Do CD4(+) T Cell Functional Responses to Epstein–Barr Virus Provide Protective Immunity Against CNS Lymphoma in AIDS?

Jacobson discusses a new study addressing the question of whether an EBV antigen-specific T cell response might be a critical component of protective immunity that is lost as part of the pathogenesis of AIDS-related primary CNS lymphoma

Renewable build-up pathways for the US: Generation costs are not system costs

The transition to a future electricity system based primarily on wind and solar PV is examined for all regions in the contiguous US. We present optimized pathways for the build-up of wind and solar power for least backup energy needs as well as for least cost obtained with a simplified, lightweight model based on long-term high resolution weather-determined generation data. In the absence of storage, the pathway which achieves the best match of generation and load, thus resulting in the least backup energy requirements, generally favors a combination of both technologies, with a wind/solar PV energy mix of about 80/20 in a fully renewable scenario. The least cost development is seen to start with 100% of the technology with the lowest average generation costs first, but with increasing renewable installations, economically unfavorable excess generation pushes it toward the minimal backup pathway. Surplus generation and the entailed costs can be reduced significantly by combining wind and solar power, and/or absorbing excess generation, for example with storage or transmission, or by coupling the electricity system to other energy sectors.Comment: 11 pages, 6 figure

Ab Initio Molecular Orbital Investigation of the Unimolecular Decomposition of CH3SiH2+

The potential energy surface for the decomposition of CH3SiH2+ was studied by ub initio electronic structure theory. At the MP2/6-31G(d,p) level of theory, CH3SiH2+ is the only minimum energy structure on the SiCH5+ potential energy surface. Lower levels of theory reported that +CH2SiH3 was also a local minimum, about 40 kcal/mol higher in energy with only a small (ca. 1-2 kcdmol) banier for conversion back to CH3SiH2+. However, at higher levels of theory, the C, structure of +CHzSiH3 has an imaginary frequency, indicating that it is a saddle point rather than a local minimum on the potential energy surface. The 0 K reaction enthalpies for 1,1 -dehydrogenation from silicon, 1,2-dehydrogenation, 1,l -dehydrogenation from carbon, and demethanation were calculated to be 30.2,69.1, 107.3, and 45.3 kcdmol, respectively. Activation energies (0 K) were calculated at the MP4/6-311++G(2df,2pd) level of theory with the classical barriers subsequently adjusted for zero-point vibrational energies. The 0 K activation energies for 1,l-dehydrogenation from silicon, l,Zdehydrogenation, and demethanation are predicted to be 66.6, 72.7, and 73.0 kcavmol, respectively. All attempts to locate a transition state for the insertion of the carbene-like species, CHSiHZ+, into Hz (reverse of the 1,l-dehydrogenation from carbon) were unsuccessful. This is not surprising since analogous carbene insertions are known to occur without a barrier. Thus, we conclude that this 1,l-H2 elimination from carbon proceeds monotonically uphill. The closed-shell structures for the products of the above reactions (CH3Si+, CH2SiH+, and CHSiH2+) were calculated at the MP2/6-31G(p,d) level of theory. Finally, triplet products were also examined

Development of cytomegalovirus (CMV) immune recovery uveitis is associated with Th17 cell depletion and poor systemic CMV-specific T cell responses.

Backgroundthe immune reconstitution inflammatory syndromes (IRIS) are a spectrum of inflammatory conditions associated with opportunistic infections and occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected patients given antiretroviral therapy. It has been proposed that these conditions are linked by a dysregulated immune system that is prone to exaggerated responses. However, immunologic studies have been limited by the availability of longitudinal samples from patients with IRIS and appropriate matched control subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS occurring in up to 38% of patients with CMV retinitis. Although the pathologic immune responses occur in the eye, immune dysregulation that allows for development of pathologic responses is presumably caused by faulty systemic immune cell reconstitution.Methodswe examined CMV-specific T cell responses, regulatory T (T(reg)) cell function and polyclonal T cell responses, including IL-17 production, in 25 patients with CMV IRU and 49 immunorestored control subjects with CMV retinitis who did not develop IRU.Resultspatients with CMV IRU had poor CMV-specific CD4(+) T cell responses, as compared with control subjects, whereas CD8(+) T cell responses were comparable. Patients with CMV IRU were characterized by smaller numbers of circulating Th17 cells. Deficiency in anti-CMV responses was not associated with differences in T(reg) cell function.Conclusionsthe T(reg) cell compartment is intact in patients with CMV IRU, and these patients do not develop exaggerated systemic CMV-specific or polyclonal immune responses. Cases are instead characterized by more profound depletion of Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to develop in persons experiencing the greatest degree of immune dysfunction before initiating highly active antiretroviral therapy

Single-stranded nucleic acid elasticity arises from internal electrostatic tension

Charged, flexible polymers, such as single-stranded nucleic acids (ssNAs), are ubiquitous in biology and technology. Quantitative description of their solution conformation has remained elusive due to the competing effects of polymer configurational freedom and salt-screened electrostatic repulsion between monomers. We investigate this by measuring the elastic response of single ssNA molecules over a range of salt concentrations. The data are well described by a model, inspired by a mean-field approach, in which intrapolymer electrostatic repulsion creates a salt-dependent internal tension whose interplay with the external force determines the elasticity. The internal tension can be related to the polymer’s charge spacing; thus, our results show how mesoscopic polymer conformation emerges from microscopic structure

Potential Environmental Impacts of Hydrogen-based Transportation and Power Systems

