bluuebunny/crossref_metadata_2025 huggingface dataset:
ECG SIGNALS PROCESSING WITH NEURAL NETWORKS
Authors: HILERA JOSE R. , MARTÍNEZ VICTOR J. , MAZO MANUEL
Published: November 2004

Nowadays, the digital register process of electrocardiographical signals (ECG) constitutes a common practice for the diagnosis and controlling of patients suffering from cardiac disorders. In this paper we study the usefulness of Artificial Neural Network (ANN) for clinical diagnosis through the detection of arrythmias and the reduction of the large spaces occupied by ECG records.
A GENERALIZED FUZZY COVARIANCE MATRIX
Authors: BARONE JOSEPH M.
Published: November 2004

This paper describes a generalized fuzzy covariance matrix based on the notion of fuzzy similitude and its application to discriminant analysis. It is shown that this generalized fuzzy covariance matrix may be useful in the determination of outliers. It is further noted that the generalized fuzzy covariance matrix may help to distinguish outliers from high-leverage points, and both of these from “normal” points, and thus may have general application to sensitivity analysis in discriminant analysis and clustering problems.
STRATEGIES FOR SELECTING COMMUNICATION STRUCTURES IN COOPERATIVE SEARCH
Authors: NARAZAKI SHUJI , YAMAMURA HIROOMI , YOSHIDA NORIHIKO
Published: November 2004

Modeling environment is essential for agents to cooperate with each other in a distributed system. In this paper, we propose two strategies for selecting agents’ communication structures in a cooperative search using their local histories as a model of their computational environment. Under the assumption of homogeneity of agents, an agent can select a proper communication structure by using a history of local computation, and the utility of communication always matches its cost. Simulations using the traveling salesman problem show that strategies produce high performance. We also describe an extension of these strategies to other areas and the means to separate them from application programs using meta-object programming in Object-Oriented Programming Languages (OOPL).
SURFACE-EMITTING SEMICONDUCTOR LASER STRUCTURES FABRICATED BY MICROLITHOGRAPHY
Authors: GOURLEY P. L. , WARREN M. E.
Published: November 2004

Vertical cavity surface-emitting lasers are semiconductor microcavity lasers created by epitaxial growth and surface processing technologies which exploit new 3-dimensional architectures. The physical properties of these microcavities are intimately related to the geometry imposed on the semiconductor materials. The surface-emitting geometry is ideal for fabricating 2-dimensional laser structures by optical and electron beam lithography. These structures include large area, phase-locked arrays with shaped beams for higher power applications and 2-dimensional nanostructures such as photonic lattices for controlling microscopic optical properties. This paper reviews the basic physics of epitaxial surface-emitting laser cavities and recent technical advances in the microfabrication of 2-dimensional surface-emitting laser arrays and photonic lattices.
FREQUENCY EFFECTS AND CLASSICAL PATHS IN STRONG-FIELD IONIZATION
Authors: REISS H. R.
Published: November 2004

The ability of the SFA (strong-field approximation) to predict the ionization of atoms at all frequencies is explored at low frequency by comparison with experiment. Excellent agreement is found over a very wide range of high intensities. At high frequency, where no precision strong-field experiments are available, a comparison is made between predictions of the SFA and a high-frequency theory due to Gavrila. Agreement in transition rates is very good. The disagreement in the assignment of energy conditions at high frequencies is explained as a difference in interpretation brought about by the gauge transformation employed by Gavrila. An examination of semiclassical path behavior of a photoelectron after ionization gives insight on the lower limits of intensity for which the SFA is applicable, and makes transparent the meaning of a recently applied Coulomb correction to the SFA for circularly polarized light. A related examination for linearly polarized light gives an effective high energy limit for intense-field photoelectron spectra.
SUBFEMTOSECOND HIGH-INTENSITY UNIPOLAR ELECTROMAGNETIC SOLITONS AND SHOCK WAVES
Authors: KAPLAN A. E. , SHKOLNIKOV P. L.
Published: November 2004

We show that atomic gasses can support solitary pulses of unipolar, non-oscillating EM-field ("EM-bubbles") of up to the atomic amplitude, with their length ranging from ~10−9 s to ~10−16 s , which propagate without dispersion and are stable and insensitive to the change of gas density. We found the condition on the atomic potential necessary for formation of EM-bubble. Atomic gasses can also support an EM shock which is a precursor of a cw ionizing field.
SIMPLIFIED DESCRIPTION OF SOLITON PERTURBATION AND INTERACTION USING AVERAGED COMPLEX POTENTIALS
Authors: ANKIEWICZ A.
Published: November 2004

We present a new physical and mathematical approach, which involves an extension of the effective potential idea, for determining the effect of various perturbations on a soliton. The method explains the results in a more simple way than has been done previously. We also analyze the interaction of two solitons as a function of their separation using this equivalent particle picture with an effective potential caused by the interaction.
Regulation of the energy sensor AMP-activated protein kinase in the kidney by dietary salt intake and osmolality
Authors: Fraser Scott , Mount Peter , Hill Rebecca , Levidiotis Vicki , Katsis Frosa , Stapleton David , Kemp Bruce E. , Power David A.
Published: November 2004

The AMP-activated protein kinase (AMPK) is a key controller of cellular energy metabolism. We studied its expression and regulation by salt handling in the kidney. Immunoprecipitation and Western blots of protein lysates from whole rat kidney using subunit-specific antibodies showed that the α1-catalytic subunit is expressed in the kidney, associated with the β2- and either γ1- or γ2-subunits. Activated AMPK, detected by immunohistochemical staining for phospho-Thr172AMPK (pThr172), was expressed on the apical surface of the cortical thick ascending limb of the loop of Henle, including the macula densa, and some parts of the distal convoluted tubule. Activated AMPK was also expressed on the basolateral surface of the cortical and medullary collecting ducts as well as some portions of the distal convoluted tubules. AMPK activity was increased by 25% in animals receiving a high-salt diet, and this was confirmed by Western blotting for pThr172. Low-salt diets were associated with reduced levels of the α-subunit of AMPK, which was highly phosphorylated on Thr172. Surprisingly, both low- and high-salt media transiently activated AMPK in the macula densa cell line MMDD1, an effect due to changes in osmolality, rather than Na+or Cl−concentration. This study, therefore, demonstrates regulation of AMPK by both a high- and a low-salt intake in vivo and suggests a role for the kinase in the response to changes in osmolality within the kidney.
Gene regulation of ENaC subunits by serum- and glucocorticoid-inducible kinase-1
Authors: Boyd Cary , Náray-Fejes-Tóth Anikó
Published: November 2004

Aldosterone is a key regulator of epithelial Na+channels (ENaC) in renal cortical collecting ducts (CCD). The goal of this study was to examine whether serum- and glucocorticoid-inducible kinase-1 (SGK1), an aldosterone-induced gene, is vital to the delayed effect of aldosterone by increasing the gene expression of ENaC subunits. To test this hypothesis, we compared the levels of ENaC mRNA in mouse CCD cells that stably express either full-length (FL)-SGK1 or a kinase-dead dominant negative (K127M)-SGK1. Our results revealed that SGK1 regulates gene expression of ENaC, whether cells are maintained in steroid-free media or in the presence of corticosteroids (CS) and/or other growth factors. Under all conditions, the loss of function of SGK1 caused a significant decrease in the expression of α- and β-ENaC, but not γ-ENaC. Compared with cells expressing FL-SGK1, K127M-SGK1 decreased the expression of α- and β-subunit mRNA by ∼45 and ∼90%, respectively. Next, to determine whether SGK1 is one of the proteins mediating the induction of α-ENaC mRNA by CS, we compared steroid induction of α-ENaC in cells expressing K127M-SGK1 vs. FL-SGK1. The maximum level of α-ENaC mRNA levels following CS was significantly (∼45%) higher in FL-SGK1- vs. K127M-SGK1-expressing cells, although the fold-induction by CS was similar in both FL-SGK1- and K127M-SGK1-expressing cells. In summary, we report for the first time that SGK1 regulates transcription of ENaC subunits. We propose that the effect of SGK1 on ENaC transcription is mediated by the activation of unidentified transcription factors.
Counseling and the Internet
Authors: Skinner Adrian , Zack Jason S.
Published: November 2004

Online counseling is the latest entry in a class of indirect therapy methods that extends back to Freud’s work with “Little Hans.” This article recounts the history of indirect counseling in general and online counseling in particular, explores the effectiveness of online counseling as a mode of therapy, deals with ethical issues, and examines the feasibility of online counseling as a business. The article concludes that online counseling is an effective and ethical form of counseling that can, with effort and care, become a feasible business.
Sensemaking and New Media at Work
Authors: Gephart Robert P.
Published: November 2004

This article examines sensemaking about new media at work in organizational settings. Two models of sensemaking are presented. Recent social science and management research on computer-mediated work is reviewed to identify aspects of sensemaking evident in computer-mediated communications at work. The sensemaking models are used to interpret this recent research on human computer interactions and computer-mediated communications in organizations. The article shows how the sensemaking perspective facilitates an understanding of the interpretive practices and problems people face in using new media for communication at work.
Using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) to Detect Psychological Distress and Dysfunction in a State Correctional Setting
Authors: Black Maureen S. , Forbey Johnathan D. , Ben-Porath Yossef S. , Graham John R. , McNulty John L. , Anderson Stephen V. , Burlew A. Kathleen
Published: November 2004

Approximately 1.3 million men and 93,000 women are currently detained in state and federal correctional facilities. The ability to identify upon admission to a correctional facility those individuals who either have or are at an increased risk for developing significant psychological difficulties is crucial in order to allow early detection of inmates requiring mental health services. This study investigates the frequency with which 34,281 male and 6,878 female inmates from a state corrections facility reported significant levels of distress and dysfunction upon intake to the correctional system as measured by various clinical scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results indicate that a substantial proportion of incarcerated adults reported significant levels of distress across a variety of psychological, social, and behavioral domains.
Structural Conflict in Contemporary Cities
Authors: Simmons James R. , Simmons Solon J.
Published: November 2004

