gebhart/patrepeval huggingface dataset:
Abstract LT008: Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy (2021)

Abstract Immune therapies have transformed the cancer therapeutic landscape but fail to benefit most patients. To elucidate the underlying mechanisms by which T cells mediate elimination of leukemia, we generated a high-resolution map of longitudinal T cell dynamics within the same tumor microenvironment (TME; bone marrow) during response or resistance to donor lymphocyte infusion (DLI), a widely used immunotherapy for relapsed leukemia. We analyzed 87,939 bone marrow-derived single T cell transcriptomes, along with chromatin accessibility and single T cell receptor clonality profiles, by developing novel machine learning tools for integrating longitudinal and multimodal data. We found that pre-treatment enrichment and post-treatment rapid, durable expansion of ‘terminal’ (TEX) and ‘precursor’ (TPEX) exhausted subsets, respectively, defined DLI response. In contrast to the common, shared pathways marking DLI response, a heterogeneous pattern of T cell dysfunction marked DLI resistance. Unexpectedly, TPEX cells that expanded in responders did not arise from the infusion product but instead from both pre-existing and novel clonotypes recruited to the TME. Further, we introduce a Bayesian method, Symphony, to define the T cell regulatory circuitry and master regulators underlying TEX and TPEX subsets that may be broadly relevant to other exhaustion antagonists across cancers. In conclusion, our data implicate the hierarchy of both TEX and TPEX subsets for immunotherapeutic responses in leukemia, extending the scope of their relevance beyond checkpoint blockade to adoptive cellular therapy. Moreover, our results provocatively suggest that immunologic ‘help’ from DLI, rather than direct transfer of anti-leukemic T cells, drove leukemic remission. Finally, we provide a general analysis paradigm for exploiting temporal single-cell genomic profiling for deep understanding of how immune therapies differentially shape the evolutionary trajectories of the TME in accordance with clinical outcome. Citation Format: Pavan Bachireddy, Elham Azizi, Cassandra Burdziak, Vinhkhang Nguyen, Christina Ennis, Zi- Ning Choo, Shuqiang Li, Kenneth Livak, Donna Neuberg, Robert Soiffer, Jerome Ritz, Edwin Alyea, Dana Pe'er, Catherine Wu. Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr LT008.
Optimized control technique of single inverter dual motor AC-brushless drives (2008)

The paper deals with controlled PM-brushless drives in configuration “single-inverter, dual-motor” operating with unbalanced loads at the shafts of the two motors. Some control techniques are analyzed and their relevant features are compared. Starting from some simple control circuits which refer to an equivalent “single-inverter, single-motor” configuration, some compensation blocks are added in order to improve steady-state and transient performances. Current and torque distortion, total efficiency, dynamic response and stability are the main quantities observed. Their values are compared in order to evidence the advantages of the different examined control techniques.
Silica-based PLC 1×128 thermo-optic switch (2002)

We successfully fabricated a silica-based 1/spl times/128 thermo-optic switch (TOSW) with an insertion loss of 4 dB and an extinction ratio of 40 dB using planar lightwave circuit (PLC) technology. This TOSW is promising for realizing a large-scale optical switch system.
Human Plasma Inactive Renin: Purification and Activation by Proteases* (1982)

A new affinity chromatographic procedure was devised to purify inactive renin by using a selective hydrophobic interaction of inactive renin to octyl-Sepharose. Additional extensive purification was accomplished by immunoaffinity chromatography on antihuman renin immunoglobulin G-Sepharose. A trace amount of active renin was removed by chromatography on pepstatin-Sepharose. Human plasma inactive renin purified by this method was free from protease inhibitors and permitted the investigation of protease-mediated activation without the acid treatment which was used previously to remove inhibitors. Human plasma kallikrein, human plasmin, cathepsin B1, and arginine esteropeptidases associated with mouse epidermis growth factor and nerve growth factor were effective activators. Human urinary kallikrein, hog pancreatic kallikrein, and rat urinary esterase A were inefficient activators of low potency. Thrombin, factor Xa, factor XIIa, and urokinase did not activate inactive renin. The in vitro activation of 56,000-dalton inactive renin by these proteases was not accompanied by a recognizable reduction in molecular weight. Activation required plasma albumin, presumably as a protecting substance. These results suggest that human inactive renin can be activated by a minimum change in its molecular size.
Inhibition of PKC ? by ruboxistaurin (RBX) does not enhance the blood pressure (BP) response to glyceryl trinitrate (GTN) (2005)

