bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroprotective action of donepezil mediated by neuronal nicotinic receptors
Authors: AKAIKE Akinori , KATSUKI Hiroshi , KUME Toshiaki , TAKADA‐TAKATORI Yuki 
Published: October 2006

AbstractAChE inhibitors used in the treatment in Alzheimer’s disease such as donepezil are effective in preventing glutamate neurotoxicity. In primary cultures of the cortical neurons, donepezil prevents glutamate neurotoxicity when the drug is applied 8–24 hr prior to glutamate exposure. Neuroprotective effect of donepezil is antagonized by mecamylamine, dihydro‐β‐erythoridine and metyllcaconitine. Prolonged (more than 4 days) exposure of the cultures to donepezil induces an increase in the nicotine‐induced Ca2+ influx and number of neurons expressing α4 and α7 subunits of nicotinic receptors. Donepezil also prevents apoptotic neuronal death induced by glutamate. Inhibitors for non‐receptor type tyrosine kinase, Fyn and janus‐activated kinase 2, suppress the neuroprotective effect of donepezil. Neuroprotective effect of donepezil is also suppressed by a phosphatidylinositol 3‐kinase (PI3K) inhibitor. Phosphorylation level of Akt, an effector of PI3K, and the expression level of Bcl‐2 increase with donepezil. These results suggest that donepezil prevents glutamate neurotoxicity through α4‐ and α7‐nicotinic acetylcholine receptors (nAChRs), followed by activation of PI3‐Akt pathway but independent from activation of ion channels associated with nAChRs. α4‐ and α7‐nAChRs may play an important role in promoting survival of cortical neurons under oxidative stress caused by excitotoxicity.
A Multi‐Line Insurance Fraud Recognition System: A Government‐Led Approach in Korea
Authors: Kim Hunsoo , Jean Kwon W. 
Published: October 2006

AbstractThis article introduces a government‐led insurance fraud detection program in Korea. The Insurance Fraud Recognition System (IFRS) uses policy and claims data from multi‐lines of insurance (life, automobile, and fire), employs a three‐stage statistical and link analysis to identify presumably fraudulent claims by claimant or by group, and generates system reports that the government regulator draws on to make decisions. The authors evaluate the system based on the fraud statistics and IFRS results for 2004, and offer recommendations for system improvement. This article examines existing studies about fraud, industry experiments using advanced technology, and government assistance to the insurance industry's fight against fraud in selected countries. It also provides a brief overview of the Korean insurance market, especially after the recent Asian economic crisis.
Opaqueness in the Insurance Industry: Why Are Some Insurers Harder to Evaluate than Others?
Authors: Pottier Steven W. , Sommer David W. 
Published: October 2006

AbstractMany articles have investigated various tools used to evaluate the financial strength of insurers. This is the first study to investigate whether certain insurers are simply inherently more difficult to evaluate than others, regardless of the tool used. The article identifies certain specific insurer characteristics that are associated with greater difficulty in financial strength evaluation, as proxied for by the level of rating disagreement by Moody's and Standard and Poor's. Specifically, the empirical results indicate that insurers that exhibit the following characteristics are more difficult to assess in terms of financial strength: smaller insurers, stock insurers, insurers with a history of reserving errors, insurers that use less reinsurance, insurers with greater levels of investment in stocks and low‐grade bonds, and insurers that are more geographically diversified.
Performance Evaluation of Pension Funds Management Companies with Data Envelopment Analysis
Authors: Barros Carlos Pestana , Garcia Maria Teresa Medeiros 
Published: October 2006

AbstractThis article uses Data Envelopment Analysis (DEA) to evaluate the performance of Portuguese pension funds management companies from 1994 to 2003, combining operational and financial variables. We evaluate how close the pension funds management companies are to the best practices frontier, also analyzing how they manage their funds. Implications of this research for managerial purposes are then drawn.
The Downfall of Equitable Life in the United Kingdom: The Mismatch of Strategy and Risk Management
Authors: O'Brien Chris 
Published: October 2006

