저널 Read more :: PLOS Development of a repeat-exposure penile SHIV infection model in macaques to evaluate biomedical preventions against HIV Penile acquisition of HIV infection contributes substantially to the global epidemic. Our goal was to establish a preclinical macaque model of penile HIV infection for evaluating the efficacy of new HIV prevention modalities. Rhesus macaques were challenged once or twice weekly with consistent doses of SHIVsf162P3 (a chimeric simian-human immunodeficiency virus containing HIV env) ranging from 4–600 TCID50 (50% tissue culture infective dose), via two penile routes, until systemic SHIV infection was confirmed. One route exposed the inner foreskin, glans and urethral os to virus following deposition into the prepuce (foreskin) pouch. The second route introduced the virus non-traumatically into the distal urethra only. Single-route challenges resulted in dose-dependent rates of SHIV acquisition informing selection of optimal SHIV dosing. Concurrent SHIV challenges via the prepuce pouch (200 TCID50) and urethra (16 TCID50) resulted in infection of 100% (10/10) animals following a median of 2.5 virus exposures (range, 1–12). We describe the first rhesus macaque repeat-exposure SHIV challenge model of penile HIV acquisition. Utilization of the model should further our understanding of penile HIV infection and facilitate the development of new HIV prevention strategies for men.
강의 Read more :: TED Math can help uncover cancer's secrets Irina Kareva translates biology into mathematics and vice versa. She writes mathematical models that describe the dynamics of cancer, with the goal of developing new drugs that target tumors. "The power and beauty of mathematical modeling lies in the fact that it makes you formalize, in a very rigorous way, what we think we know," Kareva says. "It can help guide us to where we should keep looking, and where there may be a dead end." It all comes down to asking the right question and translating it to the right equation, and back.
연구과제 Read more :: GRANTS.GOV Office of Innovation and Improvement (OII): Education Innovation and Research Program: Mid-phase Grants CFDA Number 84.411B Note: Each funding opportunity description is a synopsis of information in the Federal Register application notice. For specific information about eligibility, please see the official application notice. The official version of this document is the document published in the Federal Register. Free Internet access to the official edition of the Federal Register and the Code of Federal Regulations is available on GPO Access at: http://www.access.gpo.gov/nara/index.html. Please review the official application notice for pre-application and application requirements, application submission information, performance measures, priorities and program contact information. For the addresses for obtaining and submitting an application, please refer to our Common Instructions for Applicants to Department of Education Discretionary Grant Programs, published in the Federal Register on February 12, 2018 (83 FR 6003) and available at www.gpo.gov/fdsys/pkg/FR-2018-02-12/pdf/2018-02558.pdf. Purpose of Program: The Education Innovation and Research (EIR) program, established under section 4611 of the Elementary and Secondary Education Act, as amended (ESEA), provides funding to create, develop, implement, replicate, or take to scale entrepreneurial, evidence-based, field-initiated innovations to improve student achievement and attainment for high-need students; and rigorously evaluate such innovations. The EIR program is designed to generate and validate solutions to persistent educational challenges and to support the expansion of those solutions to serve substantially larger numbers of students. The central design element of the EIR program is its multi-tier structure that links the amount of funding that an applicant may receive to the quality of the evidence supporting the efficacy of the proposed project, with the expectation that projects that build this evidence will advance through EIR's grant tiers: ``Early-phase,'' ``Mid-phase,'' and ``Expansion.'' Applicants proposing innovative practices that are supported by limited evidence can receive relatively small grants to support the development, implementation, and initial evaluation of the practices; applicants proposing practices supported by evidence from rigorous evaluations, such as an experimental study (as defined in this notice), can receive larger grant awards to support expansion across the country. This structure provides incentives for applicants to: (1) Explore new ways of addressing persistent challenges that other educators can build on and learn from; (2) build evidence of effectiveness of their practices; and (3) replicate and scale successful practices in new schools, districts, and States while addressing the barriers to scale, such as cost structures and implementation fidelity. All EIR projects are expected to generate information regarding their effectiveness in order to inform EIR grantees' efforts to learn about and improve upon their efforts, and to help similar, non-EIR efforts across the country benefit from EIR grantees' knowledge. By requiring that all grantees conduct independent evaluations of their EIR projects, EIR ensures that its funded projects make a significant contribution to improving the quality and quantity of information available to practitioners and policymakers about which practices improve student achievement, for which types of students, and in what contexts. The Department awards three types of grants under this program: ``Early-phase'' grants, ``Mid-phase'' grants, and ``Expansion'' grants. These grants differ in terms of the level of prior evidence of effectiveness required for consideration for funding, the expectations regarding the kind of evidence and information funded projects should produce, the level of scale funded projects should reach, and, consequently, the amount of funding available to support each type of project. The Department expects that Mid-phase grants will be used to fund implementation and a rigorous evaluation of a program that has been successfully implemented under an Early-phase grant or other effort meeting similar criteria, for the purpose of measuring the program's impact and cost- effectiveness, if possible using existing administrative data. Mid-phase grants are supported by moderate evidence (as defined in this notice) for at least one population or setting, and grantees are encouraged to implement at the regional level (as defined in this notice) or at the national level (as defined in this notice). This notice invites applications for Mid-phase grants only. The notices inviting applications for Early-phase and Expansion grants are published elsewhere in this issue of the Federal Register. Background: Mid-phase projects are expected to refine and expand the use of practices with prior evidence of effectiveness in order to improve outcomes for high-need students. They are also expected to generate important information about an intervention's effectiveness, including for whom and in which contexts a practice is most effective, as well as cost-effective. With the funded Mid-phase projects, we aim to accelerate the building of a knowledge base of effective practices for addressing challenges and increase the likelihood that grantees can learn from one another while still exploring different approaches. We believe that improving outcomes across the education sector depends, in part, upon policymakers, practitioners, and researchers continually building upon one another's efforts to have the greatest impact. Mid-phase applicants are encouraged to design an evaluation that has the potential to meet the strong evidence (as defined in this notice) threshold. Mid-phase grantees should measure the cost-effectiveness of their practices using administrative or other readily available data. These types of efforts are critical to sustaining and scaling EIR-funded effective practices after the EIR grant period ends, assuming that the practice has positive effects on important student outcomes. In order to support adoption or replication by other entities, the evaluation of a Mid-phase project should identify and codify the core elements of the EIR-supported practice that the project implements, and examine the effectiveness of the project for any new populations or settings that are included in the project. The Department intends to provide grantees and their independent evaluators with evaluation technical assistance. This evaluation technical assistance could include grantees and their independent evaluators providing to the Department or its contractor updated comprehensive evaluation plans in a format as requested by the technical assistance provider and using such tools as the Department may request. Grantees will be encouraged to update this evaluation plan at least annually to reflect any changes to the evaluation, with updates consistent with the scope and objectives of the approved application. Catalog of Federal Domestic Assistance (CFDA) number 84.411B (Mid-phase Grants).