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Objective: To examine various institution and student demographics and the ratings of Satisfaction (SAT) and Importance (IMP) for several programmatic variables within Athletic Training Education Programs (ATEPs). Design and Setting: A survey of SAT and IMP ratings of programmatic variables conducted with accredited, entry-level ATEPs. Subjects: Students enrolled in their final semester/term. Measurements: Students' SAT and IMP was measured by asking students to rate, on a 10-point Likert scale, seven programmatic factors. Various institution/program (state versus private affiliation, athletic division, Carnegie classification, and university enrollment) and student (age, gender, self-reported grade point average) demographic data were collected. Results: The sample consisted of 403 students from 99 institutions. Total SAT and IMP was computed by calculating the mean score across all seven factors. An analysis of variance showed a significant difference (F2,275 = 4.25, P = .01) for SAT within Carnegie classification with master's institution students more satisfied than doctoral institution students. A repeated measures analysis found significant differences (F6,292 = 34.77, P < .001) between SAT factors with students more satisfied with instructor availability than the other factors A repeated measures analysis found significant differences (F6,292 = 53.64, P < .001) between IMP factors with the quality of instruction in the major and quality of clinical experiences rated higher than the other factors Conclusions: Our results revealed that the type of institution has a greater effect upon student ratings of SAT and IMP than the student characteristics themselves.

Objective: To establish the validity and reliability of an online assessment instrument's items developed to track educational outcomes over time. Design and Setting: A descriptive study of the validation arguments and reliability testing of the assessment items. The instrument is available to graduating students enrolled in entry-level Athletic Training Education Programs (ATEPs). Methods: Validity was established with the creation of a national advisory board of Athletic Training educators. Construct validity was established with the creation of a test blueprint to guide the development of items for the knowledge exam. Internal reliability estimates for each domain were calculated. A single scale reliability analysis was conducted using all items. An item analysis was conducted by calculating difficulty and discrimination indexes for each item. Results: The internal reliability estimates ranged from .23 to .44 suggesting that individual domain scores for this draft of the instrument were not reliable. The single scale total score reliability however, produced an alpha = .84 suggesting a high level of reliability. Difficulty index scores ranged from .03 to .99 (mean = .74 ± .25). Discrimination index scores ranged from −.01 to .41 (mean = .21 ± .09). Conclusions: While the individual domain reliability was low, the overall single scale score is acceptable. Difficulty and discrimination index scores allowed the removal and revision of items to increase the overall reliability of the test bank.

Currently, evidence-based guidelines concerning the use of oral contraceptives (OCs) containing either 20 or 30 microg ethinyloestradiol (EE) and the same progestogen, are lacking. We wanted to identify whether Swiss gynaecologists and general practitioners (GPs) have specific criteria on which they base their prescribing habit.Two questionnaires were submitted to 158 physicians. The first one contained a list of possible criteria relevant for decision making and a description of specific clinical situations. The second one concerned actual patients who received either a 20 microg (Yasminelle) or a 30 microg (Yasmin) OC containing the same progestogen drospirenone.The most relevant criteria for decision making (in hierarchical order) were family history of venous thromboembolic disease (VTE), headache, smoking, age beyond 35, stability of the menstrual cycle, breast tenderness, body mass index, irregular bleeding and acne. The 20 microg dosage was preferred for women older than 35, those smoking more than 15 cigarettes per day, those with a family history of VTE, and those complaining of breast tenderness or headache. The 30 microg dosage was preferred for patients with a history of irregular bleeding, a family history of osteoporosis, expected poor compliance and acne.Swiss gynaecologists and GPs do not preferentially prescribe the lowest possible dosage of EE. They use indirect markers they consider relevant for differential prescribing. For some markers, there is inconsistency, indicating that preferences for 20 microg and 30 microg preparations may be influenced by other factors.

Adult outcomes for students with disabilities continue to remain below their peers without disabilities, and such poor postsecondary outcomes may be due to special education teachers who are unprepared to plan and deliver effective transition services. This study examined the perceptions of 557 middle and high school special education teachers from 31 states. A transition competencies survey was developed to collect data on teacher demographic variables as well as ratings of their levels of proficiency in (a) preparation to plan and deliver transition services, (b) satisfaction with transition training, and the (c) frequency with which they deliver specific competencies. Implications for including transition content in both special education personnel preparation programs and professional development opportunities for teachers of transition-aged youth are discussed.

We have developed a microarray for identification of sweet cherry incompatibility alleles. Using intron sequence information of the S-RNase gene, we have created a microarray chip that allows the specific recognition of the incompatibility alleles present in a cultivar. Most of the probes designed showed high specificity towards their alleles. In the original set of probes, cross-hybridization was observed between a few alleles with high sequence similarity. As our identification system is based on the combined hybridization information from both introns, we were able to identify false positive and unspecific probes which could be eliminated from our microarray. The optimized microarray was tested on cultivars with known alleles. The chip correctly identified all alleles tested. Furthermore, it was also possible to identify alleles in other cultivars where, so far, only one allele has been determined and also to determine in sour cherry the alleles originating from the sweet cherry parent. Our results demonstrate the great promise of microarray technology for this novel application.

