gebhart/patrepeval huggingface dataset:
CRS free T cell therapy: T cell membrane anchored and tumor targeted IL12 (ATTIL12)-T cell therapy eliminates large tumors, overcomes heterogeneity, and avoids adverse effects (2020)

Abstract Adoptive transfer of genetic engineered T cells becomes an effective approach in treating hematologic malignancies, but shows poor responses against solid tumors due to multifactorial reasons. Interleukin-12 exhibits robust T cell activating and anti-tumor efficacy. However, its clinical application was impeded due to the lethal adverse effects. We demonstrated previously that tumor targeted IL-12 (ttIL12) gene therapy avoids the toxicity of wildtype IL12 and effectively eliminate tumor metastasis. In this study, we developed a second generation of ttIL12— membrane-anchored ttIL-12 (attIL12)—to modify naive T cells, CD19CAR-T cells and OT1 T cells. This attIL12-modified T cells silent the toxicity of both IL12 and CAR-T cells associated cytokine release syndrome (CRS). Surprisingly, this ATTIL12-T cell therapy is able to eliminate multiple types of tumors with either homo- or hetero-generous environment or large size. We are in full speed to prepare a phase I clinical trial.
Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants (2009)

Our studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak.
A SMART POLYMER LAB-ON-A-TUBE (LOT) WITH SPIRALLY-ROLLED MICROCHANNELS FOR IN-SITU DRUG DELIVERY AND BRAIN TUMOR MONITORING (2008)

A novel flexible polymer lab-on-a-tube integrated with spirally-rolled microchannels and microsensors for in situ convection-enhanced drug delivery and brain tumor monitoring was developed and characterized in this work. In specific, the novel spirally-rolled microchannels around the flexible tube can precisely control drug delivery volume and reduce the backflow. Microsensors can in situ monitor the tumor status, hence will be helpful in guiding therapies. In addition, the spirallyrolled tube platform is flexible enough laterally to shift with organ movement, but rigid enough axially to directly insert into the brain.
Optoelectronic transmitters for medical ultrasound transducers (1995)

Optoelectronics and fiber optics can be used to miniaturize and improve the flexibility of the transducer cable and transducer handle of medical diagnostic ultrasound scanners. The reduction in size has gained importance as 2-D array transducers with up to 1000 independent channels become accepted to improve diagnostic ultrasound images. The authors describe the analysis, design, fabrication and testing of a prototype silicon photoconductive semiconductor switch (PCSS). The monolithic silicon PCSS was used in combination with an infrared semiconductor diode laser with a fiber optic "pigtail" to shock excite and burst excite a 2-D array transducer element resonant at 2.5 MHz. Optically controlled voltage, current, and ultrasound pulses are compared to those from conventional electronic shock excitation and narrow band Doppler pulses. The optically triggered ultrasound pulse for single shock excitation produced 30 V spikes at the 2-D array element with a fall time of 200 nsec and a rise time of 2 /spl mu/sec with a peak current through the transducer element of 34 mA. An optically produced burst of eight pulses at a frequency of 2.5 MHz produced 11 V spikes at the transducer with a fall time under 100 nsec and a rise time of approximately 300 nsec. The peak current per pulse was 25 mA through the transducer element. These results show the feasibility of applying optoelectronic technology to replace conventional electronic transmitter technology.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Application of Phylogenetic Microarray Analysis to Discriminate Sources of Fecal Pollution (2012)

