gebhart/patrepeval huggingface dataset:
Change-Point Detection in a Sequence of Bags-of-Data (2015)

In this paper, the limitation that is prominent in most existing works of change-point detection methods is addressed by proposing a nonparametric, computationally efficient method. The limitation is that most works assume that each data point observed at each time step is a single multi-dimensional vector. However, there are many situations where this does not hold. Therefore, a setting where each observation is a collection of random variables, which we call a bag of data, is considered. After estimating the underlying distribution behind each bag of data and embedding those distributions in a metric space, the change-point score is derived by evaluating how the sequence of distributions is fluctuating in the metric space using a distance-based information estimator. Also, a procedure that adaptively determines when to raise alerts is incorporated by calculating the confidence interval of the change-point score at each time step. This avoids raising false alarms in highly noisy situations and enables detecting changes of various magnitudes. A number of experimental studies and numerical examples are provided to demonstrate the generality and the effectiveness of our approach with both synthetic and real datasets.
By Binding CD80 and CD86, the Vaccinia Virus M2 Protein Blocks Their Interactions with both CD28 and CTLA4 and Potentiates CD80 Binding to PD-L1 (2019)

The vaccinia virus harbors in its genome several genes dedicated to the inhibition of the host immune response. Among them, M2L was reported to inhibit the intracellular NF-κB pathway. We report here several new putative immunosuppressive activities of M2 protein. M2 protein is secreted and binds cornerstone costimulatory molecules (CD80/CD86). M2 binding to CD80/CD86 blocks their interaction with soluble CD28/CTLA4 but also favors the soluble PD-L1-CD80 association. These findings open the way for new investigations deciphering the immune system effects of soluble M2 protein. Moreover, a vaccinia virus with a deletion of its M2L has been generated and characterized as a new oncolytic platform. The replication and oncolytic activities of the M2L-deleted vaccinia virus are indistinguishable from those of the parental virus. More investigations are needed to characterize in detail the immune response triggered against both the tumor and the virus by this M2-defective vaccinia virus.
A Novel Galectin-1 Inhibitor Discovered through One-Bead Two-Compound Library Potentiates the Antitumor Effects of Paclitaxel in vivo (2017)

Through the one-bead two-compound (OB2C) ultra-high-throughput screening method, we discovered a new small-molecule compound LLS2 that can kill a variety of cancer cells. Pull-down assay and LC/MS-MS indicated that galectin-1 is the target protein of LLS2. Galectin-1 is known to be involved in the regulation of proliferation, apoptosis, cell cycle, and angiogenesis. Binding of LLS2 to galectin-1 decreased membrane-associated H-Ras and K-Ras and contributed to the suppression of pErk pathway. Importantly, combination of LLS2 with paclitaxel (a very important clinical chemotherapeutic agent) was found to exhibit synergistic activity against several human cancer cell lines (ovarian cancer, pancreatic cancer, and breast cancer cells) <i>in vitro</i> Furthermore, <i>in vivo</i> therapeutic study indicated that combination treatment with paclitaxel and LLS2 significantly inhibits the growth of ovarian cancer xenografts in athymic mice. Our results presented here indicate that the OB2C combinatorial technology is a highly efficient drug screening platform, and LLS2 discovered through this method can be further optimized for anticancer drug development. <i>Mol Cancer Ther; 16(7); 1212-23. ©2017 AACR</i>.
A New Model for Rapid Stretch-Induced Injury of Cells in Culture: Characterization of the Model Using Astrocytes (1995)

The purpose of this study was to develop a simple, reproducible model for examining the morphologic, physiologic, and biochemical consequences of stretch-induced injury on tissue-cultured cells of brain origin. Rat cortical astrocytes from 1- to 2-day-old rats were cultured to confluency in commercially available 25-mm-diameter tissue culture wells with a 2-mm-thick flexible silastic bottom. A cell injury controller was used to produce a closed system and exert a rapid positive pressure of known amplitude (psi) and duration (msec). The deformation of the membrane, and thus the stretch of the cells growing on the membrane, was proportional to the amplitude and duration of the air pressure pulse. Extent of cell injury was qualitatively assessed by light and electron microscopy and quantitatively assessed by nuclear uptake of the fluorescent dye propidium iodide, which is excluded from cells with intact membranes. Lactate dehydrogenase (LDH) enzyme release was measured spectrophotometrically. Cell injury was found to be proportional to the extent of the silastic membrane deformation. Increasing cell stretch caused mitochondrial swelling and vacuolization as well as disruption of glial filaments. Stretching also caused increased dye uptake, with maximum dye uptake occurring with a 50 msec pressure pulse duration, whereas deformations produced over longer periods of time (seconds) caused little dye uptake. With increasing postinjury survival fewer cells took up dye, implying cell repair. LDH release was also proportional to the amplitude of cell stretch, with maximum release occurring within 2 h of injury. In summary we have developed a simple, reproducible model to produce graded, strain-related injuries in cultured cells. Our continuing experiments suggest that this model can be used to study the biochemistry and physiology of injury as well as serve as a tool to examine the efficacy of therapeutic agents.
An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs (1994)

