bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordinating Service‐Sensitive Demand and Capacity by Adaptive Decision Making: An Application of Case‐Based Decision Theory*
Authors: Jahnke Hermann , Chwolka Anne , Simons Dirk 
Published: January 2005

ABSTRACTThe subject of this article is the simultaneous choice of product price and manufacturing capacity if demand is stochastic and service‐level sensitive. In this setting, capacity as well as price have an impact on demand because several aspects of service level depend on capacity. For example, delivery time will be reduced if capacity is increased given a constant demand rate. We illustrate the relationship between service level, capacity, and demand reaction by a stylized application problem from the after‐sales services industry.The reaction of customers to variations in service level and price is represented by a kinked price‐demand‐rate function. We first derive the optimal price‐capacity combination for the resulting decision problem under full information. Subsequently, we focus on a decision maker (DM) who lacks complete knowledge of the demand function. Hence the DM is unable to anticipate the service level and consequently cannot identify the optimal solution. However, the DM will acquire additional information during the sales process and use it in subsequent revisions of the price‐capacity decision. Thus, this decision making is adaptive and based on experience. In contrast to the literature, which assumes certain repetitive procedures somewhat ad hoc, we develop an adaptive decision process based on case‐based decision theory (CBDT) for the price‐capacity problem. Finally, we show that a CBDT DM in our setting eventually finds the optimal solution, if the DM sets the price based on absorption costs and adequately adjusts the capacity with respect to the observed demand.
Acquisition of Telecommunications Bandwidth Under Economies of Scale in Size and Duration of Contracts*
Authors: Khouja Moutaz , Kumar Ram L. 
Published: January 2005

ABSTRACTSignificant advances in information technology have brought about increased demand for bandwidth. Buyers of bandwidth often encounter bandwidth prices that are decreasing over time. Additionally, bandwidth prices at any point in time are decreasing in total bandwidth purchased and length of contracts. Therefore, buyers face complex decisions in terms of the number of contracts to buy, their bandwidth, and their lengths. In this article, we formulate models for the acquisition of bandwidth from a buyer's perspective. We begin with a model that allows varying contract durations under deterministic demand and without allowing shortages or overlapping contracts. We then formulate a simpler model, which restricts contract lengths over the planning horizon to be equal. We also solve the problem under probabilistic demand and allowing for shortages, which are satisfied by buying additional bandwidth at a premium. We perform numerical sensitivity analysis to compare the results of the models and illustrate the results with numerical examples. The numerical analyses illustrate that using relatively simple equal‐length contracts produces approximately the same results as the more complicated unequal‐length contract strategy.
Predicting System Usage from Intention and Past Use: Scale Issues in the Predictors
Authors: Kim Sung S. , Malhotra Naresh K. 
Published: January 2005

ABSTRACTThe objective of this study is to provide insights into how the predictive power for computer‐recorded system usage can be improved. Based on 386 responses from actual users of an information system, we examine the predictive power for system usage according to the scales of the predictors used, namely, intention and past use. First, we show that the predictive power of intention can be significantly improved with the choice of an appropriate measure. However, even the desirable intention measure failed to explain two‐thirds of the variance in system usage. Second, the results show that past use as measured by computer‐recorded log data can significantly enhance our ability to predict system usage. Finally, when both intention and past use are controlled for, the explained variance in system usage is shown to vary widely from 20% to 73%, depending on the predictors' scales. Overall, our findings suggest that an accurate prediction of system usage requires a more rigorous approach than that often applied in information systems research.
Heart Rate Variability Fraction—A New Reportable Measure of 24‐Hour R‐R Interval Variation
Authors: Sosnowski Maciej , Clark Elaine , Latif Shahid , Macfarlane Peter W. , Tendera Michal 
Published: January 2005