Conventional methods for fecal source tracking typically use single biomarkers to systematically identify or exclude sources. High-throughput DNA sequence analysis can potentially identify all sources of microbial contaminants in a single test by measuring the total diversity of fecal microbial communities. In this study, we used phylogenetic microarray analysis to determine the comprehensive suite of bacteria that define major sources of fecal contamination in coastal California. Fecal wastes were collected from 42 different populations of humans, birds, cows, horses, elk, and pinnipeds. We characterized bacterial community composition using a DNA microarray that probes for 16S rRNA genes of 59,316 different bacterial taxa. Cluster analysis revealed strong differences in community composition among fecal wastes from human, birds, pinnipeds, and grazers. Actinobacteria, Bacilli, and many Gammaproteobacteria taxa discriminated birds from mammalian sources. Diverse families within the Clostridia and Bacteroidetes taxa discriminated human wastes, grazers, and pinnipeds from each other. We found 1058 different bacterial taxa that were unique to either human, grazing mammal, or bird fecal wastes. These OTUs can serve as specific identifier taxa for these sources in environmental waters. Two field tests in marine waters demonstrate the capacity of phylogenetic microarray analysis to track multiple sources with one test.
Low Cost Hypercompression of Test Data (2019)

This article presents a next-generation test data compression scheme. It builds on the isometric compression paradigm, but makes it more flexible and elevates encoding efficiency to values unachievable through state-of-the-art sequential compression schemes. Furthermore, its programmable selection of full-toggle scan chains ensures high test coverage and virtually eliminates compression aborts. The presented approach follows from a fundamental observation that among test cube care bits, only a very few have a status of necessary assignments (their locations cannot be changed), whereas the remaining ones have alternative sites. These test cubes are used to form circular test templates which synergistically control a decompressor and guide back ATPG to find assignments yielding highly compressible test patterns. A redesigned low-silicon-area decompressor is also capable of reducing switching rates in scan chains with a new test power control scheme. The experimental results obtained for large industrial designs and other benchmark circuits confirm the superiority of the proposed scheme over existing techniques and are reported herein.
Toxoplasma gondii GRA8 induces ATP5A1–SIRT3-mediated mitochondrial metabolic resuscitation: a potential therapy for sepsis (2018)

The intracellular parasite Toxoplasma gondii has unique dense granule antigens (GRAs) that are crucial for host infection. Emerging evidence suggests that GRA8 of T. gondii is a promising serodiagnostic marker in toxoplasmosis. However, little is known about the intracellular regulatory mechanisms involved in GRA8-induced host responses. We found that GRA8 interacts with host proteins involved in mitochondria activation and might be useful as a therapeutic strategy for sepsis. Here, we show that protein kinase-Cα (PKCα)-mediated phosphorylation of T. gondii GRA8 (Thr220) is required for mitochondrial trafficking and regulates the interaction of C terminal of GRA8 with nucleotide binding domain of ATP5A1. Furthermore, GRA8 interacts with SIRT3 in mitochondria, facilitating ATP5A1 deacetylation (K506 and K531), adenosine triphosphate production and subsequent anti-septic activity in vivo. Taken together, these results demonstrate a new anti-sepsis therapeutic strategy using T. gondii GRA8-induced mitochondrial metabolic resuscitation. This strategy represents an urgently needed paradigm shift for therapeutic intervention.
A framework for automated performance bottleneck detection (2008)

In this paper, we present the architecture design and implementation of a framework for automated performance bottleneck detection. The framework analyzes the time-spent distribution in the application and discovers the performance bottlenecks by using given bottleneck definitions. The user can query the application execution performance to identify performance problems. The design of the framework is flexible and extensible so it can be tailored based on the actual application execution environment and performance tuning requirement. To demonstrate the usefulness of the framework, we apply the framework on a practical DARPA application and show how it helps to identify performance bottlenecks. The framework helps to automate the performance tuning process and improve the user’s productivity.
Degradation of spatial sound by the hearing aid (2013)