Two different baculovirus genes are known to be able to block apoptosis triggered upon infection of Spodoptera frugiperda cells with p35 mutants of the insect baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV):p35 (P35-encoding gene) of AcMNPV (R. J. Clem, M. Fechheimer, and L. K. Miller, Science 254:1388-1390, 1991) and iap (inhibitor of apoptosis gene) of Cydia pomonella granulosis virus (CpGV) (N. E. Crook, R. J. Clem, and L. K. Miller, J. Virol. 67:2168-2174, 1993). Using a genetic complementation assay to identify additional genes which inhibit apoptosis during infection with a p35 mutant, we have isolated a gene from Orgyia pseudotsugata NPV (OpMNPV) that was able to functionally substitute for AcMNPV p35. The nucleotide sequence of this gene, Op-iap, predicted a 30-kDa polypeptide product with approximately 58% amino acid sequence identity to the product of CpGV iap, Cp-IAP. Like Cp-IAP, the predicted product of Op-iap has a carboxy-terminal C3HC4 zinc finger-like motif. In addition, a pair of additional cysteine/histidine motifs were found in the N-terminal regions of both polypeptide sequences. Recombinant p35 mutant viruses carrying either Op-iap or Cp-iap appeared to have a normal phenotype in S. frugiperda cells. Thus, Cp-IAP and Op-IAP appear to be functionally analogous to P35 but are likely to block apoptosis by a different mechanism which may involve direct interaction with DNA.
Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution (2007)

Biomarker discovery produces lists of candidate markers whose presence and level must be subsequently verified in serum or plasma. Verification represents a paradigm shift from unbiased discovery approaches to targeted, hypothesis-driven methods and relies upon specific, quantitative assays optimized for the selective detection of target proteins. Many protein biomarkers of clinical currency are present at or below the nanogram/milliliter range in plasma and have been inaccessible to date by MS-based methods. Using multiple reaction monitoring coupled with stable isotope dilution mass spectrometry, we describe here the development of quantitative, multiplexed assays for six proteins in plasma that achieve limits of quantitation in the 1-10 ng/ml range with percent coefficients of variation from 3 to 15% without immunoaffinity enrichment of either proteins or peptides. Sample processing methods with sufficient throughput, recovery, and reproducibility to enable robust detection and quantitation of candidate biomarker proteins were developed and optimized by addition of exogenous proteins to immunoaffinity depleted plasma from a healthy donor. Quantitative multiple reaction monitoring assays were designed and optimized for signature peptides derived from the test proteins. Based upon calibration curves using known concentrations of spiked protein in plasma, we determined that each target protein had at least one signature peptide with a limit of quantitation in the 1-10 ng/ml range and linearity typically over 2 orders of magnitude in the measurement range of interest. Limits of detection were frequently in the high picogram/milliliter range. These levels of assay performance represent up to a 1000-fold improvement compared with direct analysis of proteins in plasma by MS and were achieved by simple, robust sample processing involving abundant protein depletion and minimal fractionation by strong cation exchange chromatography at the peptide level prior to LC-multiple reaction monitoring/MS. The methods presented here provide a solid basis for developing quantitative MS-based assays of low level proteins in blood.
The Evolved Transformer (2019)

Recent works have highlighted the strength of the Transformer architecture on sequence tasks while, at the same time, neural architecture search (NAS) has begun to outperform human-designed models. Our goal is to apply NAS to search for a better alternative to the Transformer. We first construct a large search space inspired by the recent advances in feed-forward sequence models and then run evolutionary architecture search with warm starting by seeding our initial population with the Transformer. To directly search on the computationally expensive WMT 2014 English-German translation task, we develop the Progressive Dynamic Hurdles method, which allows us to dynamically allocate more resources to more promising candidate models. The architecture found in our experiments -- the Evolved Transformer -- demonstrates consistent improvement over the Transformer on four well-established language tasks: WMT 2014 English-German, WMT 2014 English-French, WMT 2014 English-Czech and LM1B. At a big model size, the Evolved Transformer establishes a new state-of-the-art BLEU score of 29.8 on WMT'14 English-German; at smaller sizes, it achieves the same quality as the original "big" Transformer with 37.6% less parameters and outperforms the Transformer by 0.7 BLEU at a mobile-friendly model size of 7M parameters.
Vitronectin is expressed in the ventral region of the neural tube and promotes the differentiation of motor neurons (1997)