AbstractThis article considers the downfall of Equitable Life Assurance Society in the United Kingdom, founded in 1762 and the first life insurer to operate on an actuarial basis. Its failure to manage the risks implicit in guaranteed annuity options led to a financial crisis, and it ceased to write new business in 2000. We analyze the Society's risk management practices, and find that they were inconsistent with its strategy, which highlighted customer focus. It lacked the discipline to balance short‐term advantage to customers with the long‐term needs of the organization. We also highlight the use of participating policies, and the way in which they were used to transfer risk to policyholders. Finally, we draw some lessons for other life insurers from Equitable Life's experience.
Response of female melon fly, Bactrocera cucurbitae, to host‐associated visual and olfactory stimuli
Authors: Piñero Jaime C. , Jácome Isabel , Vargas Roger , Prokopy Ronald J. 
Published: October 2006

AbstractIn a series of studies conducted in Hawaii under seminatural conditions, we quantified the response of sexually mature, host‐seeking female melon flies, Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae), to different types of visual and chemical host‐associated stimuli with the main aim of developing a monitoring device for females. Experiments were conducted using Tangletrap‐coated fruit mimics of either spherical (8 cm diameter) or cylindrical (4.3 cm diameter; 15 cm length) shapes coated with different artificial color pigments both at the ground level and at the tree‐canopy level so as to take into account the foraging behavior of adult melon flies. Females were particularly attracted to objects of spherical shape colored either yellow, white, or orange; these three pigments offered the highest reflectance values. Cucumber (Cucumis sativus L.) (Cucurbitaceae) odor was more attractive to females than odors of three other cultivated host fruit [zucchini, Cucurbita pepo L. var. medullosa Alef. (Cucurbitaceae); papaya, Carica papaya L. (Caricaceae); or tomato Solanum lycopersicum L. (Solanaceae)] or of ivy gourd [Coccinia grandis (L.) Voigt (Cucurbitaceae)], one of the major wild hosts of melon fly in Hawaii. A combination of both visual and olfactory stimuli was needed to elicit high levels of response compared to each stimulus offered alone. We discuss our results in relation to the potential implementation of improved female monitoring and/or attract‐and‐kill strategies for melon flies in Hawaii.
Study design, recruitment, and baseline characteristics: the Department of Veterans Affairs Dental Diabetes Study
Authors: Jones Judith A. , Miller Donald R. , Wehler Carolyn J. , Rich Sharron , Krall Elizabeth , Christiansen Cindy L. , Rothendler James A. , Garcia Raul I. 
Published: October 2006

AbstractObjectives: We are conducting a clinical trial of the efficacy of periodontal therapy in the improvement of glycaemic control in veterans with poorly controlled diabetes. This report describes study design, recruitment and randomization and compares baseline characteristics of the sample frame with those randomized into study groups.Methods: Veterans with poorly controlled diabetes were randomized in two groups: immediate periodontal therapy (“early treatment”) or usual care followed by periodontal therapy (“deferred treatment”). Half of each group continued care for 12 months; the other half returned to their usual care. We studied baseline patient characteristics, self‐reported health measures, and clinical examination data. We examined means for continuous variables, frequencies for categorical variables and compared groups using t‐tests and χ2 tests (α=0.05 for both).Results: The 193 randomized participants were younger (58 years) and had slightly higher HbA1c (10.2%) than the 2534 non‐randomized participants (64 years, HbA1c =9.8%). The deferred treatment group was more likely than the early treatment group to have a history of stroke, transient ischaemic attacks, and less likely to be current or former smokers.Conclusions: The mechanism for randomization was largely successful in this study.
Going Wild: Lessons from Naturally Occurring T-Lymphotropic Lentiviruses
Authors: VandeWoude Sue , Apetrei Cristian 
Published: October 2006

