bluuebunny/crossref_metadata_2025_split huggingface dataset:
C‐reactive protein, its role in inflammation, Type 2 diabetes and cardiovascular disease, and the effects of insulin‐sensitizing treatment with thiazolidinediones
Authors: Nesto R. 
Published: July 2004

AbstractIncreased concentrations of the marker of inflammation, C‐reactive protein (CRP), are associated with insulin resistance, Type 2 diabetes and the development of cardiovascular disease. In particular, inflammation is closely associated with endothelial dysfunction and is recognized as one of the cardiovascular risk factors clustering in the Insulin Resistance Syndrome or Metabolic Syndrome. The exact mechanisms linking insulin resistance and inflammation remain unclear. However, the close association between insulin resistance and inflammation in atherogenesis suggests that therapies that address both parameters may have benefits in reducing diabetes‐related macrovascular complications. The thiazolidinedione class of oral anti‐diabetic agents are powerful insulin sensitizers that also have anti‐inflammatory properties. Treatment with these agents has a range of anti‐atherogenic effects, including reduced levels of CRP, plasminogen activator inhibitor‐1 (PAI‐1), TNF‐α and reactive oxygen species. Additionally, the insulin‐sensitizing effect of thiazolidinediones improves other factors of the Insulin Resistance Syndrome, including dyslipidaemia and hypertension. Outcome studies are underway to determine if the effects of improving insulin sensitivity and reducing inflammation will translate into clinical benefits and reduce the cardiovascular morbidity and mortality associated with insulin resistance and Type 2 diabetes.
Amelanotic malignant melanoma disguised as a diabetic foot ulcer
Authors: Gregson C. L. , Allain T. J. 
Published: July 2004

AbstractBackground/case report  A female patient with diet‐controlled Type 2 diabetes mellitus, presented with disseminated malignancy. She had a 15‐year history of a diabetic foot ulcer, which was subsequently found to be an amelanotic malignant melanoma. She had recently received immunosuppressive treatment for an episode of nephrotic syndrome secondary to focal segmental glomerulosclerosis.Conclusions  This case raises two important points. Firstly, whether non‐healing diabetic foot ulcers should be biopsied, and secondly, whether the spread of the malignant melanoma was precipitated by immunosuppressive treatment.
Marital Conflict, Child Emotional Security about Family Relationships and Child Adjustment
Authors: Harold Gordon T. , Shelton Katherine H. , Goeke‐Morey Marcie C. , Cummings E. Mark 
Published: July 2004

AbstractAddressing a gap in process‐oriented understanding of relations between marital conflict and children's adjustment, propositions of the emotional security hypothesis from a family‐wide perspective were tested in a longitudinal research design. Participants were 181 families and their 11–12 year‐old‐child (115 boys, 76 girls) living in Wales, in the United Kingdom. Relations between marital conflict, children's emotional security about marital conflict and parenting, respectively, and children's adjustment were assessed based on reports by mothers, fathers, and children and videotaped analogue procedures completed by children. Structural equation modelling indicated that children's emotional security about interparental conflict (emotional regulation, cognitive representations and behavioural regulation) mediated the relation between marital conflict and children's security about parenting. Processes pertaining to children's security in multiple family systems (i.e., interparental and parent–child) provided an indirect mechanism through which interparental conflict affected children's symptoms of psychological distress (internalising and externalising problems) assessed 12 months later. Future directions for further tests of comprehensive, theoretically based models for the effects of marital conflict on children are discussed.
Information and the Cost of Capital
Authors: Easley David , O'hara Maureen 
Published: July 2004

ABSTRACTWe investigate the role of information in affecting a firm's cost of capital. We show that differences in the composition of information between public and private information affect the cost of capital, with investors demanding a higher return to hold stocks with greater private information. This higher return arises because informed investors are better able to shift their portfolio to incorporate new information, and uninformed investors are thus disadvantaged. In equilibrium, the quantity and quality of information affect asset prices. We show firms can influence their cost of capital by choosing features like accounting treatments, analyst coverage, and market microstructure.
Diversification as a Public Good: Community Effects in Portfolio Choice
Authors: Demarzo Peter M. , Kaniel Ron , Kremer Ilan 
Published: July 2004

