gebhart/patrepeval huggingface dataset:
A QT interval detection algorithm based on ECG curve length transform (2006)

We present an algorithm that automatically computes the QT interval duration from body surface electrocardiograms (ECGs). The algorithm consists of three processing steps: (1) PQ junction detection, (2) optimal lead selection, and (3) T-wave end detection. A previously developed algorithm for QRS detection was employed to detect the onset of each QRS complex, which was taken to be the PQ junction time. In the lead selection step, the ECG lead with the largest T-wave was automatically picked by the algorithm. For the T-wave end detection, the ECG signal in the estimated T-wave portion was transformed by means of an ECG curve length transform (LT); the T-wave end was determined using the resultant LT signal. The algorithm was applied to the first 30 seconds of 532 records in the PTB Diagnostic ECG Database. A score of 29.66 was achieved, which represents the RMS difference between the reference QT intervals and the algorithm’s results. 1.
A mammalian factor that binds telomeric TTAGGG repeats in vitro. (1992)

We have identified a DNA-binding activity with specificity for the TTAGGG repeat arrays found at mammalian telomeres. This factor, called TTAGGG repeat factor (TRF), is present in nuclear extracts of human, mouse, and monkey cells. TRF from HeLa cells was characterized in detail by electrophoretic mobility shift assays. It binds double-stranded TTAGGG repeats in linear and circular DNAs. Single-stranded repeats are not recognized. The optimal site for TRF appears to contain more than six contiguous TTAGGG repeats. Tandem arrays of TAGGG, TTTAGGG, TTTTAGGG, TTGGGG, and TTAGGC repeats do not bind TRF well, indicating that TRF preferentially recognizes the telomeric repeat sequence present at mammalian chromosome ends. The apparent molecular mass of this factor, based on recovery of TRF from sodium dodecyl sulfate-polyacrylamide gels, is approximately 50 kDa. We suggest that TRF binds along the length of mammalian telomeres.
Modified RNAs as potential drug targets. (1998)

Bleomycin (BLM) is a natural antibiotic that is effective in treatment of selected cancers. Although the exact therapeutic mechanism of bleomycin is not known, its target is thought to be a nucleic acid. Besides cleaving DNA, in vitro, Fe-bleomycin cleaves the anticodon of yeast tRNA(Phe) specifically. Using CD and fluorescence spectroscopy we have found that apo-bleomycin binds to synthetic RNA analogs of the anticodon of yeast tRNA(Phe) with an affinity similar to that previously reported for DNA. In order to understand BLM's selectivity, the role magnesium ions play in RNA recognition should be explained. Many RNA substrates for Fe-BLM, including yeast tRNA(Phe), are not cleaved by the drug when the Mg2+ concentration exceeds 1 mM. Competition experiments with anticodon analogs provide insight into the role of magnesium ions in RNA recognition by BLM. These simple modified RNAs may be useful as model systems for investigating BLM/RNA recognition and development of highly selective drugs toward RNA targets.
Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway (2005)

Models of Parkinson's disease (PD) based on selective neuronal death have been used to study pathogenic mechanisms underlying nigral cell death and in some instances to develop symptomatic therapies. For validation of putative neuroprotectants, a model is desirable in which the events leading to neurodegeneration replicate those occurring in the disease. We developed a human in vitro model of PD based on the assumption that dysregulated cytoplasmic dopamine levels trigger cell loss in this disorder. Differentiated human mesencephalic neuron-derived cells were exposed to methamphetamine (METH) to promote cytoplasmic dopamine accumulation. In the presence of elevated iron concentrations, as observed in PD, increased cytosolic dopamine led to oxidative stress, c-Jun N-terminal kinase (JNK) pathway activation, neurite degeneration, and eventually apoptosis. We examined the role of the mixed-lineage kinases (MLKs) in this complex degenerative cascade by using the potent inhibitor 3,9-bis[(ethylthio)methyl]-K-252a (CEP1347). Inhibition of MLKs not only prevented FeCl2+/METH-induced JNK activation and apoptosis but also early events such as neurite degeneration and oxidative stress. This broad neuroprotective action of CEP1347 was associated with increased expression of an oxidative stress-response modulator, activating transcription factor 4. As a functional consequence, transcription of the cystine/glutamate and glycine transporters, cellular cystine uptake and intracellular levels of the redox buffer glutathione were augmented. In conclusion, this new human model of parkinsonian neurodegeneration has the potential to yield new insights into neurorestorative therapeutics and suggests that enhancement of cytoprotective mechanisms, in addition to blockade of apoptosis, may be essential for disease modulation.
Functional vector generation for assertion-based verification at behavioral level using interval analysis (2004)