SUMMARYOver 40 nonhuman primate (NHP) species harbor species-specific simian immunodeficiency viruses (SIVs). Similarly, more than 20 species of nondomestic felids and African hyenids demonstrate seroreactivity against feline immunodeficiency virus (FIV) antigens. While it has been challenging to study the biological implications of nonfatal infections in natural populations, epidemiologic and clinical studies performed thus far have only rarely detected increased morbidity or impaired fecundity/survival of naturally infected SIV- or FIV-seropositive versus -seronegative animals. Cross-species transmissions of these agents are rare in nature but have been used to develop experimental systems to evaluate mechanisms of pathogenicity and to develop animal models of HIV/AIDS. Given that felids and primates are substantially evolutionarily removed yet demonstrate the same pattern of apparently nonpathogenic lentiviral infections, comparison of the biological behaviors of these viruses can yield important implications for host-lentiviral adaptation which are relevant to human HIV/AIDS infection. This review therefore evaluates similarities in epidemiology, lentiviral genotyping, pathogenicity, host immune responses, and cross-species transmission of FIVs and factors associated with the establishment of lentiviral infections in new species. This comparison of consistent patterns in lentivirus biology will expose new directions for scientific inquiry for understanding the basis for virulence versus avirulence.
Coinfections Acquired from
Ixodes
Ticks
Authors: Swanson Stephen J. , Neitzel David , Reed Kurt D. , Belongia Edward A. 
Published: October 2006

SUMMARY

The pathogens that cause Lyme disease (LD), human anaplasmosis, and babesiosis can coexist in
Ixodes
ticks and cause human coinfections. Although the risk of human coinfection differs by geographic location, the true prevalence of coinfecting pathogens among
Ixodes
ticks remains largely unknown for the majority of geographic locations. The prevalence of dually infected
Ixodes
ticks appears highest among ticks from regions of North America and Europe where LD is endemic, with reported prevalences of ≤28%. In North America and Europe, the majority of tick-borne coinfections occur among humans with diagnosed LD. Humans coinfected with LD and babesiosis appear to have more intense, prolonged symptoms than those with LD alone. Coinfected persons can also manifest diverse, influenza-like symptoms, and abnormal laboratory test results are frequently observed. Coinfecting pathogens might alter the efficiency of transmission, cause cooperative or competitive pathogen interactions, and alter disease severity among hosts. No prospective studies to assess the immunologic effects of coinfection among humans have been conducted, but animal models demonstrate that certain coinfections can modulate the immune response. Clinicians should consider the likelihood of coinfection when pursuing laboratory testing or selecting therapy for patients with tick-borne illness.
Developmental Biology of Sporozoite-Host Interactions inPlasmodium falciparumMalaria: Implications for Vaccine Design
Authors: Garcia Javier E. , Puentes Alvaro , Patarroyo Manuel E. 
Published: October 2006

SUMMARYThePlasmodium falciparumsporozoite infects different types of cells in a mosquito's salivary glands and human epithelial and Kuppfer cells and hepatocytes. These become differentiated later on, transforming themselves into the invasive red blood cell form, the merozoite. The ability of sporozoites to interact with different types of cells requires a wide variety of mechanisms allowing them to survive in both hosts: mobility, receptor-ligand interactions with different cellular receptors, and transformation and development into other invasive parasite forms, which are vitally important for parasite survival. Sporozoite complexity is reflected in the large quantity of proteins that can be expressed. Some of them have been extensively studied, such as CSP, TRAP, STARP, LSA-1, LSA-3, SALSA, SPECT1, SPECT2, MAEBL, and SPATR, due to their importance in infection and their potential use as vaccines. Our work has been focused on the search for the molecular mechanisms of parasite-host cellular receptor-ligand interactions by identifying amino acid sequences and the critical binding residues from these proteins relevant to parasite invasion. Once such sequences have been identified, it will be possible to modify them to induce a strong immune response againstP. falciparumin the experimentalAotusmonkey model. This all leads towards developing multistage, multicomponent, subunit-based vaccines that will be effective in eradicating or controlling malaria caused byP. falciparum.
Differential Telomere Processing byBorreliaTelomere Resolvases In Vitro but Not In Vivo
Authors: Tourand Yvonne , Bankhead Troy , Wilson Sandra L. , Putteet-Driver Adrienne D. , Barbour Alan G. , Byram Rebecca , Rosa Patricia A. , Chaconas George 
Published: October 2006