Hydrogen (H2) offers advantages as an energy carrier: minimal discharge of pollutants, production from multiple sources, increased thermodynamic efficiencies compared to fossil fuels, and reduced dependence on foreign oil. However, potential impacts from the H2 generation processes, transport and distribution of H2, and releases of H2 into the atmosphere have been proposed. The goal of this project was to analyze the effects of emissions of hydrogen, the six criteria pollutants and greenhouse gases on climate, human health, materials and structures. This project was part of a larger effort by DOE to assess the life-cycle costs and benefits and environmental impacts to inform decisions regarding future hydrogen research. Technical Approach: A modeling approach was developed and used to evaluate the potential environmental effects associated with the conversion of the on-road vehicle fleet from fossil-fuel vehicles to hydrogen fuel cell vehicles. GATOR-GCMOM was the primary tool used to predict atmospheric concentrations of gases and aerosols for selected scenarios. This model accounts for all feedbacks among major atmospheric processes based on first principles. The future scenarios and the emission rates selected for this analysis of hydrogen environmental effects are based on the scenarios developed by IPCC. The scenarios selected for the model simulations are a 2000 and 2050 A1B base cases, and a 2050 A1B case with hydrogen fuel cell vehicles (HFCVs). The hydrogen fuel cell scenario assumed conversion of 90% of fossil-fuel on-road vehicles (FFOV) in developed countries and 45% of FFOVs vehicles in other countries to HFCVs, with the H2 produced by steam-reforming of natural gas (SHFCVs). Simulations were conducted to examine the effect of converting the worldâÂÂs FFOVs to HFCVs, where the H2 is produced by wind-powered electrolysis (WHFCVs). In all scenarios a 3% leakage of H2 consumed was assumed. Two new models were developed that provide the ability to evaluate a wider range of conditions and address some of the uncertainties that exist in the evaluation of hydrogen emissions. A simplified global hydrogen cycle model that simulates hydrogen dynamics in the troposphere and stratosphere was developed. A Monte Carlo framework was developed to address hydrogen uptake variability for different types of ecosystems. Findings 1.Converting vehicles worldwide in 2050 to SHFCVs at 90% penetration in developed countries and 45% penetration in other countries is expected to reduce NOx, CO, CO2, CH4, some other organic gases, ozone, PAN, black carbon, and other particle components in the troposphere, but may increase some other organic gases, depending on emissions. Conversion to SHFCVs is also expected to cool the troposphere and warm the stratosphere, but to a lesser extent than WHFCVs. Finally, SHFCVs are expected to increase UTLS ozone while decreasing upper stratospheric ozone, but to a lesser extent than WHFCVs. 2.The predicted criteria pollutant concentrations from the GATOR-GCMOM simulations indicated that near-surface annual mean concentrations in the US are likely to increase from the 2000 base case to the 2050 A1B base case for CO2 and ozone due to the increased economic activity, but to decrease for CO, NO2, SO2, and PM10 due to improved pollution control equipment and energy efficiencies. The shift to SHFCVs in 2050 was predicted to result in decreased concentrations for all the criteria pollutants, except for SO2 and PM10. The higher predicted concentrations for SO2 and PM10 were attributed to increased emissions using the steam-reforming method to generate H2. If renewable methods such as wind-based electrolysis were used to generate H2, the emissions of SO2 and PM10 would be lower. 3.The effects on air quality, human health, ecosystem, and building structures were quantified by comparing the GATOR-GCMOM model output and accepted health and ecosystem effects levels and ambient air quality criteria. Shifting to HFCVs is expected to result in improved air quality and benefits to human health. Shifting to HFCVs is unlikely to result in damage to buildings. 4.Results are thought to be robust for larger leakage rates of H2 and for greater penetrations of HFCVs, since the controlling factor for stratospheric ozone impacts is the reduction in fossil-fuel greenhouse gases and the resulting surface cooling, which reduces water vapor emissions and stratospheric warming, which increases tropopause stability reducing water vapor transport to the stratosphere. 5.The supplemental modeling results were generally supportive of the results from the GATOR-GCMOM simulations, and recommendations for additional analyses were made. Extending the duration of the simulation to coincide with the time required for hydrogen mixing ratios to attain a steady state condition was recommended. Further evaluation of algorithms to describe hydrogen uptake in the model was also recommended

Fixed-Combination Halobetasol Propionate and Tazarotene in the Treatment of Psoriasis: Narrative Review of Mechanisms of Action and Therapeutic Benefits

Psoriasis is a lifelong disease associated with cycles of remission and relapse. Topical treatments are the front line of psoriasis therapy for most patients and have antiproliferative, anti-inflammatory, and immunosuppressive mechanisms of action. Novel fixed-dose combinations of topical therapeutic agents are becoming increasingly available, leveraging multiple mechanisms of action to improve safety and efficacy with formulations that are easier to use and may allow for the use of lower doses of active ingredients. A fixed-combination lotion containing the potent-to-super-potent corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (HP 0.01%/TAZ 0.045%) was recently developed using polymeric emulsion technology. This new formulation technology allows for more uniform and efficient delivery of the active ingredients at lower doses than conventional monotherapy formulations of either ingredient while providing enhanced hydration and moisturization. This review provides an up-to-date overview of the therapeutic mechanisms of action of HP and TAZ, the rationale behind the development of HP 0.01%/TAZ 0.045% lotion, and clinical trials data on the efficacy, safety and tolerability, and maintenance of therapeutic effect with HP 0.01%/TAZ 0.045% lotion in the treatment of moderate-to-severe plaque psoriasis

Development of Cytomegalovirus (CMV) Immune Recovery Uveitis Is Associated with Th17 Cell Depletion and Poor Systemic CMV-Specific T Cell Responses

We tested whether impaired systemic immunoregulation and hyperactive immune responses are associated with an immune reconstitution inflammatory syndrome, CMV IRU. We found instead that T-regs in CMV IRU patients are functionally intact, while virus-specific immune responses and Th17 cells are compromise