1,735 research outputs found
The Effect of the Love and Logic Program on Student Motivation
This study evaluates the effect of implementing the classroom management program Love and Logic in small, middle and high school science classrooms. It focuses on science classrooms from seventh grade to twelfth grade in a small, rural district. The student population includes large percentages of white and Hispanic individuals, with a smaller percentage of Native American individuals as well as a large percentage, over 60%, of socioeconomically disadvantaged individuals. There were five cohorts, divided by type of science class and age, and the intervention was implemented by a multiple baseline across behaviors method. The cohorts were seventh grade life science, eighth grade physical science, freshmen (with a few older students) earth science, sophomore biology, and junior and senior chemistry. Student motivation was measured weekly by a sixteen question survey that each student in each class answered. The study found that Love and Logic does not improve motivation in middle and high school science classrooms and is unable to prevent a decline in motivation. The study concludes that Love and Logic needs to be studied more in middle and high school classrooms to find ways in which it can be implemented more effectively. The study encourages future research in professional development regarding the Love and Logic program including more time spent by teachers learning how to implement it and finding out the effects of school-wide or district-wide implementation
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Odor-Based Recognition of Familiar and Related Conspecifics: A First Test Conducted on Captive Humboldt Penguins (<i>Spheniscus humboldti</i>)
Studies of kin recognition in birds have largely focused on parent-offspring recognition using auditory or visual discrimination. Recent studies indicate that birds use odors during social and familial interactions and possibly for mate choice, suggesting olfactory cues may mediate kin recognition as well. Here, we show that Humboldt penguins (Spheniscus humboldti), a natally philopatric species with lifetime monogamy, discriminate between familiar and unfamiliar non-kin odors (using prior association) and between unfamiliar kin and non-kin odors (using phenotype matching). Penguins preferred familiar non-kin odors, which may be associated with the recognition of nest mates and colony mates and with locating burrows at night after foraging. In tests of kin recognition, penguins preferred unfamiliar non-kin odors. Penguins may have perceived non-kin odors as novel because they did not match the birds' recognition templates. Phenotype matching is likely the primary mechanism for kin recognition within the colony to avoid inbreeding. To our knowledge this is the first study to provide evidence of odor-based kin discrimination in a bird.</p
Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1.
BackgroundOncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death and induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development as an oncolytic immunotherapy in this study as it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis and is a potent activator of both innate and adaptive immunity. HSV-1 also has a large capacity for the insertion of additional, potentially therapeutic, exogenous genes. Finally, HSV-1 has a proven safety and efficacy profile in patients with cancer, talimogene laherparepvec (T-VEC), an oncolytic HSV-1 which expresses GM-CSF, being the only oncolytic immunotherapy approach that has received FDA approval. As the clinical efficacy of oncolytic immunotherapy has been shown to be further enhanced by combination with immune checkpoint inhibitors, developing improved oncolytic platforms which can synergize with other existing immunotherapies is a high priority. In this study we sought to further optimize HSV-1 based oncolytic immunotherapy through multiple approaches to maximize: (i) the extent of tumor cell killing, augmenting the release of tumor antigens and danger-associated molecular pattern (DAMP) factors; (ii) the immunogenicity of tumor cell death; and (iii) the resulting systemic anti-tumor immune response.MethodsTo sample the wide diversity amongst clinical strains of HSV-1, twenty nine new clinical strains isolated from cold sores from otherwise healthy volunteers were screened across a panel of human tumor cell lines to identify the strain with the most potent tumor cell killing ability, which was then used for further development. Following deletion of the genes encoding ICP34.5 and ICP47 to provide tumor selectivity, the extent of cell killing and the immunogenicity of cell death was enhanced through insertion of a gene encoding a truncated, constitutively highly fusogenic form of the envelope glycoprotein of gibbon ape leukemia virus (GALV-GP-R-). A number of further armed derivatives of this virus were then constructed intended to further enhance the anti-tumor immune response which was generated following fusion-enhanced, oncolytic virus replication-mediated cell death. These viruses expressed GMCSF, an anti-CTLA-4 antibody-like molecule, CD40L, OX40L and/or 4-1BB, each of which is expected to act predominantly at the site and time of immune response initiation. Expression of these proteins was confirmed by ELISA and/or western blotting. Immunogenic cell death was assessed by measuring the levels of HMGB1 and ATP from cell free supernatants from treated cells, and by measuring the surface expression of calreticulin. GALV-GP-R- mediated cell to cell fusion and killing was tested in a range of tumor cell lines in vitro. Finally, the in vivo therapeutic potential of these viruses was tested using human A549 (lung cancer) and MDA-MB-231(breast cancer) tumor nude mouse xenograft models and systemic anti-tumor effects tested using dual flank syngeneic 4434 (melanoma), A20 (lymphoma) mouse tumor models alone and in combination with a murine anti-PD1 antibody, and 9 L (gliosarcoma) tumors in rats.ResultsThe twenty nine clinical strains of HSV-1 isolated and tested demonstrated a broad range of tumor cell killing abilities allowing the most potent strain to be identified which was then used for further development. Oncolytic ability was demonstrated to be further augmented by the expression of GALV-GP-R- in a range of tumor cell lines in vitro and in mouse xenograft models in nude mice. The expression of GALV-GP-R- was also demonstrated to lead to enhanced immunogenic cell death in vitro as confirmed by the increased release of HMGB1 and ATP and increased levels of calreticulin on the cell