Background: The scatterplot of R‐R intervals has several unique features. Its numerical evaluation may produce a new useful index of global heart rate variability (HRV) from Holter recordings. Methods: Two‐hundred and ten middle‐aged healthy subjects were enrolled in this study. The study was repeated the next day in 165 subjects. Each subject had a 24‐hour ECG recording taken. Preprocessed data were transferred into a personal computer and the standard HRV time‐domain indices: standard deviation of total normal R‐R intervals (SDNN), standard deviation of averaged means of normal R‐R intervals over 5‐minute periods (SDANN), triangular index (TI), and pNN50 were determined. The scatterplot area (0.2–1.8 second) was divided into 256 boxes, each of 0.1‐second interval, and the number of paired R‐R intervals was counted. The heart rate variability fraction (HRVF) was calculated as the two highest counts divided by the number of total beats differing from the consecutive beat by <50 ms. The HRVF was obtained by subtracting this fraction from 1, and converting the result to a percentage. Results: The normal value of the HRVF was 52.7 ± 8.6%. The 2–98% range calculated from the normal probability plot was 35.1–70.3%. The HRVF varied significantly with gender (female 48.7 ± 8.4% vs male 53.6 ± 8.6%, P = 0.002). The HRVF correlated with RRI (r = 0.525) and showed a similar or better relationship with SDNN (0.851), SDANN (0.653), and TI (0.845) than did the standard HRV measures with each other. Bland‐Altman plot showed a good day‐by‐day reproducibility of the HRVF, with the intraclass correlation coefficient of 0.839 and a low relative standard error difference (1.8%). Conclusion: We introduced a new index of HRV, which is easy for computation, robust, reproducible, easy to understand, and may overcome the limitations that belong to the standard HRV measures. This index, named HRV fraction, by combining magnitude, distribution, and heart‐rate influences, might become a clinically useful index of global HRV.
Electrocardiographic T‐ and U‐Wave Discordance
Authors: Reinig Michael G. , Harizi Robert , Spodick David H. 
Published: January 2005

Background: Abundant information has been reported regarding the U wave, which almost entirely has been focused on U waves in isolation. There has been little investigation of discordant T and U waves. Methods: Of 18,750 consecutively recorded electrocardiograms, 143 patients were categorized resulting in three groups. Group A: 53 patients with negative T waves and positive U waves (Type I Discordance); Group B: 26 patients with positive T waves and negative U waves (Type II Discordance); and Group C: 63 patients with negative T and negative U waves. Each patient's chart was reviewed for relevant clinical, laboratory, and medical history. Results: Coronary disease was slightly more common in Group A (64%) than in Group B (46%) (P = 0.174; ns). Coronary disease in Group C was extremely common (88%; P <0.001). Hypertension in the two discordant groups was similar: Group A (60%) versus Group B (58%) (P = ns), Group C was significantly higher (88%) (P <0.001). Left ventricular hypertrophy was 49% in Group A and 58% in Group B (P = ns), but Group C was significantly higher at 70% (P = 0.038). Conclusions: This appears to be the first investigation of the associations of discordant T and U waves. We found that the significance of any U wave is not independent of their respective T wave. In addition, we propose that the U wave not be analyzed in isolation, but rather with respect to its T wave.
Surface Electrocardiography and Histologic Rejection Following Orthotopic Heart Transplantation*
Authors: Eckart Robert E. , Kolasa Mark W. , Khan Nancy A. , Kwan Michael D. , Peele Mark E. 
Published: January 2005

Background: Intraventricular conduction delay and QT interval dispersion may be related to electrical instability and the risk of ventricular arrhythmogenesis. The interlead variability of the QT interval on a surface 12‐lead electrocardiogram (ECG) has been associated with an increased likelihood of sudden death in patients with long QT syndromes, in patients recovering from myocardial infarction, and dilated cardiomyopathy. We sought to determine the incidence of increased QTc dispersion (QTc‐d) relative to biopsy grade of severity of rejection. Methods: Records of patients having undergone orthotopic heart transplantation (OHT) were reviewed focusing specifically on surface ECGs performed in temporal proximity to endomyocardial biopsy. Results: Seventy‐five patients were evaluated on 1573 occasions, to include 999 surface ECGs, and 847 endomyocardial biopsies. There were 269 interpretable surface ECGs and endomyocardial biopsies performed within 1.1 ± 4.6 days. There were no identifiable trends in atrioventricular or intraventricular conduction abnormalities (to include right bundle branch block) when comparing those with and without significant rejection on endomyocardial biopsy. The mean QTc‐d of those with none (n = 34), mild (n = 194), moderate (n = 39), and severe (n = 2) rejection was 49 ± 29, 49 ± 35, 57 ± 38, 81 ± 7 ms, respectively (P = 0.28 by ANOVA of means). When comparing those with significant rejection so as to change management there was a trend toward increased dispersion (no to mild rejection, 49 ± 34 ms vs moderate to severe rejection, 59 ± 37 ms, P = 0.09). Conclusions: In this study investigating noninvasive ventricular depolarization/repolarization and correlation to histologic manifestation of rejection, there was suggestion, but no statistical significance, of QTc‐d and severity of rejection. QTc‐d should not be considered a sensitive marker for OHT rejection.
West Nile Virus Inhibits the Signal Transduction Pathway of Alpha Interferon
Authors: Guo Ju-Tao , Hayashi Junpei , Seeger Christoph 
Published: January 2005

