007

One of the greatest demands for better communication services comes from the office automation area. The functions related to electronic mail, telephony, and teleconferencing are among these services, due to advantages it creates, such as reduction of cost and time.

LANBRETAS is a LAN-based real-time audio/data system that is being developed by the Catholic University of Rio de Janeiro and the Rio Scientific Center of IBM-Brasil and is the subject of this paper. The first part of the paper introduces the motivations to implement the system as well as the implementation environment. The second part presents the system. At first the electronic mail system LANBRETA-DMS, then the telephony system LANBRETA-DTS, and at last, the teleconferencing system LANBRETA-GCS.
Objects with roles
Authors: Pernici B.
Published: June 2007

The use of object-oriented conceptual models for modeling office applications and information systems is discussed. A model for describing object behavior based on the concept of role is presented. Roles allow one to describe different perspectives for object evolution. For each role, relevant characteristics such as role properties, role states, messages, and role-state transition rules and constraints are defined. The implications of considering several roles in parallel for an object are discussed, and a classification of possible role interactions is given.
A knowledge-based approach to the design of document-based retrieval systems
Authors: Chen H. , Dhar V.
Published: June 2007

This article presents a knowledge-based approach to the design of document-based retrieval systems. We conducted two empirical studies investigating the users' behavior using an online catalog. The studies revealed a range of knowledge elements which are necessary for performing a successful search. We proposed a semantic network based representation to capture these knowledge elements. The findings we derived from our empirical studies were used to construct a knowledge-based retrieval system. We performed a laboratory experiment to evaluate the search performance of our system. The experiment showed that our system out-performed a conventional retrieval system in recall and user satisfaction. The implications of our study to the design of document-based retrieval systems are also discussed in this article.
OTM: specifying office tasks
Authors: Lochovsky F. H. , Hogg J. S. , Mendelzon A. O. , Weiser S. P.
Published: June 2007

While there are many difficulties in computerizing office tasks, two of the major ones are a lack of appropriate end-user facilities for specifying office tasks and inadequate system-level support for managing office tasks. We are investigating these two issues within the Office Task Manager (OTM) project at the University of Toronto. To address the user-level aspects of specifying office tasks, we believe that a programming-by-example approach to office task specification holds much promise for providing office workers with facilities to help them computerize their own office activities. We outline our approach to such a facility in this paper. To address the system-level aspects of managing office tasks, we believe that object-oriented environments, because of their ability to combine data and operations on the data, can provide the support required for managing office tasks. In this paper, we also outline how office data and tasks are encoded and managed as objects. Initially, we are addressing the problem of supporting structured office tasks and our approach to this problem is the emphasis of this paper.
Computers' impact on productivity and work life
Authors: Dumais Susan , Kraut Robert , Koch Susan
Published: June 2007

Rapid spread of computer and telecommunication technologies throughout white-collar work has forced researchers to consider their impacts on the people who use them. The present study uses a multi-method, lagged, time-series design to examine the impact of a computerized record system on the work life of customer service representatives in a large utility company. Results show that the computer technology had mixed effects in terms of both productivity and quality of working life, and that these effects varied depending on local organizational culture, management quality, type of worker and their detailed work tasks. Furthermore, during the year in which the computer system was being introduced, the computer system itself, its methods of use, and the managerial goals that spawned it all evolved in response to workers and other factors. These results are used to illustrate the conceptual and methodological complexities involved in establishing the causal impact of computer technology, and to suggest alternate methods for thinking about and measuring technological impact
.
Collection and analysis of data from communication system networks
Authors: Rice Ronald E.
Published: June 2007

This paper provides a brief overview of a new, limited and specific direction in the study of computer-based information systems: the study of communication networks by means of computer-monitored usage and content. This area of research is the result of the interaction of two foci in recent research: (1) the increasing use of computer-mediated communication systems in organizations, and (2) the conceptualization of communication as a process of convergence, or networks of relations.
Document query processing strategies: cost evaluation and heuristics
Authors: Bertino E. , Gibbs S. , Rabitti F.
Published: June 2007

This paper describes query processing strategies used in a system where queries are specified on formatted data and text components of documents. The system provides different access methods: indexes for formatted data and signature files for the text. Four basic document queries, representative of a wide range of queries, are examined in detail. Strategies for query processing are presented together with an evaluation of the costs of the various strategies. Finally, general heuristics are derived.
Browsing within time-driven multimedia documents
Authors: Christodulakis Stavros , Graham Stephen
Published: June 2007

We present the software design and the interfaces of an interactive browser for time-driven multimedia objects. Time-driven multimedia objects may have as their main resource voice or animation sequences. Several important application environments such as training systems, home entertainment systems, do-it-yourself manuals may involve time-driven multimedia objects and they may be implemented with such browsing interfaces. Such applications may be implemented using easy to replicate optical disks such as CD-ROMs, and distributed to a large user community.
Aggregation and generalization hierarchies in office automation
Authors: Bever M. , Ruland D.
Published: June 2007

