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© 2018 Hogan et al. HIV-1-infected cells persist indefinitely despite the use of combination antiretroviral therapy (ART), and novel therapeutic strategies to target and purge residual infected cells in individuals on ART are urgently needed. Here, we demonstrate that CD4+T cell-associated HIV-1 RNA is often highly enriched in cells expressing CD30, and that cells expressing this marker considerably contribute to the total pool of transcriptionally active CD4+lymphocytes in individuals on suppressive ART. Using in situ RNA hybridization studies, we show co-localization of CD30 with HIV-1 transcriptional activity in gut-associated lymphoid tissues. We also demonstrate that ex vivo treatment with brentuximab vedotin, an antibody-drug conjugate (ADC) that targets CD30, significantly reduces the total amount of HIV-1 DNA in peripheral blood mononuclear cells obtained from infected, ART-suppressed individuals. Finally, we observed that an HIV-1-infected individual, who received repeated brentuximab vedotin infusions for lymphoma, had no detectable virus in peripheral blood mononuclear cells. Overall, CD30 may be a marker of residual, transcriptionally active HIV-1 infected cells in the setting of suppressive ART. Given that CD30 is only expressed on a small number of total mononuclear cells, it is a potential therapeutic target of persistent HIV-1 infection.

The gastrointestinal (GI) tract harbors most of the body's immune cells and is also a major HIV reservoir in ART-treated patients. To achieve a cure, most HIV-infected cells must be identified and eliminated. While obtaining gut biopsies is a relatively noninvasive method of sampling relevant tissue for monitoring HIV activity, immune cell isolation from these limited tissue samples has proven to be challenging. Enzymatic tissue digestion is required for maximal immune cell isolation from gut biopsies. However, these enzymatic digestions can also be detrimental for preservation of cellular surface markers that are required for accurate identification of various subsets of leukocytes. In this study, we describe an optimized protocol for isolation of lymphocytes from human gut biopsies. We also discuss our validation results, which show that compared with several other collagenase preparations, the use of CSLPA maintains high lymphocyte recovery while preserving the integrity of most cellular surface antigens that we tested. Importantly, chemokine receptors that are used to characterize various subsets of T cells, which are notorious for being digested during a typical enzymatic tissue digestion, are highly preserved using this protocol.

We analyse the semantics of aspect-oriented extensions to functional languages by presenting compositional translations of these primitives into languages with traditional notions of state and control. As a first step, we examine an existing semantic description of aspects which allows the labelling of program points. We show that a restriction of these semantics to aspects which do not preempt the execution of code can be fully abstractly translated into a functional calculus with higher order references, but that removing this restriction requires a notion of exception handling to be added to the target language in order to yield a sound semantics. Next, we proceed to show that abandoning the labelling technique, and consequently relaxing the so-called ``obliviousness'' property of aspectual languages, allows preemptive aspects to be included in the general references model without the need for exceptions. This means that the game model of general references is inherited by the aspect calculus. The net result is a clean semantic description of aspect-orientation, which mirrors recently published techniques for their implementation, and thereby provides theoretical justification for these systems. The practical validity of our semantics is demonstrated by implementing extensions to the basic calculus in Standard ML, and showing how a number of useful aspect-oriented features can be expressed using general references alone. Our theoretical methodology closely follows the proof structure that often appears in the game semantics literature, and therefore provides an operational perspective on notions such as ``bad variables'' and factorisation theorems.

Actuation frequencies in thermally triggered Shape Memory Alloy (SMA) thin films are limited by the slow heat transport into/out of the films. Carbon Nanotubes (CNTs) are known to exhibit an exceptionally high thermal conductivity. Thus, we propose to thermally contact SMA films with CNTs to increase SMA actuation frequencies by enhanced heat transport through the CNTs. The basic requirement for this envisaged nanotube application is to obtain CNT forest growth on a SMA material while retaining a reversible martensitic transformation, as required for Shape Memory Effect exploitation. We show how such growth can be achieved on thin films of the SMA material NiTi. Future work is needed to measure thermal properties and obtainable cycling frequencies of CNT-SMA structures.