Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses.

This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV). We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. The magnitude and quality of the Gag-specific CD8(+) T cells in response to these vectors post boost were measured. In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag) thirty-three days after the boost inoculation. Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+) T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+) T cell responses independent of the prime vaccine used. However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations. Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+) T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach. These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses

In the Shadow of the Tower: The View of the Undergraduate Experience

This paper reports the initial findings of a survey (N=388) conducted in Winter 1991 focusing on the quality of the academic experience for Arts and Science students at a medium size post-secondary institution in eastern Canada. Our purposes are: 1) to set out the context in which undergraduates conduct their academic work, 2) to document what their experience entails, and 3) to present some of their perceptions of the higher education process. While most students have vocational goals in mind, they are also keenly interested in acquiring a solid general education. Undergraduates attend most of their classes, are heavily committed to completing their programs, and work quite diligently in pursuit of their goals in the face of what many of them consider to be heavy workloads. They are not, however, completely satisfied with the services that they receive in return for their tuition fees and for Canadians' tax dollars. While satisfaction levels vary with the type of services provided, it is clear that there does exist substantial room in which institutions can make improvements. Specifically, our data suggest that the primary goals of universities seeking to better the undergraduate experience should be to encourage more effective teaching and its evaluation, to reduce class sizes, to increase formal and informal interaction among faculty members and students, to improve the quality of academic advising, and to support the creation of more equitable financial assistance programs for students.Cet article présente les premiers résultats d'une enquête (N=388) menée durant l'hiver 1991 portant sur la qualité de l'expérience universitaire d'étudiants en arts et en sciences inscrits à une institution de moyenne importance dans l'est du Canada. Nos intentions sont: 1) d'établir le contexte dans lequel les étudiants accomplissent leur travail scolaire, 2) de documenter en quoi consiste cette expérience et 3) de décrire quelques-unes de leurs impressions sur le système d'éducation supérieure. Bien que la plupart des étudiants poursuivent des buts professionnels, ils s'intéressent aussi vivement à acquérir une éducation générale à bases solides. Les étudiants de premier cycle assistent à la plupart de leurs cours, se sont voués à compléter leurs études, et travaillent diligemment afin de réaliser leurs buts malgré ce que beaucoup d'entre eux estiment être des programmes exigeants. Toutefois, ils ne sont pas entièrement satisfaits des services qu'ils reçoivent en échange de leurs frais de scolarité et des impôts prélevés aux Canadiens. Alors que le degré de satisfaction varie selon les services offerts, il est clair que des améliorations s'imposent dans plusieurs domaines. Plus précisément, nos donnés suggèrent que les universités cherchant à améliorer l'expérience des étudiants au niveau du premier cycle devraient se proposer comme buts prioritaires d'encourager un enseignement plus efficace et de mieux l'évaluer, de réduire la taille des classes, de favoriser l'interaction formelle et informelle entre les professeurs et les étudiants, d'améliorer la qualité des services d'orientation scolaire, et de promouvoir la création de programmes d'aide financière plus équitable pour les étudiants

Potential Targets' Analysis Reveals Dual PI3K/mTOR Pathway Inhibition as a Promising Therapeutic Strategy for Uterine Leiomyosarcomas-an ENITEC Group Initiative

Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment. Experimental Design: We investigated the expression of several druggable targets (phospho-S6(S240) ribosomal protein, PTEN, PDGFR-alpha, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues. The potential therapeutic value of the most promising target, p-S6(S240), was tested in patient-derived xenograft (PDX) leiomyosarcoma models. Results: In uterine sarcomas and STUMPs, S6S240 phosphorylation (reflecting mTOR pathway activation) was associated with higher grade (P = 0.001) and recurrence (P = 0.019), as shown by logistic regression. In addition, p-S6(S240) correlated with shorter progression-free survival (P = 0.034). Treatment with a dual PI3K/mTOR inhibitor significantly reduced tumor growth in 4 of 5 leiomyosarcoma PDX models (with tumor shrinkage in 2 models). Remarkably, the 4 responding models showed basal p-S6(S240) expression, whereas the nonresponding model was scored as negative, suggesting a role for p-S6(S240) in response prediction to PI3K/mTOR inhibition. Conclusions: Dual PI3K/mTOR inhibition represents an effective therapeutic strategy in uterine leiomyosarcoma, and p-S6(S240) expression is a potential predictive biomarker for response to treatment. (C)2017 AACR.Peer reviewe