A surprising number of modern American cities are experiencing efforts to drastically alter or even abandon their forms of local government. We discuss the major perspectives on municipal structural choice and then use both survey and census data in an attempt to explain this contemporary urban conflict over governance structure. Our findings demonstrate that no single institutional, political, social, or contextual theory satisfactorily explains this evolving struggle over governing arrangements in U.S. cities. Rather, a complex array of factors such as race, ethnicity, education, economic change, governmental composition, and specific municipal design features seem to be driving these movements for institutional change.
Whither Challenger, Wither Columbia
Authors: Garrett Terence M.
Published: November 2004

The Challenger and Columbia similarities in management decision making with regard to the ill-fated shuttle mission failures bear scrutiny. Key aspects of both tragedies include senior-level managers ignoring the advice from experts within the NASA organization leading to tragedy. NASA is typical of modern organizations in the tendency to relegate worker knowledge below that of managers and executives. The Columbia Accident Investigation Board has determined that the organizational/management culture was a key factor in the demise of the Columbia. The author argues that culture, although an important contributor to the tragedy, is inadequate for assessing the problem. Differences in knowledge between executives, managers, and the workers are key to unlocking the central problem of the NASA organization. The author uses and develops the theoretical approach that delves into multiple knowledges in organizations that is known as the “knowledge analytic.”
Beyond the Spatial Mismatch: Welfare Recipients and Transportation Policy
Authors: Blumenberg Evelyn , Manville Michael
Published: November 2004

Beneath the broad umbrella of agreement about transportation’s relationship to poverty is considerable discord about the specific nature of the problem and about where and how transportation solutions should be applied. Much of the existing scholarship on this topic focuses on the spatial mismatch hypothesis, the geographic separation between employment and housing. Although this concept has merit, to meet the transportation needs of welfare recipients, policy makers must move beyond conventional notions of the spatial mismatch hypothesis. This article draws from theoretical and empirical scholarship on travel behavior, transportation infrastructure, poverty, gender studies, and residential segregation and recommends transportation policies to better connect welfare recipients to employment.
Managing the Corporate Work-Health Culture
Authors: Mitchell Kenneth
Published: November 2004

In an attempt to control health care costs, lost time, and related employee productivity, employers devote many resources to solutions for these problems. But often the solutions are applied independently of one another, possibly in different areas of the company, even though the problems are often related. Recent studies in the disability industry suggest the relationship between health care costs and lost time is closely intertwined. Moreover, work and health are connected and are often affected by the corporate culture. The elements that make up this culture include the amount of control the company has over lost time and health care costs, employee motivation and expectations, the organization’s benefits, corporate health and safety practices, and the company’s capacity to measure lost time. By exploring the elements that contribute to and often encourage employee absences, employers can better direct their resources in the development of a comprehensive absence management plan.
Qualitative Metasynthesis: Reflections on Methodological Orientation and Ideological Agenda
Authors: Thorne Sally , Jensen Louise , Kearney Margaret H. , Noblit George , Sandelowski Margarete
Published: November 2004

In an era of pressure toward evidence-based health care, we are witnessing a new enthusiasm for qualitative metasynthesis as an enterprise distinct from conventional literature reviews, secondary analyses, and the many other scholarly endeavors with which it is sometimes confused. This article represents the reflections of five scholars, each ofwhom has authored a distinct qualitative metasynthesis strategy. By providing the reader a glimpse into the tradition of their various qualitative metasynthesis projects, these authors offer a finely nuanced examination of the tensions between comparison and integration, deconstruction and synthesis, and reporting and integration within the metasynthesis endeavor. In so doing, they account for many of the current confusions about representation and generalization within the products of these inquiries. Through understanding the bases of their unique angles of vision, the reader is invited to engage in their commitment to scholarly integrity and intellectual credibility in this emerging methodological challenge.
A Theory of Continuous Socialization for Organizational Renewal
Authors: Danielson Monica Marie
Published: November 2004

Current literature suggests that for sustained competitive success, organizations must have processes in place for continuous learning and adaptation. Any process, then, that appears to hinder agility should come under scrutiny. Examination of socialization theories revealed an intended outcome of perpetuating the organization’s way of life, its values, attitudes, beliefs, and practices. Thus, the purpose of this study was to develop an alternative socialization theory that would facilitate renewal, not encumber it. Robert Dubin’s theory-building research method was used to conceptualize and operationalize this theory. The first major output of this study is a fully conceptualized theoretical model, including the identification of units, laws of interaction, system states, and boundaries. The second major output is the operationalization of that model. This includes the development of propositions, or truth statements, concerning the operation of the model, empirical indicators of key terms, and potential hypotheses to test the theory.
Exploring Human Resource Development: A Levels of Analysis Approach
Authors: Garavan Thomas N. , McGuire David , O’Donnell David
Published: November 2004

Levels of analysis perform an important function in framing research and practice in human resource development (HRD). The purpose of this article is to examine the concept of HRD from the individual, organizational, and community-societal levels of analysis. The article highlights both the distinctiveness and usefulness of each level of analysis, identifies tensions within and between them, and outlines differences in underpinning assumptions, characteristics of HRD provision, and delivery of HRD interventions. By adopting this approach, the article draws attention to variations in meaning, intent, content, and practice with implications for developing both the theory and practice of HRD.
The Neurobiology of Category Learning
Authors: Ashby F. Gregory , Spiering Brian J.
Published: November 2004