ABSTRACT
West Nile virus (WNV) is a human pathogen that can cause neurological disorders, including meningoencephalitis. Experiments with mice and mammalian cell cultures revealed that WNV exhibited resistance to the innate immune program induced by alpha interferon (IFN-α). We have investigated the nature of this inhibition and have found that WNV replication inhibited the activation of many known IFN-inducible genes, because it prevented the phosphorylation and activation of the Janus kinases JAK1 and Tyk2. As a consequence, activation of the transcription factors STAT1 and STAT2 did not occur in WNV-infected cells. Moreover, we demonstrated that the viral nonstructural proteins are responsible for this effect. Thus, our results provided an explanation for the observed resistance of WNV to IFN-α in cells of vertebrate origin.
Resistance to Apo2 Ligand (Apo2L)/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Mediated Apoptosis and Constitutive Expression of Apo2L/TRAIL in Human T-Cell Leukemia Virus Type 1-Infected T-Cell Lines
Authors: Matsuda Takehiro , Almasan Alex , Tomita Mariko , Uchihara Jun-nosuke , Masuda Masato , Ohshiro Kazuiku , Takasu Nobuyuki , Yagita Hideo , Ohta Takao , Mori Naoki 
Published: January 2005

ABSTRACTAdult T-cell leukemia (ATL), a CD4+-T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1), is difficult to cure, and novel treatments are urgently needed. Apo2 ligand (Apo2L; also tumor necrosis factor-related apoptosis-inducing ligand [TRAIL]) has been implicated in antitumor therapy. We found that HTLV-1-infected T-cell lines and primary ATL cells were more resistant to Apo2L-induced apoptosis than uninfected cells. Interestingly, HTLV-1-infected T-cell lines and primary ATL cells constitutively expressed Apo2L mRNA. Inducible expression of the viral oncoprotein Tax in a T-cell line up-regulated Apo2L mRNA. Analysis of the Apo2L promoter revealed that this gene is activated by Tax via the activation of NF-κB. The sensitivity to Apo2L was not correlated with expression levels of Apo2L receptors, intracellular regulators of apoptosis (FLICE-inhibitory protein and active Akt). NF-κB plays a crucial role in the pathogenesis and survival of ATL cells. The resistance to Apo2L-induced apoptosis was reversed byN-acetyl-l-leucinyl-l-leucinyl-l-norleucinal (LLnL), an NF-κB inhibitor. LLnL significantly induced the Apo2L receptors DR4 and DR5. Our results suggest that the constitutive activation of NF-κB is essential forApo2Lgene induction and protection against Apo2L-induced apoptosis and that suppression of NF-κB may be a useful adjunct in clinical use of Apo2L against ATL.
Repair of the tRNA-Like CCA Sequence in a Multipartite Positive-Strand RNA Virus
Authors: Hema M. , Gopinath K. , Kao C. 
Published: January 2005

ABSTRACT
The
3′ portions of plus-strand brome mosaic virus (BMV) RNAs mimic
cellular tRNAs. Nucleotide substitutions or deletions in the 3′
CCA of the tRNA-like sequence (TLS) affect minus-strand initiation
unless repaired. We observed that 2-nucleotide deletions involving the
CCA 3′ sequence in one or all BMV RNAs still allowed RNA
accumulation in barley protoplasts at significant levels. Alterations
of CCA to GGA in only BMV RNA3 also allowed RNA accumulation at
wild-type levels. However, substitutions in all three BMV RNAs severely
reduced RNA accumulation, demonstrating that substitutions have
different repair requirements than do small deletions. Furthermore,
wild-type BMV RNA1 was required for the repair and replication of RNAs
with nucleotide substitutions. Results from sequencing of progeny viral
RNA from mutant input RNAs demonstrated that RNA1 did not contribute
its sequence to the mutant RNAs. Instead, the repaired ends were
heterogeneous, with one-third having a restored CCA and others having
sequences with the only commonality being the restoration of one
cytidylate. The role of BMV RNA1 in increased repair was
examined.
Vaccination of Rhesus Macaques with RecombinantMycobacterium bovisBacillus Calmette-Guérin Env V3 Elicits Neutralizing Antibody-Mediated Protection against Simian-Human Immunodeficiency Virus with a Homologous but Not a Heterologous V3 Motif
Authors: Someya Kenji , Cecilia Dayaraj , Ami Yasushi , Nakasone Tadashi , Matsuo Kazuhiro , Burda Sherri , Yamamoto Hiroshi , Yoshino Naoto , Kaizu Masahiko , Ando Shuji , Okuda Kenji , Zolla-Pazner Susan , Yamazaki Shudo , Yamamoto Naoki , Honda Mitsuo 
Published: January 2005

