gebhart/patrepeval huggingface dataset:
Abstract 4321: Development of pyrrolobenzodiazepine-based antibody-drug conjugates for cancer. (2013)

Abstract Pyrrolobenzodiazepine (PBD) dimers are highly cytotoxic minor groove binding DNA crosslinking agents derived from the anthramycin class of natural products. In our efforts to develop highly effective and well-tolerated treatment options for cancer patients, we have investigated several antibody-drug conjugates (ADCs) based on a PBD dimer. The fully synthetic PBD-linker, comprised of a protease-cleavable val-ala sequence and a reactive maleimide group, was conjugated via engineered cysteine residues to humanized monoclonal antibodies specific for their binding to the well-characterized cancer antigen targets, CD33 and CD70. The resulting ADCs were well-defined, monomeric and showed pronounced in vitro and in vivo activity against both hematologic and solid tumor cancer models. These included models of acute myelogenous leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma and renal cell carcinoma. The ADCs were immunologically specific, and showed potent activity in MDR-positive models, including models resistant to other ADCs. These results underscore the importance of the drug component in developing highly efficacious ADCs for cancer therapy. Citation Format: Scott C. Jeffrey, Patrick J. Burke, May K. Sutherland, David W. Meyer, Robert P. Lyon, Julie A. McEarchern, Che-Leung Law, Peter D. Senter. Development of pyrrolobenzodiazepine-based antibody-drug conjugates for cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4321. doi:10.1158/1538-7445.AM2013-4321
Behaviour of thymocyte nuclei in non activated and activated mouse oocytes (1984)

Cells originating from the thymus of newborn mice were fused with mouse oocytes using polyethylene glycol. The behaviour of thymocyte nuclei was studied in non-activated metaphase II oocytes, and in oocytes activated in vitro with ethanol. In non-activated oocytes all thymocyte nuclei undergo premature chromosome condensation with individualization of chromosomes; the chromosomes form separate groups in the cytoplasm, or are assembled around the metaphase II spindle, or located on the extra-spindle. In activated oocytes thymocyte nuclei start to develop along a pronucleus-like pathway (decondensation, visualization of nucleoli, swelling) and increase up to 200 times in volume during 24 h culture in vitro, eventually reaching the size of a fully grown pronucleus. Activation/fusion timing seems to be critical for the full remodelling of thymocyte nuclei. Nuclei introduced before (10-30 min) or shortly after (up to 60 min) activation often grow larger than the female pronucleus. Those introduced into oocytes long before activation (greater than 30 min) undergo premature condensation with subsequent reformation of nuclei that are sometimes deficient (as indicated by the presence of micronuclei), or of hybrid character. Nuclei introduced late after activation (greater than 60 min) are mostly doomed to retarded development. The implications of the present observations for nuclear transfer experiments in mammals are discussed.
CRISPR-Cas in Streptococcus pyogenes (2019)

The discovery and characterization of the prokaryotic CRISPR-Cas immune system has led to a revolution in genome editing and engineering technologies. Despite the fact that most applications emerged after the discovery of the type II-A CRISPR-Cas9 system of Streptococcus pyogenes, its biological importance in this organism has received little attention. Here, we provide a comprehensive overview of the current knowledge about CRISPR-Cas systems from S. pyogenes. We discuss how the interplay between CRISPR-mediated immunity and horizontal gene transfer might have modeled the evolution of this pathogen. We review the current literature about the CRISPR-Cas systems present in S. pyogenes (types I-C and II-A), and describe their distinctive biochemical and functional features. Finally, we summarize the main biotechnological applications that have arisen from the discovery of the CRISPR-Cas9 system in S. pyogenes.
Inactivity and weight loss: effective criteria to identify frailty. (2003)