Integrated database support is an essential part in Office Automation. Because of the variety of objects, their relationships and operations, more sophisticated data modelling concepts such as aggregation and long fields, cross references, aggregation hierarchies, and generalizations are needed. In this paper, we show their importance to Office Automation. Because long fields and aggregation are already supported by existing data models, we focus on the two data abstraction concepts: aggregation hierarchy and generalization. Besides structural aspects a restricted set of operations is defined. Then we discuss an implementation on the basis of a relational engineering prototype database system, that already supports long fields, aggregation and aggregation hierarchies.
Supporting OIS design through semantic queries
Authors: Pernici B.
Published: June 2007

Office information system design is a complex activity which needs conceptual modeling to represent office data and activities in a formal way. The problem of retrieving information from conceptual schemas of office systems is addressed, to support the designer in the different phases of office information system design. A semantic query language is proposed, based on a semantic representation of the TODOS Conceptual Model for office design
.
A commitment-based communication model for distributed office environments
Authors: Koo Charles C.
Published: June 2007

In an office environment where agents cooperate to accomplish a certain tasks, the agents perform their tasks based on certain plans. To ensure the integrity of their teamwork, agents
communicate
with one another to coordinate their plans. Meanwhile, tasks are distributed to other agents via this communication process. This report describes a commitment-based communication model for autonomous agents to synchronize and track their activities in office environments. The communication model includes a communication process, a set of protocols to bind commitments, a set of communication operators and a set of commitment tracking operators.
The Ubik configurator
Authors: de Jong Peter
Published: June 2007

Ubik is a system within which organizational structure, concepts, and actions are described and organizational applications are executed. Ubik represents an organization not with one global model, but with multiple overlapping models which can be physically distributed within multiple knowledge bases. There is a basic computational object in Ubik called the Ubik Configurator. The Configurator is used to specify organizational concepts, handlers, goals, and constraints. Configurators are linked together in lattices within a model. There are different types of models built using the configurator. Ubik models support the communication between distributed applications and the control of the parallel execution of applications. Development models support the continual evolution necessary in a large organization to cope with the changing external environment. Due process models support the resolving of conflicts between conflicting models. Organizational models describe the end-users organization and applications.
High-speed image scaling for integrated document management
Authors: Tabata Kuniaki , Machida Tetsuo , Takeda Haruo , Kambayashi Hiroaki
Published: June 2007

Document information often includes image data (eg. handwritten annotations, signatures, maps, sketches and photos) as well as alphanumeric and other coded data. Thus, the capability of handling these image data plays an important role in reforming current office-work activities.

This paper presents a high-speed scaling method to enlarge or reduce digital images defined as two-dimensional pixel arrays. Scale factors are assumed to be rational numbers R/r and S/s for the vertical and horizontal directions, respectively, where R, S, r, s denote positive integers. Under this assumption, coordinate determination for image scaling is performed by simple table look-up and shift operations. This method excludes time-consuming arithmetic operations for coordinate determination. Thus, high-speed scaling is realized. Experiments showed that the execution time per output pixel is about 150 ns when the shift clock frequency is 8 MHz.

The proposed algorithm has been successfully applied to a multi-functional office workstation featuring integrated functions of data processing, document processing and image processing.
Office form definition and processing using a relational data model
Authors: Czejdo Bogdan , Embley David W.
Published: June 2007

Office forms have a particular structure and semantics that make them a suitable communication medium. The Natural Forms Query Language, NFQL, capitalizes on these features of ordinary forms to provide a communication language between human beings and the computer. Given a form, NFQL analyzes it to deduce plausible interpretations and then generates database queries and function specifications applicable to the form. This paper explains how NFQL recognizes computational relationships between arguments and results and formulates function specifications. General rules are given, in terms of a relational data model, that can resolve computational relationships for ordinary forms.
Mnemonic strategies in word processing systems
Authors: Aderet Avshalom , Hoffman Paul J.
Published: June 2007

The useability of character mnemonics in office information systems is discussed and several issues involved in the use of mnemonics as effective design concept are highlighted in the context of word processing tasks.