It is well known that the hearing aid distorts the spatial cues used to localize sound sources and this has severe consequences for sound localization and for listening in noise. However, it is not clear how the different components in the hearing aid contribute to the degradation of spatial sound. In this study we investigate how the spatial sound is degraded by four hearing aid components: 1) the microphone location, 2) the directionality (beamforming), 3) the compressor, 4) the real ear measurement. Head Related Transfer Functions from an artificial KEMAR head are convolved with appropriate excitation sounds and processed through the respective hearing aid algorithm. The performance metrics under investigation are: 1) interaural level difference (ILD), 2) interaural time difference (ITD), 3) monaural spectral cues. It is found that the main source for ILD degradation is the position of the microphone around the pinna which distorts the ILD by up to 30 dB. It is also found that the real ear measurement compensation severely affects the monaural spectral cues.
An Integrated System for Multichannel Neuronal Recording with Spike / LFP Separation and Digital Output (2005)

A mixed-signal front-end processor for multichannel neuronal recording is described. It receives twelve differential-input channels of implanted recording electrodes. A programmable cutoff HPF blocks DC and low frequency input drift. The signals are band-split at about 200 Hz to low frequency local field potential (LFP) and high-frequency spike data (SPK), which is band limited by a programmable-cutoff LPF. Amplifier offsets are compensated by calibration DACs. The SPK and LFP channels provide variable amplification rates of up to 5000 and 500, respectively. The analog signals are converted into digital form, and streamed out over a serial digital bus. A threshold filter supresses inactive portions of the signal and emits only spike segments. A prototype has been fabricated on a 0.35/mum CMOS process and tested successfully
Automatic characterization of iron ore by digital microscopy and image analysis (2018)

This paper presents an automatic system for mineralogical and textural characterization of iron ores based on digital microscopy and image analysis. It employs a motorized and computer-controlled reflected light microscope in a correlative approach that combines bright field and circular polarization modes. Mosaic images covering large areas of polished sections are acquired to image thousands of particles. Different classifiers discriminate compact and non-compact hematite, polycrystalline and monocrystalline particles, and identify particles as granular, lamellar, and lobular. The entire process is automatic and produces a full pdf report containing typical images and the quantification of mineral and textural phases.
Computation of electrostatic complements to proteins: A case of charge stabilized binding (1998)

Recent evidence suggests that the net effect of electrostatics is generally to destabilize protein binding due to large desolvation penalties. A novel method for computing ligand-charge distributions that optimize the tradeoff between ligand desolvation penalty and favorable interactions with a binding site has been applied to a model for barnase. The result is a ligand-charge distribution with a favorable electrostatic contribution to binding due, in part, to ligand point charges whose direct interaction with the binding site is unfavorable, but which make strong intra-molecular interactions that are uncloaked on binding and thus act to lessen the ligand desolvation penalty.
<i>In Vitro</i>Metabolic Effects of Bovine Growth Hormone Fragments in Adipose Tissue (1970)

A limited tryptic digest of bovine growth hormone, which dissociated in 50% acetic acid into 2 fragments of 16,000 and 5000 molecular weight, was evaluated for bovine growth hormone (BGH) activity in rat adipose tissue in vitro. Both fragments, whether tested individually or as mixtures in equimolar ratio, possessed the several in vitro metabolic activities commonly associated with native BGH: (14C)-glucose uptake, its oxidation to CO2 and incorporation into glyceride-glycerol, glycerol release, and (14C)- histidine incorporation into adipose tissue protein. The fragments, which also possess growthpromoting activity, were effective in vitro on most parameters of BGH action at concentrations of 25 µg/ml medium. At a 10-fold increase in concentration all the several parameters of BGH which were evaluated became manifest. These results indicate that while the 2 fragments of the tryptic digest of bovine growth hormone obtained are considerably less potent than native BGH they nonetheless possess BGH activity both in vivo and in vitro. Moreover, these data demonstrate that various metabolic effects of BGH are not dissociable by limited tryptic fragmentation of the BGH molecule since each of the 2 fragments of different primary structure exerted similar metabolic effects. These studies suggest that there may be more than one active site in growth hormone. (Endocrinology87: 900, 1970)
Influence of Ancillary Ligands in Dye-Sensitized Solar Cells (2016)