The immune response to cancer has been long recognized, including both innate and adaptive responses, showing that the immune system can recognize protein products of genetic and epigenetic changes in transformed cells. The accumulation of antigen-specific T cells within the tumor, the draining lymph node, and the circulation, either in newly diagnosed patients or resultant from experimental immunotherapy, proves that tumors produce antigens and that priming occurs. Unfortunately, just as obviously, tumors grow, implying that anti-tumor immune responses are either not sufficiently vigorous to eliminate the cancer or that anti-tumor immunity is suppressed. Both possibilities are supported by current data. In experimental animal models of cancer and also in patients, systemic immunity is usually not dramatically suppressed, because tumor-bearing animals and patients develop T-cell-dependent immune responses to microbes and to either model antigens or experimental cancer vaccines. However, inhibition of specific anti-tumor immunity is common, and several possible explanations of tolerance to tumor antigens or tumor-induced immunesuppression have been proposed. Inhibition of effective anti-tumor immunity results from the tumor or the host response to tumor growth, inhibiting the activation, differentiation, or function of anti-tumor immune cells. As a consequence, anti-tumor T cells cannot respond productively to developmental, targeting, or activation cues. While able to enhance the number and phenotype of anti-tumor T cells, the modest success of immunotherapy has shown the necessity to attempt to reverse tolerance in anti-tumor T cells, and the vanguard of experimental therapy now focuses on vaccination in combination with blockade of immunosuppressive mechanisms. This review discusses several potential mechanisms by which anti-tumor T cells may be inhibited in function.

CD8+ tumor-infiltrating lymphocytes (TIL) lack in vivo and in vitro lytic function due to a signaling deficit characterized by failure to flux calcium or activate tyrosine kinase activity upon contact with cognate tumor cells. Although CD3ζ is phosphorylated by conjugation in vitro with cognate tumor cells, showing that TIL are triggered, PLCγ-1, LAT, and ZAP70 are not activated and LFA-1 is not affinity-matured, and because p56lck is required for LFA-1 activation, this implies that the signaling blockade is very proximal. Here, we show that TIL signaling defects are transient, being reversed upon purification and brief culture in vitro, implying a fast-acting “switch”. Biochemical analysis of purified nonlytic TIL shows that contact with tumor cells causes transient activation of p56lck (∼10 s) which is rapidly inactivated. In contrast, tumor-induced activation of p56lck in lytic TIL is sustained coincident with downstream TCR signaling and lytic function. Shp-1 is robustly active in nonlytic TIL compared with lytic TIL, colocalizes with p56lck in nonlytic TIL, and inhibition of Shp-1 activity in lytic TIL in vitro blocks tumor-induced defective TIL cytolysis. Collectively, our data support the notion that contact of nonlytic TIL with tumor cells, and not with tumor-infiltrating myeloid-derived suppressor cells, causes activation of Shp-1 that rapidly dephosphorylates the p56lck activation motif (Y394), thus inhibiting effector phase functions. [Cancer Res 2007;67(23):11447–54]

PURPOSE: The measurement of the nuchal translucency (NT) in the 1st trimester is a sensitive, reliable method to assess the risk of specific fetal chromosomal and other defects. Training, however, is an issue not only among experienced sonographers, but especially for ObGyn residents, since all NT measurements in a true screening setting should fulfil the quality standards. The aim of this study was therefore the evaluation of the learning curve of residents and determination of the number of measurements necessary to achieve acceptable results. MATERIALS AND METHODS: Between 30 th June, 1997 and 8 th August, 2003, we included 4450 subsequent pregnant women between 11 + 0 and 13 + 6 weeks of gestation referred for an NT scan and prenatal counselling (low and high risk patients) in the study. For analysis of the learning curve in residents, all NT scans performed either by the experienced sonographers only or by residents with less than 70 scans at the end of their training were excluded. As the main quality criterion, the percentage of cases above the median was used. To test for normal distribution of NT scans, the Kolmogorov-Smirnov test was used. RESULTS: Each of 19 residents fulfilling these criteria performed 131 NT scans (73 - 242) on average. 13 of 19 residents ultimately met the quality criteria, but the majority of residents achieved good quality only after 100 scans, whereas 6 of 19 never did. Only after at least 50 NT scans, 50 % of measurements were above the median, whereas before these 50 scans, NT was usually underestimated. CONCLUSION: It became obvious that regular supervision and quality control is mandatory to provide exact NT measurements by residents. Based on our results, a minimum of 100 NT scans is recommended before diagnostic application, which is a higher requirement than implemented in widely accepted quality assurance programs.