surface. Experiments using the rat 9 L syngeneic tumor model demonstrated that GALV-GP-R- expression increased abscopal uninjected (anenestic) tumor responses and data using mouse 4434 tumors demonstrated that virus treatment increased CD8+ T cell levels both in the injected and uninjected tumor, and also led to increased expression of PD-L1. A combination study using varying doses of a virus expressing GALV-GP-R- and mGM-CSF and an anti-murine PD1 antibody showed enhanced anti-tumor effects with the combination which was most evident at low virus doses, and also lead to immunological memory. Finally, treatment of mice with derivatives of this virus which additionally expressed anti-mCTLA-4, mCD40L, m4-1BBL, or mOX40L demonstrated enhanced activity, particularly in uninjected tumors.ConclusionThe new HSV-1 based platform described provides a potent and versatile approach to developing new oncolytic immunotherapies for clinical use. Each of the modifications employed was demonstrated to aid in optimizing the potential of the virus to both directly kill tumors and to lead to systemic therapeutic benefit. For clinical use, these viruses are expected to be most effective in combination with other anti-cancer agents, in particular PD1/L1-targeted immune checkpoint blockade. The first virus from this program (expressing GALV-GP-R- and hGM-CSF) has entered clinical development alone and in combination with anti-PD1 therapy in a number of tumor types (NCT03767348)
Comparison of immune responses in parenteral FaeG DNA primed pigs boosted orally with F4 protein or reimmunized with the DNA vaccine
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Identification of baryon resonances in central heavy-ion collisions at energies between 1 and 2 AGeV
The mass distributions of baryon resonances populated in near-central
collisions of Au on Au and Ni on Ni are deduced by defolding the spectra
of charged pions by a method which does not depend on a specific resonance
shape. In addition the mass distributions of resonances are obtained from the
invariant masses of pairs. With both methods the deduced mass
distributions are shifted by an average value of -60 MeV/c relative to the
mass distribution of the free resonance, the distributions
descent almost exponentially towards mass values of 2000 MeV/c^2. The observed
differences between and pairs indicate a contribution
of isospin resonances. The attempt to consistently describe the
deduced mass distributions and the reconstructed kinetic energy spectra of the
resonances leads to new insights about the freeze out conditions, i.e. to
rather low temperatures and large expansion velocities.Comment: 30 pages, 13 figures, Latex using documentstyle[12pt,a4,epsfig], to
appear in Eur. Phys. J.
Abundance of Delta Resonances in 58Ni+58Ni Collisions between 1 and 2 AGeV
Charged pion spectra measured in 58Ni-58Ni collisions at 1.06, 1.45 and 1.93
AGeV are interpreted in terms of a thermal model including the decay of Delta
resonances. The transverse momentum spectra of pions are well reproduced by
adding the pions originating from the Delta-resonance decay to the component of
thermal pions, deduced from the high transverse momentum part of the pion
spectra. About 10 and 18% of the nucleons are excited to Delta states at
freeze-out for beam energies of 1 and 2 AGeV, respectively.Comment: 14 pages, LaTeX with 3 included figures; submitted to Physics Letters
Stopping and Radial Flow in Central 58Ni + 58Ni Collisions between 1 and 2 AGeV
The production of charged pions, protons and deuterons has been studied in
central collisions of 58Ni on 58Ni at incident beam energies of 1.06, 1.45 and
1.93 AGeV. The dependence of transverse-momentum and rapidity spectra on the
beam energy and on the centrality of the collison is presented. It is shown
that the scaling of the mean rapidity shift of protons established for AGS and
SPS energies is valid down to 1 AGeV. The degree of nuclear stopping is
discussed; the IQMD transport model reproduces the measured proton rapidity
spectra for the most central events reasonably well, but does not show any
sensitivity between the soft and the hard equation of state (EoS). A radial
flow analysis, using the midrapidity transverse-momentum spectra, delivers
freeze-out temperatures T and radial flow velocities beta_r which increase with
beam energy up to 2 AGeV; in comparison to existing data of Au on Au over a
large range of energies only beta_r shows a system size dependence
Underground railroads: citizen entitlements and unauthorized mobility in the antebellum period and today
In recent years, some scholars and prominent political figures have advocated the deepening of North American integration on roughly the European Union model, including the creation of new political institutions and the free movement of workers across borders. The construction of such a North American Union, if it included even a very thin trans-state citizenship regime, could represent the most significant expansion of individual entitlements in the region since citizenship was extended to former slaves in the United States. With such a possibility as its starting point, this article explores some striking parallels between the mass, legally prohibited movement across boundaries by fugitive slaves in the pre-Civil War period, and that by current unauthorized migrants to the United States. Both were, or are, met on their journeys by historically parallel groups of would-be helpers and hinderers. Their unauthorized movements in both periods serve as important signals of incomplete entitlements or institutional protections. Most crucially, moral arguments for extending fuller entitlements to both groups are shown here to be less distinct than may be prima facie evident, reinforcing the case for expanding and deepening the regional membership regime
Dibaryons with Strangeness: their Weak Nonleptonic Decay using SU(3) Symmetry and how to find them in Relativistic Heavy-Ion Collisions
Weak SU(3) symmetry is successfully applied to the weak hadronic decay
amplitudes of octet hyperons. Weak nonmesonic and mesonic decays of various
dibaryons with strangeness, their dominant decay modes, and lifetimes are
calculated. Production estimates for BNL's Relativistic Heavy-Ion Collider are
presented employing wave function coalescence. Signals for detecting strange
dibaryon states in heavy-ion collisions and revealing information about the
unknown hyperon-hyperon interactions are outlined.Comment: 4 pages, 2 figures, uses RevTeX, discussion about the model of the
weak decay and experimental signals extended, references update
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