The extracellular matrix protein vitronectin and its mRNA are present in the embryonic chick notochord, floor plate and in the ventral neural tube at the time position of motor neuron generation. When added to cultures of neural tube explants of developmental stage 9, vitronectin promotes the generation of motor neurons in the absence of either notochord or exogenously added Sonic hedgehog. Conversely, the neutralisation of endogenous vitronectin with antibodies inhibits over 90% motor neuron differentiation in co-cultured neural tube/notochord explants, neural tube explants cultured in the presence of Sonic hedgehog, and in committed (stage 13) neural tube explants. Furthermore, treatment of embryos with anti-vitronectin antibodies results in a substantial and specific reduction in the number of motor neurons generated in vivo. These results demonstrate that vitronectin stimulates the differentiation of motor neurons in vitro and in vivo. Since the treatment of stage 9 neural tube explants with Sonic hedgehog resulted in induction of vitronectin mRNA expression before the expression of floor plate markers, we conclude that vitronectin may act either as a downstream effector in the signalling cascade induced by Sonic hedgehog, or as a synergistic factor that increases Shh-induced motor neuron differentiation.
Improving the iMM904 S. cerevisiae metabolic model using essentiality and synthetic lethality data (2010)

Overall, this study provides a roadmap for the computationally driven correction of multi-compartment genome-scale metabolic models and demonstrates the value of synthetic lethals as curation agents.
Pyruvate‐formate‐lyase‐deactivase and acetyl‐CoA reductase activities of Escherichia coli reside on a polymeric protein particle encoded by adhE (1991)

A 4.8 kb DNA-fragment was cloned and sequenced encompassing the structural gene of PFL-deactivase (2.7 kb) and 2 kb of the 5' flanking region that contains the elements for anaerobic induction. A mutant lacking deactivase was shown to require exogenous electron acceptors for anaerobic growth with glucose. This revealed the identity of PFL-deactivase with the alcohol and acetaldehyde dehydrogenases of E. coli. The multienzyme represents a homopolymeric protein (approximately 40 x 96 kDa) requiring Fe2+ for all functions.
General method for ultrashort light pulse chirp measurement (1989)

Conditions to retrieve pulse intensity and chirp from autocorrelation signals are mathematically discussed. The interferometric SHG autocorrelation signal and the interferogram of fundamental light are shown to be a sufficient data set for the pulseform retrieval. This measurement scheme is experimentally demonstrated on laser diode pulses. The method utilizes Fourier analysis of the signals and iterative calculations, and is especially suited to the measurement of pulses having weak peak intensity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Beneficial Effects of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Naturally Occurring Tendinopathy (2013)

Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X10(7) autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05) although no significant difference in calculated modulus of elasticity, lower (improved) histological scoring of organisation (p<0.003) and crimp pattern (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair in enhancing normalisation of biomechanical, morphological, and compositional parameters. These data in natural disease, with no adverse findings, support the use of this treatment for human tendon injuries.
Adamantylideneadamantane-1,2-dioxetane. Chemiluminescence and decomposition kinetics of an unusually stable 1,2-dioxetane (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdamantylideneadamantane-1,2-dioxetane. Chemiluminescence and decomposition kinetics of an unusually stable 1,2-dioxetaneGary B. Schuster, Nicholas J. Turro, Hans C. Steinmetzer, A. Paul Schaap, Gary Faler, Waldemar Adam, and J. C. LiuCite this: J. Am. Chem. Soc. 1975, 97, 24, 7110–7118Publication Date (Print):November 1, 1975Publication History Published online1 May 2002Published inissue 1 November 1975https://pubs.acs.org/doi/10.1021/ja00857a024https://doi.org/10.1021/ja00857a024research-articleACS PublicationsRequest reuse permissionsArticle Views921Altmetric-Citations127LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Localization of phenobarbital- and 3-methylcholanthrene-inducible cytochromes P-450 in mouse lung with monoclonal antibodies. (1986)