Lytic granule exocytosis is the major pathway used by CD8+ CTL to kill virally infected and tumor cells. Despite the obvious importance of this pathway in adaptive T cell immunity, the molecular identity of enzymes involved in the regulation of this process is poorly characterized. One signal known to be critical for the regulation of granule exocytosis-mediated cytotoxicity in CD8+ T cells is Ag receptor-induced activation of protein kinase C (PKC). However, it is not known which step of the process is regulated by PKC. In addition, it has not been determined to date which of the PKC family members is required for the regulation of lytic granule exocytosis. By combination of pharmacological inhibitors and use of mice with targeted gene deletions, we show that PKCδ is required for granule exocytosis-mediated lytic function in mouse CD8+ T cells. Our studies demonstrate that PKCδ is required for lytic granule exocytosis, but is dispensable for activation, cytokine production, and expression of cytolytic molecules in response to TCR stimulation. Importantly, defective lytic function in PKCδ-deficient cytotoxic lymphocytes is reversed by ectopic expression of PKCδ. Finally, we show that PKCδ is not involved in target cell-induced reorientation of the microtubule-organizing center, but is required for the subsequent exocytosis step, i.e., lytic granule polarization. Thus, our studies identify PKCδ as a novel and selective regulator of Ag receptor-induced lytic granule polarization in mouse CD8+ T cells.

As the field of education moves forward in the area of assessment, researchers have yet to come to a conclusion about definitions of commonly used terms. Without a consensus on the use of fundamental terms, it is difficult to engage in meaningful discourse within the field of assessment, as well as to conduct research on and communicate about best assessment practices. For this article, we reviewed journal articles, position papers, thought pieces, and classroom assessment textbooks, focusing on the definitions of the terms performance assessment, authentic assessment, and formative assessment. We provide a summary of the literal definitions provided and the components, format, and intentions of each type of assessment. In addition, we underscore the important distinctions made by researchers in the field between performance assessment and authentic assessment. Some researchers suggest performance assessment and authentic assessment are synonymous, and others view performance assessment as a component of authentic assessment. Understanding authentic and performance assessments is important to have a sound theoretical basis for decisions made within the classroom. The purpose and benefits of formative assessment represent another area of discussion within the field of assessment. Formative assessment may be used solely to inform the teacher, or it may be used as a powerful means of providing feedback to students, allowing students to alter their strategies to improve learning. We emphasize important distinctions between the formation of learning and the formation of behaviors or strategies that promote learning. Finally, to avoid confusion, classroom assessment should be classified based on the assessment's intended purpose.

Aims: Osteopontin (OPN) is a matricellular protein involved in tissue remodelling, cell-mediated immunity and malignant transformation. High OPN serum levels predict poor prognosis in non-small cell carcinoma and set patients with malignant pleural mesothelioma (MM) apart from disease-free asbestos-exposed individuals. Yet neither the spectrum of tissue expression nor the signalling pathways of OPN in MM and pulmonary adenocarcinoma have been characterized, although in vitro evidence links OPN to the epidermal growth factor receptor (EGFR) pathway. The aim of this study was to address these deficiencies. Methods and results: OPN expression was investigated immunohistochemically in 104 adenocarcinomas and 38 MM and correlated with histological features, including tumour type, grade and proliferation and with expression of activated intermediary EGFR signalling pathway molecules p65, p-AKT, p-ERK, p-STAT-3, and of metalloproteinase (MMP)-1, MMP-2 and MMP-9. In MM, OPN expression was widespread (36/38) and independent of the molecular parameters studied. In adenocarcinoma, high OPN expression was correlated with expression of p65, p-ERK and MMP-9. Conclusions: Frequent OPN expression is typical of, but not specific for MM, whereas it appears to select adenocarcinoma cases with p65 and MMP-9 expression, suggesting a link with EGFR signalling pathways.

The immune system recognizes protein antigens expressed in transformed cells evidenced by accumulation of antigen-specific T cells in tumor and tumor draining lymph nodes. However, despite demonstrable immune response, cancers grow progressively suggesting that priming of antitumor immunity is insufficiently vigorous or that antitumor immunity is suppressed, or both. Compared to virus infection, antitumor T cells are low abundance that likely contributes to tumor escape and enhancement of priming is a long-sought goal of experimental vaccination therapy. Furthermore, patient treatment with antigen-specific T cells can in some cases overcome deficient priming and cause tumor regression supporting the notion that low numbers of T cells permits tumor outgrowth. However, tumor-induced suppression of antitumor immune response is now recognized as a significant factor contributing to cancer growth and reversal of the inhibitory influences within the tumor microenvironment is a major research objective. Multiple cell types and factors can inhibit T cell functions in tumors and may be grouped in two general classes: T cell intrinsic and T cell extrinsic. T cell intrinsic factors are exemplified by T cell expression of cell surface inhibitory signaling receptors that, after contact with cells expressing a cognate ligand, inactivate proximal T Cell Receptor-mediated signal transduction therein rendering T cells dysfunctional. T cell extrinsic factors are more diverse in nature and are produced by tumors and various non-tumor cells in the tumor microenvironment. These include proteins secreted by tumor or stromal cells, highly reactive soluble oxygen and nitrogen species, cytokines, chemokines, gangliosides, and toxic metabolites. These factors may restrict T cell entrance into the tumor parenchyma, cause inactivation of effector phase T cell functions, or induce T cell apoptosis ultimately causing diminished cancer elimination. Here, we review the contributions of inhibitory factors to tumor T cell dysfunction leading to tumor escape.

