Homiletics: Outlines on the Standard Epistle Series

Outlines on the Standard Epistle Serie

Relationship between intact HIV-1 proviruses in circulating CD4+ T cells and rebound viruses emerging during treatment interruption.

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4+ T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound

Heating technology for malignant tumors: a review

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 degrees C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 degrees C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors

A mouse model for HIV-1 entry

Passive transfer of neutralizing antibodies against HIV-1 can prevent infection in macaques and seems to delay HIV-1 rebound in humans. Anti-HIV antibodies are therefore of great interest for vaccine design. However, the basis for their in vivo activity has been difficult to evaluate systematically because of a paucity of small animal models for HIV infection. Here we report a genetically humanized mouse model that incorporates a luciferase reporter for rapid quantitation of HIV entry. An antibody’s ability to block viral entry in this in vivo model is a function of its bioavailability, direct neutralizing activity, and effector functions

SMART-SREC: a stochastic model of the New Jersey solar renewable energy certificate market

Markets for solar renewable energy certificates (SRECs) are gaining in promi- nence in many states, stimulating growth of the U.S. solar industry. However, SREC market prices have been extremely volatile, causing high risk to participants and potentially less investment in solar power generation. Such concerns necessitate the development of realis- tic, flexible and tractable models of SREC prices that capture the behavior of participants given the rules that govern the market. We propose an original stochastic model called SMART-SREC to fill this role, building on established ideas from the carbon pricing liter- ature, and including a feedback mechanism for generation response to prices. We calibrate the model to the New Jersey market and backtest it, analyzing parameter sensitivity and demonstrating its ability to reproduce historical dynamics. Finally, we run simulations to investigate the role and impact of regulatory parameters, thus providing insight into the crucial role played by market design

Resilience and Resistance in Sagebrush Ecosystems Are Associated With Seasonal Soil Temperature and Water Availability

Invasion and dominance of exotic grasses and increased fire frequency threaten native ecosystems worldwide. In the Great Basin region of the western United States, woody and herbaceous fuel treatments are implemented to decrease the effects of wildfire and increase sagebrush (Artemisia spp.) ecosystem resilience to disturbance and resistance to exotic annual grasses. High cover of the exotic annual cheatgrass (Bromus tectorum) after treatments increases fine fuels, which in turn increases the risk of passing over a biotic threshold to a state of increased wildfire frequency and conversion to cheatgrass dominance. Sagebrush ecosystem resilience to wildfire and resistance to cheatgrass depend on climatic conditions and abundance of perennial herbaceous species that compete with cheatgrass. In this study, we used longer‐term data to evaluate the relationships among soil climate conditions, perennial herbaceous cover, and cheatgrass cover following fuel management treatments across the environmental gradients that characterize sagebrush ecosystems in the Great Basin. We examined the effects of woody and herbaceous fuel treatments on soil temperature, soil water availability (13–30 and 50 cm depths), and native and exotic plant cover on six sagebrush sites lacking piñon (Pinus spp.) or juniper (Juniperus spp.) tree expansion and 11 sagebrush sites with tree expansion. Both prescribed fire and mechanical treatments increased soil water availability on woodland sites and perennial herbaceous cover on some woodland and sagebrush sites. Prescribed fire also slightly increased soil temperatures and especially increased cheatgrass cover compared to no treatment and mechanical treatments on most sites. Non‐metric dimensional scaling ordination and decision tree partition analysis indicated that sites with warmer late springs and warmer and wetter falls had higher cover of cheatgrass. Sites with wetter winters and early springs (March–April) had higher cover of perennial herbs. Our findings suggest that site resistance to cheatgrass after fire and fuel control treatments decreases with a warmer and drier climate. This emphasizes the need for management actions to maintain and enhance perennial herb cover, such as implementing appropriate grazing management, and revegetating sites that have low abundance of perennial herbs in conjunction with fuel control treatments

A study of the properties of an oil-based drilling fluid with using emulsifier EM-4

The issue of maintaining the potential productivity of the well is one of the most urgent tasks of the oil and gas industry nowadays. Due to the development of deposits with complex deposits and low-permeability productive layers, the issues of increasing the flow rate of wells due to the qualitative opening of reservoirs were of fundamental importance. The drilling fluid with an oil base (OBM) does not adversely affect the properties of oil and gas collectors, also it has good lubricating properties, reducing the wear of drill bits and bits. This paper is devoted to comparing the properties of drilling muds prepared using the industrial emulsifier Cleave FM and the new synthesized emulsifier EM-4. Emulsifier EM-4 is a solution of N- (2-hydroxyethyl) amides of fatty acids in a mixture of mono- and diglycerides of fatty acids

HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals