gebhart/patrepeval huggingface dataset:
Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy (2019)

BACKGROUNDCurrent clinical biomarkers for the programmed cell death 1 (PD-1) blockade therapy are insufficient because they rely only on the tumor properties, such as programmed cell death ligand 1 expression frequency and tumor mutation burden. Identifying reliable, responsive biomarkers based on the host immunity is necessary to improve the predictive values.METHODSWe investigated levels of plasma metabolites and T cell properties, including energy metabolism markers, in the blood of patients with non-small cell lung cancer before and after treatment with nivolumab (n = 55). Predictive values of combination markers statistically selected were evaluated by cross-validation and linear discriminant analysis on discovery and validation cohorts, respectively. Correlation between plasma metabolites and T cell markers was investigated.RESULTSThe 4 metabolites derived from the microbiome (hippuric acid), fatty acid oxidation (butyrylcarnitine), and redox (cystine and glutathione disulfide) provided high response probability (AUC = 0.91). Similarly, a combination of 4 T cell markers, those related to mitochondrial activation (PPARγ coactivator 1 expression and ROS), and the frequencies of CD8+PD-1hi and CD4+ T cells demonstrated even higher prediction value (AUC = 0.96). Among the pool of selected markers, the 4 T cell markers were exclusively selected as the highest predictive combination, probably because of their linkage to the abovementioned metabolite markers. In a prospective validation set (n = 24), these 4 cellular markers showed a high accuracy rate for clinical responses of patients (AUC = 0.92).CONCLUSIONCombination of biomarkers reflecting host immune activity is quite valuable for responder prediction.FUNDINGAMED under grant numbers 18cm0106302h0003, 18gm0710012h0105, and 18lk1403006h0002; the Tang Prize Foundation; and JSPS KAKENHI grant numbers JP16H06149, 17K19593, and 19K17673.
Improved staging of B-cell non-Hodgkin's lymphoma patients with 99mTc-labeled LL2 monoclonal antibody fragment. (1995)

Radioimmunodetection (RAID) with the 99mTc-labeled Fab' fragment of monoclonal antibody (MoAb) LL2 has been reported to have a high lesion detection rate for malignant lymph nodes as well as for visceral and skeletal tumor masses (20). Our purpose in this study was to evaluate the safety and staging efficacy of the 99mTc-labeled Fab' fragment of MoAb LL2 in patients with various grades and stages of B-cell non-Hodgkin's lymphoma (NHL). Thirty adult patients, 13 male and 17 female, ranging in age from 20 to 80 years, with at least one biopsy-proved malignant node (> or = 0.5 cm) and a Karnofsky performance score of > or = 60% were enrolled in this study. Patients underwent selected planar and single photon emission computed tomographic imaging at 6 and 18 h after receiving an i.v. infusion of 0.25-1 mg of LL2 Fab' fragment labeled with 25-30 mCi of 99mTc. RAID findings were compared with physical examination, chest radiography, computed tomography, magnetic resonance imaging, and bone and 67Ga scan findings. The RAID scan was positive in all but three patients. The sensitivity for known lesions was 90% and for suspected lesions, 89%, with an overall positive predictive value of 96%. Twenty-nine of the 30 patients had either low- or intermediate-grade NHL. Fifteen of 16 (94%) low-grade patients were correctly staged by RAID; three of these patients were correctly upstaged. Twelve of the 13 (92%) intermediate-grade patients were correctly staged by RAID; two of these patients were correctly upstaged. The high-grade NHL patient was staged correctly by RAID. Infused doses of 99mTc-labeled LL2 Fab' of 0.5 and 1.0 mg did not affect lesion sensitivity. The RAID sensitivity decreased as the total tumor burden increased > or = 100 g. On the basis of these initial results, the 99mTc-labeled Fab' fragment of MoAb LL2 (LymphoScan) seems to yield useful clinical information, especially for the staging of B-cell NHL patients who do not have bulky disease (i.e., tumor burdens of < or = 100 g).
Supplementary Tables S1-S2 from Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts (2023)

&lt;p&gt;Supplementary Tables S1-S2&lt;/p&gt;
Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus‐specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis (2023)