Apoptosis and phagocytosis of apoptotic cells are crucial processes. At best the phagocytic machinery detects and swallows all apoptotic cells in a way that progression to secondary necrosis is avoided. Otherwise, inflammation and autoimmune diseases may occur. Most apoptotic cells are phagocytosed instantaneously in a silent fashion; however, some dying cells escape their clearance. If the cells are not cleared early, they lose membranes due to extensive shedding of membrane surrounded vesicles (blebbing) and shrink. It is unclear how apoptotic cells compensate their massive loss of plasma membrane. Here, we demonstrate that endoplasmic reticulum- (ER) resident proteins (calnexin, the KDEL receptor and a dysfunctional immunoglobulin heavy chain) were exposed at the surfaces of shrunken late apoptotic cells. Additionally, these cells showed an increased binding of lectins, which recognize sugar structures predominantly found as moieties of incompletely processed proteins in ER and Golgi. In addition the ER resident lipophilic ER-Tracker™ Blue-White DPX, and internal GM1 were observed to translocate to the cell surfaces during late apoptosis. We conclude that during blebbing of apoptotic cells the surface membrane loss is substituted by immature membranes from internal stores. This mechanism explains the simultaneous appearance of preformed recognition structures for several adaptor proteins known to be involved in clearance of dead cells.

Inflammation resultant from tumor growth, infection with certain pathogens, or in some cases, trauma, can result in systemic release of cytokines, especially GM-CSF, that in turn stimulate the abundant production and activation of a population of immature myeloid cells, termed myeloid suppressor cells (MSCs), that have potent immunosuppressive functions. In this issue of the JCI, Gallina and colleagues have illuminated some complex issues concerning the development, activation, and function of MSCs (see the related article beginning on page 2777). They show that activation of MSCs is initiated in response to IFN-gamma, presumably produced in situ by antitumor T cells in the tumor microenvironment. After this triggering event, MSCs express 2 enzymes involved in l-arginine metabolism, Arginase I and iNOS, whose metabolic products include diffusible and highly reactive peroxynitrites, the ultimate biochemical mediators of T cell immune suppression. The multifaceted regulation of this complex suppressive effector system provides several potential therapeutic targets.

Collaboration is a prerequisite for the sustainability of interagency programs, particularly those programs initially created with the support of time-limited grant-funding sources. From the perspective of evaluators, however, assessing collaboration among grant partners is often difficult. It is also challenging to present collaboration data to stakeholders in a way that is meaningful. In this article, the authors introduce the Levels of Collaboration Scale, which was developed from existing models and instruments. The authors extend prior work on measuring collaboration by exploring the reliability of the scale and developing a format for visually displaying the results obtained from using the scale.

T-cell receptor (TCR) engagement by antigen results in proliferation, differentiation and cytokine secretion. In the CD8+ T-cell subset, TCR triggering also induces granule exocytosis, the directional release of contents of lysosome-like granules toward the target cell presenting the antigen. This process is responsible for immediate death of target cells. The intracellular events required for granule exocytosis are distinct from those of proliferation and cytokine secretion, as the former do not require de novo protein synthesis. Consequently, the key TCR signaling events required for granule exocytosis may be distinct. In this article, we review present knowledge of regulation of granule exocytosis by molecules of the TCR signaling cascade.

Health-related studies of spirituality are threatened by the lack of conceptual distinctions between religion and spirituality, the use of small, nongeneralizable samples, and by measurement error in many instruments that unreliably and invalidly capture this domain. The authors review the construct and validity evidence for the Spirituality Index of Well-Being (SIWB), an instrument designed to measure a dimension of spirituality linked to subjective well-being in patient populations. The SIWB was developed using qualitative research methods and subsequently conceptualized with two dimensions; self-efficacy and life scheme. Primary psychometric data from three sample populations are reviewed and summarized. A secondary, confirmatory factor analysis, using pooled data from all samples, supports the theoretical two-factor structure. In addition, SIWB scores correlate more strongly with established measures of well-being than the Spiritual Well-Being Scale (SWB) or other recognized religiosity instruments. The SIWB is a valid and reliable instrument that can be used in health-related studies.

Robert Albert examined key conceptual shifts in the pertinent professional literature language over the first part of the 20th century in his 1969 American Psychologist article, “Genius: Present‐Day Status of the Concept and Its Implications for the Study of Creativity and Giftedness. “ His findings indicated profound changes in pertinent terminology in the professional knowledge base after 1945 from an emphasis on concepts such as genius, eminence, fame, and distinction to giftedness, talent, and creativity. The goal of the current project was to investigate empirically changes in conceptions of exceptional ability and performance, as reflected in the professional literature published since 1969. Over 28,000 articles were culled from three data bases: Educational Resources Information Center (ERIC), PsycINFO and Exceptional Children Educational Resources (ECER). Conceptual themes and types of research were analyzed for a sample of the articles, drawn from the midpoint year of each decade. Significant res...

In student assessment, teachers place the greatest weight on tests they have constructed themselves and have an equally great interest in the quality of those tests. To increase the validity of teacher-made tests, many item-writing rules-of-thumb are available in the literature, but few rules have been tested experimentally. In light of the paucity of empirical studies, the validity of any given guideline might best be established by relying on experts. This study analyzed twenty classroom assessment textbooks to identify a consensus list of item-writing rules. Forty rules for which there was agreement among textbook authors are presented. The rules address four different validity concerns—potentially confusing wording or ambiguous requirements, the problem of guessing, test-taking efficiency, and controlling for testwiseness.

