Non-syncytium-inducing HIV type 1 isolated from infected individuals replicates in MT-2 cells

Human immunodeficiency virus type 1 (HIV-1) isolates from six infected individuals less then 4 years of age were phenotyped for their syncytium-inducing (SI) ability in MT-2 cells. Three viral isolates that induced syncytia were detected. One SI isolate was from an individual who was in disease stage P2A,B,C and two SI isolates were recovered sequentially from another individual who switched from disease stage P1B to P2F. Non-syncytium-inducing (NSI) isolates were detected in two individuals who were in stage P1B of disease, and in a third individual who was in stage P2A of disease. Three sequential isolates obtained over a 2-year period from a fourth individual who progressed from disease stage P1B to P2A,B,C and subsequently died of AIDS-related disease were also found to have the NSI phenotype. To test whether NSI isolates can replicate in the absence of syncytium formation, we analyzed NSI-infected MT-2 cells for production of viral p24 antigen and expression of viral RNA by in situ hybridization. By day 12 postinfection, 6 of 7 NSI viral isolates produced 7- to 36-fold increases in p24 antigen compared to day 6, and expressed viral RNA in 13-20% of cells. A single NSI isolate that did not replicate in MT-2 cells was obtained from an individual who was asymptomatic (stage P1B). The individual rapidly progressed to symptomatic stage P2F and two sequential SI viruses were isolated. These SI isolates replicated in MT-2 cells and induced cytopathic effects.(ABSTRACT TRUNCATED AT 250 WORDS

Detection of HIV-1-infected cells from patients using nonisotopic in situ hybridization

We have demonstrated that a sensitive, nonisotopic in situ hybridization (ISH) assay can be used to detect HIV-infected cells from seropositive, asymptomatic individuals. Our assay is based on the detection of a biotinated HIV DNA probe hybridized to human immunodeficiency virus (HIV)-infected peripheral blood lymphocytes (PBL) using streptavidin and alkaline phosphatase to identify positive cells. This assay is rapid in that it can be performed within a day and is sensitive enough to unambiguously identify a rare, single, positive cell. Patient samples derived from HIV-seropositive hemophiliacs and HIV-seropositive infants were analyzed before and after coculture with normal PBL. The same samples were investigated using a Dupont P24 antigen-capture kit. It was found that ISH always detected the same positive samples as antigen capture, often in shorter times of coculture. In situ hybridization detected over half of our HIV-infected hemophilia patient population as virus positive, whereas the antigen capture assay detected less than one fourth as virus positive. In situ hybridization detected positive cells directly, without coculture, in 12 out of 35 (34%) hemophiliacs and in three out of eight (37%) infants. The speed, sensitivity, and confidence of ISH and nonisotopic detection indicates that it will be useful as a tool for clinical research and diagnosis

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.National Institutes of Health (U.S.) (Grant R01 EB006365-06)Brain Science Foundation (Private Grant 106708

The 'pause' in global warming in historical context : (II). Comparing models to observations

We review the evidence for a putative early 21st-century divergence between global mean surface temperature (GMST) and Coupled Model Intercomparison Project Phase 5 (CMIP5) projections. We provide a systematic comparison between temperatures and projections using historical versions of GMST products and historical versions of model projections that existed at the times when claims about a divergence were made. The comparisons are conducted with a variety of statistical techniques that correct for problems in previous work, including using continuous trends and a Monte Carlo approach to simulate internal variability. The results show that there is no robust statistical evidence for a divergence between models and observations. The impression of a divergence early in the 21st century was caused by various biases in model interpretation and in the observations, and was unsupported by robust statistics

Creating Markets for Captured Carbon: Retrofit of Abbott Power Plant and Future Utilization of Captured CO2

The successful implementation of CCUS requires the confluence of technology, regulatory, and financial factors. One of the factors that impact this confluence is the ability to utilize and monetize captured CO2. The generally accepted utilization approach has been CO2-based Enhanced Oil Recovery (EOR), yet this is not always feasible and/or a preferable approach. There is a need to be able to explore a multitude of utilization approaches in order to identify a portfolio of potential utilization mechanisms. This portfolio must be adapted based on the economy of the region. In response to this need, the University of Illinois has formed a Carbon Dioxide Utilization and Reduction (COOULR) Center. The open nature of the university, coupled with a university policy to reduce CO2 emissions, provides a model for the issues communities will face when attempting to reduce emissions while still maintaining reliable and affordable power. This Center is one of the key steps in the formation of a market for captured CO2. The goal of the Center is to not only evaluate technologies, but also demonstrate at a large pilot scale how communities may be able to adjust to the need to reduce GHG emissions.U.S. Department of Energy Award Number DE-FE0026588Ope

Designing the climate observing system of the future

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth's Future 6 (2018): 80–102, doi:10.1002/2017EF000627.Climate observations are needed to address a large range of important societal issues including sea level rise, droughts, floods, extreme heat events, food security, and freshwater availability in the coming decades. Past, targeted investments in specific climate questions have resulted in tremendous improvements in issues important to human health, security, and infrastructure. However, the current climate observing system was not planned in a comprehensive, focused manner required to adequately address the full range of climate needs. A potential approach to planning the observing system of the future is presented in this article. First, this article proposes that priority be given to the most critical needs as identified within the World Climate Research Program as Grand Challenges. These currently include seven important topics: melting ice and global consequences; clouds, circulation and climate sensitivity; carbon feedbacks in the climate system; understanding and predicting weather and climate extremes; water for the food baskets of the world; regional sea-level change and coastal impacts; and near-term climate prediction. For each Grand Challenge, observations are needed for long-term monitoring, process studies and forecasting capabilities. Second, objective evaluations of proposed observing systems, including satellites, ground-based and in situ observations as well as potentially new, unidentified observational approaches, can quantify the ability to address these climate priorities. And third, investments in effective climate observations will be economically important as they will offer a magnified return on investment that justifies a far greater development of observations to serve society's needs

Substantial contribution of iodine to Arctic ozone destruction

Unlike bromine, the effect of iodine chemistry on the Arctic surface ozone budget is poorly constrained. We present ship-based measurements of halogen oxides in the high Arctic boundary layer from the sunlit period of March to October 2020 and show that iodine enhances springtime tropospheric ozone depletion. We find that chemical reactions between iodine and ozone are the second highest contributor to ozone loss over the study period, after ozone photolysis-initiated loss and ahead of bromine.Iodine chemistry plays a more important role than bromine chemistry in tropospheric ozone losses in the Arctic, according to ship-based observations of halogen oxides from March to October 2020.Peer reviewe

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure