gebhart/patrepeval huggingface dataset:
Abstract 607: CD8+ T cell clones maintain a pool of memory-like Ly108+ cells in the tumor during their contraction phase (2023)

Abstract The immune response against cancer is effectuated by the recruitment of expanding CD8+ T cell clones. However, the fate of these clonal populations that have migrated into the tumor environment - whether they persist, contract, and/or produce memory cells - is unknown. An improved understanding of clonal durability and potency will be essential for the development of novel cancer immunotherapies. Here, we applied our previously developed bilateral tumor mouse model to track the fate of endogenous T cell clones responding to tumors in the same individual. This approach relied on the fact that the clonal composition of the two tumors is identical, allowing the sampling and comparison of tumor-infiltrating cells from the same clonal populations on different days in the same individual. Mice were inoculated bilaterally with Lewis lung carcinoma (LLC), and tumors were resected, one after the other, on days 14 and 21 post-inoculation. At each timepoint, sampled CD8+ T cells were gated on PD1, Ly108, and TIM-3 expression and subjected to T-cell receptor (TCR) sequencing to identify clones. We utilized this data to quantify changes in the fraction of memory-like (Ly108+TIM-3-) and exhausted (Ly108-TIM-3+, Ly108+TIM-3+) cells of individual clonal populations over time. The majority (75%) of tumor-infiltrating CD8+ T cells on day 14 belonged to clonal populations that persisted on day 21. These clonal populations were classed as ‘expanding’ or ‘contracting’ based on changes in their clone size. Despite the polyclonal response to the tumor, almost all expanding clones contained a high fraction of memory-like (Ly108+TIM-3-) cells, whereas almost all ‘contracting’ clones contained a high fraction of exhausted (TIM-3+) cells. These characteristics were sufficient to predict whether a clonal population at day 14 would later expand or contract. We further quantified how the makeup of ‘contracting’ clonal populations changed over time. While all ‘contracting’ clonal populations lost a considerable number of exhausted (TIM3+) cells, half of the clonal populations maintained a pool of memory-like (Ly108+TIM-3-) cells in the tumor. These results demonstrate that clonal dynamics can be predicted from static measurements, facilitating the development of novel methods to infer patient immune activity. The results also demonstrate the possibility of altering clonal fate. Reinvigoration of the pool of memory-like cells maintained in the tumor could re-expand contracting clonal populations, and thereby enhance the immune response against the tumor. Citation Format: Munetomo Takahashi, Mikiya Tsunoda, Hiroyasu Aoki, Haru Ogiwara, Shigeyuki Shichino, Kouji Matsushima, Satoshi Ueha. CD8+ T cell clones maintain a pool of memory-like Ly108+ cells in the tumor during their contraction phase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 607.
Intelligent sort‐timing prediction for image‐activated cell sorting (2022)

Intelligent image-activated cell sorting (iIACS) has enabled high-throughput image-based sorting of single cells with artificial intelligence (AI) algorithms. This AI-on-a-chip technology combines fluorescence microscopy, AI-based image processing, sort-timing prediction, and cell sorting. Sort-timing prediction is particularly essential due to the latency on the order of milliseconds between image acquisition and sort actuation, during which image processing is performed. The long latency amplifies the effects of the fluctuations in the flow speed of cells, leading to fluctuation and uncertainty in the arrival time of cells at the sort point on the microfluidic chip. To compensate for this fluctuation, iIACS measures the flow speed of each cell upstream, predicts the arrival timing of the cell at the sort point, and activates the actuation of the cell sorter appropriately. Here, we propose and demonstrate a machine learning technique to increase the accuracy of the sort-timing prediction that would allow for the improvement of sort event rate, yield, and purity. Specifically, we trained an algorithm to predict the sort timing for morphologically heterogeneous budding yeast cells. The algorithm we developed used cell morphology, position, and flow speed as inputs for prediction and achieved 41.5% lower prediction error compared to the previously employed method based solely on flow speed. As a result, our technique would allow for an increase in the sort event rate of iIACS by a factor of ~2.
All-Dielectric Infrared Metamaterials (2011)