In a series of studies, the mnemonics technique was compared to other user interfaces, such as function-key interface or menu-driven interface. In these studies we found significant differences between novices and experienced operators with respect to ease of performance and ease of recall of word processing operations. Our results suggest that experience plays an important role in operating a mnemonics-driven system compared to a non-mnemonics driven system. Additional research is needed in order to understand the ways by which mnemonics strategies affect the performance of office information systems.
Dialogue and process design for interactive information systems using Taxis
Authors: Barron John
Published: June 2007

This paper deals with dialogue and process management for interactive information systems [abbrev. IISs) within the framework of Taxis Mylopoulos
et al
80, a language for IIS design. Dialogues between a user and the system are represented through a small set of primitives incorporated into Taxis while process control is accomplished by incorporating Hoare's I/O commands for communicating sequential processes {Hoare 78}. The overall organization and structure of dialogue and process control for a particular IIS is achieved using scripts, a modified version of augmented Petri nets {Zisman 77}, and the Taxis conceptual framework which stresses generalization abstraction. A journal editing procedure is used to illustrate the proposed extension.
An OIS model for internal control evaluation
Authors: Bailey Andrew D. , Gerlach James , McAfee R. Preston , Whinston Andrew B.
Published: June 2007

Satisfactory accountability, that is, a control structure which protects corporate assets from theft, misuse, and fraud, is an important aspect of office information system design. The OIS design goals of flexibility, efficiency, and modularity must not preclude the accountability needs of managers, stockholders, and auditors. This will require meticulous examination of the OIS to ensure that it satisfies the multi-attribute control criteria used by auditors.
How do people really use text editors?
Authors: Whiteside John , Archer Norman , Wixon Dennis , Good Michael
Published: June 2007

Keystroke statistics were collected on editing systems while people performed their normal work. Knowledge workers used an experimental editor, and secretaries used a word processor. Results show a consistent picture of free use patterns in both settings. Of the total number of keystrokes, text entry accounted for approximately 1/2, cursor movement for about 1/4, deletion for about 1/8, and all other functions for the remaining 1/8. Analysis of keystroke transitions and editing states is also presented. Implications for past research, editor design, keyboard layout, and benchmark tests are discussed.
Toward a new framework for office support
Authors: Panko Raymond R. , Sprague Ralph H.
Published: June 2007

Office automation is the outgrowth of one form of corporate information technology—the office products category. If we are really to enhance the total office function, however, we will need a much broader concept of office information systems. This paper proposes one such concept, which we call office support.
Implementing office automation
Authors: Tucker Jeffrey H.
Published: June 2007

This paper discusses reasons for resistance to office automation and proposes a method of implementing change drawn from the literature on organizational development and on the implementation of management information systems. The general method is applied to a pilot project of an electronic mail system. Data gathered from the 36 project participants are summarized. Although the project data indicate a need for an EMS, the project failed to produce an adequate user communication volume, and it was cancelled. The paper describes the problems which prevented the effective utilization of the system.
OfficeTalk-D
Authors: Ellis Clarence A. , Bernal Marc
Published: June 2007

WHAT: Herein is described an experimental Office Information System designed and built at the Xerox Palo Alto Research Center to allow multi-computer experiments in distribution and sharing of control within an office environment.

WHY: Current office systems go a long way toward aiding the individual user to transact his/her personal office work. Future office information systems need to aid tightly coupled communities of users. Thus, this investigation into communal computing systems is motivated.

HOW: Using the Alto/Dorado machines, and the Cedar database and programming environment, we have devised a system which allows the flexible manipulation of electronic forms on the display screen of users and helps to coordinate and control the flow of forms between user workstations. Novel facilities implemented in the system include distributed schedulers, dispatchers, office observer workstations, alerters, a data dictionary synthesizer, change agents, and on-line office modeling, simulation and design facilities.
Effects of glossopharyngeal insufflation on cardiac function: an echocardiographic study in elite breath-hold divers
Authors: Potkin Ralph , Cheng Victor , Siegel Robert
Published: June 2007

Glossopharyngeal insufflation (GI), a technique used by breath-hold divers to increase lung volume and augment diving depth and duration, is associated with untoward hemodynamic consequences. To study the cardiac effects of GI, we performed transthoracic echocardiography, using the subcostal window, in five elite breath-hold divers at rest and during GI. During GI, heart rate increased in all divers (mean of 53 beats/min to a mean of 100 beats/min), and blood pressure fell dramatically (mean systolic, 112 to 52 mmHg; mean diastolic, 75 mmHg to nondetectable). GI induced a 46% decrease in mean left ventricular end-diastolic area, 70% decrease in left ventricular end-diastolic volume, 49% increase in mean right ventricular end-diastolic area, and 160% increase in mean right ventricular end-diastolic volume. GI also induced biventricular systolic dysfunction; left ventricular ejection fraction decreased from 0.60 to a mean of 0.30 ( P = 0.012); right ventricular ejection fraction, from 0.75 to a mean of 0.39 ( P < 0.001). Wall motion of both ventricles became significantly abnormal during GI; the most prominent left ventricular abnormalities involved hypokinesis or dyskinesis of the interventricular septum, while right ventricular wall motion abnormalities involved all visible segments. In two divers, the inferior vena cava dilated with the appearance of spontaneous contrast during GI, signaling increased right atrial pressure and central venous stasis. Hypotension during GI is associated with acute biventricular systolic dysfunction. The echocardiographic pattern of right ventricular systolic dysfunction is consistent with acute pressure overload, whereas concurrent left ventricular systolic dysfunction is likely due to ventricular interdependence.
Effect of denervation on ATP consumption rate of diaphragm muscle fibers
Authors: Sieck Gary C. , Zhan Wen-Zhi , Han Young-Soo , Prakash Y. S.
Published: June 2007