The effectiveness was examined of inactivity and weight loss as criteria to identify a frail subgroup within independently living elderly persons participating in the SENECA study (Survey in Europe on Nutrition and the Elderly, a Concerted Action). Eight-hundred-forty-nine participants (aged 75 to 80) from nine countries were classified in four subgroups: 1) inactive elderly (lowest tertile activity score: n = 204); 2) weight losing elderly (lowest quintile: * 6.3% weight loss over 4-5 years: n = 108); 3) both inactive and weight losing (n = 54); 4) neither inactive nor weight losing: reference (n = 483). Differences in health, physical functioning and nutritional characteristics between groups 1, 2 and 3 respectively, and the reference group were evaluated. Compared to the weight-stable, active reference group, both inactive, weight losing (group 3) and inactive subjects (group 1) reported significantly more chronic diseases (2.2 and 1.8 vs. 1.1), disabilities (81 and 80 vs. 43%), use of medications (both 2.3 vs. 1.1) and care services (26 and 21 vs. 6%), and a lower self-rated health (2.8 and 3.1 vs. 3.8), relative health (1.9 and 2.1 vs. 2.6), and physical performance score (17 and 18 vs. 22). In addition, inadequate micronutrient intake and biochemical deficiencies were more prevalent. Weight-losing elderly were not significantly different from the reference group with respect to these characteristics. Therefore, physical inactivity alone or in combination with weight loss seems to be a practical and inexpensive screening criterion for identifying a subgroup of elderly with less favourable health and nutritional characteristics and poorer physical functioning among non-institutionalised elderly.
An anti-GD2 single chain Fv selected by phage display and fused to Pseudomonas exotoxin A develops specific cytotoxic activity against neuroblastoma derived cell lines (2001)

Since the disialoganglioside GD2 is abundantly present on the surface of neuroblastoma cells, we constructed a new recombinant immunotoxin for possible clinical use in patients with neuroblastoma. A functional 14.18 scFv-phage was obtained by selection of an anti-GD2 hybridoma derived phage antibody mini-library on the neuroblastoma-derived, GD2-expressing cell line IMR5. By insertion into the bacterial expression vector pBM1.1 the selected scFv was fused to a deletion mutant of Pseudomonas exotoxin A (ETA'). Periplasmically expressed 14.18(scFv)-ETA' bound to the GD2 expressing cell line IMR5, but not to the GD2 negative Hodgkin-derived cell line L540Cy as documented by ELISA and flow cytometry. The recombinant immunotoxin (rIT) inhibited cell viability of IMR5 cells by 50% at concentrations (IC(50)) of 0.326 microg/ml. This recombinant immunotoxin will be further investigated in vivo for its value as a new immunotherapeutic agent for the treatment of patients with neuroblastoma.
IGF-1 mediated Neurogenesis Involves a Novel RIT1/Akt/Sox2 Cascade (2017)

Insulin-like growth factor 1 (IGF-1) is known to have diverse effects on brain structure and function, including the promotion of stem cell proliferation and neurogenesis in the adult dentate gyrus. However, the intracellular pathways downstream of the IGF-1 receptor that contribute to these diverse physiological actions remain relatively uncharacterized. Here, we demonstrate that the Ras-related GTPase, RIT1, plays a critical role in IGF-1-dependent neurogenesis. Studies in hippocampal neuronal precursor cells (HNPCs) demonstrate that IGF-1 stimulates a RIT1-dependent increase in Sox2 levels, resulting in pro-neural gene expression and increased cellular proliferation. In this novel cascade, RIT1 stimulates Akt-dependent phosphorylation of Sox2 at T118, leading to its stabilization and transcriptional activation. When compared to wild-type HNPCs, RIT1 <sup>-/-</sup> HNPCs show deficient IGF-1-dependent Akt signaling and neuronal differentiation, and accordingly, Sox2-dependent hippocampal neurogenesis is significantly blunted following IGF-1 infusion in knockout (RIT1 <sup>-/-</sup> ) mice. Consistent with a role for RIT1 function in the modulation of activity-dependent plasticity, exercise-mediated potentiation of hippocampal neurogenesis is also diminished in RIT1 <sup>-/-</sup> mice. Taken together, these data identify the previously uncharacterized IGF1-RIT1-Akt-Sox2 signaling pathway as a key component of neurogenic niche sensing, contributing to the regulation of neural stem cell homeostasis.
Evaluation of Network Connection Credibility based on Neural Network (2011)