We describe the design, fabrication, and characterization of an all-dielectric metamaterial operating in the thermal infrared. The dielectric metamaterials is based on cubic dielectric resonators fabricated from Tellurium and arrayed on a Barium Fluoride substrate. As predicted by analytical and numerical simulation, the metamaterial exhibits a magnetic resonance near 10 μm wavelength, as well as an electric resonance at a slightly shorter wavelength. The retrieved effective parameters indicate a negative permeability (permittivity) in the vicinity of the magnetic (electric) resonance. This work represents a first step toward the development of low loss infrared metamaterials suitable for device applications.
Nitric Oxide Induces Thymocyte Apoptosis Via a Caspase-1-Dependent Mechanism (2000)

We previously showed that NO induces apoptosis in thymocytes via a p53-dependent pathway. In the present study, we investigated the role of caspases in this process. The pan-caspase inhibitor, ZVAD-fmk, and the caspase-1 inhibitor, Ac-YVAD-cho, both inhibited NO-induced thymocyte apoptosis in a dose-dependent manner, whereas the caspase-3 inhibitor, Ac-DEVD-cho, had little effect even at concentrations up to 500 microM. ZVAD-fmk and Ac-YVAD-cho were able to inhibit apoptosis when added up to 12 h, but not 16 h, after treatment with the NO donor S-nitroso-N-acetyl penicillamine (SNAP). Caspase-1 activity was up-regulated at 4 h and 8 h and returned to baseline by 24 h; caspase-3 activity was not detected. Cytosolic fractions from SNAP-treated thymocytes cleaved the inhibitor of caspase-activated deoxyribonuclease. Such cleavage was completely blocked by Ac-YVAD-cho, but not by Ac-DEVD-cho or DEVD-fmk. Poly(ADP-ribose) polymerase (PARP) was also cleaved in thymocytes 8 h and 12 h after SNAP treatment; addition of Ac-YVAD-cho to the cultures blocked PARP cleavage. Furthermore, SNAP induced apoptosis in 44% of thymocytes from wild-type mice; thymocytes from caspase-1 knockout mice were more resistant to NO-induced apoptosis. These data suggest that NO induces apoptosis in thymocytes via a caspase-1-dependent but not caspase-3-dependent pathway. Caspase-1 alone can cleave inhibitor of caspase-activated deoxyribonuclease and lead to DNA fragmentation, thus providing a novel pathway for NO-induced thymocyte apoptosis.
Trapezoidal block split using orthogonal C2 transforms for HEVC video coding (2017)

We present an extension for HEVC intra-frame coding with trapezoidal splits and orthogonal transforms. A block can be split into two 180-degrees rotationally-symmetric (C2) trapezoidal parts, each coded separately using standard DCT implementation. We also introduce part-to-part prediction from a diagonal edge. The optimal trapezoidal split of a quad tree block is selected in a rate-distortion sense. We achieved 0.8% reduction in BD-rate over HEVC in standard test conditions for intra coding.
Direct gap Ge1-ySny alloys: Fabrication and design of mid-IR photodiodes (2016)