Denervation (DNV) of rat diaphragm muscle (DIAm) decreases myosin heavy chain (MHC) content in fibers expressing MHC2Xisoform but not in fibers expressing MHCslowand MHC2A. Since MHC is the site of ATP hydrolysis during muscle contraction, we hypothesized that ATP consumption rate during maximum isometric activation (ATPiso) is reduced following unilateral DIAm DNV and that this effect is most pronounced in fibers expressing MHC2X. In single-type-identified, permeabilized DIAm fibers, ATPisowas measured using NADH-linked fluorometry. The maximum velocity of the actomyosin ATPase reaction ( VmaxATPase) was determined using quantitative histochemistry. The effect of DNV on maximum unloaded shortening velocity ( Vo) and cross-bridge cycling rate [estimated from the rate constant for force redevelopment ( kTR) following quick release and restretch] was also examined. Two weeks after DNV, ATPisowas significantly reduced in fibers expressing MHC2X, but unaffected in fibers expressing MHCslowand MHC2A. This effect of DNV on fibers expressing MHC2Xpersisted even after normalization for DNV-induced reduction in MHC content. With DNV, Voand kTRwere slowed in fibers expressing MHC2X, consistent with the effect on ATPiso. The difference between VmaxATPase and ATPisoreflects reserve capacity for ATP consumption, which was reduced across all fibers following DNV; however, this effect was most pronounced in fibers expressing MHC2X. DNV-induced reductions in ATPisoand VmaxATPase of fibers expressing MHC2Xreflect the underlying decrease in MHC content, while reduction in ATPisoalso reflects a slowing of cross-bridge cycling rate.
Molecular Windows into Speech and Language Disorders
Authors: Fisher Simon E.
Published: June 2007

Why do some children fail to acquire speech and language skills despite adequate environmental input and overtly normal neurological and anatomical development? It has been suspected for several decades, based on indirect evidence, that the human genome might hold some answers to this enigma. These suspicions have recently received dramatic confirmation with the discovery of specific genetic changes which appear sufficient to derail speech and language development. Indeed, researchers are already using information from genetic studies to aid early diagnosis and to shed light on the neural pathways that are perturbed in these inherited forms of speech and language disorder. Thus, we have entered an exciting era for dissecting the neural bases of human communication, one which takes genes and molecules as a starting point. In the current article I explain how this recent paradigm shift has occurred and describe the new vistas that have opened up. I demonstrate ways of bridging the gaps between molecules, neurons and the brain, which will provide a new understanding of the aetiology of speech and language impairments.
Simulated Point Mutations in the Aα-Chain of Human Fibrinogen Support a Role of the αC Domain in the Stabilization of Fibrin Gel
Authors: Colafranceschi Mauro , Papi Massimiliano , Giuliani Alessandro , Amiconi Gino , Colosimo Alfredo
Published: June 2007

The hydrophobicity pattern distribution in the Aα-, Bβ- and γ-chains of human fibrinogen has been studied by a nonlinear method, recurrence quantification analysis, in the wild type and in a number of naturally occurring or simulated mutants. The aim was to find a structural basis for distinguishing between silent and pathological mutants. We were successful in the case of mutations on the Aα-chain, thanks to the peculiar features of this chain as compared to the other two. Relevant findings concerning the point mutants of the Aα-chain are the following: (a) the recurrence quantification analysis-based classification of such mutants is in good agreement with the clinical classification, and (b) the location of the mutated residue on the sequence plays a more relevant role than its hydrophobic features. Artificial point mutants in the terminal zone (600–866 residues) of the extended isoform of the Aα-chain cluster together with the natural hemorrhagic mutants of the first (1–207) residues.
Enhanced Suppression of Adrenocorticotropic Hormone and Cortisol Responses to Hypothalamic-Pituitary-Adrenal Function and Thyrotropin-Releasing Hormone Tests after Stressful Life Events in Patients with Major Depressive Disorder
Authors: Hikichi Takatoshi , Akiyoshi Jotaro , Ichioka Shugo , Tanaka Yoshihiro , Tsuru Jusen , Goto Shinjirou , Matsushita Hirotaka , Hanada Hiroaki , Isogawa Koichi , Nagayama Haruo
Published: June 2007