Dye-sensitized solar cells (DSSCs) have motivated many researchers to develop various sensitizers with tailored properties involving anchoring and ancillary ligands. Ancillary ligands carry favorable light-harvesting abilities and are therefore crucial in determining the overall power conversion efficiencies. The use of ancillary ligands having aliphatic chains and/or π-extended aromatic units decreases charge recombination and permits the collection of a large fraction of sunlight. This review aims to provide insight into the relationship between ancillary ligand structure and DSSC properties, which can further guide the function-oriented design and synthesis of different sensitizers for DSSCs. This review outlines how the new and rapidly expanding class of chelating ancillary ligands bearing 2,2'-bipyridyl, 1,10-phenanthroline, carbene, dipyridylamine, pyridyl-benzimidazole, pyridyl-azolate, and other aromatic ligands provides a conduit for potentially enhancing the performance and stability of DSSCs. Finally, these classes of Ru polypyridyl complexes have gained increasing interest for feasible large-scale commercialization of DSSCs due to their more favorable light-harvesting abilities and long-term thermal and chemical stabilities compared with other conventional sensitizers. Therefore, the main idea is to inspire readers to explore new avenues in the design of new sensitizers for DSSCs based on different ancillary ligands.
Optical coupling between a microresonator and an adjacent dielectric structure: effects of resonator size (2001)

Optical coupling between a spherical microresonator and a plane dielectric substrate is investigated for a small sphere whose diameter is only a few ten times as large as the optical wavelength. A unique characteristic of small microresonators, relaxation of the phase-matching requirement that is due to the small size, is demonstrated on the basis of experimental results and model numerical calculations. The difference between the frequency and the propagation constant as parameters to describe the resonances of microresonators is clarified. Based on the numerical results, intrinsic restriction on a distance between the resonator and the coupler is also suggested.
An incremental flow- and context-sensitive pointer aliasing analysis (1999)

Pointer aliasing analysis is used to determine if two object names containing dereferences and/or field selectors, (e.g., *p,q->t), may refer to the same location during execution. Such information is necessary for applications such as dataflow-based testers, program understanding tools, and debuggers, but is expensive to calculate with acceptable precision.
Inverted Top-emitting Organic Light-emitting Diodes with a Multilayered Graphene Top Electrode (2015)

Organic light-emitting diodes (OLEDs) have recently received peculiar attention as a next display and various products using OLEDs panels are released on the market. Especially, top-emitting (TE) OLEDs are of great interest because they have several advantages for active-matrix (AM) OLED displays such as diversity of substrate selection and large aperture ratio for high-resolution displays. 1 However, transparent top electrode is one of critical issues in TEOLED. Semitransparent thin metals and transparent conductive oxides (TCOs) are used as a top electrode in TEOLED, but thin metals have low transmittance in visible spectral region, causing low efficiency and color distortion depending on the viewing angles and TCOs deposition process for top electrode can cause degradation of top organic layer in TEOLEDs. 2, 3
Ultrasonic endoscope having elongated array mounted in manner allowing it to remain flexible (1985)

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Ultrasmall Structure Fabrication <i>via</i> a Facile Size Modification of Nanoimprinted Functional Silsesquioxane Features (2011)

We propose a simple and robust scheme for a precise and controlled fabrication of ultrasmall structures through the direct size modification (either reduction or increment) of functional nanoimprinted silsesquioxane (SSQ) patterns. The size modification of nanopatterned SSQ polymer features was achieved according to two different independent approaches. In the first approach, feature size was reduced by a simple heat-induced mass loss mechanism; in the second approach structure size increment was achieved by building multiple polymeric layers on top of imprinted patterns. The fabricated arrays follow the shape contour of the patterned structures so the original imprinted profile is preserved. The engineered capabilities were applied to produce high resolution stamps for nanoimprinting. These approaches free the need for sophisticated nanofabrication techniques and expensive facilities required for nanopatterning.
PyzoFlex: a printed piezoelectric pressure sensing foil for human machine interfaces (2013)

