gebhart/patrepeval huggingface dataset:
Abstract 605: Potency of Gp96-Ig/Fc-OX40L cell-based combination vaccine in cancer immunotherapy (2017)

Abstract The breakthrough discoveries of checkpoint inhibitors in the field of tumor immunology have driven the clinical success of immunotherapies for cancer, despite their beneficial efficacy in only a small portion of patients. This is due in part to immuno-evasive mechanisms and the inability of the immune system to recognize tumor antigens as foreign. As a therapeutic approach to effectively present these tumor antigens in order to elicit an anti-tumor immune response, we previously designed and characterized an allogenic, gp96-Ig secreting, cell-based vaccine (ImPACT); currently being assessed in a phase II study in non-muscle invasive bladder cancer and a phase Ib study in non-small cell lung cancer – the latter, in combination with the PD-1 antagonist Nivolumab. We recently characterized a ‘next-generation’ vaccine (ComPACT) that combines the tumor antigen chaperone Gp96-Ig along with the T cell costimulator Fc-OX40L, which are both secreted from the same cell (Fromm et. al. Cancer Immunology Research. 2016). In preclinical assays, ComPACT is effective at stimulating CD4+ and CD8+ antigen-specific T cell expansion, the programing of a durable memory T cell phenotype, and the elimination of melanoma and colon tumors. This anti-tumor efficacy is enhanced when ComPACT is combined with checkpoint inhibition (anti-PD1 or anti-PDL1). To support manufacturing and clinical efforts of both ImPACT and ComPACT, in anticipation of phase III expansion and/or new trial initiation, we have developed novel potency assays to quantify the biologically active form of Gp96-Ig and the in vitro activity of Fc-OX40L on T cell costimulation. It has been shown that gp96 can interact with toll-like receptors (TLR) and that this interaction results in the activation of the NF-κB pathway. Since THP1 cells express abundant TLR2/4, we engineered a THP1 cell line to express luciferase that is regulated by NF-κB response elements. Furthermore, we utilized the human T cell line; Jurkat, as host cells in which we also express NF-κB-luciferase, to quantify Fc-OX40L costimulation. Jurkat/NF-κB-luciferase cells primed with either CD3/CD28 or TNFα, and subsequently cultured with ComPACT-secreted Fc-OX40L, results in a dose dependent increase in NF-κB (luciferase) expression. Our current data in both assays shows a linear correlation with the input of Gp96-Ig and Fc-OX40L, and may serve as an effective potency assay to facilitate the manufacturing of our vaccine product as it transitions into more advanced cancer immunotherapy clinical studies. Citation Format: Xin Xu, Louise E. Gonzalez, George J. Fromm, Suresh de Silva, Louise Giffin, Jason Rose, Taylor H. Schreiber. Potency of Gp96-Ig/Fc-OX40L cell-based combination vaccine in cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 605. doi:10.1158/1538-7445.AM2017-605
Hypermethylation of Syk gene in promoter region associated with oncogenesis and metastasis of gastric carcinoma (2004)

Hypermethylation leads to silencing of the Syk gene in human gastric carcinoma. Methylation of Syk promoter is correlated to oncogenesis and metastasis of gastric carcinoma. Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human gastric cancer.
Discrete-Time Systems (2010)

Rapid advances in digital system technology have radically altered the control system design options. It has become routinely practicable to design very complicated digital controllers and to carry out the extensive calculations required for their design. These advances in implementation and design capability can be obtained at low cost because of the widespread availability of inexpensive and powerful digital computers and their related devices. A digital control system uses digital hardware, usually in the form of a programmed digital computer, as the heart of the controller. A typical digital controller has analog components at its periphery to interface with the plant. It is the processing of the controller equations that distinguishes analog from digital control. Analogous to the differential equations that describe continuous-time systems, the input-output behavior of a discrete-time system can be described by difference equations. A linear step-invariant discrete-time system is said to be input-output stable if its pulse response decays to zero asymptotically.
Generation-Guided Multi-Level Unified Network for Video Grounding (2023)