This paper presents an innovative method to evaluate the credibility of network connections based on neural network with back propagation (BP) network model and Levenberg-Marquardt (LM) optimization algorithm. In it, the second-level index values are taken as input and expected evaluation values as output, based on which, L test samples are used to test the trained neural network. At last, a prediction is made to evaluate the current connection credibility according to the trained neural network and corresponding security strategies are adopted on the basis of the evaluation values. It is shown that the nonlinear relationship between the attributes and the credibility of network connections can be established by training neural-network using LM algorithm. Simulation results indicate this method could achieve high evaluation accuracy.
SPIGAN: Privileged Adversarial Learning from Simulation (2018)

Deep Learning for Computer Vision depends mainly on the source of supervision.Photo-realistic simulators can generate large-scale automatically labeled syntheticdata, but introduce a domain gap negatively impacting performance. We propose anew unsupervised domain adaptation algorithm, called SPIGAN, relying on Sim-ulator Privileged Information (PI) and Generative Adversarial Networks (GAN).We use internal data from the simulator as PI during the training of a target tasknetwork. We experimentally evaluate our approach on semantic segmentation. Wetrain the networks on real-world Cityscapes and Vistas datasets, using only unla-beled real-world images and synthetic labeled data with z-buffer (depth) PI fromthe SYNTHIA dataset. Our method improves over no adaptation and state-of-the-art unsupervised domain adaptation techniques.
Computer-aided surface representation and design (1984)

New methods for representing and approximating three and four dimensional surfaces were created. These schemes are the core of our forthcoming Surface Software Package. Surfaces are understood adequately only through the use of dynamic computer graphics; therefore, graphics capability is also included. The numerous applications of surface methods include modeling physical phenomena (e.g., combustion) and designing objects (e.g., airplanes and cars).
Wavelet coefficients cross-correlation analysis of times series (2013)

The discrete wavelet transform (DWT) is becoming very widely used in the analysis of discrete time stochastic processes. In this paper we explore the maximal overlap discrete wavelet transform (MODWT) which carries out the same filtering steps as the ordinary DWT but does not subsample by 2, and is well defined for any sample size. We address the problem of examining the wavelet auto and cross-correlation structure between wavelet coefficients at different scales of a time series. We construct an estimator of this quantity based on wavelets coefficients. The asymptotic distribution of this estimator is derived for a wide class of stochastics processes. A simulation experiment is reported which demonstrates how the cross-correlation is spreaded out over higher scales for linear and nonlinear processes
PDGF-BB increases endothelial migration on cord movements during angiogenesis in vitro. (1997)

To explore direct effects of platelet-derived growth factor (PDGF) on endothelial cells during angiogenesis in vitro, we have used cloned bovine aortic endothelial cells that spontaneously form cord structures. Recently we have shown that cells forming these endothelial cords express PDGF beta-receptors and that PDGF-BB can contribute to cellular proliferation and cord formation. In this study we investigated whether PDGF-induced cellular migration might also contribute to endothelial repair and angiogenesis in vitro. Ten individual endothelial cells in cords were tracked at an early stage of cord formation by video-timelapse microscopy. PDGF-BB (100 ng/ml) induced an increase in endothelial cell movement of 67 +/- 15% as compared with diluent control. Interestingly, PDGF-BB also increased movements of entire cord structures, followed at branching points, by 53 +/- 12% over diluent control. Taken together, these video-timelapse experiments suggested that the apparent movements of single endothelial cord cells might also be due to the motion of entire underlying cord structures in response to PDGF. To analyze the response of single endothelial cord cells we therefore examined whether PDGF-induced migration contributes to endothelial repair. Abrasions were applied with a razor blade to confluent monolayers of endothelial cells at an intermediate stage of cord formation. PDGF-BB concentration-dependently increased the distance to which cord-forming endothelial cells migrated into the abrasion. An increased number of elongated, i.e., probably migrating, endothelial cells was found in the abrasion in response to PDGF-BB. However, there was no effect of PDGF-BB on the total number of endothelial cells found in the abrasion. PDGF-AA affected neither the distance to which the cells migrated nor the number of elongated cells. Actin and tubulin stainings revealed that these cytoskeletal structures were not appreciably altered by PDGF-BB. Furthermore, urokinase-type plasminogen activator transcripts were not modulated in response to PDGF-BB. We conclude that in this model of angiogenesis in vitro PDGF-BB can elicit the movement of entire cord structures, possibly via u-PA-independent mechanisms. PDGF-BB also controls the migration of single cord-forming endothelial cells. Thus, PDGF-BB possibly contributes to endothelial repair and angiogenesis by direct effects on proliferation and composite movements of PDGF beta-receptor-expressing endothelial cells and cords.
Helicobacter pylori and the Pathogenesis of Gastroduodenal Inflammation (1990)

Helicobacter pylori is a newly discovered gram-negative bacterium that lives in the human stomach and duodenum. Infection with this organism is strongly associated with type B antral gastritis and with peptic ulcer disease. Recent evidence from human volunteer studies, therapeutic trials with antimicrobial agents, and experiments with animal models indicates that H. pylori plays an etiologic role in the pathogenesis of type B gastritis. Gastric metaplasia is observed in virtually all patients with duodenal ulceration and may be the target tissue for these bacteria in the duodenum. Patients in whom H. pylori can no longer be identified after ulcer therapy remain in remission for significantly longer than do patients in whom the organism can be found. The data concerning an etiologic role of H. pylori in duodenal ulcer are suggestive but not yet conclusive. Present antimicrobial therapy can suppress but usually cannot eliminate H. pylori.
Pomegranate Juice, Total Pomegranate Ellagitannins, and Punicalagin Suppress Inflammatory Cell Signaling in Colon Cancer Cells (2006)

Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. In previous studies, pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced apoptosis in HT-29 colon cancer cells. The present study examined the effects of PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ reduced phosphorylation of the p65 subunit and binding to the NFkappaB response element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold, whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity. Therefore, the polyphenolic phytochemicals in the pomegranate can play an important role in the modulation of inflammatory cell signaling in colon cancer cells.
An 11 $\mu$w, two-electrode transimpedance biosignal amplifier with active current feedback stabilization (2009)

A novel two-electrode biosignal amplifier circuit is demonstrated by using a composite transimpedance amplifier input stage with active current feedback. Micropower, low gain-bandwidth product operational amplifiers can be used, leading to the lowest reported overall power consumption in the literature for a design implemented with off-the-shelf commercial integrated circuits (11 μW). Active current feedback forces the common-mode input voltage to stay within the supply rails, reducing baseline drift and amplifier saturation problems that can be present in two-electrode systems. The bandwidth of the amplifier extends from 0.05-200 Hz and the midband voltage gain (assuming an electrode-to-skin resistance of 100 kΩ) is 48 dB. The measured output noise level is 1.2 mV pp, corresponding to a voltage signal-to-noise ratio approaching 50 dB for a typical electrocardiogram (ECG) level input of 1 mVpp. Recordings were taken from a subject by using the proposed two-electrode circuit and, simultaneously, a three-electrode standard ECG circuit. The residual of the normalized ensemble averages for both measurements was computed, and the power of this residual was 0.54% of the power of the standard ECG measurement output. While this paper primarily focuses on ECG applications, the circuit can also be used for amplifying other biosignals, such as the electroencephalogram.
The role of tau (MAPT) in frontotemporal dementia and related tauopathies (2004)

Tau is a multifunctional protein that was originally identified as a microtubule-associated protein. In patients diagnosed with frontotemporal dementia and parkinsonism linked to chromosome 17, mutations in the gene encoding tau (MAPT) have been identified that disrupt the normal binding of tau to tubulin resulting in pathological deposits of hyperphosphorylated tau. Abnormal filamentous tau deposits have been reported as a pathological characteristic in several other neurodegenerative diseases, including frontotemporal dementia, Pick Disease, Alzheimer disease, argyrophilic grain disease, progressive supranuclear palsy, and corticobasal degeneration. In the last five years, extensive research has identified 34 different pathogenic MAPT mutations in 101 families worldwide. In vitro, cell-free and transfected cell studies have provided valuable information on tau dysfunction and transgenic mice carrying human MAPT mutations are being generated to study the influence of MAPT mutations in vivo. This mutation update describes the considerable differences in clinical and pathological presentation of patients with MAPT mutations and summarizes the effect of the different mutations on tau functioning. In addition, the role of tau as a genetic susceptibility factor is discussed, together with the genetic evidence for additional causal genes for tau-positive as well as tau-negative dementia.
Tumor rejection antigens of chemically induced sarcomas of inbred mice. (1986)