ABSTRACTAlthough the correlates of vaccine-induced protection against human immunodeficiency virus type 1 (HIV-1) are not fully known, it is presumed that neutralizing antibodies (NAb) play a role in controlling virus infection. In this study, we examined immune responses elicited in rhesus macaques following vaccination with recombinantMycobacterium bovisbacillus Calmette-Guérin expressing an HIV-1 Env V3 antigen (rBCG Env V3). We also determined the effect of vaccination on protection against challenge with either a simian-human immunodeficiency virus (SHIV-MN) or a highly pathogenic SHIV strain (SHIV-89.6PD). Immunization with rBCG Env V3 elicited significant levels of NAb for the 24 weeks tested that were predominantly HIV-1 type specific. Sera from the immunized macaques neutralized primary HIV-1 isolates in vitro, including HIV-1BZ167/X4, HIV-1SF2/X4, HIV-1CI2/X4, and, to a lesser extent, HIV-1MNp/X4, all of which contain a V3 sequence homologous to that of rBCG Env V3. In contrast, neutralization was not observed against HIV-1SF33/X4, which has a heterologous V3 sequence, nor was it found against primary HIV-1 R5 isolates from either clade A or B. Furthermore, the viral load in the vaccinated macaques was significantly reduced following low-dose challenge with SHIV-MN, and early plasma viremia was markedly decreased after high-dose SHIV-MN challenge. In contrast, replication of pathogenic SHIV-89.6PD was not affected by vaccination in any of the macaques. Thus, we have shown that immunization with an rBCG Env V3 vaccine elicits a strong, type-specific V3 NAb response in rhesus macaques. While this response was not sufficient to provide protection against a pathogenic SHIV challenge, it was able to significantly reduce the viral load in macaques following challenge with a nonpathogenic SHIV. These observations suggest that rBCG vectors have the potential to deliver an appropriate virus immunogen for desirable immune elicitations.
Virus Particle Core Defects Caused by Mutations in the Human Immunodeficiency Virus Capsid N-Terminal Domain
Authors: Scholz Isabel , Arvidson Brian , Huseby Doug , Barklis Eric 
Published: January 2005

ABSTRACT
The N-terminal domains (NTDs) of the human immunodeficiency virus type 1 (HIV-1) capsid (CA) protein have been modeled to form hexamer rings in the mature cores of virions. In vitro, hexamer ring units organize into either tubes or spheres, in a pH-dependent fashion. To probe factors which might govern hexamer assembly preferences in vivo, we examined the effects of mutations at CA histidine residue 84 (H84), modeled at the outer edges of NTD hexamers, as well as a nearby histidine (H87) in the cyclophilin A (CypA) binding loop. Although mutations at H87 yielded infectious virions, mutations at H84 produced assembly-competent but poorly infectious virions. The H84 mutant viruses incorporated wild-type levels of CypA and viral RNAs and showed nearly normal signals in virus entry assays. However, mutant CA proteins assembled aberrant virus cores, and mutant core fractions retained abnormally high levels of CA but reduced reverse transcriptase activities. Our results suggest that HIV-1 CA residue 84 contributes to a structure which helps control either NTD hexamer assembly or the organization of hexamers into higher-order structures.
Sindbis Virus Translation Is Inhibited by a PKR/RNase L-Independent Effector Induced by Alpha/Beta Interferon Priming of Dendritic Cells
Authors: Ryman K. D. , Meier K. C. , Nangle E. M. , Ragsdale S. L. , Korneeva N. L. , Rhoads R. E. , MacDonald M. R. , Klimstra W. B. 
Published: January 2005