Video grounding aims to locate the timestamps best matching the query description within an untrimmed video. Prevalent methods can be divided into moment-level and clip-level frameworks. Moment-level approaches directly predict the probability of each transient moment to be the boundary in a global perspective, and they usually perform better in coarse grounding. On the other hand, clip-level ones aggregate the moments in different time windows into proposals and then deduce the most similar one, leading to its advantage in fine-grained grounding. In this paper, we propose a multi-level unified framework to enhance performance by leveraging the merits of both moment-level and clip-level methods. Moreover, a novel generation-guided paradigm in both levels is adopted. It introduces a multi-modal generator to produce the implicit boundary feature and clip feature, later regarded as queries to calculate the boundary scores by a discriminator. The generation-guided solution enhances video grounding from a two-unique-modals' match task to a cross-modal attention task, which steps out of the previous framework and obtains notable gains. The proposed Generation-guided Multi-level Unified network (GMU) surpasses previous methods and reaches State-Of-The-Art on various benchmarks with disparate features, e.g., Charades-STA, ActivityNet captions.
[Effect of D1 and D2 dopamine receptor antagonists on acupuncture analgesia]. (1993)

Some highly selective D1 or D2 receptor antagonists were tested on rabbit skin pain model to investigate the effect of the subtypes of dopamine receptor on acupuncture analgesia. It was found that iv. of D2 receptor antagonists haloperidol and clozapine, had a potentiating effect on acupuncture analgesia. Icv. of D2 receptor antagonists domperidone and sulpiride and D1 receptor antagonist SCH23390 also enhanced acupuncture analgesia markedly. The effect of D1 and D2 receptor on acupuncture analgesia was discussed.
The myristylation signal of p60v-src functionally complements the N-terminal fps-specific region of P130gag-fps. (1989)

The P130gag-fps protein-tyrosine kinase of Fujinami sarcoma virus contains an N-terminal fps-specific domain (Nfps) that is important for oncogenicity. The N-terminal 14 amino acids of p60v-src, which direct myristylation and membrane association, can replace the gag-Nfps sequences of P130gag-fps (residues 1 to 635), producing a highly transforming src-fps polypeptide. Conversely, gag-Nfps can restore modest transforming activity to a nonmyristylated v-src polypeptide. These results emphasize the modular construction of protein-tyrosine kinases and indicate that Nfps, possibly in conjunction with gag, functions in the subcellular localization of P130gag-fps.
Growth inhibition of an Araucaria angustifolia (Coniferopsida) fungal seed pathogen, Neofusicoccum parvum, by soil streptomycetes (2013)

Streptomycetes from the rhizosphere of Araucariaceae produce exudates which can suppress the development of pathogenic fungi in their seeds.
Investigation into the relationship between tool‐wear and cutting environments when turning EN32 steel (2004)

New environmental legislation is forcing companies to realign their use of metalworking fluids in favour of non‐polluting cutting environments that will return acceptable tool wear rates and reduced costs. Studies have been undertaken to determine the effectiveness of various environments on tool wear, in order to either reduce or even eliminate totally, the dependency on flood coolants. Industrially reproducible cutting tests were devised, where an EN32 case hardening steel material was turned in a range of different cutting environments and tool life measured. Low oxygen gaseous environments were compared with conventional cutting environments and a 55 per cent flank wear reduction has been recorded using uncoated tooling.
An Empirical Evaluation of Genetic Algorithms on Noisy Objective Functions (2017)

Genetic algorithms have particular potential as a tool for optimization when the evaluation function is noisy. Several types of genetic algorithms are compared against a mutation-driven stochastic hill-climbing algorithm on a standard set of benchmark functions which have had Gaussian noise added to them. Different criteria for judging the effectiveness of the search are also considered. The genetic algorithms used in these comparisons include an elitist simple genetic algorithm, the CHC adaptive search algorithm, and the delta coding genetic algorithm. The chapter describes several hybrid genetic algorithms and compares on a very large and noisy seismic data imaging problem. J. M Fitzpatrick and J. Grefenstette have provided empirical and analytic evidence suggesting that genetic algorithms exhibit a certain tolerance for noise. Additional performance comparisons involving a version of the delta coding algorithm combined with a local search algorithm were carried out for a seismic data interpretation problem known to have a noisy objective function.
Design and synthesis of fluorescent substrates for human tyrosyl-DNA phosphodiesterase I (2004)

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that acts upon protein-DNA covalent complexes. Tdp1 hydrolyzes 3'-phosphotyrosyl bonds to generate 3'-phosphate DNA and free tyrosine in vitro. Mutations in Tdp1 have been linked to patients with spinocerebellar ataxia, and over-expression of Tdp1 results in resistance to known anti-cancer compounds. Tdp1 has been shown to be involved in double-strand break repair in yeast, and Tdp1 has also been implicated in single-strand break repair in mammalian cells. Despite the biological importance of this enzyme and the possibility that Tdp1 may be a molecular target for new anti-cancer drugs, there are very few assays available for screening inhibitor libraries or for characterizing Tdp1 function, especially under pre-steady-state conditions. Here, we report the design and synthesis of a fluorescence-based assay using oligonucleotide and nucleotide substrates containing 3'-(4-methylumbelliferone)-phosphate. These substrates are efficiently cleaved by Tdp1, generating the fluorescent 4-methylumbelliferone reporter molecule. The kinetic characteristics determined for Tdp1 using this assay are in agreement with the previously published values, and this fluorescence-based assay is validated using the standard gel-based methods. This sensitive assay is ideal for kinetic analysis of Tdp1 function and for high-throughput screening of Tdp1 inhibitory molecules.
Flow control protocols for integrated networks with partially observed voice traffic (1987)

The design of flow control protocols for integrated networks with partially observed voice traffic on the data link level is investigated. A closed Markovian queueing network with two classes of users and a preemptive resume queueing discipline for modeling the integrated link is introduced. The class of admissible flow control policies analyzed maximizes the average data link throughput subject to an average system time delay constraint on a finite horizon. A separation principle between the flow control policy and an estimate of the state of the voice traffic is derived. In particular, it is shown that the optimum control law is bang-bang and the conditional mean estimate of the state of the voice traffic is a sufficient statistic for the optimal control strategy. Since the complexity of the analytical results prohibits finding the explicit flow control policy, a suboptimum and easily implementable adaptive window flow control mechanism is proposed. The window size changes dynamically according to the estimated state of the voice traffic at the destination node. The robustness of the estimator, the dynamics of the window size, and the effectiveness of the suboptimum scheme are verified by means of simulations.
Academic Cardiology Division in the Era of Managed Care (1997)

The ability of academic divisions of cardiology to pursue educational and research missions in an era of market-driven managed care is being increasingly jeopardized. Indeed, several academic medical centers have been sold to for-profit entities, and many cardiology divisions have been forced to decrease staff and faculty reimbursements. Despite these threats, the academic division has unique strengths: (1) premium quality of care, (2) a single employer, (3) a somewhat uniform practice culture, (4) high-volume operators performing interventional procedures, (5) expertise in highly technical aspects of cardiology, and (6) the availability of physicians for outreach ventures. Therefore, we hypothesized that the cardiology division could be strengthened by collaborating with the medical center in the development of an aggressive and proactive managed care strategy. To this end, we developed a cardiovascular network having the academic center as its central focus but including a group of high-quality and geographically dispersed community-based physicians. These physicians were attracted by an economic package that provided protection from downside risk, participation in our managed care initiatives, and geographic exclusivity in an over-crowded market. In turn, the community-based physicians increasingly used the academic medical center for tertiary care, resulting in increased volumes and incremental profitability. Using this paradigm, we have now recruited approximately 40 community cardiologists. The resulting network provides access to a university cardiologist in most of the surrounding urban and rural counties and will allow us to compete effectively for capitated contracts.
Isolated leptomeningeal infiltration of a primary CNS B-cell lymphoma diagnosed by flow cytometry and confirmed by necropsy (2011)

Our case shows that flow cytometry of the CSF in addition to conventional CSF cytology has the potential to accelerate diagnosis of lymphomeningeal infiltration of B-cell lymphoma.
Optical innovations in surgery (2015)

Abstract Background In the past decade, there has been a major drive towards clinical translation of optical and, in particular, fluorescence imaging in surgery. In surgical oncology, radical surgery is characterized by the absence of positive resection margins, a critical factor in improving prognosis. Fluorescence imaging provides the surgeon with reliable and real-time intraoperative feedback to identify surgical targets, including positive tumour margins. It also may enable decisions on the possibility of intraoperative adjuvant treatment, such as brachytherapy, chemotherapy or emerging targeted photodynamic therapy (photoimmunotherapy). Methods This article reviews the use of optical imaging for intraoperative guidance and decision-making. Results Image-guided cancer surgery has the potential to be a powerful tool in guiding future surgical care. Photoimmunotherapy is a theranostic concept (simultaneous diagnosis and treatment) on the verge of clinical translation, and is highlighted as an effective combination of image-guided surgery and intraoperative treatment of residual disease. Multispectral optoacoustic tomography, a technique complementary to optical image-guided surgery, is currently being tested in humans and is anticipated to have great potential for perioperative and postoperative application in surgery. Conclusion Significant advances have been achieved in real-time optical imaging strategies for intraoperative tumour detection and margin assessment. Optical imaging holds promise in achieving the highest percentage of negative surgical margins and in early detection of micrometastastic disease over the next decade.
Plant defenses interact with insect enteric bacteria by initiating a leaky gut syndrome (2019)

Plants produce suites of defenses that can collectively deter and reduce herbivory. Many defenses target the insect digestive system, with some altering the protective peritrophic matrix (PM) and causing increased permeability. The PM is responsible for multiple digestive functions, including reducing infections from potential pathogenic microbes. In our study, we developed axenic and gnotobiotic methods for fall armyworm (<i>Spodoptera frugiperda</i>) and tested how particular members present in the gut community influence interactions with plant defenses that can alter PM permeability. We observed interactions between gut bacteria with plant resistance. Axenic insects grew more but displayed lower immune-based responses compared with those possessing <i>Enterococcus</i>, <i>Klebsiella</i>, and <i>Enterobacter</i> isolates from field-collected larvae. While gut bacteria reduced performance of larvae fed on plants, none of the isolates produced mortality when injected directly into the hemocoel. Our results strongly suggest that plant physical and chemical defenses not only act directly upon the insect, but also have some interplay with the herbivore's microbiome. Combined direct and indirect, microbe-mediated assaults by maize defenses on the fall armyworm on the insect digestive and immune system reduced growth and elevated mortality in these insects. These results imply that plant-insect interactions should be considered in the context of potential mediation by the insect gut microbiome.
Detecting Oriented Text in Natural Images by Linking Segments (2017)

Most state-of-the-art text detection methods are specific to horizontal Latin text and are not fast enough for real-time applications. We introduce Segment Linking (SegLink), an oriented text detection method. The main idea is to decompose text into two locally detectable elements, namely segments and links. A segment is an oriented box covering a part of a word or text line, A link connects two adjacent segments, indicating that they belong to the same word or text line. Both elements are detected densely at multiple scales by an end-to-end trained, fully-convolutional neural network. Final detections are produced by combining segments connected by links. Compared with previous methods, SegLink improves along the dimensions of accuracy, speed, and ease of training. It achieves an f-measure of 75.0% on the standard ICDAR 2015 Incidental (Challenge 4) benchmark, outperforming the previous best by a large margin. It runs at over 20 FPS on 512x512 images. Moreover, without modification, SegLink is able to detect long lines of non-Latin text, such as Chinese.
An antibody to VacA of Helicobacter pylori in the CSF of patients with Miller-Fisher syndrome (2004)

The authors examined antibodies against native vacuolating cytotoxin (VacA) of Helicobacter pylori in CSF from 12 patients with Miller-Fisher syndrome (MFS). The VacA protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting analysis was carried out. Eight of 12 MFS patients had a specific immunoglobulin G antibody against VacA in the CSF. There is sequence homology between VacA and some membrane ion transport proteins, raising the possibility that A-VacA-Ab involves the ion channels in the node of Ranvier in some patients with MFS.
Wireless optical communications via diversity reception and optical preamplification (2005)