ABSTRACTCausative agents of Lyme disease and relapsing fever, includingBorrelia burgdorferiandBorrelia hermsii, respectively, are unusual among bacteria in that they possess a segmented genome with linear DNA molecules terminated by hairpin ends, known as telomeres. During replication, these telomeres are processed by the essential telomere resolvase, ResT, in a unique biochemical reaction known as telomere resolution. In this study, we report the identification of theB. hermsii resTgene through cross-species hybridization. Sequence comparison of theB. hermsiiprotein with theB. burgdorferiorthologue revealed 67% identity, including all the regions currently known to be crucial for telomere resolution. In vitro studies, however, indicated thatB. hermsiiResT was unable to process a replicatedB. burgdorferitype 2 telomere substrate. In contrast, in vivo cross-species complementation in which the nativeresTgene ofB. burgdorferiwas replaced withB. hermsii resThad no discernible effect, even thoughB. burgdorferistrain B31 carries at least two type 2 telomere ends. TheB. burgdorferiResT protein was also able to process two telomere spacing mutants in vivo that were unresolvable in vitro. The unexpected differential telomere processing in vivo versus in vitro by the two telomere resolvases suggests the presence of one or more accessory factors in vivo that are normally involved in the reaction. Our current results are also expected to facilitate further studies into ResT structure and function, including possible interaction with otherBorreliaproteins.
Cell Envelope Stress Response inBacillus licheniformis: Integrating Comparative Genomics, Transcriptional Profiling, and Regulon Mining To Decipher a Complex Regulatory Network
Authors: Wecke Tina , Veith Birgit , Ehrenreich Armin , Mascher Thorsten 
Published: October 2006

ABSTRACTThe envelope is an essential structure of the bacterial cell, and maintaining its integrity is a prerequisite for survival. To ensure proper function, transmembrane signal-transducing systems, such as two-component systems (TCS) and extracytoplasmic function (ECF) σ factors, closely monitor its condition and respond to harmful perturbations. Both systems consist of a transmembrane sensor protein (histidine kinase or anti-σ factor, respectively) and a corresponding cytoplasmic transcriptional regulator (response regulator or σ factor, respectively) that mediates the cellular response through differential gene expression. The regulatory network of the cell envelope stress response is well studied in the gram-positive model organismBacillus subtilis. It consists of at least two ECF σ factors and four two-component systems. In this study, we describe the corresponding network in a close relative,Bacillus licheniformis. Based on sequence homology, domain architecture, and genomic context, we identified five TCS and eight ECF σ factors as potential candidate regulatory systems mediating cell envelope stress response in this organism. We characterized the corresponding regulatory network by comparative transcriptomics and regulon mining as an initial screening tool. Subsequent in-depth transcriptional profiling was applied to define the inducer specificity of each identified cell envelope stress sensor. A total of three TCS and seven ECF σ factors were shown to be induced by cell envelope stress inB. licheniformis.We noted a number of significant differences, indicative of a regulatory divergence between the twoBacillusspecies, in addition to the expected overlap in the respective responses.
Inhibition of Mammalian Target of Rapamycin or Apoptotic Pathway Induces Autophagy and Radiosensitizes PTEN Null Prostate Cancer Cells
Authors: Cao Carolyn , Subhawong Ty , Albert Jeffrey M. , Kim Kwang Woon , Geng Ling , Sekhar Konjeti R. , Gi Young Jin , Lu Bo 
Published: October 2006