Balanced literacy is a philosophical orientation that assumes that reading and writing achievement are developed through instruction and support in multiple environments in which teachers use various approaches that differ by level of teacher support and child control. The authors describe 1 urban school district's real-world attempt to create a balance between reading and writing, between teacher-directed and student-centered activities, and between skills-based and meaning-based approaches to literacy instruction. To measure balanced literacy components, the authors used a triangulation strategy with multiple methods of data collection that included classroom observations, inventories of physical environments of classrooms and school buildings, teacher surveys, and student interviews. Results suggest that teacher-directed instruction, a fundamental aspect of balanced literacy, was implemented less often than either independent reading or writing activities. Teachers appeared to allocate instructional ti...

Marker-assisted selection (MAS) is an increasingly important tool in current breeding efforts for improved crop plants and animal breeds. It enables detection of favourable alleles in early developmental stages and thus may result in substantial cost savings. Until now, however, the high costs of the required chemicals and materials, together with the still very labour-intensive methods, have been an obstacle to widespread application of MAS. A new multiplex-polymerase chain reaction (PCR)-based method has been developed for reliable low-cost, high-throughput screening. By its use 3366 apple seedlings were screened with an average hands-on time from DNA extraction to data ready for analysis of < 4 h per 96 plants, and at a cost below US$ 0.5 per marker per plant. Factors that have a strong effect on segregation ratios such as elevated levels of outcrossing are easily detected, as a significant correlation was observed between deviation from expected segregation ratios in some affected markers and the level of outcrossing in a cross. The new method is suitable for many crop species and, provided that suitable buffers are used for DNA extraction, for animals too.

This investigation used quantitative and qualitative methods to address preservice teacher education students' perceptions regarding a collaborative cohort experience where seamless instruction was provided by four faculty to illustrate effective collaboration fundamentals. Results of pre- and post-survey data as well as follow-up focus groups revealed that, in contrast to campus-based teacher preparation instruction, a collaborative cohort model improved preservice teacher attitude towards integrating effective collaboration, even while measured levels of actual collaborative behavior decreased. These changes related to an enhancement of the preservice teacher education students' perceived ability to meet the needs of diverse learners in a inclusive general education environment. Challenges that occurred as a result of the collaborative cohort model, as well as implications for teacher preparation, professional development internships, and future research are discussed.

Purpose: We studied the incidence, treatment, and outcome of fetuses with pyelectasis diagnosed prenatally. Methods: Sonography of the kidneys was performed in 6165 fetuses between 1996 and 2000. Pyelectasis was diagnosed if the anterior-posterior diameter of the collecting system measured ≥5 mm before 20 weeks' gestation, ≥7 mm between 20 and 30 weeks, or ≥10 mm after 30 weeks. Karyoptying was offered if there was evidence of other abnormalities. Postnatal findings were based on reports from nephrologists, pediatricians, pathologists and parents. Progression of pyelectasis was evalated by regression analysis and a receiver-operated curve. Results: Pyelectasis was diagnosed in 156 fetuses (2.5%), 113 of which had an isolated dilatation. Of these 113 cases, 22 (19%) were identified before 20 weeks' gestation, 45 (40%) between 20 and 30 weeks, and 46 (41 %) after 30 weeks. Postpartum, 35 of 113 (38%) fetus-neonates had an anatomic abnormality of the urogenital tract, most commonly ureteropelvic obstruction. Sixteen (14%) of the 113 children underwent surgery and 53 (47%) were managed conservatively. Ninety-two fetuses were studied multiple times during pregnancy, the others were seen only once. During pregnancy pyelectasis decreased in 55 of 92 fetuses (60%) and progressed in 37 (40%). There was no association between the time of diagnosis and the incidence of uropathy and surgical treatment. Seven of 18 fetuses with associated abnormalities had an abnormal karyoptype whereas no children with isolated pyelectasis had chromosomal abnormalities. Conclusion: Fetal pyelectasis is a common finding. Most cases are diagnosed in the second or third trimester. In most cases the prognosis is good. Progressive pyelectasis is predictive of the need for surgical treatment.

Foliar applications of a number of inorganic fertilizer salts were found to significantly reduce powdery mildew [Erysiphe orontii] on greenhouse tomato (Lycopersicon esculentum, cv. Trust) leaves. In a series of single-application experiments, the foliar applications, each with 0.1% surfactant, were applied to the third and fourth leaves of young tomato plants 24 h before inoculation with an atomized application of mildew conidia. Control treatments consisted of a water application and a water plus surfactant application. Powdery mildew colonies were counted 7–10 days later. Surfactant alone significantly reduced mildew colony numbers. CaCl2, Ca(NO3)2, and K2HPO4 reduced colony counts compared with the surfactant alone. All combinations of Ca salts, or Ca salts plus elemental S, significantly reduced mildew colony counts compared with surfactant alone. In a second set of experiments, the effects of repeated applications on already naturally infected tomato plants were evaluated. Young tomato plants were m...