ABSTRACTThe tropism of Sindbis virus (SB) for cells of the dendritic cell (DC) lineage and the virulence of SB in vivo are largely determined by the efficacy of alpha/beta interferon (IFN-α/β)-mediated antiviral responses. These responses are essentially intact in the absence of PKR and/or RNase L (K. D. Ryman, L. J. White, R. E. Johnston, and W. B. Klimstra, Viral Immunol.15:53-76, 2002). In the present studies, we investigated the nature of antiviral effects and identity of antiviral effectors primed by IFN-α/β treatment of bone marrow-derived DCs (BMDCs) generated from mice deficient in PKR and RNase L (TD). IFN-α/β priming exerted significant antiviral activity at very early stages of SB replication and most likely inhibited the initial translation of infecting genomes. The early effect targeted cap-dependent translation as protein synthesis from an SB-like and a simple RNA were inhibited by interferon treatment, but an encephalomyocarditis virus internal ribosome entry site-driven element exhibited no inhibition. Phosphorylation of the α subunit of eukaryotic translation initiation factor 2 was defective after virus infection of TD cells, suggesting other mechanisms of translation inhibition. To identify components of these alternative antiviral pathway(s), we have compared global gene regulation in BMDCs derived from normal 129 Sv/Ev, IFNAR1−/−, and TD mice following infection with SB or treatment with IFN-α/β. Candidate effectors of alternative antiviral pathways were those genes induced by virus infection or IFN-α/β treatment in 129 Sv/Ev and TD-derived BMDC but not in virus-infected or IFN-α/β-treated IFNAR1−/−cells. Statistical analyses of gene array data identified 44 genes that met these criteria which are discussed.
Conditional Mutations in the Mitotic Chromosome Binding Function of the Bovine Papillomavirus Type 1 E2 Protein
Authors: Zheng Peng-Sheng , Brokaw Jane , McBride Alison A. 
Published: January 2005

ABSTRACT
The papillomavirus E2 protein is required for viral transcriptional regulation, DNA replication and genome segregation. We have previously shown that the E2 transactivator protein and BPV1 genomes are associated with mitotic chromosomes; E2 links the genomes to cellular chromosomes to ensure efficient segregation to daughter nuclei. The transactivation domain of the E2 protein is necessary and sufficient for association of the E2 protein with mitotic chromosomes. To determine which residues of this 200-amino-acid domain are important for chromosomal interaction, E2 proteins with amino acid substitutions in each conserved residue of the transactivation domain were tested for their ability to associate with mitotic chromosomes. Chromatin binding was assessed by using immunofluorescence on both spread and directly fixed mitotic chromosomes. E2 proteins defective in the transactivation and replication functions were unable to associate with chromosomes, and those that were competent in these functions were attached to mitotic chromosomes. However, several mutated proteins that were defective for chromosomal interaction could associate with chromosomes after treatment with agents that promote protein folding or when cells were incubated at lower temperatures. These results indicate that precise folding of the E2 transactivation domain is crucial for its interaction with mitotic chromosomes and that this association can be modulated.
Complex Formation between the UL16 and UL21 Tegument Proteins of Pseudorabies Virus
Authors: Klupp Barbara G. , Böttcher Sindy , Granzow Harald , Kopp Martina , Mettenleiter Thomas C. 
Published: January 2005

ABSTRACT
The products of the UL16 and UL21 genes represent tegument proteins which are conserved throughout the mammalian herpesviruses. To identify and functionally characterize the respective proteins in the alphaherpesvirus pseudorabies virus, monospecific antisera against bacterially expressed fusion proteins were generated. In immunoblots the UL16 antiserum detected a ca. 40-kDa protein in infected cells and purified virion preparations, whereas the anti-UL21 serum recognized a protein of approximately 60 kDa. Interestingly, in immunoprecipitations using either antiserum, both proteins were coprecipitated, demonstrating the formation of a physical complex. To investigate protein function, viruses lacking either UL16, UL21, or both were constructed. Mutant viruses could be propagated on noncomplementing cells, indicating that these proteins, either alone or in combination, are not required for viral replication in cell culture. However, plaque sizes and viral titers were reduced. Electron microscopy showed only slight alterations in cytoplasmic virion morphogenesis, whereas intranuclear maturation stages were not affected. Similar results were obtained with a triple mutant simultaneously lacking the three conserved tegument proteins UL11, UL16, and UL21. In summary, our results uncover a novel interaction between conserved herpesvirus tegument proteins that increases the complexity of the intricate network of protein-protein interactions involved in herpesvirus morphogenesis.