Physical Electronics and Surface Physics

Contains report on one research project.Joint Services Electronics Program (Contract DA36-039-AMC-03200(E)

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Treatment of Alaska-produced food products by ionizing radiation may benefit the seafood and agricultural industries and the Alaskan consumer. A feasibility study to evaluate the potential social and economic benefits and risks as well as the costs of using the process in Alaska on Alaskan products is being coordinated by the Institute of Northern Engineering. A research and development project to determine effects on the quality o f Alaskan products could be the next phase in the introduction o f a new food-preservation technique to Alaska

Designing for emergence and innovation: Redesigning design

We reveal the surprising and counterintuitive truth that the design process, in and of itself, is not always on the forefront of innovation. Design is a necessary but not a sufficient condition for the success of new products and services. We intuitively sense a connection between innovative design and emergence. The nature of design, emergence and innovation to understand their interrelationships and interdependencies is examined. We propose that design must harness the process of emergence; for it is only through the bottom-up and massively iterative unfolding of emergence that new and improved products and services are successfully refined, introduced and diffused into the marketplace. The relationships among design, emergence and innovation are developed. What designers can learn from nature about emergence and evolution that will impact the design process is explored. We examine the roles that design and emergence play in innovation. How innovative organizations can incorporate emergence into their design process is explored. We demarcate the boundary between invention and innovation. We also articulate the similarities and differences of design and emergence. We then develop the following three hypotheses: Hypothesis 1: “An innovative design is an emergent design.” Hypothesis 2: “A homeostatic relationship between design and emergence is a required condition for innovation.”Hypothesis 3: “Since design is a cultural activity and culture is an emergent phenomenon, it follows that design leading to innovation is also an emergent phenomenon” We provide a number of examples of how design and emergence have worked together and led to innovation. Examples include the tool making of early man; the evolutionary chain of the six languages speech, writing, math, science, computing and the Internet; the Gutenberg printing press and techniques of collaborative filtering associated with the Internet. We close by describing the relationship between human and naturally “designed” systems and the notion a key element of a design is its purpose as is the case with a living organism

Brønsted basicity of the air–water interface

Differences in the extent of protonation of functional groups lying on either side of water–hydrophobe interfaces are deemed essential to enzymatic catalysis, molecular recognition, bioenergetic transduction, and atmospheric aerosol–gas exchanges. The sign and range of such differences, however, remain conjectural. Herein we report experiments showing that gaseous carboxylic acids RCOOH(g) begin to deprotonate on the surface of water significantly more acidic than that supporting the dissociation of dissolved acids RCOOH(aq). Thermodynamic analysis indicates that > 6 H_(2)O molecules must participate in the deprotonation of RCOOH(g) on water, but quantum mechanical calculations on a model air–water interface predict that such event is hindered by a significant kinetic barrier unless OH− ions are present therein. Thus, by detecting RCOO− we demonstrate the presence of OH− on the aerial side of on pH > 2 water exposed to RCOOH(g). Furthermore, because in similar experiments the base (Me)_(3)N(g) is protonated only on pH 1 nm) deeper shear planes probed in electrophoresis, thereby implying the existence of OH− gradients in the interfacial region. This fact could account for the weak OH− signals detected by surface-specific spectroscopies

Deletion of the protein tyrosine phosphatase PTPN22 for adoptive T cell therapy facilitates CTL effector function but promotes T cell exhaustion

Background Adoptive cell therapy (ACT) is a promising strategy for treating cancer, yet it faces several challenges such as lack of long term protection due to T cell exhaustion induced by chronic TCR stimulation in the tumor microenvironment. One benefit of ACT, however, is that it allows for cellular manipulations, such as deletion of the phosphotyrosine phosphatase non-receptor type 22 (PTPN22), which improves CD8+ T cell anti-tumor efficacy in ACT. We tested whether Ptpn22KO cytolytic T cells (CTL) were also more effective than Ptpn22WT CTL in controlling tumors in scenarios that favor T cell exhaustion. Methods Tumor control by Ptpn22WT and Ptpn22KO CTL was assessed following adoptive transfer of low numbers of CTL to mice with subcutaneously implanted MC38 tumors. Tumor infiltrating lymphocytes were isolated for analysis of effector functions. An in vitro assay was established to compare CTL function in response to acute and chronic re-stimulation with antigen-pulsed tumor cells. The expression of effector and exhaustion-associated proteins by Ptpn22WT and Ptpn22KO T cells was followed over time in vitro and in vivo using the ID8 tumor model. Finally, the effect of PD-1 and TIM-3 blockade on Ptpn22KO CTL tumor control was assessed using monoclonal antibodies and CRISPR/Cas9-mediated knockout. Results Despite having improved effector function at the time of transfer, Ptpn22KO CTL became more exhausted than Ptpn22WT CTL, characterized by more rapid loss of effector functions, and earlier and higher expression of inhibitory receptors (IRs), particularly the terminal exhaustion marker TIM-3. TIM-3 expression, under the control of the transcription factor NFIL3, was induced by IL-2 signaling which was enhanced in Ptpn22KO cells. Anti-tumor responses of Ptpn22KO CTL were improved following PD-1 blockade in vivo, yet knockout or antibody-mediated blockade of TIM-3 did not improve but further impaired tumor control, indicating TIM-3 signaling itself did not drive the diminished function seen in Ptpn22KO CTL. Conclusions This study questions whether TIM-3 plays a role as an IR and highlights that genetic manipulation of T cells for ACT needs to balance short term augmented effector function against the risk of T cell exhaustion in order to achieve longer term protection. What is already known on this topic • T cell exhaustion in the tumor microenvironment is a major factor limiting the potential success of adoptive cell therapy (ACT) in the treatment of solid tumors. • Deletion of the phosphatase PTPN22 in CD8+ T cells improves their response to tumors, but it is not known whether this influences development of exhaustion. What this study adds • Under conditions which promote exhaustion, CTL lacking PTPN22 exhaust more rapidly than WT cells, despite displaying enhanced effector function in their initial response to antigen. • Ptpn22KO CTL express high levels of the inhibitory receptor TIM-3, but TIM-3 signaling does not directly contribute to Ptpn22KO CTL dysfunction. • Ptpn22KO T cells are more responsive to IL-2 through JAK-STAT signaling, which induces TIM-3 expression via the transcription factor NFIL3. How this study might affect research, practice or policy • Strategies aimed at augmenting T cell effector function for ACT should balance improved responses against an increased risk of T cell exhaustion

Physical Electronics and Surface Physics

Contains research objectives and reports on four research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 36-039-AMC-03200(E)National Aeronautics and Space Administration (Grant NGR-22-099-091)National Aeronautics and Space Administration (Grant NsG-496