Background Activation of PKC β by hyperglycemia impairs endothelial- and nitric oxide (NO)-dependent vasodilation. RBX, a specific inhibitor of PKC β undergoing clinical testing for the treatment of diabetic microvascular complications, normalizes NO signaling in diabetic animals and restores vascular function. This study assessed a possible interaction between RBX and the exogenous NO donor, GTN, on BP. Methods A randomized, double masked, placebo (PL)-controlled, 2 period crossover study was performed in 21 stable angina pectoris subjects. RBX (96 mg/d; 3x the therapeutic dose) or PL was given orally to steady state. Graded GTN was then infused with dose escalation until discontinued for hypotension or when 120 mcg/min was achieved. Primary treatment comparison was the slope of the change in standing systolic BP from predose (ΔSSBP)/ ln(GTN dose) curve. Treatment difference in ΔSSBP at a GTN rate producing a 10 mmHg fall with PL treatment (GTN*) was also assessed. Results RBX did not alter the slope of ΔSSBP/ ln(GTN dose) curve (p=0.272 ANCOVA) or affect the ΔSSBP at the 8.44 mcg/min GTN* rate (mean −0.9 mmHg; 95% CI −3.3, 1.5). Conclusion Ruboxistaurin can be coadministered with organic nitrates as it does not potentiate their BP lowering effect. Clinical Pharmacology & Therapeutics (2005) 77, P15–P15; doi: 10.1016/j.clpt.2004.11.060
Immunological Stimulant Effect of Linseed Oil and Fennel Oil Supplemented Diet on Broilers (2020)

This study was designed to assess the effect of Linseed oil and Fennel oil supplemented diet on the immunity of Cobb broiler chickens through one day age to 35 days. A total of 90 broiler chicks were allocated to 3 treatment groups with 3 replicates of ten birds each. The control group (G1) was fed a basal diet. The Linseed oil group (G2) was fed the basal diet supplemented with 0.2 ml of linseed oil/Kg ration. The Fennel oil group (G3) was fed the basal diet supplemented with 0.3 ml of fennel oil/Kg ration. Feeding on diet supplemented with linseed oil and fennel oil significantly increased WBCs, Heterophils %, phagocytic activity %, phagocytic index, total protein, globulins, IgM, IgG, A/G ratio, T3, and T4 of broiler chicks compared to control group. There was a non-significant difference in Ca, Ph, albumin, AST, ALT, urea, and creatinine levels between all groups. The histological examination of the duodenum in linseed oil treated group (G2) and Fennel oil treated group (G3) compared to the control group showing normal intestinal villi with an increase in goblet cells count. In conclusion, the daily supplementation of Linseed oil and Fennel oil in the diet of broiler chicks for 35 days was enough to improve their immunity and subsequent biochemical parameters.
Curing a consumption coagulopathy with transcatheter embolization of a visceral artery aneurysm. (1996)

April 1996Curing a consumption coagulopathy with transcatheter embolization of a visceral artery aneurysm.Authors: P V Suhocki, J H Lawson, R C Harland, and T P SmithAuthor Info & AffiliationsVolume 166, Issue 4https://doi.org/10.2214/ajr.166.4.8610585 METRICS PDFotherformats
Data from Mechanistic Contribution of Ubiquitous 15-Lipoxygenase-1 Expression Loss in Cancer Cells to Terminal Cell Differentiation Evasion (2023)