Mice with fibroblast-specific expression of TAP-1 were generated by expressing the TAP-1 transgene under the control of the fibroblast-specific protein (FSP) 1 promoter/enhancer on TAP-1-deficient background. MHC class I expression in primary fibroblast cultures isolated from the resulting strain mimicked that of wild-type counterparts. MHC class I was detected in both types of fibroblasts following treatment with IFN-αβ. Positive selection of CD4−CD8+ thymocytes was observed in neither adult nor fetal/neonatal thymus of transgenic mice. IFN-αβ-induced expression of MHC class I rescued positive selection of CD4−CD8+ T cells in fetal thymic organ cultures, but not in adult mice. Contrary to previous suggestions, our results indicate a limited role of fibroblasts in promoting positive selection. In addition, the results suggest that positive selection may occur by a different mechanism in fetal vs adult thymus.

Crry is a rodent membrane–bound inhibitor of complement activation and is a structural and functional analog of the human complement inhibitors decay-accelerating factor and membrane cofactor protein. We found previously that expression of rat Crry on a human tumor cell line enhances tumorigenicity in nude rats. In this study, we investigated the effect that rat Crry expressed on tumor cells has on rat cell–mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The expression of rat Crry on the surface of different human tumor cell lines inhibited ADCC mediated by rat natural killer (NK) cells. C3 opsonization is known to enhance NK cell–mediated cytolysis, and a potential mechanism for Crry-mediated inhibition of NK cell lysis is through Crry modulation of C3 deposition on target cells. However, the transfection of tumor cell lines with Crry enhanced their resistance to NK cell–mediated lysis in the absence of exogenous complement. The resistance of Crry-expressing tumor cells to NK cell–mediated ADCC could be reversed by treatment with anti–Crry F(ab)2. In addition, anti–Crry F(ab)2 enhanced the susceptibility of 13762 rat mammary adenocarcinoma cells (that endogenously express Crry) to ADCC mediated by allogeneic rat NK cells in the absence of added complement. We found no evidence that rat NK cells were a source of complement for target cell deposition during the in vitro cytolysis assay. These data suggest a novel function for rat Crry in tumor immune surveillance that may be unrelated to complement inhibition.

In this article, the authors discuss research findings of an evaluation of Web-based courses in which the researcher controlled for student input information-using Alexander Astin's (1993) Input-Environment-Outcome assessment model. Controlling for student characteristics decreased bias and minimized the chance of incorrectly attributing outcomes to the virtual environment. The results of this study support the view that students' satisfaction was influenced by the online environment and was not due to student characteristics.

The processes of understanding and solving word problems proceed through the phases of problem translation, problem interpretation, solution planning, solution execution, and solution monitoring. The authors developed a heuristic strategy (SOLVED) to explain these phases in language appropriate to third-, fourth-, and fifth-grade students. Children were trained over several lessons to use it to solve different types of mathematical problems. Results of 2 experiments involving 223 elementary students indicated that SOLVED was more effective in aiding both short-term and delayed problem solving than traditional problem-solving instruction. Accuracy in problem solving was significantly correlated with metacognitive processing. Third-grade students used SOLVED more rapidly and effectively than did older students, and no interaction of learning rate with ability or gender occurred.

Background: Computed tomography (CT) guided core needle biopsy (CT-guided CNB) is a minimally invasive, safe and effective manner of tissue sampling in many organs. The aim of our study is to determine the impact of on-site evaluation of touch imprint cytology (TIC) to minimize the number of passes required to obtain adequate tissue for diagnosis. Design: A retrospective review of all CT-guided CNBs performed during 4 year period, where pathologists were present for on-site TIC evaluation. Each case was evaluated for the number of passes required before TIC was interpreted as adequate for diagnosis. Results: A total of 140 CT-guided CNBs were included in the study (liver, lung, kidney, sacral, paraspinal, omental, splenic and adrenal masses). Of the 140 cases, 109 were diagnosed as malignant, 28 as benign and three insufficient. In 106 cases (75.7%), the biopsies were determined adequate by TIC on the first pass, 19 cases (13%) on the second pass and 7 cases (5%) on the third pass. Only in 5 cases (3.6%), more than three passes were required before diagnostic material was obtained. Three cases (2.14%) were interpreted as inadequate both on TIC and on the final diagnosis. Of the biopsies deemed adequate on the first pass, 71% resulted in either termination of the procedure, or only one additional pass was obtained. In five cases, based on the TIC evaluation, a portion of the sample was sent for either flow cytometric analysis or cytogenetic studies. Conclusions: In the majority of cases, adequate material was obtained in the first pass of CT-guided CNB and once this was obtained, either no additional passes, or one additional pass was performed. This study demonstrates the utility of on-site evaluation in minimizing the number of passes required for obtaining adequate diagnostic material and for proper specimen triage for ancillary studies, which in turn decreases the risk to the patient and costs. However, tumor exhaustion in the tissue as a result of TIC is an important pitfall of the procedure, which occurred in 9 (8.2%) of our malignant cases.