Many recent studies have examined the neural basis of category learning. Behavioral neuroscience results suggest that both the prefrontal cortex and the basal ganglia play important category-learning roles; neurons that develop category-specific firing properties are found in both regions, and lesions to both areas cause category-learning deficits. Similar studies indicate that the inferotemporal cortex does not mediate the learning of new categories. The cognitive neuroscience literature on category learning appears contradictory until the results are partitioned according to the type of category-learning task that was used. Three major tasks can be identified: rule based, information-integration, and prototype-distortion. Recent results are consistent with the hypotheses that (a) learning in rule-based tasks requires working memory and executive attention and is mediated by frontal-striatal circuits, (b) learning in information-integration tasks requires procedural memory and is mediated primarily within the basal ganglia, and (c) learning in prototype-distortion tasks depends on multiple memory systems, including the perceptual representation system.
The Role of Technology in Task-Oriented Training in Persons with Subacute Stroke: A Randomized Controlled Trial
Authors: Richards Carol L. , Malouin Francine , Bravo Gina , Dumas Francine , Wood-Dauphinee Sharon
Published: November 2004

This trial compares the effects of task-oriented physical therapy (PT) provided with and without the use of rehabilitation technology on locomotor recovery in 63 persons with subacute stroke. Participants in the experimental (EXP) group used a treadmill, a Kinetron isokinetic exerciser, and a limb-load monitor, whereas those in the control (CTL) group did not while engaging in PT 1 h per day, 5 days per week for 2 months. Locomotor recovery was assessed by clinical (gait speed, Fugl Meyer motor leg and arm subscores, the Balance Scale, the Timed Up and Go, and the Barthel ambulation subscore) and laboratory outcomes (gait kinematics and kinetics) pre- and posttherapy and 3 months later. Within groups, gait speed (P < 0.01) and all secondary measures improved posttherapy (P < 0.01-0.05), and improvements in clinical measures were maintained at follow-up, but there was no difference between groups (P > 0.05). When the groups were pooled, the increase in gait speed was associated (r = 0.52, P = 0.003) with an increase in ankle power generation of the affected leg. The results demonstrate that the efficacy of the task-oriented approach is not dependent on rehabilitation technology.
RGS2 is an important target gene of Flt3-ITD mutations in AML and functions in myeloid differentiation and leukemic transformation
Authors: Schwäble Joachim , Choudhary Chunaram , Thiede Christian , Tickenbrock Lara , Sargin Bülent , Steur Claudia , Rehage Maike , Rudat Annika , Brandts Christian , Berdel Wolfgang E. , Müller-Tidow Carsten , Serve Hubert
Published: November 2004

Activating fetal liver tyrosine kinase 3 (Flt3) mutations represent the most common genetic aberrations in acute myeloid leukemia (AML). Most commonly, they occur as internal tandem duplications in the juxtamembrane domain (Flt3-ITD) that transform myeloid cells in vitro and in vivo and that induce aberrant signaling and biologic functions. We identified RGS2, a regulator of G-protein signaling, as a gene specifically repressed by Flt3-ITD. Here we demonstrate an important role of RGS2 in Flt3-ITD–mediated transformation. RGS2 was repressed after forced expression of activating Flt3 mutations in 2 myeloid cell lines (32Dcl3 and NB4). Furthermore, RGS2 was repressed in Flt3-mutation–positive AML cases in comparison to Flt3-mutation–negative cases, especially in Flt3-ITD–positive cases with a high ITD-to–wild-type (WT) ratio. Coexpression of RGS2 with Flt3-ITD inhibited Flt3-ITD–induced autonomous proliferation and clonal growth of 32D cells. RGS2 also inhibited Flt3-ITD–induced phosphorylation of Akt and glycogen synthase kinase β (Gsk3-β) without influencing signal transducer and activator of transcription 5 (STAT5) activation. In addition, RGS2 reinduced the expression of Flt3-ITD–repressed CCAAT/enhancer-binding protein α (c/EBPα) and antagonized the Flt3-ITD–induced differentiation block in 32D cells. Expression analyses in myeloid cell lines revealed induction of RGS2 during granulocytic but not during monocytic differentiation. Taken together, RGS2 is a novel mediator of myeloid differentiation, and its repression is an important event in Flt3-ITD–induced transformation.
Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor–reactive cytotoxic T lymphocytes
Authors: Biagi Ettore , Dotti Gianpietro , Yvon Eric , Lee Edward , Pule Martin , Vigouroux Stephane , Gottschalk Stephen , Popat Uday , Rousseau Raphael , Brenner Malcolm
Published: November 2004

Clinical benefits from monoclonal antibody therapy for B-chronic lymphocytic leukemia (B-CLL) have increased interest in developing additional immunotherapies for the disease. CD40 ligand is an accessory signal for T-cell activation and can overcome T-cell anergy. The OX40-OX40 ligand pathway is involved in the subsequent expansion of memory antigen-specific T cells. We expressed both CD40L and OX40L on B-CLL cells by exploiting the phenomenon of molecular transfer from fibroblasts overexpressing these ligands. We analyzed the effects of the modified B-CLL cells on the number, phenotype, and cytotoxic function of autologous T cells in 7 B-CLL patients. Transfer of CD40L and OX40L was observed in all and was followed by the up-regulation of B7-1 and B7-2. The culture of CD40L/OX40L-expressing B-CLL cells with autologous T cells generated CD4+/CD8+ cytotoxic T-cell lines, which secreted interferon-γ (IFN-γ) and granzyme-B/perforin in response to autologous, but not to allogeneic, B-CLL cells or to autologous T-cell blasts. CD40L or OX40L alone was insufficient to expand tumor-reactive T cells. The combination of CD40L and OX40L on B-CLL cells may allow the generation of therapeutic immune responses to B-CLL, either by active immunization with modified tumor cells or by adoptive immunotherapy with tumor-reactive autologous T cells.
Balance of proliferation and cell death between thyrocytes and myofibroblasts regulates thyroid fibrosis in granulomatous experimental autoimmune thyroiditis (G-EAT)
Authors: Chen Kemin , Wei Yongzhong , Sharp Gordon C , Braley-Mullen Helen
Published: November 2004

Severe granulomatous experimental autoimmune thyroiditis (G-EAT), which progresses to fibrosis, is induced in DBA/1 mice by adoptive transfer of mouse thyroglobulin-primed and -activated spleen cells. There is extensive destruction of thyrocytes and inflammatory cell infiltration including T cells, macrophages, neutrophils, and myofibroblasts (myofbs). Suppression of transforming growth factor-β (TGF-β) and deficiency of interferon-γ (IFN-γ) inhibit fibrosis, and inflammation eventually resolves. Thyrocyte destruction in wild-type (WT) mice was a result of apoptosis, as many deoxynucleotide triphosphate nick-end labeling + apoptotic thyrocytes were present in these thyroids. The balance of apoptosis and proliferation between thyrocytes and myofbs may be important factors determining the outcome of inflammation to fibrosis versus resolution. Apoptosis and proliferation in thyrocytes versus myofbs were evaluated by dual-staining of cell-proliferating marker (Ki-67) or in situ cell death and cytokeratin or α-smooth muscle actin and were analyzed by confocal microscopy. Apoptotic and antiapoptotic molecules in G-EAT thyroids were detected by immunostaining. In WT thyroids, which develop fibrosis, only a few myofbs were apoptotic, and many myofbs were Ki-67+, Fas-associated death domain protein-like interleukin-1β-converting enzyme-like inhibitory protein (FLIP)+, and Bcl-XL+. In contrast, proliferation was predominant on thyrocytes of IFN-γ−/− mice or anti-TGF-β-treated WT mice. These results indicate that apoptosis of inflammatory cells and regeneration of thyrocytes in IFN-γ−/− mice and anti-TGF-β-treated WT mice may limit development of fibrosis, whereas excessive proliferation of myofbs and loss of thyrocytes in WT mice may contribute to fibrosis.
Lichenometric dating of the ‘Little Ice Age’ maximum in Mt Cook National Park, Southern Alps, New Zealand
Authors: Winkler Stefan
Published: November 2004

Lichenometric dating studies using the yellow-green Rhizocarpon subgenus at the Eugenie, Hooker, Mueller and Tasman Glaciers in Mt Cook National Park, Southern Alps, New Zealand, reveal a ‘Little Ice Age’ maximum during the mid-eighteenth century (around AD 1725-1740). Lichenometric dating curves, constructed for Mueller Glacier in a preliminary study, were modified using local control points at the other glaciers. Modification was necessary because of variations in local ecological conditions. The ‘Little Ice Age’ chronology is similar for three out of the four glaciers studied. All except Tasman Glacier underwent a major glacier front oscillation directly following the ‘Little Ice Age’ maximum. After a slow but constant retreat during the second half of the eighteenth and the first half of the nineteenth centuries, the glaciers experienced major readvances during the second half of the nineteenth century (around AD 1860 and 1890/95), and during the early decades of the twentieth century. Tasman Glacier, as the exception, returned to its ‘Little Ice Age’ maximum frontal position during the late nineteenth century, overtopping pre-existing ‘Little Ice Age’ moraines, and therefore preventing detailed dating of these moraines. Differences in dating from previous lichenometric studies may be due to the different methods used.
Review of ACR renal criteria in systemic lupus erythematosus
Authors: Dooley M A , Aranow C , Ginzler E M
Published: November 2004

The American College of Rheumatology renal criteria require re-evaluation to incorporate recent advances in the classification of glomerulonephritidies. Renal biopsy is now common and safely performed by experienced nephrologists in community as well as academic settings. The optimal criterion is renal histopathology findings of an immune complex mediated glomerulonephritis as interpreted by an experienced pathologist employing accepted criteria. Renal biopsies should be analysed by routine histopathology, immunofluorescent and electron microscopy. Rating of activity and chronicity should be noted. Secondary criteria for patients unable to undergo renal biopsy includes a combination of findings. These include proteinuria, hypocomplementemia, elevated anti-dsDNA antibodies and an active urine sediment. Proteinuria is a nonspecific finding and, most importantly, can be associated with a number of comorbidities including diabetes, hypertension and atherosclerotic disease. Persistent proteinuria > 0.5 g per day or a spot protein to creatine ratio of > 0.5 should be accompanied by an additional feature supporting active lupus such as positive serologies (hypocomplementemia and/or elevated anti-dsDNA antibodies) and/or active urinary sediment. Similarly, active urinary sediment should be accompanied by the additional criterion of proteinuria to meet renal criteria. Decline in renal function is not a reliable criterion given the numerous medications, comorbidities and other clinical circumstances which may result in this feature.
Anti-dsDNA antibodies: still a useful criterion for patients with systemic lupus erythematosus?
Authors: Isenberg D
Published: November 2004