ABSTRACTWithin a rational general equilibrium model in which agents care only about personal consumption, we consider a setting in which, due to borrowing constraints, individuals endowed with local resources underparticipate in financial markets. As a result, investors compete for local resources through their portfolio choices. Even with complete financial markets and no aggregate risk, agents may herd into risky portfolios. This yields a Pareto‐dominated outcome as agents introduce “community” risk unrelated to fundamentals. Moreover, if some agents are behaviorally biased, or cannot completely diversify their holdings, rational agents may choose more extreme portfolios and amplify the effect.
Tobin's Q, Debt Overhang, and Investment
Authors: Hennessy Christopher A. 
Published: July 2004

ABSTRACTIncorporating debt in a dynamic real options framework, we show that underinvestment stems from truncation of equity's horizon at default. Debt overhang distorts both the level and composition of investment, with underinvestment being more severe for long‐lived assets. An empirical proxy for the shadow price of capital to equity is derived. Use of this proxy yields a structural test for debt overhang and its mitigation through issuance of additional secured debt. Using measurement error‐consistent GMM estimators, we find a statistically significant debt overhang effect regardless of firms' ability to issue additional secured debt.
What Do Entrepreneurs Pay for Venture Capital Affiliation?
Authors: Hsu David H. 
Published: July 2004

ABSTRACTThis study empirically evaluates the certification and value‐added roles of reputable venture capitalists (VCs). Using a novel sample of entrepreneurial start‐ups with multiple financing offers, I analyze financing offers made by competing VCs at the first professional round of start‐up funding, holding characteristics of the start‐up fixed. Offers made by VCs with a high reputation are three times more likely to be accepted, and high‐reputation VCs acquire start‐up equity at a 10–14% discount. The evidence suggests that VCs' “extra‐financial” value may be more distinctive than their functionally equivalent financial capital. These extra‐financial services can have financial consequences.
Short‐Selling Prior to Earnings Announcements
Authors: Christophe Stephen E. , Ferri Michael G. , Angel James J. 
Published: July 2004

ABSTRACTThis paper examines short‐sales transactions in the five days prior to earnings announcements of 913 Nasdaq‐listed firms. The tests provide evidence of informed trading in pre‐announcement short‐selling because they reveal that abnormal short‐selling is significantly linked to post‐announcement stock returns. Also, the tests indicate that short‐sellers typically are more active in stocks with low book‐to‐market valuations or low SUEs. The levels of pre‐announcement short‐selling, however, mostly appear to reflect firm‐specific information rather than these fundamental financial characteristics. We believe that these results should encourage financial market regulators to consider providing more extensive and timely disclosures of short‐selling to investors.
Electricity Forward Prices: A High‐Frequency Empirical Analysis
Authors: Longstaff Francis A. , Wang Ashley W. 
Published: July 2004

ABSTRACTWe conduct an empirical analysis of forward prices in the PJM electricity market using a high‐frequency data set of hourly spot and day‐ahead forward prices. We find that there are significant risk premia in electricity forward prices. These premia vary systematically throughout the day and are directly related to economic risk factors, such as the volatility of unexpected changes in demand, spot prices, and total revenues. These results support the hypothesis that electricity forward prices in the Pennsylvania, New Jersey, and Maryland market are determined rationally by risk‐averse economic agents.
Values in clinical nursing practice and caring
Authors: GREGG Misuzu F. , MAGILVY Joan K. 
Published: July 2004