Shock-wave induced nanopore collapse (average diameter 100 nm) at 4.2 GPa in a 3-μm-thick poly-methyl methacrylate (PMMA) layer is measured in real time using coherent anti-Stokes Raman spectroscopy (CARS). Pore collapse is monitored via CARS transitions of a dye probe embedded in the porous medium. A pore collapse time constant of 3 ns in PMMA is in poor agreement with hydrodynamic pore collapse models but in excellent agreement with a viscoplastic model that uses the “shock viscosity” determined from the PMMA viscoelastic response to shock. The shock viscosity is more than 12 orders of magnitude smaller than the ordinary viscosity. A downstream gauge of polycrystalline anthracene monitors changes in the steeply rising shock front (

In an effort to develop a safe and effective vaccine for the prevention of Lyme borreliosis that addresses concerns raised over currently available vaccines, dogs were vaccinated twice with a multiantigenic preparation of Borrelia burgdorferi, strain N40, on days 0 and 20 of the experiment. About 70 and 154 days after the first immunization, dogs were challenged by exposing them to field-collected Ixodes scapularis ticks harboring B. burgdorferi. Vaccinated dogs were completely protected from infection by all criteria utilized to assess infection, developed high-titer anti-B. burgdorferi serum antibodies and growth inhibitory activity which persisted for over 200 days, and did not demonstrate any untoward consequence of vaccination. Serum absorption experiments revealed that borreliacidal and most likely protective antibodies in dogs receiving the multiantigenic preparation were not only elicited against the OspA antigen, but were also produced against additional yet to be determined targets on B. burgdorferi organisms. These data demonstrate that a multiantigenic vaccine is effective in preventing Lyme disease transmitted via the natural vector.

OBJECTIVES: This study was undertaken to determine the degree to which selected demographic and clinical variables are associated with the use of feeding tubes in older nursing home residents with very severe and irreversible cognitive impairment. DESIGN: Descriptive, cross-sectional, population-based study. SETTING: Kansas nursing homes from January 1, 1994, through June 30, 1998. PARTICIPANTS: A total of 4997 nursing home residents with very severe and irreversible cognitive impairment comprised the study population. Subjects were identified using data in Minimum Data Set (MDS) reports. Those who were included in the study population were over the age of 65, had two consecutive Cognitive Performance Scale scores of 6, were without evidence of significant subsequent improvement, and were not comatose. MEASUREMENTS: The MDS data on each resident were examined to determine subjects' age, ethnicity, gender, Medicaid eligibility, disease diagnoses, physical functioning, and oral/nutritional status, including feeding tube status. The MDS was also used to determine urban versus rural location of the nursing home. The association between the use of feeding tubes and selected demographic and clinical characteristics was then examined using bivariate and logistic regression tests. RESULTS: Of the 4997 residents in the study population, 577 (11.6%) had feeding tubes. In multivariate analysis, feeding tube use was found to be associated with swallowing problems (odds ratio (OR) 5.4, 95% confidence interval (CI) 4.3–6.8); urban location of nursing home (OR 2.9, 95% CI 2.3–3.5); non-white race (OR 2.7, 95% CI 1.9–3.6); stroke (OR 2.5, 95% CI 2.0–3.1); and absence of dementia (OR 2.5, 95% CI 2.0–3.1). Feeding tubes were also more weakly associated with age

The intervening domain of the thermostable Thermus aquaticus DNA polymerase (TAQ: polymerase), which has no catalytic activity, has been exchanged for the 3'-5' exonuclease domain of the homologous mesophile Escherichia coli DNA polymerase I (E.coli pol I) and the homologous thermostable Thermotoga neapolitana DNA polymerase (TNE: polymerase). Three chimeric DNA polymerases have been constructed using the three-dimensional (3D) structure of the Klenow fragment of the E.coli pol I and 3D models of the intervening and polymerase domains of the TAQ: polymerase and the TNE: polymerase: chimera TaqEc1 (exchange of residues 292-423 from TAQ: polymerase for residues 327-519 of E.coli pol I), chimera TaqTne1 (exchange of residues 292-423 of TAQ: polymerase for residues 295-485 of TNE: polymerase) and chimera TaqTne2 (exchange of residues 292-448 of TAQ: polymerase for residues 295-510 of TNE: polymerase). The chimera TaqEc1 showed characteristics from both parental polymerases at an intermediate temperature of 50 degrees C: high polymerase activity, processivity, 3'-5' exonuclease activity and proof-reading function. In comparison, the chimeras TaqTne1 and TaqTne2 showed no significant 3'-5' exonuclease activity and no proof-reading function. The chimera TaqTne1 showed an optimum temperature at 60 degrees C, decreased polymerase activity compared with the TAQ: polymerase and reduced processivity. The chimera TaqTne2 showed high polymerase activity at 72 degrees C, processivity and less reduced thermostability compared with the chimera TaqTne1.

Most reports of human Pasteurella multocida infections consist of case reports or short series. Although 1 large series was published from France, none of comparable size has been reported from North America. We, therefore, reviewed all our cases of infections due to P. multocida identified

Rheumatoid arthritis (RA) displays a chronic inflammatory joint disease, accompanied by symmetric polyarthritis (PA) which evokes synovial inflammation, cartilage damage, and bone erosion. Patients with RA are routinely treated by immunosuppressive drugs. The therapy of inflammatory diseases and degenerative disorders with Low-dose radiotherapy (LD-RT) (single doses from 0.3 to 1.0 Gy) represents a low cost therapy with low toxicity, and is able to substitute at least in part treatment with drugs. The efficiency of LD-RT has already been proven in several animal models of inducible arthritis. In the present study we used a human TNF transgenic mouse model to examine the effects of LD-RT on PA. We observed a significant temporal improvement of the clinical progression of disease when mice were irradiated at the beginning of the disease. These data emphasize the role of LD-RT in clinical settings to treat patients with chronic and degenerative disorders and diseases.

The weed Senecio vulgaris acquired high levels of resistance to triazine herbicides soon after the latter's introduction. As in most weeds, triazine resistance is conferred by a point mutation in the chloroplast psbA gene that negatively affects the fitness of its carrier. To assess levels of triazine resistance in S. vulgaris field populations, we adopted a PCR-RFLP-based molecular diagnostic test recently developed for the triazine resistance-conferring region of the psbA gene of other weeds, including Brassica napus, Chenopodium spp. and Amaranthus spp., and compared these molecular results to the phenotypic response after triazine application. A highly significant linear correlation was found between phytotoxic symptoms and biomass reduction. Variability in phenotypic response was not only found between populations or inbred lines of S. vulgaris but also within replicates of the same inbred line. No clear relationship, however, was found between the DNA restriction pattern and the phenotypic response to triazine application, thereby throwing doubt on the use of such molecular diagnostic tests to track triazine resistance in S. vulgaris. Our results indicate that the chloroplast genome of S. vulgaris is polymorphic and that the level of polymorphism may be variable within single leaves of individual plants. We discuss the possible genetic basis of this polymorphism and its consequence for the acquisition and inheritance of chloroplast-based traits.

Thymic T cell function in streptozotocin-treated (STZ) diabetic mice has been examined. STZ administration suppresses thymic T cell proliferation in response to mitogen stimulation in vitro. Secretion of IL-4 was dramatically reduced; however, secretion of IL-2 or IFN-gamma was not significantly inhibited. RT-PCR analysis of thymocyte RNA revealed that levels of IL-4 mRNA were dramatically decreased in STZ-treated mice. Levels of mRNA encoding IFN-gamma were similar, but the appearance was delayed in thymocytes derived from STZ-treated mice, implying differential regulation of IL-4 and IFN-gamma. Defective thymocyte proliferation was partially restored by exposure to IL-2 in vitro; however, IL-4 completely reversed the STZ-induced defect. Administration in vivo of IL-4 before STZ treatment reversed the STZ-induced thymocyte proliferation defect and prevented both pancreatic islet destruction and hyperglycemia. Thymocyte cell surface differentiation markers were not appreciably different from control mice. Collectively these experiments suggest that STZ treatment of mice reduces expression of IL-4 which is associated with development of autoimmune diabetes.

SUMMARYCD59, decay accelerating factor (DAF) and membrane cofactor protein (MCP) are widely expressed cell surface glycoproteins that protect host cells from the effects of homologous complement attack. Complement inhibitory activity of these proteins is species-selective. We show that the human breast cancer cell line MCF7 is relatively resistant to lysis by human complement, but is effectively lysed by rat or mouse complement. CD59, DAF and MCP were all shown to be expressed by MCF7. The species-selective nature of CD59 activity was used to demonstrate directly the effectiveness of CD59 at protecting cancer cells from complement-mediated lysis. cDNAs encoding rat and mouse CD59 were separately transfected into MCF7 cells, and cell populations expressing high levels of the rodent CD59 were isolated by cell sorting. Data show that rat and mouse CD59 were highly effective at protecting transfected MCF7 cells from lysis by rat and mouse complement, respectively. Data further reveal that rat CD59 is not effective against mouse complement, whereas mouse CD59 is effective against both mouse and rat complement. These studies establish a model system for relevant in vivo studies aimed at determining the effect of complement regulation on tumourigenesis, and show that for effective immunotherapy using complement-activating anti-tumour antibodies, the neutralization of CD59 and/or other complement inhibitory molecules will probably be required.

Fractionation of Borrelia burgdorferi was made by extraction of infectious spirochetes using the detergent Triton X-114. Gel electrophoresis analysis of hydrophilic and hydrophobic proteins demonstrated that detergent extraction resulted in two populations of proteins with nonoverlapping electrophoretic profiles. Immunoblot analysis with monoclonal antibodies reactive with two abundant membrane proteins demonstrated that hydrophilic proteins were uncontaminated with hydrophobic proteins. In addition, assay of thymidine incorporation into and secretion of tumor necrosis factor-alpha from splenocytes cocultured in vitro with either detergent or aqueous phase proteins showed that lymphocyte mitogenic and macrophage activation activities of B. burgdorferi were completely absent from the hydrophilic phase proteins. The Triton X-114 aqueous and detergent phase proteins were used to immunize BALB/c and separately microMT/microMT (B cell knockout) mice that were subsequently challenged with infectious B. burgdorferi. The hydrophilic phase proteins were able to induce protective resistance to infection in either strain of mice demonstrating that potential candidate vaccine antigens are contained in the biochemical class of antigens which is devoid of both lymphocyte mitogen activity and major outer surface proteins. Furthermore, the ability to vaccinate B cell knockout mice suggests that the humoral antispirochete immune response is not the exclusive basis for protective immunity.