bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of a Cytotoxic-T-Lymphocyte Epitope-Defined, AlternativegagOpen Reading Frame in the Pathogenesis of a Murine Retrovirus-Induced Immunodeficiency Syndrome
Authors: Gaur Arti , Green William R. 
Published: March 2005

ABSTRACTLP-BM5 murine leukemia virus-infected C57BL/6 mice develop profound immunodeficiency and B-cell lymphomas. The LP-BM5 complex contains a mixture of defective (BM5def) and replication-competent helper viruses among which BM5def is the primary causative agent of disease. The BM5def primary open reading frame (ORF1) encodes the singlegagprecursor protein (Pr60gag). Our lab has recently demonstrated that a novel immunodominant cytotoxic-T-lymphocyte (CTL) epitope (SYNTGRFPPL) is expressed from a +1-nucleotide translational open reading frame of BM5def during the course of normal retrovirus expression. The SYNTGRFPPL CTL epitope may be generated from either of two initiation methionines present, ORF2a or ORF2b, located downstream of the ORF1 initiation site. This study investigates the role(s) of the alternative ORF2-derivedgagprotein(s) of BM5def in viral pathogenesis. We have examined the disease-inducing capabilities of mutant viruses in which the translational potential of either the initiating ORF2a or ORF2b AUG has been disrupted. Although these mutated viruses are capable of wild-type ORF1 expression, they are unable to induce disease. Our data strongly suggest the existence of a novel ORF2 product(s) that is required for LP-BM5-induced pathogenesis and have potentially broad implications for other retroviral diseases.
NK and NKT Cell-Independent Contribution of Interleukin-15 to Innate Protection against Mucosal Viral Infection
Authors: Gill Navkiran , Rosenthal Kenneth L. , Ashkar Ali A. 
Published: March 2005

ABSTRACTInterleukin-15 (IL-15) is essential for the development, maturation, and function of NK and NKT cells, which are critical components of the innate immune defense against viral infections. We recently showed that mice lacking IL-15 and/or NK/NKT cells are significantly more susceptible to intravaginal (IVAG) herpes simplex virus type 2 (HSV-2) infection than control mice. For this study, we examined whether IL-15 has any direct antiviral activity, independent of NK/NKT cells, in innate protection against HSV-2 infection. A sensitive enzyme-linked immunosorbent assay for murine IL-15 was developed and used to show that IVAG HSV-2 infection induces IL-15 in vaginal washes. Using immunohistochemistry, we detected IL-15-positive cells in the submucosa and vaginal epithelium following IVAG HSV-2 infection. Local, but not systemic, delivery of murine recombinant IL-15 (mrIL-15) to the genital mucosae of IL-15−/−and RAG-2−/−γc−/−mice, which both lack NK and NKT cells, resulted in significant reductions in HSV-2 titers in genital washes and 60% survival following IVAG HSV-2 challenge. Furthermore, we showed that IL-15 is important for CpG oligodeoxynucleotide (ODN)-induced innate protection against genital HSV-2 infection. While 100% of CpG ODN-treated RAG2−/−γc−/−mice, which are capable of producing IL-15 but lack NK/NKT cells, survived an IVAG HSV-2 challenge, only 60% of CpG ODN-treated IL-15−/−mice survived, and all of these mice had similar vaginal viral titers to those in control mice by day 3 postchallenge. Lastly, a treatment of RAW264.7 cells with mrIL-15 induced the production of tumor necrosis factor alpha and beta interferon (IFN-β), but not IFN-α, and significantly protected them against HSV-2 infection in vitro. The results of these studies indicate that IL-15 can act independently of NK/NKT cells in mediating the innate defense against viral infection.
Overlap in the Functional Neural Systems Involved in Semantic and Episodic Memory Retrieval
Authors: Rajah M. N. , McIntosh A. R. 
Published: March 2005

Abstract
Neuroimaging and neuropsychological data suggest that episodic and semantic memory may be mediated by distinct neural systems [Cabeza, R., & Nyberg, L. Imaging cognition II: An empirical review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience, 12, 1–47, 2000; Gabrieli, J. D. Disorders of memory in humans. Current Opinion in Neurology and Neurosurgery, 6, 93–97, 1993; Gabrieli, J. D. Cognitive neuroscience of human memory. Annual Review of Psychology, 49, 87–115, 1998; Squire, L. R. The organization and neural substrates of human memory. International Journal of Neurology, 21–22, 218–222, 1987; Squire, L. R., & Zola, S. M. Structure and function of declarative and nondeclarative memory systems. Proceedings of the National Academy of Sciences, U.S.A., 93, 13515–13522, 1996; Tulving, E. Multiple memory systems and consciousness. Human Neurobiology, 6, 67–80, 1987]. However, an alternative perspective is that episodic and semantic memory represent different modes of processing within a single declarative memory system. To examine whether the multiple or the unitary system view better represents the data we conducted a network analysis using multivariate partial least squares (PLS) activation analysis followed by covariance structural equation modeling (SEM) of positron emission tomography data obtained while healthy adults performed episodic and semantic verbal retrieval tasks [Duzel, E., Cabeza, R., Picton, T. W., Yonelinas, A. P., Heinze, H. J., Scheich, H., & Tulving, E. Task-related and item related processes in episodic and semantic retrieval: A combined PET and ERP study. Proceedings of the National Academy of Sciences, U.S.A., 96, 1794–1799, 1999]. It is argued that if performance of episodic and semantic retrieval tasks are mediated by different memory systems, then there should differences in both regional activations and interregional correlations related to each type of retrieval task, respectively. The PLS results identified brain regions that were differentially active during episodic retrieval versus semantic retrieval. Regions that showed maximal differences in regional activity between episodic retrieval tasks were used to construct separate functional models for episodic and semantic retrieval. Omnibus tests of these functional models failed to find a significant difference across tasks for both functional models. The pattern of path coefficients for the episodic retrieval model were not different across tasks, nor were the path coefficients for the semantic retrieval model. The SEM results suggest that the same memory network/system was engaged across tasks, given the similarities in path coefficients. Therefore, activation differences between episodic and semantic retrieval may reflect variation along a continuum of processing during task performance within the context of a single memory system.
Second Language Interferes with Word Production in Fluent Bilinguals: Brain Potential and Functional Imaging Evidence
Authors: Rodriguez-Fornells Antoni , Lugt Arie van der , Rotte Michael , Britti Belinda , Heinze Hans-Jochen , Münte Thomas F. 
Published: March 2005

Abstract
Bilingual individuals need effective mechanisms to prevent interference between their languages. Using event-related brain potentials (ERPs) and functional magnetic resonance imaging (fMRI), we present evidence for interference of phonological information from the nontarget language in German—Spanish bilinguals. A tacit picture-naming task was used in which bilinguals and monolinguals had to make speeded responses based on the first letter of the picture's name in the target language. In one condition, subjects were required to respond when the name began with a vowel and to withhold a response if it started with a consonant. Stimuli had been selected such that in half of the trials, the names in both languages necessitated the same response, whereas in the other half, responses were different for the two languages. For the bilinguals, the language in which the stimuli had to be named was changed after each block. Bilinguals showed phonological interference compared with monolingual performance, which was evident in their performance, ERPs, and fMRI patterns. Nonlanguage-specific brain areas such as the left middle prefrontal cortex were found to be crucial for the control of interference.
Right Hemisphere Activation of Joke-related Information: An Event-related Brain Potential Study
Authors: Coulson Seana , Wu Ying Choon 
Published: March 2005