To enhance protective cytomegalovirus (CMV)-specific T cells in immunosuppressed recipients of an allogeneic hematopoietic cell transplant (HCT), we evaluated post-HCT impact of vaccinating healthy HCT donors with Triplex. Triplex is a viral vectored recombinant vaccine expressing three immunodominant CMV antigens. The vector is modified vaccinia Ankara (MVA), an attenuated, non-replicating poxvirus derived from the vaccinia virus strain Ankara. It demonstrated tolerability and immunogenicity in healthy adults and HCT recipients, in whom it also reduced CMV reactivation. Here, we report feasibility, safety, and immunological outcomes of a pilot phase 1 trial (NCT03560752 at ClinicalTrials.gov) including 17 CMV-seropositive recipients who received an HCT from a matched related donor (MRD) vaccinated with 5.1 × 10<sup>8</sup> pfu/ml of Triplex before cell harvest (median 15, range 11-28 days). Donor and recipient pairs who committed to participation in the trial resulted in exceptional adherence to the protocol. Triplex was well-tolerated with limited adverse events in donors and recipients, who all engrafted with full donor chimerism. On day 28 post-HCT, levels of functional vaccinia- and CMV-specific CD137<sup>+</sup> CD8<sup>+</sup> T cells were significantly higher (p < .0001 and p = .0174, respectively) in recipients of Triplex vaccinated MRD than unvaccinated MRD (control cohort). Predominantly, central and effector memory CMV-specific T-cell responses continued to steadily expand through 1-year follow-up. CMV viremia requiring antivirals developed in three recipients (18%). In summary, this novel approach represents a promising strategy applicable to different HCT settings for limiting the use of antiviral prophylaxis, which can impair and delay CMV-specific immunity, leading to CMV reactivation requiring treatment.
Wednesday Plenary: Machine Learning and Hardware Security Technologies for the Nanoscale era: Challenges & Opportunities (2019)

Summary form only given. The complete presentation was not made available for publication as part of the conference proceedings. This talk will highlight some of the emerging challenges and opportunities for next generation nanoscale machine learning and hardware security technologies in the rapidly evolving loT industry. New and emerging loT markets for autonomous vehicles, drones and wearables require even higher performance and security at much lower cost while reducing energy consumption. Some of the prominent barriers to designing high performance and energy-efficient multi-core microprocessors and SoCs in the sub-10nm technology nodes will be outlined. Emerging trends in SoC circuit design for machine learning and deep neural networks, specialized accelerators for nearest neighbor computing and reconfigurable multi-precision matrix multipliers, ultra-low-voltage logic and memory circuits, on-chip interconnect fabric circuits, ultra-lightweight encryption engines, physically unclonable functions and fully-digital random number generator security building blocks are described. Future brain-inspired neuromorphic computing circuit design challenges and technologies will also be reviewed.
Additive Manufacture of Graphene Electrodes for Supercapacitor Applications (2022)

Electrochemical energy storage devices, such as supercapacitors, are essential contributors to the implementation of sustainable energy. Supercapacitors exhibit fast charging/discharging ability and have attracted considerable attention within the automotive, aerospace, and telecommunication industries. Although these devices show great potential to meet power density metrics, they lack in terms of their energy density. To overcome this challenge, we are investigating better materials, architectures, and additive manufacturing techniques to print electrodes that increase the energy density while maintaining their high-power densities. Topology optimization was used to design an electrode with optimum performance. These electrodes were printed by projection micro stereolithography (PµSL) using PR48, a commercially available polymer resin. The printed electrodes were converted to carbon electrodes through pyrolysis at 1050 ֯C and characterized by cyclic voltammetry (CV), galvanostatic charge/discharge (GCD), and electrical impedance spectroscopy. The performance of the PR48 optimized electrodes were compared against PR48 electrodes printed as a simple cubic lattice structure previously shown to improve capacitance and rate capability. The results show that our optimized electrodes have higher areal capacitances for all the current densities tested and they perform better in GCD and CV tests. Lastly, to increase the surface area of the electrodes and increase the capacitance further, we developed a resin formulation by combining graphene oxide (GO) into TMPTA polymer. Electrodes printed with 3%GO/TMPTA have improved electrochemical performance compared to PR48 as evidenced by their higher capacitances and their better GCD and CV curves. This work demonstrates the benefits of using topology optimization to design electrodes and materials development to improve the functional properties of 3D printable resins. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. Lawrence Livermore National Security, LLC Figure 1
Tools for expressive text-to-speech markup (2001)

This paper describes handicapped accessible text-to-speech markup software developed for poetry and performance. Most text-to-speech software allows the user to select a voice, but provides no control over performance parameters such as rate, volume, and pitch. For users with vocal disabilities, the default computer is often dreaded since it provides no personalization. Evolving standards exist for text-to-speech markup (Sable, Java Speech Markup Language, Spoken Text Markup Language), but few tools exist for non-experts to modify documents using these prosody options [1, 5]. Furthermore, we could find fewer tools allowing for straightforward live performance using a synthesized voice [3]. Thus we created an easy to learn text-to-speech markup tool that requires little training to use.
Performance of oligoculm spring wheats grown in a semiarid environment (1991)