Background: It is commonly believed that there exists a relationship between the outcome of thyrotropin-releasing hormone (TRH) test, the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test and stressful life events (SLEs) in major depressive disorder. Objective: SLEs influence the TRH and DEX/CRH tests in major depressive disorder when administered at the time of admission and improvement. Methods: The TRH and DEX/CRH tests were administered to patients hospitalized for major depressive disorders – on the 4th through the 7th hospital day and at the time of improvement. We measured ΔMAX TSH, ΔMAX ACTH, ACTH AUC, ΔMAX cortisol, cortisol AUC, ΔMAX ACTH/ΔMAX TSH and ΔMAX cortisol/ΔMAX TSH. Results: SLEs were significantly negatively associated with ΔMAX ACTH, ACTH AUC and cortisol AUC at the time of admission. However, these relationships lost significance at the time of improvement. The sample (41 patients at the time of admission, 18 patients at the time of improvement) was relatively small, which may have contributed to false-negative results. Conclusion: SLEs may be negatively associated with the outcome of the DEX/CRH tests in major depressive disorder. The hypothalamic-pituitary-adrenal axis in the DEX/CRH test was modulated by SLEs.
Changes in the Hypothalamic-Pituitary-Adrenal Axis and Leptin Levels during Antidepressant Treatment
Authors: Himmerich Hubertus , Zimmermann Petra , Ising Marcus , Kloiber Stefan , Lucae Susanne , Künzel Heike E. , Binder Elisabeth B. , Holsboer Florian , Uhr Manfred
Published: June 2007

Background: In depressed patients, overstimulation of the hypothalamo-pituitary-adrenocortical (HPA) system, probably caused by glucocorticoid receptor resistance, is the most consistent neurobiological finding. Glucocorticoids themselves are reported to increase leptin synthesis and secretion in humans. Methods: We examined alterations in plasma levels of leptin as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 74 depressed inpatients. Results: Mean leptin concentration did not change significantly between admission and discharge. However, changes in ACTH response and partial cortisol response to the combined dex/CRH test between admission and discharge were significantly correlated with leptin levels at discharge. Conclusions: Leptin levels at discharge rise as the HPA axis normalizes. These findings may be explained by an improvement in glucocorticoid receptor sensitivity among depressed patients during antidepressant therapy and a consecutively increased influence of glucocorticoids on leptin levels via the glucocorticoid receptor.
Aging of the Mammalian Circadian Timing System: Changes in the Central Pacemaker and Its Regulation by Photic and Nonphotic Signals
Authors: Duncan Marilyn J.
Published: June 2007

Aging alters many aspects of endogenously regulated, 24-hour (circadian) rhythms, such as their amplitude, relationship to the ambient lighting cycle, and sensitivity to phase resetting signals. In order to elucidate the mechanisms responsible for these age-related changes, many studies have investigated age-related changes in the neural components of the circadian timing system, which include the hypothalamic suprachiasmatic nucleus (SCN), the site of the mammalian master circadian pacemaker, its afferent projections from the retina, thalamus, and midbrain raphe, and its efferent projections to the hypothalamus, thalamus and limbic system. Studies have shown that the SCN exhibits age-related changes in electrical activity rhythms in the absence of neurodegeneration. Also, aging selectively decreases SCN expression of the circadian clock genes, Clock and Bmal1, as well as vasoactive intestinal peptide. The latter participates in mediating light-induced phase resetting of the circadian pacemaker and the amplitude of the preovulatory luteinizing hormone surge, which are both attenuated by aging. Furthermore, by decreasing serotonin 5-HT7 receptors in the dorsal raphe, aging reduces one type of nonphotic input to the SCN. This review describes which aspects of circadian rhythm regulation exhibit changes during aging, as well as which mechanisms appear to be spared or remain to be explored.
Early Microcirculatory Changes after Ischemic Preconditioning and Small Bowel Autotransplantation
Authors: Wolfárd A. , Kaszaki J. , Varga S. , Lázár G. , Boros M.
Published: June 2007