Abstract
The phosphatidylinositol 3-kinase/Akt pathway plays a critical role in oncogenesis, and dysregulation of this pathway through loss of PTEN suppression is a particularly common phenomenon in aggressive prostate cancers. The mammalian target of rapamycin (mTOR) is a downstream signaling kinase in this pathway, exerting prosurvival influence on cells through the activation of factors involved in protein synthesis. The mTOR inhibitor rapamycin and its derivatives are cytotoxic to a number of cell lines. Recently, mTOR inhibition has also been shown to radiosensitize endothelial and breast cancer cells in vitro. Because radiation is an important modality in the treatment of prostate cancer, we tested the ability of the mTOR inhibitor RAD001 (everolimus) to enhance the cytotoxic effects of radiation on two prostate cancer cell lines, PC-3 and DU145. We found that both cell lines became more vulnerable to irradiation after treatment with RAD001, with the PTEN-deficient PC-3 cell line showing the greater sensitivity. This increased susceptibility to radiation is associated with induction of autophagy. Furthermore, we show that blocking apoptosis with caspase inhibition and Bax/Bak small interfering RNA in these cell lines enhances radiation-induced mortality and induces autophagy. Together, these data highlight the emerging importance of mTOR as a molecular target for therapeutic intervention, and lend support to the idea that nonapoptotic modes of cell death may play a crucial role in improving tumor cell kill. (Cancer Res 2006; 66(20): 10040-7)
Correction for chromosome-17 is critical for the determination of true Her-2/neu gene amplification status in breast cancer
Authors: Dal Lago Lissandra , Durbecq Virginie , Desmedt Christine , Salgado Roberto , Verjat Thibault , Lespagnard Laurence , Ma Yan , Veys Isabelle , Di Leo Angelo , Sotiriou Christos , Piccart Martine , Larsimont Denis 
Published: October 2006

Abstract
Purpose: Trastuzumab is the cornerstone for treatment of women with HER2-overexpressing breast cancer, both in the adjuvant and in the metastatic settings. The accurate assessment of HER2 is, therefore, critical to identifying patients who may benefit from trastuzumab-based therapy. This project aimed to determine the optimal scoring method for fluorescence in situ hybridization (FISH) assay. Methods: FISH assay was done on 893 samples of breast cancer. Three scoring methods were evaluated: Her2/CEP17≥2, Her2&gt;4, or Her2&gt;6. Protein and gene expression were evaluated by immunohistochemistry (n = 584) and mRNA/assay/nucleic acid sequence–based amplification (NASBA; n = 90). Results: Samples were divided into five groups based on FISH results: disomic amplified and nonamplified, polysomic amplified, nonamplified, and discordant (10.8% of cases, mostly positive with Her2&gt;4 scoring, but negative with the others). Her2/CEP17≥2 and Her2&gt;6 scoring methods showed the best association (a) with regard to FISH scoring (κ = 0.906, P &lt; 10−6) and (b) between FISH and immunohistochemistry (3+ as positive; κ &gt; 0.650, P &lt; 10−6) or NASBA (κ &gt; 0.536, P &lt; 10−6). Polysomy had an effect on Her2 copy number (P &lt; 10−6), but had no effect on protein and mRNA content. Therefore, within the discordant subgroup, for which additive Her-2 gene copies are due to high polysomy, protein and mRNA levels were similar to those of the nonamplified samples. For this subgroup, the best concordance between FISH/immunohistochemistry/NASBA was observed with the Her2/CEP17 ratio and Her-2&gt;6 scoring (68% and 58% perfect matches, respectively). No perfect matches were observed using the Her2&gt;4 scoring method. Conclusion: Correction for chromosome-17 is the method of choice for clinical practice; Her-2&gt;6, but not Her-2&gt;4, could be used as an alternative. [Mol Cancer Ther 2006;5(10):2572–9]
Comparing Aurora A and Aurora B as molecular targets for growth inhibition of pancreatic cancer cells
Authors: Warner Steven L. , Munoz Ruben M. , Stafford Phillip , Koller Erich , Hurley Laurence H. , Von Hoff Daniel D. , Han Haiyong 
Published: October 2006

AbstractTo address the increased need to understand the similarities and differences in targeting Aurora A or Aurora B for the treatment of cancer, we systematically evaluated the relative importance of Aurora A and/or Aurora B as molecular targets using antisense oligonucleotides. It was found that perturbations in Aurora A and Aurora B signaling result in growth arrest and apoptosis preferentially in cancer cells. The biological fingerprints of Aurora A and Aurora B inhibition were compared and contrasted in efforts to identify the superior therapeutic target. Due to the different biological responses, we conclude that each Aurora kinase should be treated as autonomous drug targets, which can be targeted independently or in combination. We observed no advantages to targeting both kinases simultaneously and feel that an Aurora A–targeted therapy may have some beneficial consequences over an Aurora B–targeted therapy, such as mitotic arrest and the rapid induction of apoptosis. [Mol Cancer Ther 2006;5(10):2450–8]