&lt;div&gt;Abstract&lt;p&gt;Loss of terminal cell differentiation promotes tumorigenesis. 15-Lipoxygenase-1 (15-LOX-1) contributes to terminal cell differentiation in normal cells. The mechanistic significance of 15-LOX-1 expression loss in human cancers to terminal cell differentiation suppression is unknown. In a screen of 128 cancer cell lines representing more than 20 types of human cancer, we found that 15-LOX-1 mRNA expression levels were markedly lower than levels in terminally differentiated cells. Relative expression levels of 15-LOX-1 (relative to the level in terminally differentiated primary normal human–derived bronchial epithelial cells) were lower in 79% of the screened cancer cell lines than relative expression levels of &lt;i&gt;p16 (INK4A)&lt;/i&gt;, which promotes terminal cell differentiation and is considered one of the most commonly lost tumor suppressor genes in cancer cells. 15-LOX-1 was expressed during terminal differentiation in three-dimensional air–liquid interface cultures, and 15-LOX-1 expression and terminal differentiation occurred in immortalized nontransformed bronchial epithelial but not in lung cancer cell lines. 15-LOX-1 expression levels were lower in human tumors than in paired normal lung epithelia. Short hairpin RNA–mediated downregulation of 15-LOX-1 in Caco-2 cells blocked enterocyte-like differentiation, disrupted tight junction formation, and blocked E-cadherin and ZO-1 localization to the cell wall membrane. 15-LOX-1 episomal expression in Caco-2 and HT-29 colon cancer cells induced differentiation. Our findings indicate that 15-LOX-1 downregulation in cancer cells is an important mechanism for terminal cell differentiation dysregulation and support the potential therapeutic utility of 15-LOX-1 reexpression to inhibit tumorigenesis. &lt;i&gt;Cancer Prev Res; 4(12); 1961–72. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Optimizing radiation for cancer immunotherapy (2016)

Various protocols are under investigation for the purpose of optimizing radiotherapy for cancer treatment. Due to recent advances in image guidance and radiation delivery, a new option is to treat tumors with a single intense dose of radiation, 30 Gy or more (1,2). Alternatively, radiation doses can be “fractionated” over multiple treatment periods. Radiotherapy kills tumor cells and their associated stromal and vascular cells, and in some instances can induce T cell-mediated immunity that is effective at killing tumors outside the radiated area, a phenomenon called the “abscopal effect” (3,4). Since complete tumor remission usually depends on an effective anti-tumor immune response, it is important to determine how different radiation regimens influence anti-tumor immune responses. Filatenkov and coworkers (5) investigated the effect of radiation delivery protocols on the numbers and properties of immune cells in the microenvironments of colon cancer cells in mice. Weakly immunogenic ectopic CT26 colon tumors grown in syngeneic Balb/c mice usually responded to a single 30 Gy dose of intense radiation with durable tumor remissions due to T cell-mediated tumor killing. Fractionated radiation regimens were not as effective at stimulating T cells responses or durable remissions. The authors conclude that an examination of the tumor immune response may be useful for optimizing radiation regimens applied to various tumors.
Comprehensive FDTD modelling of photonic crystal waveguide components (2004)

Planar photonic crystal waveguide structures have been modelled using the finite-difference-time-domain method and perfectly matched layers have been employed as boundary conditions. Comprehensive numerical calculations have been performed and compared to experimentally obtained transmission spectra for various photonic crystal waveguides. It is found that within the experimental fabrication tolerances the calculations correctly predict the measured transmission levels and other major transmission features.
Simple In Vitro Assays to Identify Amyloid-β Aggregation Blockers for Alzheimer's Disease Therapy (2010)

Compounds that will inhibit buildup of amyloid-beta(Abeta) deposits in Alzheimer's disease (AD) brain are potential therapeutic agents. Here we report the development of two simple in vitro screening assays to identify such agents. We use these assays to evaluate the relative potency of some possible candidates. One assay is based on binding of fluorescence-tagged Abeta{1-42} to synthetic Abeta{1-42} plated in wells of fluorescent black-wall microplates. Fluorescence-tagged Abeta{1-42} solutions with and without blockers are then added to the plates, and the amount of bound fluorescence is measured. Another is a tissue type assay, where sections of unfixed AD or AD model transgenic mouse brains are mounted on glass slides. The same solutions assayed in the microplate test are then added to tissue sections. Binding of fluorescence-tagged Abeta{1-42} to the Abeta deposits in AD or transgenic brain tissue is detected with a fluorescence microscope. Good agreement is obtained between the two methods. Most of the tested agents have too low an affinity for Abeta {1-42} to be effective clinically. Agents that may have marginal affinity according to these tests include 1,2,3,4,6-penta-O-galloyl-b-D-glucopyranose (PGG), S-diclofenac, epigallocatechin gallate (EGCG), resveratrol, and extracts of spirulina, ginger, rhubarb, cinnamon, blueberries, and turmeric. Compounds which failed to show binding include scyllo-inositol, myo-inositol, rhamnose, ginkgolide A, emodin, rhein, caryophellene, curcumin, valproic acid, tramiprosate, and garlic extract.
Abstract P6 (2014)

AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK
Molecular determinants of bacterial adhesion monitored by atomic force microscopy (1998)

Bacterial adhesion and the subsequent formation of biofilm are major concerns in biotechnology and medicine. The initial step in bacterial adhesion is the interaction of cells with a surface, a process governed by long-range forces, primarily van der Waals and electrostatic interactions. The precise manner in which the force of interaction is affected by cell surface components and by the physiochemical properties of materials is not well understood. Here, we show that atomic force microscopy can be used to analyze the initial events in bacterial adhesion with unprecedented resolution. Interactions between the cantilever tip and confluent monolayers of isogenic strains of Escherichia coli mutants exhibiting subtle differences in cell surface composition were measured. It was shown that the adhesion force is affected by the length of core lipopolysaccharide molecules on the E. coli cell surface and by the production of the capsular polysaccharide, colanic acid. Furthermore, by modifying the atomic force microscope tip we developed a method for determining whether bacteria are attracted or repelled by virtually any biomaterial of interest. This information will be critical for the design of materials that are resistant to bacterial adhesion.
On the reverse link performance of the cdma2000 1xEV-DO revision A system with antenna array receivers (2005)

cdma2000 1xEV-DO revision A (DO Rev. A), also known as IS-856-A, is a third generation (3G) wireless solution to providing wide-area high-speed mobile Internet access with high spectral efficiency and advanced quality-of-service (QoS) support. In this paper we evaluate the reverse link performance improvement (in terms of coverage and data throughput) of IS-856-A with the use of more advanced antenna array receivers. Specifically, we consider the effect of increasing the receiver antenna array size and utilizing more sophisticated beamforming schemes. We quantify the capacity improvement via analysis as well as comprehensive system simulations that incorporate realistic channel models and the dynamics associated with MAC-layer algorithms in addition to the physical-layer interactions. We show that DO Rev. A with 4-way antenna diversity on the reverse link achieves more than 3 dB gain over 2-way diversity receivers in sector throughput. We also demonstrate a coverage improvement on the order of 6 dB, which can be translated into further throughput gains by relaxing the interference control mechanism.
0245 CLOSED-LOOP TACS DURING SWS BOOSTS SLOW-WAVE AND DELTA POWER AND POST-SLEEP MEMORY FOR THREAT DETECTION ON NOVEL STIMULI (2017)

Few studies have shown transcranial alternating current stimulation (tACS) applied in open loop during slow-wave sleep (SWS) could improve declarative memory performance following sleep. The present study investigates the mechanisms by which closed-loop tACS can enhance sleep consolidation more robustly. Participants (n=7) underwent a within-subjects counterbalanced protocol involving baseline, training, and post-training tests (immediate and morning). Similar to prior work in our lab, participants viewed static images, half of which contained a target signaling a potential threat. Subjects made a response (target present or absent), received feedback via a short video during training, and then were tested for two image types: repeated (identical from training to test) and generalized (same scene from training to test, but novel spatial viewpoint). During sleep after training, participants received 1.5 mA of closed-loop tACS (adapted to ongoing slow-wave oscillations) to F3 and F4 with returns on mastoids, or sham stimulation on different nights. Normalized spectral power changes in sleep EEG across stimulation events were correlated with performance changes over the night. We observed not only a robust performance improvement but also a significant post-stimulation increase in power of slow-wave (0.5–1.5 Hz), delta (1.2–3 Hz), spindle (11–16 Hz), and gamma (30–50 Hz) bands relative to pre-stimulation baseline (ps<0.002). Further, we identified a cluster in the delta band at 3–4 s post stimulation that significantly correlated with the overnight change in performance for generalized images (p=0.0160). Performance for repeated images did not change overnight due to ceiling effects. Our results suggest that closed-loop tACS during sleep increases slow-wave and delta activity, which then triggers spindle and gamma band activity. These mechanisms promote memory consolidation wherein performance becomes less tied to a specific event and instead more generalized to the goals of the task. This material is based upon work supported by the Defense Advanced Research Project Agency (DARPA) and the Army Research Office under Contract No. W911NF-16-C-0018. The views, opinions and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government.
LSPR Biosensor Signal Enhancement Using Nanoparticle−Antibody Conjugates (2011)

A method to amplify the wavelength shift observed from localized surface plasmon resonance (LSPR) bioassays is developed using gold nanoparticle-labeled antibodies. The technique, which involves detecting surface-bound analytes using gold nanoparticle conjugated antibodies, provides a way to enhance LSPR shifts for more sensitive detection of low-concentration analytes. Using the biotin and antibiotin binding pair as a model, we demonstrate up to a 400% amplification of the shift upon antibody binding to analyte. In addition, the antibody-nanoparticle conjugate improves the observed binding constant by 2 orders of magnitude, and the limit of detection by nearly 3 orders of magnitude. This amplification strategy provides a way to improve the sensitivity of plasmon-based bioassays, paving the way for single molecule-based detection and clinically relevant diagnostics.
Managing Stress (2019)

Video calling (VC) aims to create multi-modal, collaborative environments that are "just like being there." However, we found that autistic individuals, who exhibit atypical social and cognitive processing, may not share this goal. We interviewed autistic adults about their perceptions of VC compared to other computer- mediated communications (CMC) and face-to-face interactions. We developed a neurodiversity-sensitive model of CMC that describes how stressors such as sensory sensitivities, cognitive load, and anxiety, contribute to their preferences for CMC channels. We learned that they apply significant effort to construct coping strategies to support their sensory, cognitive, and social needs. These strategies include moderating their sensory inputs, creating mental models of conversation partners, and attempting to mask their autism by adopting neurotypical behaviors. Without effective strategies, interviewees experience more stress, have less capacity to interpret verbal and non-verbal cues, and feel less empowered to participate. Our findings reveal critical needs for autistic users. We suggest design opportunities to support their ability to comfortably use VC, and in doing so, point the way towards making VC more comfortable for all.
Ticagrelor Removal From Human Blood (2017)

The authors devised an efficient method for ticagrelor removal from blood using sorbent hemadsorption. Ticagrelor removal was measured in 2 sets of in vitro experiments. The first set was a first-pass experiment using bovine serum albumin (BSA) solution pre-incubated with ticagrelor, whereas the second set, performed in a recirculating manner, used human blood mixed with ticagrelor. Removal of ticagrelor from BSA solution reached values >99%. The peak removal rate was 99% and 94% from whole blood and 99.99% and 90% from plasma during 10 h and 3 to 4 h of recirculating experiments, respectively. In conclusion, hemadsorption robustly removes ticagrelor from BSA solution and human blood samples.
Genomic Analysis of the Hydrocarbon-Producing, Cellulolytic, Endophytic Fungus Ascocoryne sarcoides (2012)

The microbial conversion of solid cellulosic biomass to liquid biofuels may provide a renewable energy source for transportation fuels. Endophytes represent a promising group of organisms, as they are a mostly untapped reservoir of metabolic diversity. They are often able to degrade cellulose, and they can produce an extraordinary diversity of metabolites. The filamentous fungal endophyte Ascocoryne sarcoides was shown to produce potential-biofuel metabolites when grown on a cellulose-based medium; however, the genetic pathways needed for this production are unknown and the lack of genetic tools makes traditional reverse genetics difficult. We present the genomic characterization of A. sarcoides and use transcriptomic and metabolomic data to describe the genes involved in cellulose degradation and to provide hypotheses for the biofuel production pathways. In total, almost 80 biosynthetic clusters were identified, including several previously found only in plants. Additionally, many transcriptionally active regions outside of genes showed condition-specific expression, offering more evidence for the role of long non-coding RNA in gene regulation. This is one of the highest quality fungal genomes and, to our knowledge, the only thoroughly annotated and transcriptionally profiled fungal endophyte genome currently available. The analyses and datasets contribute to the study of cellulose degradation and biofuel production and provide the genomic foundation for the study of a model endophyte system.