Background/Aims: Ischemia-reperfusion injury contributes to the high complication rate of small bowel transplantation (SBTX). Ischemic preconditioning (IPC) protects against reperfusion injury in several organs, but the IPC-induced microcirculatory reaction in the intestine is unknown. Methods: We examined the effects of IPC on the macrohemodynamics and graft microcirculation in a canine model of SBTX during a 4-hour reperfusion period. In group 1 SBTX was performed, in group 2 IPC was induced before graft harvesting (ischemia 3 times for 5 min, followed by 10 min of reperfusion). Cardiac index and mesenteric blood flow were measured, and the mucosal microcirculation, villus epithelial thickness and functional capillary density were monitored by orthogonal polarization spectral imaging. Leukocyte-endothelial cell interactions were monitored in the postcapillary venules, with intravital fluorescence microscopy. Results: Reperfusion decreased cardiac index and mesenteric blood flow during reperfusion; IPC significantly improved these changes. Reperfusion was accompanied by decreased functional capillary density and epithelial thickness of the villi and increased leukocyte-endothelial cell interactions. IPC increased functional capillary density, prevented epithelial narrowing and reduced leukocyte rolling and adherence. Conclusion: IPC improves the macrohemodynamics and the intestinal microcirculation and reduces leukocyte-mediated tissue injury during reperfusion. IPC can be an effective tool to limit reperfusion injury during SBTX.
Interferon-γ Suppresses Cyclooxygenase-2 Promoter Activity by Inhibiting C-Jun and C/EBPβ Binding
Authors: Deng Wu-Guo , Montero Alberto J. , Wu Kenneth K.
Published: June 2007

Objective—

Cyclooxygenase-2 (COX-2) and interferon γ (IFNγ) are overexpressed in vascular inflammatory and atherosclerotic lesions. We postulated that IFNγ suppresses COX-2 expression at the transcriptional level.

Methods and Results—

The effect of IFNγ on COX-2 expression was evaluated in several types of human cells stimulated with phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-1β, or tumor necrosis factor (TNF) α. IFNγ concentration-dependently inhibited COX-2 proteins and promoter activities induced by PMA or cytokines in human fibroblasts and monocytic and endothelial cells. PMA and cytokines stimulate binding of C-Jun, C-Fos, CCAAT/enhancer binding protein β (C/EBPβ), or NF-κB to their respective regulatory elements on COX-2 promoter. IFNγ blocked C-Jun and C/EBPβ but not C-Fos or p50 NF-κB binding as determined by in vitro binding assays and chromatin immunoprecipitation assay. p300 binding to COX-2 promoter was inhibited by IFNγ in a manner comparable to C-Jun and C/EBPβ binding.

Conclusions—

IFNγ suppresses proinflammatory mediator-induced COX-2 transcription by selective inhibition of C-Jun and C/EBPβ DNA binding activity and p300 recruitment in human cells. Because IFNγ is coexpressed with COX-2 in vascular lesions, it may play a role in controlling COX-2–mediated inflammatory changes.
Knock-In Mouse Model of Dilated Cardiomyopathy Caused by Troponin Mutation
Authors: Du Cheng-Kun , Morimoto Sachio , Nishii Kiyomasa , Minakami Reiko , Ohta Mika , Tadano Naoto , Lu Qun-Wei , Wang Yuan-Yuan , Zhan Dong-Yun , Mochizuki Misato , Kita Satomi , Miwa Yoshikazu , Takahashi-Yanaga Fumi , Iwamoto Takahiro , Ohtsuki Iwao , Sasaguri Toshiyuki
Published: June 2007

We created knock-in mice in which a deletion of 3 base pairs coding for K210 in cardiac troponin (cTn)T found in familial dilated cardiomyopathy patients was introduced into endogenous genes. Membrane-permeabilized cardiac muscle fibers from mutant mice showed significantly lower Ca
2+
sensitivity in force generation than those from wild-type mice. Peak amplitude of Ca
2+
transient in cardiomyocytes was increased in mutant mice, and maximum isometric force produced by intact cardiac muscle fibers of mutant mice was not significantly different from that of wild-type mice, suggesting that Ca
2+
transient was augmented to compensate for decreased myofilament Ca
2+
sensitivity. Nevertheless, mutant mice developed marked cardiac enlargement, heart failure, and frequent sudden death recapitulating the phenotypes of dilated cardiomyopathy patients, indicating that global functional defect of the heart attributable to decreased myofilament Ca
2+
sensitivity could not be fully compensated by only increasing the intracellular Ca
2+
transient. We found that a positive inotropic agent, pimobendan, which directly increases myofilament Ca
2+
sensitivity, had profound effects of preventing cardiac enlargement, heart failure, and sudden death. These results verify the hypothesis that Ca
2+
desensitization of cardiac myofilament is the absolute cause of the pathogenesis of dilated cardiomyopathy associated with this mutation and strongly suggest that Ca
2+
sensitizers are beneficial for the treatment of dilated cardiomyopathy patients affected by sarcomeric regulatory protein mutations.
Augmented Protein Kinase C-α–Induced Myofilament Protein Phosphorylation Contributes to Myofilament Dysfunction in Experimental Congestive Heart Failure
Authors: Belin Rashad J. , Sumandea Marius P. , Allen Edward J. , Schoenfelt Kelly , Wang Helen , Solaro R. John , de Tombe Pieter P.
Published: June 2007