The presence of antibodies to dsDNA has been a criterion for systemic lupus erythematosus (SLE) in each of three attempts to classify the disease that have been undertaken by the American College of Rheumatology. The generally good specificity of the test, the fact that it is widely available and often undertaken by an enzyme linked immunosorbent assay (ELISA) which is relatively cheap and easy to perform have encouraged its continued presence in the list of lupus criteria. The detection of anti-dsDNA antibodies is not, however, straightforward and the real significance of the presence of these antibodies, their true specificity (or otherwise), the question of whether they are truly linked to disease pathogenicity and how accurately they reflect disease activity are all questions that have been posed in the past 20 years.
Requirements for the destruction of human Aurora-A
Authors: Crane Richard , Kloepfer Angela , Ruderman Joan V.
Published: November 2004

The mitotic kinase Aurora A (Aur-A) is overexpressed in a high proportion of human tumors, often in the absence of gene amplification. In somatic cells, Aur-A protein levels fall following mitosis or upon overexpression of Cdh1, an activator of the ubiquitin ligase APC/C. Thus, mutations that reduce or block the rate of Aur-A destruction might also be expected to contribute to its oncogenic potential. Previous work had defined two short sequences of Xenopus Aur-A that are required for its Cdh1-inducible destruction in extracts of Xenopus eggs, an N-terminal A box and a C-terminal D box, and a serine residue within the A box whose phosphorylation might inhibit destruction. Here, we show that these same sequences are required for the destruction of human Aur-A during mitotic exit and G1 in the somatic cell cycle. Expression of a dominant negative Cdh1 protein leads to accumulation of Aur-A, further indicating that the Cdh1-activated form of the APC/C is responsible for destruction of Aur-A during the somatic cell cycle in vivo. During the course of this work, we found some previously unsuspected problems in commonly used in vitro destruction assays, which can result in misleading results. Potentially confounding factors include: (i) the presence of D-box- and A-box-dependent destruction-promoting activities in the reticulocyte in vitro translation mix that is used to produce radiolabeled substrates for destruction assays; and (ii) the ability of green-fluorescent-protein tags to reduce the destruction rate of Aur-A substantially. These findings have direct relevance for studies of Aur-A destruction itself, and for broader approaches that use in vitro translation products in screens for additional APC/C targets.
Alteration of chromosome positioning during adipocyte differentiation
Authors: Kuroda Masahiko , Tanabe Hideyuki , Yoshida Keiichi , Oikawa Kosuke , Saito Akira , Kiyuna Tomoharu , Mizusawa Hiroshi , Mukai Kiyoshi
Published: November 2004

Chromosomes are highly restricted to specific chromosome territories within the interphase nucleus. The arrangement of chromosome territories is non-random, exhibiting a defined radial distribution as well as a preferential association with specific nuclear compartments, which indicates a functional role for chromosome-territory organization in the regulation of gene expression. In this report, we focus on changes in adipocyte differentiation that are related to a specific chromosomal translocation associated with liposarcoma tumorigenesis, t(12;16). We have examined the relative and radial positioning of the chromosome territories of human chromosomes 12 and 16 during adipocyte differentiation, and detected a close association between the territories of chromosomes 12 and 16 in differentiated adipocytes, an association not observed in preadipocytes. Although further studies are required to elucidate the underlying reasons for the adipocyte-specific translocation of chromosomes 12 and 16, our observations indicate that alteration of relative chromosome positioning might play a key role in the tumorigenesis of human liposarcomas. In addition, these results demonstrate the potential impact of higher order chromatin organization on the epigenetic mechanisms that control gene expression and gene silencing during cell differentiation.
Formation of multivesicular endosomes in Dictyostelium
Authors: Marchetti Anna , Mercanti Valentina , Cornillon Sophie , Alibaud Laeticia , Charette Steve J. , Cosson Pierre
Published: November 2004

Multivesicular endosomes are present in virtually every eucaryotic cell, where they arise by intra-endosomal budding of the limiting endosomal membrane. Some genetic diseases such as Chediak-Higashi syndrome are characterized by enlarged membrane-filled endosomes. The same altered endosomal morphology can be observed in cells exposed to certain drugs, for example U18666A. The mechanisms involved are still poorly characterized, partially because this atypical budding event is particularly difficult to observe in mammalian cells. Taking advantage of the simplicity of the endosomal structure in Dictyostelium discoideum, we could visualize intraendosomal budding at the ultrastructural level. In this model organism, the drug U18666A was shown to stimulate intra-endosomal budding, while an inhibitor of PI 3-kinase activity was found to have no effect on this process. Inactivation of a Dictyostelium gene with similarity to the gene responsible for Chediak-Higashi syndrome did not alter the intra-endosomal budding or the accumulation of intra-endosomal membranes. Thus, although treatment with U18666A and inactivation of the Chediak-Higashi gene cause similar morphological defects in mammalian cells, observations in a different model reveal that their respective modes of action are different.
Scribble protein domain mapping reveals a multistep localization mechanism and domains necessary for establishing cortical polarity
Authors: Albertson Roger , Chabu Chiswili , Sheehan Amy , Doe Chris Q.
Published: November 2004

