Ultrathin transition metal dichalcogenides (TMDCs) of Mo and W show great potential for digital electronics and optoelectronic applications. Whereas early studies were limited to mechanically ...exfoliated flakes, the large-area synthesis of 2D TMDCs has now been realized by chemical vapor deposition (CVD) based on a sulfurization reaction. The optoelectronic properties of CVD grown monolayer MoS2 have been intensively investigated, but the influence of stoichiometry on the electrical and optical properties has been largely overlooked. Here we systematically vary the stoichiometry of monolayer MoS2 during CVD via controlled sulfurization and investigate the associated changes in photoluminescence and electrical properties. X-ray photoelectron spectroscopy is employed to measure relative variations in stoichiometry and the persistence of MoO x species. As MoS2−δ is reduced (increasing δ), the field-effect mobility of monolayer transistors increases while the photoluminescence yield becomes nonuniform. Devices fabricated from monolayers with the lowest sulfur content have negligible hysteresis and a threshold voltage of ∼0 V. We conclude that the electrical and optical properties of monolayer MoS2 crystals can be tuned via stoichiometry engineering to meet the requirements of various applications.
Antibody-based therapeutics have experienced a rapid growth in recent years and are now utilized in various modalities spanning from conventional antibodies, antibody-drug conjugates, bispecific ...antibodies to chimeric antigen receptor (CAR) T cells. Many next generation antibody therapeutics achieve enhanced potency but often increase the risk of adverse events. Antibody scaffolds capable of exhibiting inducible affinities could reduce the risk of adverse events by enabling a transient suspension of antibody activity. To demonstrate this, we develop conditionally activated, single-module CARs, in which tumor antigen recognition is directly modulated by an FDA-approved small molecule drug. The resulting CAR T cells demonstrate specific cytotoxicity of tumor cells comparable to that of traditional CARs, but the cytotoxicity is reversibly attenuated by the addition of the small molecule. The exogenous control of conditional CAR T cell activity allows continual modulation of therapeutic activity to improve the safety profile of CAR T cells across all disease indications.
This paper proposes the use of notebooks for the design documentation and tool interaction in the rigorous design of embedded systems. Conventionally, a notebook is a sequence of cells alternating ...between (textual) code and prose to form a document that is meant to be read from top to bottom, in the spirit of literate programming. We extend the use of notebooks to embedded systems specified by pCharts. The charts are visually edited in cells inline. Other cells can contain statements that generate code and analyze the charts qualitatively and quantitatively; in addition, notebook cells can contain other instructions to build the product from the generated code. This allows a notebook to be replayed to re-analyze the design and re-build the product, like a script, but also allows the notebook to be used for presentations, as for this paper, and for the inspection of the design. The interaction with the notebook is done through a web browser that connects to a local or remote server, thus allowing a computationally intensive analysis to run remotely if needed. The pState notebooks are implemented as an extension to Jupyter. The underlying software architecture is described and the issue of proper placement of transition labels in charts embedded in notebooks is discussed.
Inner Ear is a browser-based aural training software designed to improve and better understand the process and means through which students acquire sound-focused aural skills. Its ongoing development ...follows educational principles established through years of research with undergraduate
music students who major in electroacoustic studies, beginning in 2005. It provides users with ongoing detailed feedback about their performance, areas that need additional work, and an accessible notepad for students to record their insights during practice. It collects data on users'
performance and settings that can later be analysed and shared with their instructor. The design of Inner Ear follows insights that emerged in students' feedback, provided mostly in home practice reports. Primary among these insights are the needs for individualizable practice
environments, diversified exercises, speedy and informative feedback and progress evaluation methods.
Abstract The lattice of noncrossing partitions is well-known for its wide variety of combinatorial appearances and properties. For example, the lattice is rank-symmetric and enumerated by the Catalan ...numbers. In this article, we introduce a large family of new noncrossing partition lattices with both of these properties, each parametrized by a configuration of n points in the plane.