Chemically induced sarcomas of inbred mice are immunogenic in syngeneic hosts, and preimmunization with tumor cells leads to resistance to subsequent tumor transplants. The tumor rejection antigens (TRAs) that mediate this reaction are highly specific for each tumor; cross-protection between different syngeneic sarcomas is rare. Isolated membrane and cytosol fractions from two antigenically distinct BALB/c sarcomas, Meth A and CMS5, have TRA activity, and biochemical characterization of the active components from the cytosol and plasma membranes of these two tumors identified a glycoprotein of Mr 96,000. Immunization with unfractionated Meth A cytosol frequently leads to tumor enhancement, but the tumor-enhancing activity (TEA) is lost on fractionation and TRA activity becomes demonstrable. As Meth A and CMS5 lack expression of murine leukemia virus (MuLV) antigens or transcripts, MuLV-related antigens cannot be involved in the TEA or TRA activities of these tumors. In contrast to the lack of cross-reactivity between Meth A and CMS5 TRAs in transplantation tests, rabbit antiserum prepared against the Meth A Mr 96,000 antigen reacted with the CMS5 Mr 96,000 antigen. In view of the biochemical and antigenic similarities of Meth A and CMS5 TRAs, we propose that structurally related but distinct Mr 96,000 glycoproteins are expressed in chemically induced sarcomas and that these molecules are responsible for the individually specific immunogenicity of these tumors.
Implementation of the RELP vocoder using the TMS320 (2005)

A very small, high quality RELP Vocoder has been implemented with commercially available Integrated Circuits. This full-duplex, single-card design uses two TI TMS320 Digital Signal Processors. One processor implements the RELP Vocoder Analysis algorithm and the second implements the Synthesis algorithm. The Vocoder operates with a software-controlled, flexible data rate between 9.6 and 32 KBPS. It occupies less than 35 square inches with a power consumption of less than 5 W. A real-time demonstration is available.
Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus (2007)

In this study, 221 phytocompounds were evaluated for activity against anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) activities using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. Ten diterpenoids (1-10), two sesquiterpenoids (11 and 12), two triterpenoids (13 and 14), five lignoids (15-19), curcumin (20), and reference controls niclosamide (21) and valinomycin (22) were potent inhibitors at concentrations between 3.3 and 10 microM. The concentrations of the 22 compounds to inhibit 50% of Vero E6 cell proliferation (CC50) and viral replication (EC50) were measured. The selective index values (SI = CC50/EC50) of the most potent compounds 1, 5, 6, 8, 14, and 16 were 58, >510, 111, 193, 180, and >667, respectively. Betulinic acid (13) and savinin (16) were competitive inhibitors of SARS-CoV 3CL protease with Ki values = 8.2 +/- 0.7 and 9.1 +/- 2.4 microM, respectively. Our findings suggest that specific abietane-type diterpenoids and lignoids exhibit strong anti-SARS-CoV effects.
Detection and typing of human papillomaviruses present in fixed and stained archival cervical smears by a consensus polymerase chain reaction and direct sequence analysis allow the identification of a broad spectrum of human papillomavirus types (1992)

DNA well suited for polymerase chain reaction (PCR) amplification was purified from archival Papanicolaou smears. The detection of a wide range of human papillomavirus (HPV) types was made possible using a HPV-specific consensus primer pair, and typing was conveniently done by direct sequence analysis of the PCR product. The method could be of unique value in longitudinal and cross-sectional studies aimed at answering a number of fundamental pathological and epidemiological questions regarding HPV infection of the genital tract.