AbstractAim: The aims of this study were to describe nurses’ values in clinical nursing practice and to identify how caring exists in their practice, based on the description of values. In this paper, the definition of caring was adopted from the theory of human caring, where caring is depicted as the moral ideal of nursing.Methods: Data were generated by participant observations from 24 nurses, semistructured formal interviews with seven nurses, and informal interviews. The nurses were associated with an internal medicine ward within an acute hospital in Japan. Data were analysed by using a qualitative descriptive method.Results: Twelve categories emerged from the data analysis: considering a patient's feelings, having nursing knowledge and skills, advocating for their patients, having a relationship as a human being, being with a patient, touching a patient, listening to a patient, making a difference, helping each other as nurses, being connected to a patient, denoting the ‘meaning of one's life’, and realizing nursing as a means of self‐actualization. These categories were illustrated as a schematic model of values in clinical nursing practice.Conclusions: This study described nurses’ values in clinical nursing practice. The results showed that there was evidence of caring in daily Japanese clinical nursing practice, even within a strong medical model acute hospital.
A randomized controlled trial of a group care program for community‐dwelling elderly people with dementia
Authors: TADAKA Etsuko , KANAGAWA Katsuko 
Published: July 2004

AbstractAim:  To examine the effectiveness of a group care program consisting of reminiscence and reality orientation care methods to prevent the decline of cognitive and daily activity function in community‐dwelling elderly persons with dementia in a randomized controlled trial with a 6‐month follow‐up period.Methods:  Sixty community‐dwelling elderly persons with dementia were randomly assigned to either an intervention or a control group. The intervention group followed the group care program consisting of reminiscence and reality orientation care methods in addition to a routine day‐care service once a week for 10 consecutive weeks; the control group followed only a routine day‐care service in the same institution as the intervention group for the same study period.Results:  On cognitive function, the intervention group exhibited a significant effect compared with the control group immediately after the intervention (P < 0.05), but no significant effect was observed after 6 months. On daily activity function, the intervention group exhibited significant effects compared with the control group in disorientation and withdrawal immediately after the intervention (P < 0.05) and after 6 months (P < 0.05).Conclusions:  The group care program consisting of reminiscence and reality orientation care methods can be effective for the improvement of cognitive function in the short‐term and on the improvement of disorientation and withdrawal in the long‐term. It is suggested, however, that sustained intervention may be necessary to maintain the effect over time.
Quantitative Gene Expression Profiling Implicates Genes for Susceptibility and Resistance to Alveolar Bone Loss
Authors: Hart G. T. , Shaffer D. J. , Akilesh S. , Brown A. C. , Moran L. , Roopenian D. C. , Baker P. J. 
Published: July 2004

ABSTRACTPeriodontal disease is one of the most prevalent chronic inflammatory diseases. There is a genetic component to susceptibility and resistance to this disease. Using a mouse model, we investigated the progression of alveolar bone loss by gene expression profiling of susceptible and resistant mouse strains (BALB/cByJ and A/J, respectively). We employed a novel and sensitive quantitative real-time PCR method to compare basal RNA transcription of a 48-gene set in the gingiva and the spleen and the subsequent changes in gene expression due toPorphyromonas gingivalisoral infection. Basal expression of interleukin-1 beta (Il1b) and tumor necrosis factor alpha (Tnf) mRNA was higher in the gingiva of the susceptible BALB/cByJ mice than in the gingiva of resistant A/J mice. GingivalIl1bgene expression increased further andStat6gene expression was turned on afterP. gingivalisinfection in BALB/cByJ mice but not in A/J mice. The basal expression of interleukin-15 (Il15) in the gingiva and the basal expression of p-selectin (Selp) in the spleen were higher in the resistant A/J mice than in the susceptible BALB/cByJ mice. In the resistant A/J mice the expression of no genes detectably changed in the gingiva after infection. These results suggest a molecular phenotype in which discrete sets of differentially expressed genes are associated with genetically determined susceptibility (Il1b,Tnf, andStat6) or resistance (Il15andSelp) to alveolar bone loss, providing insight into the genetic etiology of this complex disease.
Immunostimulatory CpG Oligodeoxynucleotide Confers Protection in a Murine Model of Infection withBurkholderia pseudomallei
Authors: Wongratanacheewin Surasakdi , Kespichayawattana Wannapa , Intachote Pakamas , Pichyangkul Sathit , Sermswan Rasana W. , Krieg Arthur M. , Sirisinha Stitaya 
Published: July 2004