Adoptive transfer of high-affinity chimeric antigen receptor (CAR) T cells targeting hematological cancers has yielded impressive clinical results. However, safety concerns regarding target ...expression on healthy tissue and poor efficacy have hampered application to solid tumors. Here, a panel of affinity-variant CARs were constructed targeting overexpressed ICAM-1, a broad tumor biomarker, using its physiological ligand, LFA-1. Anti-tumor T cell potency in vitro was directly proportional to CAR affinity and ICAM-1 density. In a solid tumor mouse model allowing simultaneous monitoring of anti-tumor potency and systemic off-tumor toxicity, micromolar affinity CAR T cells demonstrated superior anti-tumor efficacy and safety compared to their nanomolar counterparts. Longitudinal T cell tracking by PET/CT and concurrent cytokine measurement revealed superior expansion and contraction kinetics of micromolar affinity CAR T cells. Therefore, we developed an ICAM-1 specific CAR with broad anti-tumor applicability that utilized a reduced affinity targeting strategy to significantly boost efficacy and safety.
The lattice of noncrossing partitions is well-known for its wide variety of combinatorial appearances and properties. For example, the lattice is rank-symmetric and enumerated by the Catalan numbers. ...In this article, we introduce a large family of new noncrossing partition lattices with both of these properties, each parametrized by a configuration of n points in the plane.
Poorly differentiated thyroid cancer and anaplastic thyroid cancer (ATC) are rare yet lethal malignancies with limited treatment options. Many malignant tumors, including papillary thyroid cancer ...(PTC) and ATC, are associated with increased expression of ICAM-1, providing a rationale for utilizing ICAM-1-targeting agents for the treatment of aggressive cancer. We developed a third-generation chimeric antigen receptor (CAR) targeting ICAM-1 to leverage adoptive T-cell therapy as a new treatment modality.
ICAM-1 CAR T cells were applied to multiple malignant and nonmalignant target cells to investigate specific target cell death and "off-tumor" toxicity
therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models established from a cell line and patient-derived tumors that rapidly develop systemic metastases.
ICAM-1 CAR T cells demonstrated robust and specific killing of PTC and ATC cell lines
Interestingly, although certain ATC cell lines showed heterogeneous levels of ICAM-1 expression, addition of cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell lines became targetable. In mice with systemic ATC, a single administration of ICAM-1 CAR T cells mediated profound tumor killing that resulted in long-term remission and significantly improved survival. Patient-derived ATC cells overexpressed ICAM-1 and were largely eliminated by autologous ICAM-1 CAR T cells
and in animal models.
Our findings are the first demonstration of CAR T therapy against both a metastatic, thyroid cancer cell line and advanced ATC patient-derived tumors that exhibit dramatic therapeutic efficacy and survival benefit in animal studies.
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Alzheimer’s Disease is a very pressing disease that presents neurodegeneration of those affected, with no foreseeable cure as of yet. While there are many treatments that may reduce the level of ...neurodegeneration, or treat some of the root causes, a definitive solution to Alzheimer’s Disease does not exist. Therefore, its harmful effects must be minimized to the greatest extent possible. As such, this paper reviews the current status quo on Alzheimer’s Disease treatment, including possible lifestyle choices that have caused Alzheimer’s Disease or could potentially contribute to reducing neurodegeneration. In addition, it also considers meditation as an adjuvant treatment to primary treatments to combat Alzheimer's Disease through cognitive stimulation. By reviewing the current scientific literature of meditation where it stands, the aim is to establish meditation as a clear addition to boost the efficiency of prior Alzheimer’s Disease treatments including but not limited to pharmacotherapy, behavioral therapy, and cognitive therapy.
Single-element and periodic arrays of plasmonic nanoantennas have been used to enhance light–matter interactions in 2D materials to improve their suitability for optoelectronic devices. However, ...single nanoantennas with discrete resonances do not readily enable separation of enhancements in excitation and emission, each of which influences total Raman and photoluminescence (PL) enhancement. Here we use a single Au tapered plasmonic nanoantenna with optical resonances that extend above and below the band gap to observe a broad enhancement in PL of MoS2. The largest peak enhancement of ∼3.2 is observed at an antenna position between the position of maximum excitation-field enhancement and the position of maximum Purcell factor, indicating a contribution of both excitation and emission rate enhancements. In contrast, the peak Raman enhancement occurs at the position of the excitation-field maximum because it is only dependent on the enhancement of the electric field. This independent determination of excitation and emission rate enhancements via spatial separation provides a more comprehensive picture of light–matter interactions in MoS2 monolayers interfaced with plasmonic materials.
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