It is becoming clear that upregulated protein kinase C (PKC) signaling plays a role in reduced ventricular myofilament contractility observed in congestive heart failure. However, data are scant regarding which PKC isozymes are involved. There is evidence that PKC-α may be of particular importance. Here, we examined PKC-α quantity, activity, and signaling to myofilaments in chronically remodeled myocytes obtained from rats in either early heart failure or end-stage congestive heart failure. Immunoblotting revealed that PKC-α expression and activation was unaltered in early heart failure but increased in end-stage congestive heart failure. Left ventricular myocytes were isolated by mechanical homogenization, Triton-skinned, and attached to micropipettes that projected from a force transducer and motor. Myofilament function was characterized by an active force–[Ca
2+
] relation to obtain Ca
2+
-saturated maximal force (F
max
) and myofilament Ca
2+
sensitivity (indexed by EC
50
) before and after incubation with PKC-α, protein phosphatase type 1 (PP1), or PP2a. PKC-α treatment induced a 30% decline in F
max
and 55% increase in the EC
50
in control cells but had no impact on myofilament function in failing cells. PP1-mediated dephosphorylation increased F
max
(15%) and decreased EC
50
(≈20%) in failing myofilaments but had no effect in control cells. PP2a-dependent dephosphorylation had no effect on myofilament function in either group. Lastly, PP1 dephosphorylation restored myofilament function in control cells hyperphosphorylated with PKC-α. Collectively, our results suggest that in end-stage congestive heart failure, the myofilament proteins exist in a hyperphosphorylated state attributable, in part, to increased activity and signaling of PKC-α.
ATP-Binding Cassette Transporter A1 Gene Transcription Is Downregulated by Activator Protein 2α
Authors: Iwamoto Noriyuki , Abe-Dohmae Sumiko , Ayaori Makoto , Tanaka Nobukiyo , Kusuhara Masatoshi , Ohsuzu Fumitaka , Yokoyama Shinji
Published: June 2007

ATP-binding cassette transporter A1 (ABCA1) is a rate-limiting factor for high-density lipoprotein (HDL) biogenesis. The ABCA1 gene expression is known to be upregulated by various transcriptional factors. However, negative regulation factors would be better targets for pharmacological modulation of HDL biogenesis. Doxazosin, an α
1
-adrenoceptor blocker, increased ABCA1 mRNA, its protein, and apolipoprotein A-I–mediated HDL biogenesis in THP-1 macrophages and CHO-K1 cells, independent of α
1
-adrenoceptor blockade. Analysis of the human ABCA1 promoter indicated that the region between the positions −368 and −147 that contains an activator protein (AP)2-binding site responsible for the effects of doxazosin. Overexpression of AP2α inhibited ABCA1 transcription in a dose-dependent fashion. Mutation in the AP2-binding site caused increase of the basal promoter activity and canceling both the transactivation by doxazosin and the trans-repression by AP2α. Doxazosin had no effect on ABCA1 mRNA level in HepG2 cells, which lack endogenous AP2α, and it reversed the inhibitory effect of AP2α expression in this type of cells. Chromatin immunoprecipitation and gel shift assays revealed that doxazosin reduced specific binding of AP2α to the ABCA1 promoter, as it suppressed phosphorylation of AP2α. Finally, doxazosin increased ABCA1 expression and plasma HDL in mice. We thus concluded that AP2α negatively regulates the ABCA1 gene transcription. Doxazosin inhibits AP2α activity independent of α
1
-adrenoceptor blockade and increases the ABCA1 expression and HDL biogenesis. AP2α is a potent pharmacological target for the increase of HDL.
Polyunsaturated Fatty Acids Are Cerebral Vasodilators via the TREK-1 Potassium Channel
Authors: Blondeau Nicolas , Pétrault Olivier , Manta Stella , Giordanengo Valérie , Gounon Pierre , Bordet Régis , Lazdunski Michel , Heurteaux Catherine
Published: June 2007

Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially α-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly α-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. α-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1
−/−
mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as α-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.
Gene Therapy to Inhibit the Calcium Channel β Subunit
Authors: Cingolani Eugenio , Ramirez Correa Genaro A. , Kizana Eddy , Murata Mitsushige , Cho Hee Cheol , Marbán Eduardo
Published: June 2007