Oligoculm and low-tillering spring wheat (Triticum aestivum L.) genotypes were compared to free-tillering cultivars in each of 3 yr. On average, oligoculms yielded 20–40 and 4–27% less than the free- and low-tillering genotype groups, respectively. Averaged over years, oligoculms produced 44% fewer tillers and headed 3 d earlier than the free-tillering genotypes. These two groups did not differ consistently in tiller mortality across years. Key words: Triticum aestivum L., restricted tillering, grain yield, wheat (spring)
Video-rate optical dosimetry and dynamic visualization of IMRT and VMAT treatment plans in water using Cherenkov radiation (2014)

The results from this initial study demonstrate the first documented use of Cherenkov radiation for video-rate optical dosimetry of dynamic IMRT and VMAT treatment plans. The proposed modality has several potential advantages over alternative methods including the real-time nature of the acquisition, and upon future refinement may prove to be a robust and novel dosimetry method with both research and clinical applications.
Design and synthesis of iso-allo-DNJ and l-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase (2023)

A series of iso-<i>allo</i>-DNJ and L-isoDALDP derivatives were synthesized from dithioacetal 16 with sequential and highly diastereoselective Ho and Henry reactions, and aziridinium intermediate-mediated ring rearrangement as key steps. Glycosidase inhibition assay found four of them as selective α-glucosidase inhibitors, and the less substituted compound 30 showed more potent α-glucosidase inhibition (IC<sub>50</sub> = 9.3 μM) than the others. Molecular docking study revealed different docking modes of the iso-<i>allo</i>-DNJ and L-isoDALDP derivatives from their parent compounds, and also the similarity of compound 30 to isofagomine.
Delay Generated Offset: A Direction Sensitive Pulse-Coherent Doppler Detection Technique (1977)

An offset-frequency (heterodyne) direction sensitive coherentpulsed Doppler detection method requiring a single digitally synthesized phase-shiftable oscillator and a single mixer is described. Less stringent demands are imposed on hardware in obtaining offset-frequency stability and rejection of internally generated electrical clutter, as compared with the conventional offset method employing two oscillators. Simplification of hardware and postdetector signal processing as compared with the quadrature method (two parallel homodyne detectors) is anticipated. This technique has direct application in medical ultrasonics and is generally applicable to sonar and radar systems.
Peptide Conjugated Phosphorodiamidate Morpholino Oligomers Increase Survival of Mice Challenged with Ames Bacillus anthracis (2012)

Targeting bacterial essential genes using antisense phosphorodiamidate morpholino oligomers (PMOs) represents an important strategy in the development of novel antibacterial therapeutics. PMOs are neutral DNA analogues that inhibit gene expression in a sequence-specific manner. In this study, several cationic, membrane-penetrating peptides were conjugated to PMOs (PPMOs) that target 2 bacterial essential genes: acyl carrier protein ( acpP ) and gyrase A ( gyrA ). These were tested for their ability to inhibit growth of Bacillus anthracis , a gram-positive spore-forming bacterium and causative agent of anthrax. PPMOs targeted upstream of both target gene start codons and conjugated with the bacterium-permeating peptide (RFF) 3 R were found to be most effective in inhibiting bacterial growth in vitro . Both of the gene-targeted PPMOs protected macrophages from B. anthracis induced cell death. Subsequent, in vivo testing of the PPMOs resulted in increased survival of mice challenged with the virulent Ames strain of B. anthracis . Together, these studies suggest that PPMOs targeting essential genes have the potential of being used as antisense antibiotics to treat B. anthracis infections.
Effect of Tightening Speed on Clamp Load Distribution in Gasketed Joints (2006)

&lt;div class="htmlview paragraph"&gt;An experimental study is presented in order to determine the effect of tightening speed on clamp load distribution in a gasketed steel joint. Two gasket materials are considered, namely, Styrene Butadiene Rubber and Flexible Graphite. Flange tightening is achieved using a multiple spindle fastening system that has speed and torque controls; the fastening system is also capable of performing simultaneous tightening of all fasteners using other advanced control modes such as torque-turn or torque-to-yield strategies. Two tightening patterns are investigated, namely, simultaneous tightening of all bolts and individual tightening of one bolt at a time following a star pattern. The tightening speed in this study ranges from 1 rpm to 100 rpm.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Clamp load loss due to the combined effects of gasket creep relaxation and elastic interaction is investigated. Additionally, data is presented to show the effect of using a two-pass tightening method on the residual value of the clamp load in gasketed joints.&lt;/div&gt;
Swiss 3T3 mouse embryo fibroblasts transfected with a human prepro‐GRP gene synthesize and secrete pro‐GRP rather than GRP (1988)

A prepro-gastrin-releasing peptide (GRP) gene was introduced into Swiss 3T3 mouse embryo fibroblasts by DNA transfection in an attempt to establish autocrine growth stimulation. Clonal transfectants expressed varying amounts of GRP encoding mRNA. They synthesized and secreted a approximately 15-kd pro-GRP hormone but not fully processed 2.8-kd GRP. Accordingly, no changes in growth properties were associated with GRP gene expression. We postulate that Swiss 3T3 fibroblasts lack the enzymes necessary to process significantly pro-GRP into biologically active peptides and that this deficiency may be responsible for the failure to establish autocrine growth stimulation in the transfected cells.
Experiences with a New Soil Gas Technique for Detecting Petroleum Pollution (1996)

This paper presents field experiences obtained with a new technology for detecting petroleum pollution in soil and ground water based on “in situ” determination of hydrocarbon concentrations in soil air. Ecoprobe is a new soil gas device from RS-Dynamics in the Czech Republic. The rugged waterproof device is equipped with a built-in computer controlled semiconductor sensor. Three case histories are presented that demonstrate the use of the equipment under typical conditions. Two case histories present the use of the device under typical field conditions; the third case history compares results from the Ecoprobe and a commercial photoionization detector (PID) device.
Kinetics and Mechanism of Ethanol Dehydration on γ-Al2O3: The Critical Role of Dimer Inhibition (2013)

Steady state, isotopic, and chemical transient studies of ethanol dehydration on γ-alumina show unimolecular and bimolecular dehydration reactions of ethanol are reversibly inhibited by the formation of ethanol–water dimers at 488 K. Measured rates of ethylene synthesis are independent of ethanol pressure (1.9–7.0 kPa) but decrease with increasing water pressure (0.4–2.2 kPa), reflecting the competitive adsorption of ethanol–water dimers with ethanol monomers; while diethyl ether formation rates have a positive, less than first order dependence on ethanol pressure (0.9–4.7 kPa) and also decrease with water pressure (0.6–2.2 kPa), signifying a competition for active sites between ethanol–water dimers and ethanol dimers. Pyridine inhibits the rate of ethylene and diethyl ether formation to different extents verifying the existence of acidic and nonequivalent active sites for the dehydration reactions. A primary kinetic isotope effect does not occur for diethyl ether synthesis from deuterated ethanol and only occurs for ethylene synthesis when the β-proton is deuterated; demonstrating olefin synthesis is kinetically limited by either the cleavage of a Cβ-H bond or the desorption of water on the γ-alumina surface and ether synthesis is limited by the cleavage of either the C–O bond of the alcohol molecule or the Al–O bond of a surface bound ethoxide species. These observations are consistent with a mechanism inhibited by the formation of dimer species. The proposed model rigorously describes the observed kinetics at this temperature and highlights the fundamental differences between the Lewis acidic γ-alumina and Brønsted acidic zeolite catalysts.
A fully integrated power supply unit for fine grain power management application to embedded Low Voltage SRAMs (2008)

In complex embedded applications, optimization and adaptation at run time of both dynamic and leakage power have become an issue at SoC coarse grain. We propose in this paper a fully integrated Power Supply Unit for fine grain DVFS and adaptive leakage control. The proposed PSU offers five power modes and can be easily integrated in any IP unit. The PSU has been implemented and validated in a STMicroelectronics 65 nm technology. Dedicated Low-Voltage SRAMs have been designed to allow full DVFS. Using a Hopping technique, the dynamic power consumption can be reduced by a factor of 35%. Using an Ultra-Cut-Off technique, the static power consumption is strongly reduced in stand-by mode, 18 times better than classical MTCMOS.
Inflammatory pathways are upregulated in the nasal epithelium in patients with idiopathic pulmonary fibrosis (2018)

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive scarring of the lung parenchyma, leading to respiratory failure and death. High resolution computed tomography of the chest is often diagnostic for IPF, but its cost and the risk of radiation exposure limit its use as a screening tool even in patients at high risk for the disease. In patients with lung cancer, investigators have detected transcriptional signatures of disease in airway and nasal epithelial cells distal to the site of disease that are clinically useful as screening tools. Here we assessed the feasibility of distinguishing patients with IPF from age-matched controls through transcriptomic profiling of nasal epithelial curettage samples, which can be safely and repeatedly sampled over the course of a patient's illness. We recruited 10 patients with IPF and 23 age-matched healthy control subjects. Using 3' messenger RNA sequencing (mRNA-seq), we identified 224 differentially expressed genes, most of which were upregulated in patients with IPF compared with controls. Pathway enrichment analysis revealed upregulation of pathways related to immune response and inflammatory signaling in IPF patients compared with controls. These findings support the concept that fibrosis is associated with upregulation of inflammatory pathways across the respiratory epithelium with possible implications for disease detection and pathobiology.