ABSTRACTAlthough CpG oligodeoxynucleotides (CpG ODNs) are known to enhance resistance against infection in a number of animal models, little is known about the CpG-induced protection against acute fatal sepsis such as that associated with the highly virulent bacteriumBurkholderia pseudomallei. We previously demonstrated in an in vitro study that immunostimulatory CpG ODN 1826 enhances phagocytosis ofB. pseudomalleiand induces nitric oxide synthase and nitric oxide production by mouse macrophages. In the present study, CpG ODN 1826 given intramuscularly to BALB/c mice 2 to 10 days prior toB. pseudomalleichallenge conferred better than 90% protection. CpG ODN 1826 given 2 days before the bacterial challenge rapidly enhanced the innate immunity of these animals, judging from the elevated serum levels of interleukin-12 (IL-12)p70 and gamma interferon (IFN-γ) over the baseline values. No bacteremia was detected on day 2 in 85 to 90% of the CpG-treated animals, whereas more than 80% of the untreated animals exhibited heavy bacterial loads. Although marked elevation of IFN-γ was found consistently in the infected animals 2 days after the bacterial challenge, it was ameliorated by the CpG ODN 1826 pretreatment (P= 0.0002). Taken together, the kinetics of bacteremia and cytokine profiles presented are compatible with the possibility that protection by CpG ODN 1826 against acute fatal septicemic melioidosis in this animal model is associated with a reduction of bacterial load and interference with the potential detrimental effect of the robust production of proinflammatory cytokines associated withB. pseudomalleimultiplication.
Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK
Authors: Pinto Eduardo Fonseca , Pinheiro Roberta Olmo , Rayol Alice , Larraga Vicente , Rossi-Bergmann Bartira 
Published: July 2004

ABSTRACTWe have previously demonstrated that oral delivery of a disease-promoting particulated antigen ofLeishmania amazonensis(LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 μg of LaAg and were challenged 1 week postvaccination withL. amazonensisdeveloped delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-γ) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 μg/dose) had no effect. Interestingly, LACK DNA (30 μg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-γ. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA.
Molecular Interactions of Surface Protein Peptides ofStreptococcus gordoniiwith Human Salivary Components
Authors: Hamada Tomoyuki , Kawashima Masatsugu , Watanabe Haruo , Tagami Junji , Senpuku Hidenobu 
Published: July 2004

ABSTRACTOral streptococci play a large role in dental biofilm formation, and several types interact as early colonizers with the enamel salivary pellicle to form the primary biofilm, as well as to incorporate other bacteria on tooth surfaces. Interactions of surface molecules of individual streptococci with the salivary pellicle on the tooth surface have an influence on the etiological properties of an oral biofilm. To elucidate the molecular interactions of streptococci with salivary components, binding between surface protein (SspB and PAg) peptides ofStreptococcus gordoniiandStreptococcus sobrinuswere investigated by utilizing BIAcore biosensor technology. The analogous peptide [change of T at position 400 to K in SspB(390-402), resulting in the SspB(390-T400K-402) peptide] fromS. gordoniishowed the greatest response for binding to salivary components and inhibited the binding ofStreptococcus sanguisby more than 50% in a competitive inhibition assay in a comparison with other SspB and PAg peptides. This peptide also bound to the high-molecular-weight protein complex of salivary components and the agglutinin (gp340/DMBT1) peptide (scavenger receptor cysteine-rich domain peptide 2 [SRCRP 2]). In addition, the SspB(390-T400K-402) peptide was visualized by two surface positive charges in connection with the positively charged residues, in which lysine was a key residue for binding. Therefore, the region containing lysine may have binding activity inS. gordoniiandS. sanguis, and the SRCRP 2 region may function as a receptor for the binding. These findings may provide useful information regarding the molecular mechanism of early biofilm formation by streptococci on tooth surfaces.
Proapoptotic Effect of Proteolytic Activation of Matrix Metalloproteinases byStreptococcus pyogenesThiol Proteinase (StreptococcusPyrogenic Exotoxin B)
Authors: Tamura Fumio , Nakagawa Rumiko , Akuta Teruo , Okamoto Shigefumi , Hamada Shigeyuki , Maeda Hiroshi , Kawabata Shigetada , Akaike Takaaki 
Published: July 2004