Abstract
Two studies tested the hypothesis that the right hemisphere engages in relatively coarse semantic coding that aids high-level language tasks such as joke comprehension. Scalp-recorded event-related brain potentials (ERPs) were collected as healthy adults read probe words (CRAZY) preceded either by jokes or nonfunny controls (“Everyone had so much fun jumping into the swimming pool, we decided to put in a littlewater/platform”). Probes were related to the meaning of the jokes, but not the controls. In Experiment 1a, with central presentation, probes following jokes (related) elicited less negative ERPs 300–700 msec postonset (N400) than did probes following nonfunny controls (unrelated). This finding suggests related probes were primed by the jokes. In addition, unrelated probes elicited a larger anterior positivity 700– 900 msec than did related, as irrelevant stimuli impacted control processes invoked by task demands. In Experiment 1b, probes (CRAZY) were preceded only by sentence-final words from jokes (water) or controls (platform). No ERP effects were observed in Experiment 1b, suggesting the N400 priming effect and the anterior positivity observed in Experiment 1a reflect semantic activations at the discourse level. To assess hemispheric differences in semantic activations, in Experiment 2, ERPs were recorded as participants read probe words presented in their left and right visual fields (LVF and RVF, respectively). Probes elicited a smaller N400 component when preceded by jokes than controls. This N400 priming effect was larger with presentation to the LVF, suggesting joke-relevant information was more active in the right hemisphere. The anterior positivity was observed with RVF but not LVF presentation, suggesting an important role for the left hemisphere in controlled retrieval in language comprehension.
Close Encounters: Some Preliminary Observations on the Transmission of Impurity in Early Sunnī Jurisprudence
Authors: Maghen Ze'ev 
Published: March 2005

AbstractThe Prophet said, al-tahāra shatr al-īmān, "purity is half of faith." In this essay, I attempt to elucidate what appears to be a uniquely Islamic approach to the acquisition and impartation of ritually pollutive states. Based on a survey of relevant hadīth exempla and fiqh discussions—including sections dealing with saliva as a premier conductor of pollution, janāba (sexually induced impurity), menstruation, mulāmasa (contact with the opposite sex), and the question of water already used in ablutions—I argue that the sharī'a accords all human beings a clean ritual slate from birth, and, what is more surprising, flatly denies the possibility of persons becoming ceremonially contaminated or contributing to the ritual defilement of others under any circumstances. These characteristics make the Islamic tahāra system an intriguing anomaly in the world of religious purity codes.
Swimming and jumping in a semi-aquatic frog
Authors: Nauwelaerts Sandra , Stamhuis Eize , Aerts Peter 
Published: March 2005

Abstract
Locomotion has a clear ecological relevance for many animals. As animals need to move in order to escape from predators, find food, defend territories, etc., it is expected that locomotor performance might affect an individual's survival and reproduction. Clear links have also been found between an animal's performance and its morphology. A function analysis can unravel the underlying mechanistic facets of this link.Frogs are interesting model species because they add an extra element to this topic; they have to perform in two entirely different physical environments, particularly semi-aquatic species. However, no trade-off was found between jumping and swimming performance. Morphological correlates were found but, to understand causations, a thorough understanding of the mechanics of locomotion is required.When comparing the mechanics of jumping and swimming, the question arises of how to ensure a sound comparison. Ideally, some measure of 'effort' has to be added to the analysis. We suggest the use of the propulsive impulse. Unexpectedly, the impulse of swimming proved to be significantly smaller than the jumping impulses during locomotion in a semi-aquatic frog, Rana esculenta, even when maximal performance had been induced in both media.To verify our impulse calculations, we analysed the external forces during both locomotor modes. The forces during terrestrial locomotion can be measured directly using a force plate; determining the forces in water requires a more complex set-up. For that reason, we performed a DPIV (Digital Particle Image Velocimetry) analysis on the flow generated by swimming frogs. These experiments confirmed the results of our impulse calculations.
A Modeling Study of Summertime East Pacific Wind-Induced Ocean–Atmosphere Exchange in the Intraseasonal Oscillation
Authors: Maloney Eric D. , Esbensen Steven K. 
Published: March 2005