Chemical vapor deposition methods were developed, using stoichiometric reactions of specialty Ge3H8 and SnD4 hydrides, to fabricate Ge1-ySny photodiodes with very high Sn concentrations in the 12%–16% range. A unique aspect of this approach is the compatible reactivity of the compounds at ultra-low temperatures, allowing efficient control and systematic tuning of the alloy composition beyond the direct gap threshold. This crucial property allows the formation of thick supersaturated layers with device-quality material properties. Diodes with composition up to 14% Sn were initially produced on Ge-buffered Si(100) featuring previously optimized n-Ge/i-Ge1-ySny/p-Ge1-zSnz type structures with a single defected interface. The devices exhibited sizable electroluminescence and good rectifying behavior as evidenced by the low dark currents in the I-V measurements. The formation of working diodes with higher Sn content up to 16% Sn was implemented by using more advanced n-Ge1-xSnx/i-Ge1-ySny/p-Ge1-zSnz architectures incorporating Ge1-xSnx intermediate layers (x ∼ 12% Sn) that served to mitigate the lattice mismatch with the Ge platform. This yielded fully coherent diode interfaces devoid of strain relaxation defects. The electrical measurements in this case revealed a sharp increase in reverse-bias dark currents by almost two orders of magnitude, in spite of the comparable crystallinity of the active layers. This observation is attributed to the enhancement of band-to-band tunneling when all the diode layers consist of direct gap materials and thus has implications for the design of light emitting diodes and lasers operating at desirable mid-IR wavelengths. Possible ways to engineer these diode characteristics and improve carrier confinement involve the incorporation of new barrier materials, in particular, ternary Ge1-x-ySixSny alloys. The possibility of achieving type-I structures using binary and ternary alloy combinations is discussed in detail, taking into account the latest experimental and theoretical work on band offsets involving such materials.
Development of a Practical Synthesis of Toll-like Receptor Agonist PF-4171455: 4-Amino-1-benzyl-6-trifluoromethyl-1,3-dihydroimidazo [4,5-c] pyridin-2-one (2011)

The development and implementation of a scalable process for the manufacture of the Toll-like receptor (TLR7) agonist PF-4171455 (1) is described. Initial routes used to synthesise 1 in milligram quantities were unsuitable for large-scale synthesis to provide bulk material. As part of the transfer between Medicinal Chemistry and Research-API, collaboration provided a fit for purpose route for the kilo-scale synthesis of 1. Key aspects of the synthesis included (i) a safe and practical synthesis of a key nitropyridone intermediate 7 over four steps, (ii) a sequential regioselective chlorination to selectively functionalise 7 and (iii) use of a carbamate as a tethered carbonyl group, allowing an efficient regiospecific synthesis of 1.
Tunable slow light in semiconductor optical amplifier without external pump laser (2008)

This investigation experimentally demonstrates tunable slow light in a semiconductor optical amplifier (SOA) without an external pump laser. Tunable time delays are achieved by adjusting the feedback signal from the SOA.
Photoemission study of the band bending and chemistry of sodium sulfide on GaAs (100) (1989)

Recently, there has been a great deal of interest in Na2S⋅9H2O as a passivating chemical treatment for GaAs surfaces. It has been shown that it reduces the high surface recombination velocity characteristic of GaAs surfaces, and may offer hope for ‘‘unpinning’’ the surface Fermi level. We have used photoemission spectroscopy to study the band bending and chemistry of these overlayers on n-type GaAs (100). Identically prepared samples show the characteristic increase in the photoluminescence signal, and have also been characterized using surface conductivity measurements. We find using photoemission that the surface Fermi level of the treated wafer is still near midgap. We also observe the chemistry at the interface, and offer a possible explanation of the photoluminescence and surface conductivity data in terms of it and the advanced unified defect model.
Selective Targeting of Ras Mutant Cancers via a New Small Molecule (2020)

ABSTRACT Mutations in the Ras family of oncogenes are implicated in 33% of human cancers, making Ras an intensely pursued target in drug discovery. As an alternative to direct pharmacological inhibition of Ras, we looked for sensitivities in RAS mutant cells. Using a small molecule screen in cell lines with mutations in Ras and its effector Raf, we discovered 249C as a Ras-mutant selective cytotoxic agent against a spectrum of RAS-mutant cancers. By combining CRISPR chemical-genetic screening, comparative profiling and chemoproteomics, we identified that 249C binds to a unique subunit on vacuolar (V)-ATPase with nanomolar affinity, inhibiting its biochemical activity and, unexpectedly, altering V-ATPase translocation in Ras-induced macropinocytosis. Via binding to V-ATPase, 249C prevents lysosomal acidification and inhibits autophagy and macropinocytosis pathways that several Ras-driven cancers rely on for survival. In characterizing 249C’s mechanism, we show that potency varies with the identity of the RAS driver mutation highlighting a mutant-specific dependence on autophagy and macropinocytosis. Indeed, 249C potently inhibits tumor growth without adverse side effects in a mouse xenograft model of KRAS -driven non-small cell lung cancer. These data establish proof-of-concept for targeting V-ATPase as a way to indirectly target specific Ras mutants, and provide a fundamental link between V-ATPase localization and specific Ras mutant tumor-related activity.
Investigations on the Impact of the Parasitic Bottom Transistor in Gate-All-Around Silicon Nanowire SONOS Memory Cells Fabricated on Bulk Si Substrate (2009)