ABSTRACTStreptococcus pyogenesthiol proteinase, also known as streptococcal pyrogenic exotoxin B (SpeB), has been suggested to be a major virulence factor inS. pyogenesinfection. SpeB was reported to induce apoptosis of host cells, but its mechanism of action is not yet fully understood. In this study, we examined the involvement of matrix metalloproteinases (MMPs) in SpeB-induced apoptosis. We first developed a large-scale preparation of recombinant SpeB and precursors of human MMP-9 and -2 (proMMPs) by usingEscherichia coliRosetta (DE3)pLysS and baculovirus-insect cell expression systems, respectively. Treatment with SpeB induced effective proteolytic activation of both proMMP-9 and -2. When RAW264 murine macrophages were incubated with SpeB-activated proMMP-9, the level of tumor necrosis factor alpha (TNF-α) in conditioned medium (CM), assessed by an enzyme immunoassay, was elevated. This increase was completely inhibited by addition of the MMP inhibitor SI-27 to the cell culture. The CM also produced marked induction of apoptosis of U937 human monocytic cells. Similarly, soluble Fas ligand (sFasL) was detected in CM of cultures of SW480 cells expressing FasL after treatment with SpeB-activated proMMPs; this CM also induced apoptosis in U937 cells. SpeB had a direct effect as well and caused the release of TNF-α and sFasL from the cells. SpeB-dependent production of MMP-9 and -2 and proapoptotic molecules (TNF-α and sFasL) was evident in a murine model of severe invasiveS. pyogenesinfection. These results suggest that SpeB or SpeB-activated MMPs contribute to tissue damage and streptococcal invasion in the host via extracellular release of TNF-α and sFasL.
Effects of building blocks on the performance of super-scalar architecture
Authors: Fernandes Edil S. T. , Barbosa Fernando M. B. 
Published: July 2004

The inherent low level parallelism of Super-Scalar architectures plays an important role in the processing power provided by these machines: independent functional units promote opportunities for executing several machine operations simultaneously. From the viewpoint of the hardware designer it is very important to assess the influence of each functional unit, and the way they communicate, on the overall performance of the machine. Particularly, it is highly desirable to determine an upper bound in the number of additional functional units which give significant performance improvement ratios.
This work describes experiments that have been carried out to assess the effect of alternative instruction issue mechanisms, multiple functional units, instruction queues, common data bus and other hardware solutions on the performance of Super-Scalar machines. The assessment was obtained by interpreting non optimized object code fo an actual processor on some basic machine models. The paper outline the main aspects of the research, and shows that speed-up ratios of up to 3.35 times were observed during the interpretation of benchmark programs.
Cache replacement with dynamic exclusion
Authors: McFarling Scott 
Published: July 2004

Most recent cache designs use direct-mapped caches to provide the fast access time required by modern high speed CPU's. Unfortunately, direct-mapped caches have higher miss rates than set-associative caches, largely because direct-mapped caches are more sensitive to conflicts between items needed frequently in the same phase of program execution.
This paper presents a new technique for reducing direct-mapped cache misses caused by conflicts for a particular cache line. A small finite state machine recognizes the common instruction reference patterns where storing an instruction in the cache actually harms performance. Such instructions are dynamically excluded, that is they are passed directly through the cache without being stored. This reduces misses to the instructions that would have been replaced.
The effectiveness of dynamic exclusion is dependent on the severity of cache conflicts and thus on the particular program and cache size of interest. However, across the SPEC benchmarks, simulation results show an average reduction in miss rate of 33% for a 32KB instruction cache with 16B lines. In addition, applying dynamic exclusion to one level of a cache hierarchy can improve the performance of the next level since instructions do not need to be stored on both levels. Finally, dynamic exclusion also improves combined instruction and data cache miss rates.