We report on the fabrication of crystalline lithium niobate microresonators with quality factors above 10, as measured around 770 nm wavelength. Our technique relies on femtosecond laser micromachining for patterning a mask coated on the lithium niobate on insulate (LNOI) into a microdisk, followed by a chemo-mechanical polishing process for transferring the disk-shaped pattern to the LNOI. Nonlinear processes including second-harmonic generation and Raman scattering have been demonstrated in the fabricated microdisk.

Transactional memory (TM) promises to simplify concurrent programming while providing scalability competitive to fine-grained locking. Language-based constructs allow programmers to denote atomic regions declaratively and to rely on the underlying system to provide transactional guarantees along with concurrency. In contrast with fine-grained locking, TM allows programmers to write simpler programs that are composable and deadlock-free.TM implementations operate by tracking loads and stores to memory and by detecting concurrent conflicting accesses by different transactions. By automating this process, they greatly reduce the programmer's burden, but they also are forced to be conservative. In certain cases, conflicting memory accesses may not actually violate the higher-level semantics of a program, and a programmer may wish to allow seemingly conflicting transactions to execute concurrently.Open nested transactions enable expert programmers to differentiate between physical conflicts, at the level of memory, and logical conflicts that actually violate application semantics. A TM system with open nesting can permit physical conflicts that are not logical conflicts, and thus increase concurrency among application threads.Here we present an implementation of open nested transactions in a Java-based software transactional memory (STM) system. We describe new language constructs to support open nesting in Java, and we discuss new abstract locking mechanisms that a programmer can use to prevent logical conflicts. We demonstrate how these constructs can be mapped efficiently to existing STM data structures. Finally, we evaluate our system on a set of Java applications and data structures, demonstrating how open nesting can enhance application scalability.

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TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with ASPSCR1-TFE3 fusion. Here, we describe the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.

No abstract

Purpose: Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC. Experimental Design: Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded. Results: We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade–based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months; P = 0.03). Conclusions: These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.

Electronic skin, a class of wearable electronic sensors that mimic the functionalities of human skin, has made remarkable success in applications including health monitoring, human-machine interaction and electronic-biological interfaces. While electronic skin continues to achieve higher sensitivity and faster response, its ultimate performance is fundamentally limited by the nature of low-frequency AC currents. Herein, highly sensitive skin-like wearable optical sensors are demonstrated by embedding glass micro/nanofibers (MNFs) in thin layers of polydimethylsiloxane (PDMS). Enabled by the transition from guided modes into radiation modes of the waveguiding MNFs upon external stimuli, the skin-like optical sensors show ultrahigh sensitivity (1870 kPa-1), low detection limit (7 mPa) and fast response (10 μs) for pressure sensing, significantly exceeding the performance metrics of state-of-the-art electronic skins. Electromagnetic interference (EMI)-free detection of high-frequency vibrations, wrist pulse and human voice are realized. Moreover, a five-sensor optical data glove and a 2×2-MNF tactile sensor are demonstrated. These initial results pave the way toward a new category of optical devices ranging from ultrasensitive wearable sensors to optical skins.

TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer that has no standard treatment for advanced disease. We described comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion, certain fusion isoforms and high somatic copy number alteration burdens were associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibited low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis revealed five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which showed association with fusion patterns and prognosis. Specifically, the high angiogenesis/stroma/proliferation cluster exclusively consisted of tumors with ASPSCR1-TFE3 fusion, which was likely to benefit from combination of immune checkpoint and anti-angiogenesis inhibitors. Our findings reveal the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.