Calcium cycling figures prominently in excitation-contraction coupling and in various signaling cascades involved in the development of left ventricular hypertrophy. We hypothesized that genetic suppression of the L-type calcium channel accessory β-subunit would modulate calcium current and suppress cardiac hypertrophy. A short hairpin RNA template sequence capable of mediating the knockdown of the L-type calcium channel accessory β-subunit gene was incorporated into a lentiviral vector (PPT.CG.H1.β
2
). Transduction of ventricular myocytes in vivo with the active short hairpin RNA partially inhibited the L-type calcium current. In neonatal rat cardiomyocytes, L-type calcium channel accessory β-subunit gene knockdown reduced calcium transient amplitude. Similarly, [
3
H]leucine incorporation was attenuated in PPT.CG.H1.β
2
-transduced neonatal rat cardiomyocytes compared with nonsilencing controls in a phenylephrine-induced hypertrophy model. In vivo gene transfer attenuated the hypertrophic response in an aortic-banded rat model of left ventricular hypertrophy, with reduced left ventricular wall thickness and heart weight/body weight ratios in PPT.CG.H1.β
2
-injected rats at four weeks post transduction. Fractional shortening was preserved in rats treated with PPT.CG.H1.β
2
. These findings indicate that knockdown of L-type calcium channel accessory β-subunit is capable of attenuating the hypertrophic response both in vitro and in vivo without compromising systolic performance. Suppression of the calcium channel β subunit may represent a novel and useful therapeutic strategy for left ventricular hypertrophy.
Diabetes Education: A Multidisciplinary Team Approach
Authors: Kortas Kenneth J. , Quinn Laurie
Published: June 2007

Diabetes mellitus is one of the leading causes of mortality and morbidity in the United States, showing an incidence of over 14 million individuals, with the numbers increasing yearly. Current evidence suggests that maintaining normal blood glucose levels will result in preventing or lessening the degree of acute and chronic complications of diabetes. Therefore, because many of the complications of diabetes may be prevented or lessened by strict glycemic control, it is of the utmost importance that the individual with diabetes understand the roles of diet, exercise, and insulin/oral hypoglycemics in the management of his or her diabetes. This is an area in which diabetic education plays an important role. The properly educated individual with diabetes can learn to increase or decrease insulin, to change diet, or to modify exercise regimens based on results of home blood glucose-monitoring to achieve normoglycemia. This article discusses a multidisciplinary team approach to educating the diabetic patient. This involves using the skills of physicians, pharmacists, nurses, dieticians, and other health care professionals, as well as teaching tools such as diabetes patient assessment forms, diabetes education, and teaching documentation records. It should become clear from this discussion the active role that pharmacists can play as an important member of the diabetic education team. Copyright © 1992 by W.B. Saunders Company
Radiopaque Contrast Media: The Role of the Pharmacist
Authors: Swanson Dennis P. , Jurgens Raymond W.
Published: June 2007

Radiopaque contrast media (ROCM) are diagnostic drugs used for the enhancement of radiographic (x-ray) examinations. Although these agents have been used extensively for several years, pharmacist involvement with this category of drugs, to date, has been minimal. This article outlines several aspects of contrast media use in which pharmacists can or should become actively involved. Included in this discussion are possible roles of the pharmacist in decisions regarding respective product efficacy and use; adverse reaction prevention, reporting, monitoring, and treatment; and the evaluation of potential contrast media-drug or contrast media-laboratory test interactions. Pharmacist involvement associated with the use of traditional drugs in the performance of radiographic examinations and with technological advancements in radiology are also addressed. The overall magnitude of drug activity encountered in a radiology department suggests a needed and important role for pharmacists interested in this area.
A Statewide Program to Stimulate Reporting of Adverse Drug Reactions
Authors: Fincham Jack
Published: June 2007

The purpose of a 26-month Food and Drug Administration sponsored study conducted in Mississippi was to determine how the reporting of adverse drug reactions (ADRs) might be stimulated. The program included both institutional and community based health care facilities located in urban as well as rural settings. Methods used in the study increased the monthly average of reported ADRs from 3.94 to 16.5. Pharmacists have the expertise and responsibility to assume a more active role in the reporting of ADRs.
Primary attempts at research-based evaluation of clinical supervision
Authors: Butterworth Tony
Published: June 2007

The subject of evaluating clinical supervision for nurses and health visitors in the United Kingdom is considered in this paper. Some of the methodological problems and possible solutions are debated. A multi-site project funded by the Department of Health is described. The paper seeks to identify the debate which currently surrounds the possibilities of evaluating clinical supervision. Research methods and tools are presented, along with a brief summary of some, and an assessment is made of their potential value. The dilemmas of evaluation on a 'grand scale' are considered and arguments are made for a broad methodological approach to evaluating clinical supervision. [NT Research 1996; 1: 2, 96-101]
Evidence-based nursing
Authors: Bishop Veronica
Published: June 2007

The Focus papers in this issue on the theme of evidence-based nursing, and the Commentary from a member of the executive of the Council of Deans and Heads, aim to stimulate the debate which will develop at the Nursing Times Research Symposium for Evidence-based Nursing to be held at the Manchester Conference Centre on October 22-23. NTResearch has published papers and scientific reviews in past issues on this important issue and abstracts from these papers are published below. They will, it is hoped, offer readers further ammunition for effecting change.