The Farm, the city, and the emergence of social security

We study the social, demographic and economic origins of social security. The data for the U.S. and for a cross section of countries suggest that urbanization and industrialization are associated with the rise of social insurance. We describe an OLG model in which demographics, technology, and social security are linked together in a political economy equilibrium. In the model economy, there are two locations (sectors), the farm (agricultural) and the city (industrial) and the decision to migrate from rural to urban locations is endogenous and linked to productivity differences between the two locations and survival probabilities. Farmers rely on land inheritance for their old age and do not support a pay-as-you-go social security system. With structural change, people migrate to the city, the land loses its importance and support for social security arises. We show that a calibrated version of this economy, where social security taxes are determined by majority voting, is consistent with the historical transformation in the United States

Patents and Industrialisation. An Historical Overview of the British Case, 1624-1907

A Report to the Strategic Advisory Board on Intellectual Property Policy (SABIP), U

Outside the gate: sub-urban legal practices in early medieval England

Many aspects of English early medieval (Anglo-Saxon) legal landscapes can be discerned in archaeological and toponymic evidence, ranging from the locations of legislative councils and judicial assemblies to sites of capital punishment. Among the corpus of such sites a striking group can be detected at the periphery of urban spaces. Gates into a number of towns appear to have functioned as legislative meeting-places, and even gave their names to some legally constituted communities, while suburban locations also feature prominently as sites of gallows and public punishment. In this paper historical, archaeological and toponymic evidence is used to examine this phenomenon of suburban legal practices and to pose questions about the wider dimensions of the early medieval legal landscape

Unifying Time-to-Build Theory

Several contributions have recently reconsidered the role of the time to build assumption in explaining some relevant stylized facts. In this paper, the similarities and differences which may emerge when the time to build structure of capital is introduced in a continuous or discrete time framework are studied and enlightened. The most striking difference lies in the dimensionality of the two frameworks, which is always finite in discrete but infinite in continuous time. Then, the deterministic version of the traditional time to build model developed by Kydland and Prescott is presented, and it is shown how the typical time to build model setup in continuous time can be obtained. Moreover, the richest dynamics in continuous time is investigated and, more importantly, it is shown that the predictions in terms of capital, output, and consumption behavior are not signi¯cantly di®erent from its discrete version once the economy is calibrated properly

The Optimal Tax Treatment of Housing Capital in the Neoclassical Growth Model

In a dynamic setting, housing is both an asset and a consumption good.But should it be taxed like other forms of consumption or like other forms of saving?We consider the optimal taxation of the imputed rent from owner housing within a version of the neoclassical growth model.We find that the optimal tax rate on the imputed rent is quite sensitive to the constraints imposed on the other available tax rates.In general, it is not optimal to tax the imputed rent at the same rate as the business capital income

Plasma proteome changes in cardiovascular disease patients: novel isoforms of apolipoprotein A1

<p>Abstract</p> <p>Background</p> <p>The aim of this proteomic study was to look for changes taking place in plasma proteomes of patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP).</p> <p>Methods</p> <p>Depleted plasma proteins were separated by 2D SDS-PAGE (pI 4-7), and proteomes were compared using Progenesis SameSpots statistical software. Proteins were identified by nanoLC-MS/MS. Proteins were quantified using commercial kits. Apolipoprotein A1 was studied using 1D and 2D SDS-PAGE, together with western blotting.</p> <p>Results</p> <p>Reciprocal comparison revealed 46 unique, significantly different spots; proteins in 34 spots were successfully identified and corresponded to 38 different proteins. Discrete comparisons of patient groups showed 45, 41, and 8 significantly different spots when AMI, UAP, and SAP were compared with the control group. On the basis of our proteomic data, plasma levels of two of them, alpha-1 microglobulin and vitamin D-binding protein, were determined. The data, however, failed to prove the proteins to be suitable markers or risk factors in the studied groups. The plasma level and isoform representation of apolipoprotein A1 were also estimated. Using 1D and 2D SDS-PAGE, together with western blotting, we observed extra high-molecular weight apolipoprotein A1 fractions presented only in the patient groups, indicating that the novel high-molecular weight isoforms of apolipoprotein A1 may be potential new markers or possible risk factors of cardiovascular disease.</p> <p>Conclusion</p> <p>The reported data show plasma proteome changes in patients with AMI, UAP, and SAP. We propose some apolipoprotein A1 fractions as a possible new disease-associated marker of cardiovascular disorders.</p