Abstract
Intraseasonal precipitation variability over the northeast Pacific warm pool during June–October in the National Center for Atmospheric Research Community Atmosphere Model 2.0.1 with a relaxed Arakawa–Schubert convection parameterization is found to be strongly sensitive to wind-induced variations in surface latent heat flux. A control simulation with interactive surface fluxes produces northeast Pacific warm pool intraseasonal wind and precipitation variations that are of similar magnitude and structure to those associated with the observed intraseasonal oscillation (ISO). Periods of low-level westerly intraseasonal wind anomalies are associated with enhanced surface latent heat fluxes and enhanced precipitation, as in observations. Variations in surface wind speed primarily control the surface flux anomalies.
A simulation in which eastern North Pacific oceanic latent heat fluxes are fixed produces intraseasonal precipitation variations that are significantly weaker than those in the control simulation and in observations. These results support the observational findings of Maloney and Esbensen, who suggested that wind-induced latent heat flux variability is a significant driver of ISO-related convective variability over the northeast Pacific warm pool during Northern Hemisphere summer. East Pacific ISO-related convection in this model, thus, appears to be forced by an analogous wind-induced surface heat exchange mechanism to that proposed by Maloney and Sobel to explain the forcing of west Pacific ISO-related convection. The surface exchange mechanism is apparently active within regions of mean westerly low-level flow.
In contrast, summertime eastern North Pacific intraseasonal wind variance and spatial structure does not differ significantly between the control and fixed-evaporation simulations. A strong coupling between the east Pacific flow and precipitation over Central America may be responsible for the relatively small changes in wind variability between the simulations. Interactions among the coarsely resolved Central American orography, the large-scale flow, and the convection parameterization in the model likely contribute to this anomalous coupling.
A simplified high-throughput method for pyrethroid knock-down resistance (kdr) detection in Anopheles gambiae
Authors: Lynd Amy , Ranson Hilary , McCall P J , Randle Nadine P , Black William C , Walker Edward D , Donnelly Martin J 
Published: March 2005

Abstract

Background
A single base pair mutation in the sodium channel confers knock-down resistance to pyrethroids in many insect species. Its occurrence in Anopheles mosquitoes may have important implications for malaria vector control especially considering the current trend for large scale pyrethroid-treated bednet programmes. Screening Anopheles gambiae populations for the kdr mutation has become one of the mainstays of programmes that monitor the development of insecticide resistance. The screening is commonly performed using a multiplex Polymerase Chain Reaction (PCR) which, since it is reliant on a single nucleotide polymorphism, can be unreliable. Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation.

Methods
A Hot Ligation Oligonucleotide Assay (HOLA) was developed to detect both the East and West African kdr alleles in the homozygous and heterozygous states, and was optimized for use in low-tech developing world laboratories. Results from the HOLA were compared to results from the multiplex PCR for field and laboratory mosquito specimens to provide verification of the robustness and sensitivity of the technique.

Results and Discussion
The HOLA assay, developed for detection of the kdr mutation, gives a bright blue colouration for a positive result whilst negative reactions remain colourless. The results are apparent within a few minutes of adding the final substrate and can be scored by eye. Heterozygotes are scored when a sample gives a positive reaction to the susceptible probe and the kdr probe. The technique uses only basic laboratory equipment and skills and can be carried out by anyone familiar with the Enzyme-linked immunosorbent assay (ELISA) technique. A comparison to the multiplex PCR method showed that the HOLA assay was more reliable, and scoring of the plates was less ambiguous.

Conclusion
The method is capable of detecting both the East and West African kdr alleles in the homozygous and heterozygous states from fresh or dried material using several DNA extraction methods. It is more reliable than the traditional PCR method and may be more sensitive for the detection of heterozygotes. It is inexpensive, simple and relatively safe making it suitable for use in resource-poor countries.
Assessment of readiness to change in patients with osteoarthritis. Development and application of a new questionnaire
Authors: Heuts Peter HTG , de Bie Rob A , Dijkstra Arie , Aretz Karin , Vlaeyen Johan WS , Schouten Hubert JA , Hopman-Rock Marijke , van Weel Chris , van Schayck Constant P 
Published: March 2005

