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To investigate the possibility that HIV-1 replication in lymph nodes sustains the reservoir during ART, we looked for evidence of viral replication in 5 donors after up to 13 years of viral suppression. We characterized proviral populations in lymph nodes and peripheral blood before and during ART, evaluated the levels of viral RNA expression in single lymph node and blood cells, and characterized the proviral integration sites in paired lymph node and blood samples. Proviruses with identical sequences, identical integration sites, and similar levels of RNA expression were found in lymph nodes and blood samples collected during ART, and no single sequence with significant divergence from the pretherapy population was present in either blood or lymph nodes. These findings show that all detectable persistent HIV-1 infection is consistent with maintenance in lymph nodes by clonal proliferation of cells infected before ART and not by ongoing viral replication during ART.

The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication-competent proviruses has been controversial. Here, we used single-genome sequencing to probe for identical HIV sequence matches among viruses recovered in different viral outgrowth cultures and between the sequences of outgrowth viruses and proviral or intracellular HIV RNA sequences in uncultured blood mononuclear cells from eight donors on suppressive ART with diverse proviral populations. All eight donors had viral outgrowth virus that was fully susceptible to their current ART drug regimen. Six of eight donors studied had identical near full-length HIV RNA sequences recovered from different viral outgrowth cultures, and one of the two remaining donors had identical partial viral sequence matches between outgrowth virus and intracellular HIV RNA. These findings provide evidence that clonal expansion of HIV-infected cells is an important mechanism of reservoir persistence that should be targeted to cure HIV infection.

The advent of combined antiretroviral therapy (cART) has been instrumental in controlling HIV-1 replication and transmission and decreasing associated morbidity and mortality. However, cART alone is not able to cure HIV-1 due to the presence of long-lived, latently infected immune cells, which re-seed plasma viremia when cART is interrupted. Assessment of HIV-cure strategies using ex vivo culture methods for further understanding of the diversity of reactivated HIV, viral outgrowth, and replication dynamics are enhanced using ultrasensitive digital ELISA based on single-molecule array (Simoa) technology to increase the sensitivity of endpoint detection. In viral outgrowth assays (VOA), exponential HIV-1 outgrowth has been shown to be dependent upon initial virus burst size surpassing a critical growth threshold of 5100 HIV-1 RNA copies. Here, we show an association between ultrasensitive HIV-1 Gag p24 concentrations and HIV-1 RNA copy number that characterize viral dynamics below the exponential replication threshold. Single-genome sequencing (SGS) revealed the presence of multiple identical HIV-1 sequences, indicative of low-level replication occurring below the threshold of exponential outgrowth early during a VOA. However, SGS further revealed diverse related HIV variants detectable by ultrasensitive methods that failed to establish exponential outgrowth. Overall, our data suggest that viral outgrowth occurring below the threshold necessary for establishing exponential growth in culture does not preclude replication competence of reactivated HIV, and ultrasensitive detection of HIV-1 p24 may provide a method to detect previously unquantifiable variants. These data strongly support the use of the Simoa platform in a multi-prong approach to measuring latent viral burden and efficacy of therapeutic interventions aimed at an HIV-1 cure.

This qualitative case study examined practical, effective applications of implementing a cognitive training curriculum into a high school curriculum. The case study analyzed the 2011-2012 research project conducted by the National Science Foundation (NSF) performed at Waskom High School in Waskom, Texas. The intent was to help students increase student achievement by targeting areas of learning deficiency, assertively focusing on intensive remediation, and ultimately decreasing or removing those areas of weakness in the learning altogether. This study investigated how cognitive training can help both regular education students and students with disabilities. The notion of training or re-training the brain to think faster, more efficiently, and at higher levels was the focus of this research and the experiments that were discussed. The purpose of this qualitative case study was to examine practical, effective applications of implementing a cognitive training curriculum into a school with the intent of helping all students be successful. A cognitive training program was defined as any program that attempts to help a student learn faster, easier, and better (Hill, 2012). In a time where school districts are held to higher accountability standards than ever before, many districts may be interested in investing significant monies toward a program or programs that will effectively increase their student success in the classroom and on standardized tests. However, it is also important to note that those same school districts and systems are being required to stretch their budget further than ever before and do more with less funding. This study was conducted using a qualitative design methodology to gather data on the use of cognitive training with all high school students in grades 9-12 at a small 3-A rural school district located in East Texas.

In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non-controllers who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers is due to a lower fraction of the infected cells having HIV-1 unspliced RNA (HIV usRNA) compared with non-controllers. To directly test this possibility, we used sensitive and quantitative single cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and non-controllers. The fraction of infected cells containing HIV usRNA did not differ between the two groups. Rather, the levels of viremia were strongly associated with the total number of infected cells that had HIV usRNA, as reported by others, with controllers having 34-fold fewer infected cells per million PBMC. These results reveal for the first time that viremic control is not associated with a lower fraction of proviruses expressing HIV usRNA, unlike what is reported for elite controllers, but is only related to having fewer infected cells overall, maybe reflecting greater immune clearance of infected cells. Our findings show that proviral silencing is not a key mechanism for viremic control and will help to refine strategies towards achieving HIV remission without ART.

[...]the closest they came to changing the tax code was to expand the Angel Investor Tax Credit program, which NJBIA supports because it provides greater incentives for investors in qualified innovation-based businesses. NJBIA has continually raised concerns about being able to sustain this level of spending, particularly when the state's public employee pension liability and post-employment benefit obligation has grown to more than $151 billion. [...]the state maintains the top Corporate Business Tax rate, income tax rate, sales tax rate and property tax rate in our region and is among the highest in these categories nationwide.

[...]year graduates grew employment at 14 percent and third year at 8 percent.Participants bring their own existing talents to the table, but then learn good business practices that can help them for years after they graduate - things like regularly using financial data and analysis to tell them what's going on in the market, and sticking to a business growth plan to make sure they stay on the right track.[...]no matter how much public funding is put into job training and infrastructure programs, successful economic development will always need private-sector businesses to maintain growth.Since the program was launched in 2008, more than 3,300 business owners have participated in the training.

[...]EDA is the primary source for the incentives to bring Amazon's second headquarters to Newark.[...]there's the Angel Investor Tax Credit Program; in 2016, the state approved 251 applications through the program, which represented over $96 million in private capital into technology and life sciences companies throughout the Garden State.Additionally, NJBIA worked with lawmakers in 2017 to extend the successful Angel Investor Tax Credit Program to holding companies.

[...]NJBIA's goal is to make sure New Jersey businesses have a pipeline of skilled workers that are ready for the 21st century workplace. NJB FAST FACTS 600,000 The increase in degrees, certificates and credentials needed to reach 65 percent 204 Industry-valued credentials requiring postsecondary education 50 Current percentage of NJ residents with some postsecondary education New Jersey's rank for education attainment > 65 by '25 means 65 percent of working-age residents attaining some post-secondary school education by 2025.