Ferroelectric material supports both pyro- and piezoelectric effects that can be used for sensing pressures on large, bended surfaces. We present PyzoFlex, a pressure-sensing input device that is based on a ferroelectric material (PVDF:TrFE). It is constructed by a sandwich structure of four layers that can easily be printed on any substrate. The PyzoFlex foil is sensitive to pressure- and temperature changes, bendable, energy-efficient, and it can easily be produced by a screen-printing routine. Even a hovering input-mode is feasible due to its pyroelectric effect. In this paper, we introduce this novel, fully printed input technology and discuss its benefits and limitations.
Analysis of nonablative skin resurfacing (1997)

Nonablative skin resurfacing is a dermatologic procedure utilizing pulsed laser irradiation and dynamic cooling to induce selectively a wound healing response in the papillary and upper reticular dermis. Using temperature measurements of human skin provided by pulsed photothermal radiometry immediately following laser irradiation (lambda equals 1.32 micrometer), spatial distribution of thermal damage is predicted in response to various potential therapeutic laser- cryogen doses. Results of our analysis suggest that appropriate application of pulsed laser irradiation and cryogen spray cooling may be used to protect the epidermis and selectively confine thermal injury to the papillary and upper reticular dermis. Development of nonablative skin resurfacing will require understanding the relationship between the degree of dermal photocoagulation and the cutaneous wound healing response following laser irradiation.
Multi-atlas segmentation with joint label fusion and corrective learning—an open source implementation (2013)

Label fusion based multi-atlas segmentation has proven to be one of the most competitive techniques for medical image segmentation. This technique transfers segmentations from expert-labeled images, called atlases, to a novel image using deformable image registration. Errors produced by label transfer are further reduced by label fusion that combines the results produced by all atlases into a consensus solution. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity is a simple and highly effective label fusion technique. However, one limitation of most weighted voting methods is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this problem, we recently developed the joint label fusion technique and the corrective learning technique, which won the first place of the 2012 MICCAI Multi-Atlas Labeling Challenge and was one of the top performers in 2013 MICCAI Segmentation: Algorithms, Theory and Applications (SATA) challenge. To make our techniques more accessible to the scientific research community, we describe an Insight-Toolkit based open source implementation of our label fusion methods. Our implementation extends our methods to work with multi-modality imaging data and is more suitable for segmentation problems with multiple labels. We demonstrate the usage of our tools through applying them to the 2012 MICCAI Multi-Atlas Labeling Challenge brain image dataset and the 2013 SATA challenge canine leg image dataset. We report the best results on these two datasets so far.
Development of Indole Alkaloid-Type Dual Immune Checkpoint Inhibitors Against CTLA-4 and PD-L1 Based on Diversity-Enhanced Extracts (2021)

Cancer immunotherapy involves the use of the immune system for cancer treatment. Recently, immune checkpoint-blocking antibodies have become integral for the treatment of some cancers. However, small molecules exhibit advantages over monoclonal antibody drugs, such as cell penetration, long half-life, and low manufacturing costs, and the possibility of oral administration. Thus, it is imperative to develop small-molecule immune checkpoint inhibitors. Previously, we have screened a library of synthetic indole-alkaloid-type compounds, which are produced by diversity-enhanced extracts of Japanese cornelian cherry, and reported that an unnatural pentacyclic compound inhibits CTLA-4 gene expression. In this study, immune checkpoint inhibitors with increased potency were developed by introducing substituents and conversion of functional groups based on the unnatural pentacyclic compound. The developed compounds suppressed not only CTLA-4 and PD-L1 gene expression but also protein expression on the cell surface. Their efficacy was not as potent as that of the existing small-molecule immune checkpoint inhibitors, but, to the best of our knowledge, the developed compounds are the first reported dual small-molecule inhibitors of CTLA-4 and PD-L1.