The Drosophila tumor suppressor protein Scribble is required for epithelial polarity, neuroblast polarity, neuroblast spindle asymmetry and limiting cell proliferation. It is a member of the newly described LAP protein family, containing 16 leucine rich repeats (LRRs), four PDZ domains and an extensive carboxyl-terminal (CT) domain. LRR and PDZ domains mediate protein-protein interactions, but little is know about their function within LAP family proteins. We have determined the role of the LRR, PDZ and CT domains for Scribble localization in neuroblasts and epithelia, and for Scribble function in neuroblasts. We found that the LRR and PDZ domains are both required for proper targeting of Scribble to septate junctions in epithelia; that the LRR domain is necessary and sufficient for cortical localization in mitotic neuroblasts, and that the PDZ2 domain is required for efficient cortical and apical localization of Scribble in neuroblasts. In addition, we show that the LRR domain is sufficient to target Miranda protein to the neuroblast cortex, but that LRR+PDZ will exclude Miranda from the cortex. Our results highlight the importance of both LRR and PDZ domains for the proper localization and function of Scribble in neuroblasts.
The case for nuclear translation
Authors: Iborra Francisco J. , Jackson Dean A. , Cook Peter R.
Published: November 2004

Although it is frequently assumed that translation does not occur in eukaryotic nuclei, recent evidence suggests that some translation can take place and that it is closely coupled to transcription. The first evidence concerns the destruction of nuclear mRNAs containing premature termination codons by nonsense-mediated decay (NMD). Only ribosomes can detect termination codons, and as some NMD occurs within the nuclear fraction, active nuclear ribosomes could perform the required detection. The second evidence is the demonstration that tagged amino acids are incorporated into nascent polypeptides in a nuclear process coupled to transcription. The third evidence is that components involved in translation, NMD and transcription colocalize, coimmunoprecipitate and co-purify. All these results are simply explained if nuclear ribosomes scan nascent transcripts for premature termination codons at the site of transcription. Alternatively, the scanning needed for NMD might take place at the nuclear membrane, and contaminating cytoplasmic ribosomes might give the appearance of some nuclear translation. We argue, however, that the balance of evidence favours bona fide nuclear translation.
Tau phosphorylation in neuronal cell function and dysfunction
Authors: Johnson Gail V. W. , Stoothoff William H.
Published: November 2004

Tau is a group of neuronal microtubule-associated proteins that are formed by alternative mRNA splicing and accumulate in neurofibrillary tangles in Alzheimer's disease (AD) brain. Tau plays a key role in regulating microtubule dynamics, axonal transport and neurite outgrowth, and all these functions of tau are modulated by site-specific phosphorylation. There is significant evidence that a disruption of normal phosphorylation events results in tau dysfunction in neurodegenerative diseases, such as AD, and is a contributing factor to the pathogenic processes. Indeed, the abnormal tau phosphorylation that occurs in neurodegenerative conditions not only results in a toxic loss of function (e.g. decreased microtubule binding) but probably also a toxic gain of function (e.g. increased tau-tau interactions). Although tau is phosphorylated in vitro by numerous protein kinases, how many of these actually phosphorylate tau in vivo is unclear. Identification of the protein kinases that phosphorylate tau in vivo in both physiological and pathological processes could provide potential therapeutic targets for the treatment of AD and other neurodegenerative diseases in which there is tau pathology.
Acute Renal Failure and Intravenous Immune Globulin: Occurs with Sucrose-Stabilized, but Not with D-Sorbitol–Stabilized, Formulation
Authors: Chapman Scott A , Gilkerson Kristine L , Davin Thomas D , Pritzker Marc R
Published: November 2004

OBJECTIVE

To report 2 cases of acute renal failure (ARF) following administration of sucrose-stabilized intravenous immune globulin (IVIG), one of which did not recur following subsequent doses of d-sorbitol–stabilized formulation, and review the relevant literature.

CASE SUMMARIES

A 44-year-old white man awaiting heart transplantation developed ARF requiring hemodialysis following administration of sucrose-stabilized IVIG for high alloreactivity to population human leukocyte antigens. Following a return of renal function to baseline, subsequent doses of d-sorbitol–stabilized IVIG were administered without incident. A 90-year-old white man developed ARF after administration of sucrose-stabilized IVIG for monoclonal gammopathy. Renal function returned to baseline, and no subsequent IVIG doses were administered. An objective causality assessment revealed that sucrose-stabilized IVIG was the probable cause of the adverse drug event for both cases.

