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Abstract Quantum emitters in transition metal dichalcogenides (TMDs) have recently emerged as a promising platform for generating single photons for optical quantum information processing. In this work, we present an approach for deterministically controlling the polarization of fabricated quantum emitters in a tungsten diselenide (WSe2) monolayer. We employ novel nanopillar geometries with long and sharp tips to induce a controlled directional strain in the monolayer, and we report on fabricated WSe2 emitters producing single photons with a high degree of polarization (99 ± 4%) and high purity (g (2)(0) = 0.030 ± 0.025). Our work paves the way for the deterministic integration of TMD-based quantum emitters for future photonic quantum technologies.

Abstract No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

Single-photon emitters play a crucial role in integrated photonic quantum systems across various material platforms. In this study, we present a cavity-enhanced quantum dot single-photon source in a high-index contrast material platform (GaAs-on-insulator). A quantum dot is embedded in a microring resonator with a quality factor of approximately 9000, where the cavity-induced light enhancement results in a spontaneous emission acceleration factor of around 2.6, and we achieve a $g^{(2)}(0)$ as low as 0.03 ± 0.02 and post-selected two-photon interference visibility of 51.7 $\%\pm3.2\%$ for the single-photon source. This demonstration shows the potential of the GaAs-on-Insulator platform for scalable on-chip quantum information processing.

High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up to 4 cycles, thereafter every 4 weeks for a maximum of 2 cycles. The primary endpoint was the immunological efficacy of the combined RT/HD IL-2 treatment (assessed by IFN-γ ELISPOT). Nineteen out of 22 patients were evaluable for immunological and clinical response. Partial response occurred in 3 (15.7%) patients and stable disease was observed in 7 (36.8%). The disease control rate was 52.6% after a median follow up of 39.2 months. According to Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), the majority of toxicities were grade 1-2. Immunological responses were frequent and detected in 16 (84.2%) patients. Increased levels of IL-8 and IL-10 in melanoma, circulating effector memory CD4+ and intratumoral CD8+ T cells in both tumor types were detected after therapy. Overall the treatment was well tolerated and immunologically active. Immunomonitoring and correlative data on tumor and peripheral blood cell subsets suggest that this combination treatment could be a promising strategy for patients progressing after standard treatments.

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute. The DC-based vaccine is prepared via CD14+ monocyte differentiation. A fresh dose of 10 million DCs is administered to the patient, while the remaining DCs are aliquoted, frozen, and stored in nitrogen vapor for subsequent treatment doses. To evaluate the maintenance of quality parameters and to establish a shelf life of frozen vaccine aliquots, a stability program was developed. Several parameters of the DC final product at 0, 6, 12, 18, and 24 months were evaluated. Our results reveal that after 24 months of storage in nitrogen vapor, the cell viability is in a range between 82% and 99%, the expression of maturation markers remains inside the criteria for batch release, the sterility tests are compliant, and the cell costimulatory capacity unchanged. Thus, the data collected demonstrate that freezing and thawing do not perturb the DC vaccine product maintaining over time its functional and quality characteristics.

There has been a growing awareness about the need to pay attention to the role of different semiotic modes, other than language, in the discursive construction of knowledge in the science classroom. Our research was conducted through extended videorecorded observations of secondary school Biology lessons and aimed at contributing to the current debate by analysing the multimodal character of discursive interactions in science classrooms with respect to two main aspects: (i) the context of use of different semiotic modes with respect to classroom activity in the context of four lessons (macroanalyses) and; (ii) the relationships between different semiotic modes through the analysis of one selected episode (microanalyses). Our results reveal that actions, gesture and verbal language were used in specific contexts, valued and legitimised by participants in the discursive interactions. The analysis also shows the teacher's ability in the rhetorical orchestration of the process through which students construct explanations.

Resumo: Questionar a centralidade atribuída à linguagem como recurso para a construção de significações nas salas de aula de Ciências é algo que se faz necessário e urgente no atual contexto de reconhecimento do caráter híbrido semiótico do texto científico e das mudanças nas possibilidades comunicativas da sociedade globalizada e que acabam por ter impacto na educação. Com este trabalho pretendemos contribuir para o corrente debate através da documentação, classificação e análise das interações discursivas em eventos de comunicação multimodal em uma sala de aula de Ciências, com respeito a dois aspectos principais: (i) o contexto de utilização dos diferentes modos semióticos relacionados com as atividades desenvolvidas em uma lição; (ii) as relações estabelecidas entre diferentes modos semióticos através da análise de um episódio selecionado. Nossos resultados mostram que ações, gestos e linguagem verbal modos foram mobilizados em contextos específicos, valorizados pelos interlocutores e tornados legítimos para efeito da comunicação pretendida naquela situação social. Os resultados destacam ainda a sensibilidade da professora na orquestração retórica do processo de construção de explicações coletivas pelos estudantes.