203 research outputs found
Teachersâ and studentsâ perceptions of studentsâ ability and importance value in math and reading: a latent difference score analysis of intra-individual cross-domain differences
Informed by Eccles and colleaguesâ expectancy-value theory and Möller and Marshâs dimensional comparison theory, we examined cross-domain intra-individual differences in elementary teachersâ (NâŻ=â57) and their studentsâ (NâŻ=â469) ratings of studentsâ ability and subjective importance of math and reading. Latent difference score analyses revealed that students perceived greater intra-individual differences in their own math versus reading ability than did their teachers. Analogous results emerged for studentsâ and teachersâ ratings of studentsâ valuing (i.e., perceived importance) of math versus reading, suggesting differing dimensional comparison processes for studentsâ self-judgments vs. their teachersâ judgments. Cross-domain differences in teachersâ and studentsâ perceptions were positively associated for ratings of studentsâ ability but not for ratings of studentsâ perceived importance. Moreover, intra-individual differences varied substantially across students, in both studentsâ and teachersâ ratings. Studentsâ gender and prior achievement in math and reading contributed to this variation.Auf Basis der Erwartungs-Wert-Theorie von Eccles et al. und der Theorie dimensionaler Vergleiche von Möller und Marsh untersucht dieser Beitrag intra-individuelle Differenzen der Lernenden zwischen Mathe und Lesen bezĂŒglich ihrer fachspezifischen FĂ€higkeiten und subjektiven Wichtigkeit der FĂ€cher, beurteilt von den Lernenden (NâŻ=â469) und ihren GrundschullehrkrĂ€ften (NâŻ=â57). Latente Differenzmodelle ergaben, dass die Lernenden gröĂere intra-individuelle Unterschiede zwischen Mathe und Lesen sowohl in ihrer FĂ€higkeit als auch der Wichtigkeit des Fachs wahrnahmen als ihre LehrkrĂ€fte, was auf unterschiedliche dimensionale Vergleichsprozesse bei Selbst- und Lehrkrafturteilen hindeutet. Lernenden- und Lehrkraftbeurteilung der Differenzen zwischen Mathe und Lesen waren positiv assoziiert fĂŒr die Beurteilung der FĂ€higkeiten, aber nicht fĂŒr die Beurteilung der wahrgenommenen Wichtigkeit des Fachs. DarĂŒber hinaus variierten die intra-individuellen Unterschiede zwischen den Lernenden, sowohl in den Beurteilungen der Lernenden als auch der LehrkrĂ€fte. Das Geschlecht der Lernenden und ihre Vorleistungen in beiden FĂ€chern erwiesen sich als PrĂ€diktoren dieser inter-individuellen Unterschiede
Nonequilibrium dynamics of mixtures of active and passive colloidal particles
We develop a mesoscopic field theory for the collective nonequilibrium
dynamics of multicomponent mixtures of interacting active (i.e., motile) and
passive (i.e., nonmotile) colloidal particles with isometric shape in two
spatial dimensions. By a stability analysis of the field theory, we obtain
equations for the spinodal that describes the onset of a motility-induced
instability leading to cluster formation in such mixtures. The prediction for
the spinodal is found to be in good agreement with particle-resolved computer
simulations. Furthermore, we show that in active-passive mixtures the spinodal
instability can be of two different types. One type is associated with a
stationary bifurcation and occurs also in one-component active systems, whereas
the other type is associated with a Hopf bifurcation and can occur only in
active-passive mixtures. Remarkably, the Hopf bifurcation leads to moving
clusters. This explains recent results from simulations of active-passive
particle mixtures, where moving clusters and interfaces that are not seen in
the corresponding one-component systems have been observed.Comment: 17 pages, 3 figure
In-vivo optical monitoring of the efficacy of epidermal growth factor receptor targeted photodynamic therapy: The effect of fluence rate
Targeted photodynamic therapy (PDT) has the potential to improve the therapeutic effect of PDT due to significantly better tumor responses and less normal tissue damage. Here we investigated if the efficacy of epidermal growth factor receptor (EGFR) targeted PDT using cetuximab-IRDye700DX is fluence rate dependent. Cell survival after treatment with different fluence rates was investigated in three cell lines. Singlet oxygen formation was investigated using the singlet oxygen quencher sodium azide and singlet oxygen sensor green (SOSG). The long-term response (to 90 days) of solid OSC-19-luc2-cGFP tumors in mice was determined after illumination with 20, 50, or 150 mW·cmâ2. Reflectance and fluorescence spectroscopy were used to monitor therapy. Singlet oxygen was formed during illumination as shown by the increase in SOSG fluorescence and the d
T Cells expressing a TCR-like antibody selected against the heteroclitic variant of a shared MAGE-A epitope do not recognise the cognate epitope
Antibodies-recognising peptides bound to the major histocompatibility complex (pMHC) represent potentially valuable and promising targets for chimeric antigen receptor (CAR) T cells to treat patients with cancer. Here, a human phage-Fab library has been selected using HLA-A2 complexed with a heteroclitic peptide variant from an epitope shared among multiple melanoma-associated antigens (MAGEs). DNA restriction analyses and phage ELISAs confirmed selection of unique antibody clones that specifically bind to HLA-A2 complexes or HLA-A2-positive target cells loaded with native or heteroclitic peptide. Antibodies selected against heteroclitic peptide, in contrast to native peptide, demonstrated significantly lower to even negligible binding towards native peptide or tumour cells that naturally expressed peptides. The binding to native peptide was not rescued by phage panning with antigen-positive tumour cells. Importantly, when antibodies directed against heteroclitic peptides were engineered into CARs and expressed by T cells, binding to native peptides and tumour cells was minimal to absent. In short, TCR-like antibodies, when isolated from a human Fab phage library using heteroclitic peptide, fail to recognise its native peptide. We therefore argue that peptide modifications to improve antibody selections should be performed with caution as resulting antibodies, either used directly or as CARs, may lose activity towards endogenously presented tumour epitope
Tumour basement membrane laminin expression predicts outcome following curative resection of pancreatic head cancer
Background: Although widely fragmented BMs have been associated with adverse outcome in several cancer types, comparatively little is known with respect to its effect on the prognosis of pancreatic cancer. The aim of the current study was therefore to determine the prognostic value of tumour basement membrane (BM) continuity in two anatomically closely related, however, prognostically different tumours, pancreatic head-and periampullary cancer. Methods: Tumour BM continuity was determined by immunohistochemical staining of its two major components, laminin and collagen type IV. Associations were made with recurrence free survival (RFS), cancer-specific survival (CSS), overall survival (OS) and conventional prognostic factors. Results: Fifty-nine and 61% of pancreatic head and periampullary tumours, respectively, showed limited BM laminin expression. Whereas 43% and 41% of pancreatic head and periampullary cancers, respectively, showed limited BM collagen type IV expression. Limited BM laminin was associated with poor outcome following curative resection of pancreatic head cancer (P=0.034, 0.013 and 0.017 for RFS, CSS and OS, respectively). Two and a half times as many patients with 25% BM laminin were recurrence free and alive 5 years following resection compared with those with limited BM laminin. Although staining patterns of both BM components were weakly correlated with each other, BM collagen type IV expression was not significantly associated with outcome in either tumour type.Conclusion: Discontinuous BMs, determined by laminin expression, are associated with poor outcome following curative resection of pancreatic head cancer
N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers
N-acetylgalactosaminyl transferase-3 (GalNAc-T3) is an enzyme involved in the initial glycosylation of mucin-type O-linked proteins. In the present study, we used immunohistochemistry to examine GalNAc-T3 expression in 215 surgically resected non-small cell lung cancers. We analysed the biological and clinical importance of GalNAc-T3 expression, especially with regard to its potential as a prognostic factor. We found that normal bronchial epithelial cells, bronchial gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for GalNAc-T3. Low expression of GalNAc-T3, observed in 93 of 215 tumours (43.4%), was found more frequently in tumours from smokers than those from nonsmokers (P=0.001), in squamous cell carcinomas than nonsquamous cell carcinomas (P<0.0001), and in moderately and poorly differentiated tumours than well differentiated tumours (P=0.0002). Multivariate logistic regression analysis showed that an association of low GalNAc-T3 expression with squamous cell carcinomas was the only one significant relationship of GalNAc-T3 expression with various factors (P<0.0001). Moreover, tumours losing GalNAc-T3 expression had a significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3 expression (P=0.0003). Patients with low GalNAc-T3 expression survived a significantly shorter time than patients with high GalNAc-T3 expression in 103 pStage I non-small cell lung cancers (5-year survival rates, 58% and 78%, respectively; P=0.02 by log-rank test) as well as in 61 pStage I nonsquamous cell carcinomas (5-year survival rates, 63% and 85%, respectively; P=0.03). Low GalNAc-T3 expression was an unfavourable prognostic factor in pStage I non-small cell lung cancers (hazards ratio, 2.04; P=0.03), and in pStage I nonsquamous cell carcinomas (hazards ratio, 2.70; P=0.03). These results suggest that GalNAc-T3 is a new marker of non-small cell lung cancers with specificity for histology and prognosis
Phase equilibria and glass transition in colloidal systems with short-ranged attractive interactions. Application to protein crystallization
We have studied a model of a complex fluid consisting of particles
interacting through a hard core and a short range attractive potential of both
Yukawa and square-well form. Using a hybrid method, including a self-consistent
and quite accurate approximation for the liquid integral equation in the case
of the Yukawa fluid, perturbation theory to evaluate the crystal free energies,
and mode-coupling theory of the glass transition, we determine both the
equilibrium phase diagram of the system and the lines of equilibrium between
the supercooled fluid and the glass phases. For these potentials, we study the
phase diagrams for different values of the potential range, the ratio of the
range of the interaction to the diameter of the repulsive core being the main
control parameter. Our arguments are relevant to a variety of systems, from
dense colloidal systems with depletion forces, through particle gels,
nano-particle aggregation, and globular protein crystallization.Comment: 20 pages, 10 figure
The low temperature interface between the gas and solid phases of hard spheres with a short-ranged attraction
At low temperature, spheres with a very short-ranged attraction exist as a
close-packed solid coexisting with an infinitely dilute gas. We find that the
ratio of the interfacial tension between these two phases to the thermal energy
diverges as the range of the attraction goes to zero. The large tensions when
the interparticle attractions are short-ranged may be why globular proteins
only crystallise over a narrow range of conditions.Comment: 6 pages, no figures (v2 has change of notation to agree with that of
Stell
Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature
Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies
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