The cytochromes P-450 are key components of the mixed-function oxidase system responsible for the biotransformation of many foreign compounds to mutagens and carcinogens. In the present study, the distribution of these hemoproteins in frozen sections of mouse lung was determined immunohistochemically, using monoclonal antibodies (Mabs). Mab 1-7-1 is specific for 3-methylcholanthrene-inducible cytochromes P-450; this Mab reacted intensely with parenchymal cells, but not epithelial cells of pulmonary bronchioles of 3-methylcholanthrene-treated mice. Mab 1-7-1 did not react with pulmonary cells of either untreated or phenobarbital-treated mice. Mab specific for phenobarbital-inducible cytochromes P-450, Mab 2-66-3, reacted with parenchymal and bronchiolar epithelial cells in the lungs of phenobarbital-treated, 3-methylcholanthrene-treated, and untreated mice. The localization of constitutive and induced forms of cytochrome P-450 in different cells of the lung may provide insight into the mechanisms by which cell-specific damage and carcinogenicity are evoked by xenobiotics.
A class of asymptotically optimum iterated-decision multiuser detectors (2002)

A promising class of nonlinear multiuser detector is introduced for CDMA systems. These "iterated-decision" multiuser detectors use optimized multipass algorithms to successively cancel multiple-access interference (MAI) from received data and generate symbol decisions whose reliability increases monotonically with each iteration. They significantly outperform decorrelating detectors and linear minimum mean-square error (MMSE) multiuser detectors, but have the same order of computational complexity. When the ratio of the number of users to the spreading factor is below a certain threshold, iterated-decision multiuser detectors asymptotically achieve the performance of the "optimum" multiuser detector, ie, maximum-likelihood (ML) decoding.
Reflectarray Design for 120-GHz Radar Application: Measurement Results (2013)

In this paper, we present design and experimental results on reflectarrays at 120 GHz. The offset-fed reflectarrays consist of conductor-backed coplanar patch antennas with phase-shifting stubs. Three 138-mm reflectarrays are lithographically fabricated and evaluated in a near-field measurement range. Their measured beam patterns are compared to the theoretical ones. The theoretical -3-dB beam width is 60-64 mm at 3-m distance from the reflectarray. Measured beam widths of the different reflectarrays deviate less than 10% from the theoretical values. The beam pointing is found to be close to theoretical, whereas the sidelobe level is up to 5 dB higher. The efficiency, alignment accuracy, and surface shape of the reflectarray are studied with near-field imaging of the reflectarray aperture field. The measured average efficiency is 0.11 whereas the predicted average efficiency is 0.54. The low efficiency is most likely due to over-etching of the structures of the reflectarray element, and could be improved in future fabrication processing rounds. Beam pattern measurement close to the main beam is well suited for evaluating the beam width and pointing accuracy, but it gives little information on the element performance. We propose near-field imaging of the reflectarray to evaluate both element efficiency and phase shift.
Research on flywheel energy storage system for power quality (2003)

This paper presents a design of flywheel energy storage (FES) system in power network, which is composed of four parts: (1) the flywheel that stores energy, (2) the bearing that supports the flywheel, (3) the asynchronous motor/generator, and (4) the AC power converter regulated by a microprocessor controller. The control methods and strategy of the FES system for power quality are introduced in detail. A new rapid method to calculate the amplitude of sinusoidal voltage and current is presented which could improve the performance of the FES system. To realize the high efficiency of the energy conversion and to minimize the torque ripple of the motor/generator, the waveform of the AC power converter output currents is controlled to be sinusoidal by using sinusoidal pulse width modulation (SPWM) control method. During the storage period, the AC power converter accelerates the flywheel storing energy. At the generating times, the AC power converter drives the flywheel to decelerate and then the kinetic energy is transformed into electric energy and returned to power system. This paper also presents an experimental study of the FES system storing energy and synchronous operating with power system, and the control validity is verified through the experimental results.
Identification of semaphorin E as a non-MDR drug resistance gene of human cancers (1997)

To improve cancer chemotherapy, a better understanding of the molecular mechanisms of drug resistance is essential. To identify the molecules responsible for drug resistance that is unrelated to MDR1 or MRP gene products, a eukaryotic expression cDNA library of cis-diamminedichloroplatinum(II) (CDDP)-resistant ovarian cancer TYKnuR cells was introduced into Cos-7 cells. After repeated CDDP selection, cDNA homologous to murine semaphorin E was isolated from surviving cells. Human semaphorin E (H-sema E) was overexpressed in CDDP-resistant cell lines and was readily induced not only by diverse chemotherapeutic drugs but also by x-ray and UV irradiation. Transfection of H-sema E conferred a drug-resistant phenotype to CDDP-sensitive cells. In addition, the aberrant expression of H-sema E protein was detected immunohistochemically in 14 of 42 (33.3%) recurrent squamous cell carcinomas removed at autopsy after extensive radiochemotherapy. Recently, another member of the semaphorin family, CD100, was shown to significantly improve the viability of B lymphocytes. These results suggest the involvement of semaphorins in diverse cell survival mechanisms.