Objective: To develop a self-report measure for assessment of the stage of change in patients with osteoarthritis, in order to identify patients who would benefit from a self-management programme. Methods: According to the ‘stages of change’ model a questionnaire was developed with three groups of items corresponding to the precontemplation stage (Pre), the contemplation (Cont) and the action (Act) stage. Internal consistency and factor structure of this questionnaire were investigated by assessing Cronbach's alphas and by performing factor analysis. Subjects and setting: The questionnaire was offered to 273 patients who entered a randomized clinical trial on self-management in a general health care setting. Results: Factor analysis revealed that most items corresponded to the a priori described groups, while some items were not loading on the presumed factor. In each subgroup some items were deleted, resulting in a 15-item questionnaire. After this item reduction Cronbach's alphas were 0.72 (Pre), 0.76 (Cont) and 0.79 (Act) and all factor loadings were satisfactory (above 0.35). Classification revealed some differences between parts of the total group, for example in the proportion of patients in the preparation stage (recruited by general practitioner 33.6%; advertisement 49.2%). Conclusions: The Stages of Change Questionnaire in Osteoarthritis, a 15-item questionnaire to assess the ‘stage of change’ of a patient with osteoarthritis showed good internal consistency and adequate factor structure. These findings warrant further studies on validity and applicability in a clinical context.
Adult-Type Soft Tissue Sarcomas in Pediatric-Age Patients: Experience at the Istituto Nazionale Tumori in Milan
Authors: Ferrari Andrea , Casanova Michela , Collini Paola , Meazza Cristina , Luksch Roberto , Massimino Maura , Cefalo Graziella , Terenziani Monica , Spreafico Filippo , Catania Serena , Gandola Lorenza , Gronchi Alessandro , Mariani Luigi , Fossati-Bellani Franca 
Published: March 2005

Purpose Nonrhabdomyosarcoma soft tissue sarcomas are a heterogeneous group of tumors for which optimal treatment remains controversial. We report on a large group of 182 patients younger than 18 years old treated at a single institution over a 25-year period. Patients and Methods In this relatively homogeneous subgroup of adult-type histotypes, surgery was the mainstay of treatment; radiotherapy was administered to 73 patients, and chemotherapy was administered to 114 patients (70 received chemotherapy as adjuvant therapy). Results Overall survival at 5 years was 89% in patients who underwent complete resection at diagnosis, 79% in patients who had marginal resection, 52% in initially unresected patients, and 17% in patients with metastases at onset. Outcome was unsatisfactory in patients with large and high-grade tumors, even after gross resection; adjuvant chemotherapy seemed to improve the results in this group. Initially unresected patients who responded well to chemotherapy and subsequently underwent complete resection had an event-free survival rate of approximately 70%. The rate of response to chemotherapy was 58%. Conclusion The identification of prognostic variables should enable risk-adapted therapies to be planned. Patients with initially unresectable disease and patients with resected large and high-grade tumors are at high risk of metastases and treatment failure. Although the limits of this retrospective analysis are self-evident, our data would suggest that intensive chemotherapy (with an ifosfamide-doxorubicin regimen) might have a more significant role in these patients than what is generally assumed.
Epidermal Growth Factor Receptor Mutations, Small-Molecule Kinase Inhibitors, and Non–Small-Cell Lung Cancer: Current Knowledge and Future Directions
Authors: Pao William , Miller Vincent A. 
Published: March 2005

Purpose Gefitinib and erlotinib are small molecules that selectively inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. When these drugs were introduced into the clinic, the specific targets affected in human tumors were unknown. In April 2004, two groups reported that mutations in the tyrosine kinase domain of EGFR are strongly associated with gefitinib sensitivity in patients with non–small-cell lung cancer (NSCLC). We subsequently extended these findings and showed that such mutations are also associated with sensitivity to erlotinib. Here, we present current knowledge about EGFR mutations in the context of clinical trials involving gefitinib and erlotinib in NSCLC. Design This article reviews the rationale for targeting EGFR, the development of gefitinib and erlotinib, the discovery of EGFR mutations, and subsequent studies to define the incidence, spectrum, and functions of EGFR mutations. Results The discovery of EGFR mutations promises to alter the ways in which we consider and treat NSCLC. Conclusion This information can guide practitioners and help them inform their patients about EGFR mutations and their impact on the treatment of NSCLC.