Gate-all-around (GAA) Si nanowire SONOS memory cells (SNWMs) have been fabricated on Si substrate using fully epi-free compatible CMOS technology. A parasitic bottom SONOS memory (PBM) was formed when the SNWM was fabricated on bulk Si substrate. The impact of the PBM on the performance of the SNWM is investigated in this paper. The PBM shows a slower program speed, a faster erase speed, and worse retention characteristics than the SNWM. Therefore, the PBM severely degrades the performance of the SNWM due to its slower program speed and worse retention characteristics, and should be carefully controlled for the SNWM based on bulk Si substrate.
Electron-beam lithography of nanostructures at the tips of scanning probe cantilevers (2022)

We developed a process to fabricate nanoscale metallic gate electrodes on scanning probe cantilevers, including on the irregular surface of protruding cantilever tips. The process includes a floating-layer technique to coat the cantilevers in electron-beam resist. We demonstrate gate definition through a lift-off process, as well as through an etching process. The cantilevers maintain a high force sensitivity after undergoing the patterning process. Our method allows the patterning of nanoscale devices on fragile scanning probes, extending their functionality as sensors.
Effect of Covalent Modification of Graphene Nanosheets on the Electrical Property and Electromagnetic Interference Shielding Performance of a Water-Borne Polyurethane Composite (2015)

Flexible and lightweight graphene nanosheet (GN)/waterborne polyurethane (WPU) composites which exhibit high electrical conductivity and electromagnetic shielding performance were prepared. Covalently modifying GNs with aminoethyl methacrylate (AEMA; AEMA-GNs) through free radical polymerization effectively inhibited the restacking and aggregation of the GNs because of the -NH3(+) functional groups grafted on the AEMA-GNs. Moreover, the AEMA-GNs exhibited high compatibility with a WPU matrix with grafted sulfonated functional groups because of the electrostatic attraction, which caused the AEMA-GNs to homogeneously disperse in the WPU matrix. This homogeneous distribution enabled the GNs to form electrically conductive networks. Furthermore, AEMA-GNs with different amounts of AEMA segments were introduced into the WPU matrix, and the effects of the surface chemistry of the GNs on the electrical conductivity and EMI shielding performance of composites were investigated. AEMA-GN/WPU composites with a GN loading of 5 vol % exhibited remarkable electrical conductivity (approximately 43.64 S/m) and EMI shielding effectiveness (38 dB) over the frequency of 8.2 to 12.4 GHz.
Decentralized search in expert networks: Generic models and performance bounds (2016)

We investigate the problem of query answering in expert networks, which are composed of inter-connected experts with various specialties. Upon receiving a query, the expert network is tasked to route this query to experts with sufficient expertise in a timely and reliable manner. However, the efficiency of query answering depends on the underlying query routing protocol being used. Among all possible query routing protocols, decentralized search, operating purely on each expert's local information without any network global knowledge, represents the most basic and scalable routing protocol. However, there is still a lack of fundamental understanding on the efficiency of decentralized search in different expert networks. In this regard, we establish a generic model that can abstract diversified social and structural attributes in various expert networks into a common framework, thus applicable to a wide range of network scenarios. On top of such generic network model, we then study decentralized search by quantifying its performance under a variety of network parameters. Our key findings reveal the existence of network conditions, under which decentralized search can achieve significantly short query routing paths (i.e., between O(log n) and O(log <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> n) hops, n: total number of experts in the network). To the best of our knowledge, this is the first work studying fundamental behaviors of decentralized search without relying on strict underlying network structures in expert networks. Experiments in both synthetic and real expert networks confirm the efficacy of the developed performance bounds in understanding and reasoning the network performance.
Toward an ontology of rhetorical figures (2010)