Atmospheric optical communication systems that use optical preamplifiers and diversity reception are addressed. The particular diversity techniques that are investigated include aperture averaging, linear combining, and adaptive optics. On-off keying and binary pulse position modulation are considered. The effects of atmospheric turbulence, background light, source extinction ratio, amplified spontaneous emission, and receiver thermal noise are studied in the context of a semiclassical photon-counting approach. Numerical results are presented using a conditional Gaussian approximation method. By this method, we can measure the power penalty incurred under various operating conditions as well as the link margin improvement due to optical preamplification and diversity reception.
Involvement of the Ca2+-dependent phosphorylation of a 20 kDa protein in the proliferative effect of high-density lipoproteins (subclass 3) on the adenocarcinoma cell line A549 (1995)

Previous studies from our laboratory demonstrated that high-density lipoproteins (subclass 3; HDL3) bind to sites specific for apolipoprotein AI on the human adenocarcinoma cell line A549 and that HDL3 binding promotes a mitogenic effect [Favre, Tazi, Le Gaillard, Bennis, Hachem and Soula (1993) J. Lipid Res. 34, 1093-1106]. In the present study, we have examined the cell proteins that showed modified phosphorylation after binding of HDL3 to specific sites, and the roles of Ca2+ and protein kinase C. Native HDL3 (but not tetranitromethane-modified HDL3) and Ca2+ ionophore A23187 strongly enhanced the phosphorylation of a 20 kDa protein (x 3.6) and, to a lower extent, the phosphorylation of 24 and 28 kDa proteins (x 2.2 and 2.6 respectively). The two effectors were equally able to stimulate cell growth. Down-regulation of protein kinase C by a 24 h incubation of cells with phorbol myristate acetate prevented the effects of HDL3 on the phosphorylation of 24 and 28 kDa proteins. However, the extent of phosphorylation of the 20 kDa protein was not affected. In contrast, activation of protein kinase C by a short incubation with phorbol myristate acetate resulted in inhibition of proliferation and an increase in 24 and 28 kDa (but not 20 kDa) protein phosphorylation. These results suggest that HDL3 putative receptors exert their proliferative effect on A549 cells through activation of a Ca(2+)-dependent protein kinase. This kinase activity is not modulated by phorbol ester and thus may be a calmodulin kinase or an isoenzyme of protein kinase C that is independent of phorbol ester. It allows a subsequent 20 kDa protein to be phosphorylated.
Self-Assembly of a Porphyrin Array via the Molecular Recognition Approach:  Synthesis and Properties of a Cyclic Zinc(II) Porphyrin Trimer Based on Coordination and Hydrogen Bonding (2001)

Self-assembly of [5-(pyrazol-4-yl)-10,20-bis(p-tolyl)-15- (2-ethoxycarbonylphenyl)porphyrinato]-zinc(II) (1), designed to have both a coordination site and a hydrogen bonding site, leads to a stable cyclic trimer array where coordination of the pyrazole nitrogen to the zinc(II) ion as well as hydrogen bonding between carbonyl oxygen and pyrazole NH holds each zinc(II) porphyrin. The recognition event for pyrazole has been confirmed preliminarily in the model studies using [5-(2-ethoxycarbonylphenyl)tris(p-tolyl)porphyrinato]-zinc(II) (3). The zinc(II) porphyrin 3 has large affinity for pyrazole due to the hydrogen bond between pyrazole and the 2-ethoxycarbonyl group in addition to the coordination bonding accompanied by the conformational change of the ethoxycarbonyl group in the coordination process. The (1)H NMR, IR, and UV-vis spectra of 1 and its ESI-MS and VPO measurements have revealed the cyclic trimer structure with an overall association constant of 6.0 x 10(13) M(-2) at 22 degrees C. The contribution of the hydrogen bond to the total free energy change in trimer formation is estimated to be 7.5 kcal/mol based on a reference trimer system without a hydrogen bonding site. The trimer geometry causes characteristic exitonic interaction between porphyrin units to yield a broad Soret band which is deconvoluted into four components by UV-vis and MCD spectral analyses. Electrochemical measurements have shown that only the first ring-oxidation process proceeds stepwise in the trimer.