DISCUSSION

Several case reports of ARF secondary to IVIG have been published. Recent publications note that sucrose-stabilized IVIG products have a disproportionately high rate of ARF occurrence (∼88%) versus non–sucrose-stabilized formulations. Recent market data for IVIG products indicate that sucrose-stabilized products account for approximately 40% of the total IVIG market. When administered intravenously, sucrose is excreted unchanged in the urine. ARF has been reported in patients receiving large doses of intravenous sucrose.

CONCLUSIONS

ARF secondary to IVIG may be more likely to occur with sucrose-stabilized formulations. Before prescribing IVIG, clinicians should consider other nephrotoxic medications, preexisting renal function, age, diabetes mellitus, and rate of infusion. In patients at risk, it may be best to avoid sucrose-stabilized formulations.
Role of Low-Molecular-Weight Heparin in Invasive Management of Non–ST-Elevation Acute Coronary Syndromes
Authors: Moser Lynette R , Kalus James S
Published: November 2004

OBJECTIVE

To review the available literature addressing the role of low-molecular-weight heparin (LMWH) as an alternative to unfractionated heparin (UFH) in percutaneous coronary intervention (PCI) for treatment of non–ST-elevation acute coronary syndromes (NSTEACS).

DATA SOURCES

A MEDLINE search (1966–March 2004) identified pertinent articles using the key words acute coronary syndromes, unstable angina, non–ST-elevation myocardial infarction, low-molecular-weight heparin, enoxaparin, dalteparin, glycoprotein IIb/IIIa receptor antagonists, abciximab, tirofiban, eptifibatide, percutaneous transluminal coronary angioplasty, and percutaneous coronary intervention. The references of these articles were reviewed for additional pertinent references.

STUDY SELECTION AND DATA EXTRACTION

All human trials of LMWH in PCI for treatment of NSTEACS were evaluated. All pertinent studies were included in the review.

DATA SYNTHESIS

Administration of LMWH with or without a glycoprotein IIb/IIIa inhibitor during PCI appears to be similar to UFH in terms of efficacy. LMWH, especially in combination with a glycoprotein IIb/IIIa inhibitor, may increase risk of bleeding compared with UFH.

CONCLUSIONS

Available clinical trials do not provide definitive evidence to suggest superiority of LMWH over UFH when managing NSTEACS during PCI; however, dosing strategies are available if an LMWH is to be used in this setting. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-038-H01
Regulation of the NMDA Receptor Complex and Trafficking by Activity-Dependent Phosphorylation of the NR2B Subunit PDZ Ligand
Authors: Chung Hee Jung , Huang Yan Hua , Lau Lit-Fui , Huganir Richard L.
Published: November 2004

Interactions between NMDA receptors (NMDARs) and the PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domains of PSD-95/SAP90 (synapse-associated protein with a molecular weight of 90 kDa) family proteins play important roles in the synaptic targeting and signaling of NMDARs. However, little is known about the mechanisms that regulate these PDZ domain-mediated interactions. Here we show that casein kinase II (CK2) phosphorylates the serine residue (Ser1480) within the C-terminal PDZ ligand (IESDV) of the NR2B subunit of NMDARin vitroandin vivo. Phosphorylation of Ser1480 disrupts the interaction of NR2B with the PDZ domains of PSD-95 and SAP102 and decreases surface NR2B expression in neurons. Interestingly, activity of the NMDAR and Ca2+/calmodulin-dependent protein kinase II regulates CK2 phosphorylation of Ser1480. Furthermore, CK2 colocalizes with NR1 and PSD-95 at synaptic sites. These results indicate that activity-dependent CK2 phosphorylation of the NR2B PDZ ligand regulates the interaction of NMDAR with PSD-95/SAP90 family proteins as well as surface NMDAR expression and may be a critical mechanism for modulating excitatory synaptic function and plasticity.
Progesterone Attenuates Corticotropin-Releasing Factor-Enhanced But Not Fear-Potentiated Startle via the Activity of Its Neuroactive Metabolite, Allopregnanolone
Authors: Toufexis Donna J. , Davis Carrie , Hammond Alexis , Davis Michael
Published: November 2004

Intact female rats and ovariectomized (OVX) rats with different ovarian steroid replacement regimens were tested for changes in corticotropin-releasing factor (CRF)-enhanced startle (increased acoustic startle amplitude after intracerebroventricular infusion of 1 μg of CRF). OVX rats injected with estradiol (E) followed by progesterone (P) showed a blunted CRF-enhanced startle effect compared with OVX and E-injected rats. CRF-enhanced startle also was reduced significantly in lactating females (high endogenous P levels) compared with cycling rats (low to moderate P levels), as well as in non-E-primed rats when P was administered acutely (4 hr before testing) or chronically (7 d P replacement). The ability of P to attenuate CRF-enhanced startle was probably mediated by its metabolite allopregnanolone [tetrahydroprogesterone (THP)], because THP itself had a similar effect, and chronic administration of medroxyprogesterone, which is not metabolized to THP, did not blunt CRF-enhanced startle but instead slightly increased it. These data suggest that P blunts CRF-enhanced startle through a mechanism involving its neuroactive metabolite THP, although a role for the P receptor cannot be completely ruled out. Finally, neither chronic P replacement nor acute THP affected fear-potentiated startle, suggesting that P metabolites have an effect on the bed nucleus of the stria terminalis and anxiety rather than on the amygdala and stimulus-specific fear.