Our paper describes the Rhetorical Figure Ontology Project, a multidisciplinary research project that is presently working towards the development of a comprehensive database of rhetorical figures, an associated wiki, and, ultimately, an ontology of rhetorical figures. The database and wiki project provide the dataset and space for the conceptual development, respectively, to create an ontology. We define an ontology as a formalized taxonomy or system of classification of concepts and associated descriptions of said concepts. Here we provide an overview of the present state of the project and a discussion of the development of ontological descriptions of rhetorical figures. This work is a joint venture between Dr. Randy Allen Harris (English) and Dr. Chrysanne DiMarco (Computer Science, and English) at the University of Waterloo, Canada.
An LCMV filter for single-channel noise cancellation and reduction in the time domain (2013)

In this paper, we consider a recent class of optimal rectangular filtering matrices for single-channel speech enhancement. This class of filters exploits the fact that the dimension of the signal subspace is lower than that of the full space. Then, extra degrees of freedom in the filters, that are otherwise reserved for preserving the signal subspace, can be used for achieving an improved output signal-to-noise ratio (SNR). Interestingly, these filters unify the ideas of optimal filtering and subspace methods. We propose an optimal LCMV filter in this framework with minimum output power that passes the desired signal undistorted and cancels correlated noise. The cancellation was not facilitated by the filters derived so far in this framework. The results show that the proposed filter can achieve output SNRs similar to that of competing filter designs, while having a much higher output signal-to-interference ratio. This is showed for both synthetic and real speech signals.
Lumbar Bone Mineral Density Phantomless Computed Tomography Measurements and Correlation with Age and Fracture Incidence (2015)

Because lumbar vBMD was estimated from phantomless CT scans with accuracy similar to qCT, the phantomless technique can be broadly applied to both prospectively and retrospectively assess patient bone quality for research and clinical studies related to MVCs, falls, and aging.
Optical triggering of 12 kV, 100 A 4H-SiC thyristors (2011)

Optical switch-on of a high-voltage (12 kV class) 4H-SiC thyristor to a current I = 100 A is reported. The importance of the dI/dt ramp and the turn-on spread for obtaining the maximum switched-on current Imax is discussed. It is demonstrated that Imax can be substantially raised by using a mixed resistive–inductive load.
G-quadruplex ligands targeting telomeres do not inhibit HIV promoter activity and cooperate with latency reversing agents in killing latently infected cells (2020)

Altered telomere maintenance mechanism (TMM) is linked to increased DNA damage at telomeres and telomere uncapping. We previously showed that HIV-1 latent cells have altered TMM and are susceptible to ligands that target G-quadruplexes (G4) at telomeres. Susceptibility of latent cells to telomere targeting could potentially be used to support approaches to eradicate HIV reservoirs. However, G4 ligands also target G-quadruplexes in promoters blocking gene transcription. Since HIV promoter sequence can form G-quadruplexes, we investigated whether G4 ligands interfere with HIV-1 promoter activity and virus reactivation from latency, and whether telomere targeting could be combined with latency reversing agents (LRAs) to promote elimination of HIV reservoirs. Our results indicate that Sp1 binding region in HIV-1 promoter can adopt G4 structures in duplex DNA, and that <i>in vitro</i> binding of Sp1 to G-quadruplex is blocked by G4 ligand, suggesting that agents targeting telomeres interfere with virus reactivation. However, our studies show that G4 agents do not affect HIV-1 promoter activity in cell culture, and do not interfere with latency reversal. Importantly, primary memory CD4 + T cells infected with latent HIV-1 are more susceptible to combined treatment with LRAs and G4 ligands, indicating that drugs targeting TMM may enhance killing of HIV reservoirs. Using a cell-based DNA repair assay, we also found that HIV-1 infected cells have reduced efficiency of DNA mismatch repair (MMR), and base excision repair (BER), suggesting that altered TMM in latently infected cells could be associated with accumulation of DNA damage at telomeres and changes in telomeric caps.