The 2001 International Technology Roadmap for Semiconductors (ITRS) predicts that it is unlikely that verification will be manageable for designs envisioned beyond 2007 without design-for-verifiability. Some CAD vendors have promoted assertion-based verification (ABV) as one of the first commercial design-for-verification techniques. In order to handle complex design, this methodology has to be complemented with tools that automatically generate vectors or counterexamples that violate/verify proposed assertions or constraints. This paper presents an assertion checking technique for behavioral models that combines a non-linear solver and state exploration techniques and avoids expanding behavior into logic equations. The kernel of the technique is a modified interval analysis (MODIA) that avoids most of the problems of classical interval analysis (IA) and improves reuse during vector generation. The results show that the proposed technique is able to handle very efficiently data-dominated designs, which research and commercial assertion/property checkers are unable or need more CPU effort to verify.
Fiber-optic Raman spectroscopy of joint tissues (2011)

In this study, we report adaptation of Raman spectroscopy for arthroscopy of joint tissues using a custom-built fiber-optic probe. Differentiation of healthy and damaged tissue or examination of subsurface tissue, such as subchondral bone, is a challenge in arthroscopy because visual inspection may not provide sufficient contrast. Discrimination of healthy versus damaged tissue may be improved by incorporating point spectroscopy or hyperspectral imaging into arthroscopy where the contrast is based on the molecular structure or chemical composition. Articular joint surfaces of knee cadaveric human tissue and tissue phantoms were examined using a custom-designed Raman fiber-optic probe. Fiber-optic Raman spectra were compared against reference spectra of cartilage, subchondral bone and cancellous bone collected using Raman microspectroscopy. In fiber-optic Raman spectra of the articular surface, there was an effect of cartilage thickness on recovery of signal from subchondral bone. At sites with intact cartilage, the bone mineralization ratio decreased but there was a minimal effect in the bone mineral chemistry ratios. Tissue phantoms were prepared as experimental models of the osteochondral interface. Raman spectra of tissue phantoms suggested that optical scattering of cartilage has a large effect on the relative cartilage and bone signal. Finite element analysis modeling of light fluence in the osteochondral interface confirmed experimental findings in human cadaveric tissue and tissue phantoms. These first studies demonstrate the proof of principle for Raman arthroscopic measurement of joint tissues and provide a basis for future clinical or animal model studies.
SILAM for quantitative proteomics of liver Akt1/PKBα after burn injury (2011)

Akt1/protein kinase Bα (Akt1/PKBα) is a downstream mediator of the insulin signaling system. In this study we explored mechanism(s) for its role in burn injury. Akt1/PKBα in liver extracts from mice with burn injury fed with (2H7)-L-Leu was immunoprecipitated and isolated with SDS-PAGE. Two tryptic peptides, one in the kinase loop and a control peptide just outside of the loop were sequenced via nano-LC interfaced with quadruple time-of-flight tandem mass spectrometry (Q-TOF tandem MS). Their relative isotopologue abundances were determined by stable isotope labeling by amino acids in mammalians (SILAM). Relative quantifications based on paired heavy/light peptides were obtained in 3 steps. The first step included homogenization of mixtures of equal amounts of tissue from burned and sham-treated animals (i.e., isotope dilution) and acquisition of uncorrected data based on parent monoisotopic MS ion ratios. The second step included determination of isotopic enrichment of the kinase from burned mice on Day 7 and the third step enrichment correction of partially labeled heavy and light monoisotopic MS ion ratios for relative quantification of bioactivity (loop peptide) and expression level (control peptide). Protein synthesis and enrichment after injury were found to be dependent on tissue and turnover of individual proteins. Three heavy and light monoisotopic ion ratios for albumin peptides from burned mice indicated ~55% enrichment and ~16.7-fold downregulation. In contract, serum amyloid P had ~66% enrichment and was significantly upregulated. Akt1/PKBα had ~56% enrichment and kinase level in response to the burn injury was upregulated compared with the control peptide. However, kinase bioactivity, represented by the Cys296 peptide, was significantly reduced. Overall, we demonstrated that i) quantitative proteomics can be performed without completely labeled mice; ii) measurement of enrichment of acyl-tRNAs is unnecessary and iii) Cys296 plays an important role in kinase activity after burn injury.
Construction and humanization of a functional bispecific EGFR × CD16 diabody using a refolding system (2011)

We previously reported the construction and activity of a humanized, bispecific diabody (hEx3) that recruited T cells towards an epidermal growth factor receptor (EGFR) positive tumor. Herein, we describe the construction of a second functional, fully humanized, anti-EGFR bispecific diabody that recruits another subset of lymphocyte effectors, the natural killer cells, to EGFR-expressing tumor cells. After we confirmed that an anti-EGFR × anti-CD16 bispecific diabody (Ex16) consisting of a previously humanized anti-EGFR variable fragment (Fv) and a mouse anti-CD16 Fv had growth inhibitory activity, we designed a humanized anti-CD16 Fv to construct the fully humanized Ex16 (hEx16). However, the humanized form had lower activity for inhibition of cancer growth. To restore its growth inhibitory activity, we introduced mutations into the Vernier zone, which is located near the complementarity-determining regions and is involved in their binding activity. We efficiently prepared 15 different hEx16 mutants by expressing each chimeric single-chain component for hEx16 separately. We then used our in vitro refolding system to select the most functional mutant, which had a growth inhibitory effect comparable with that of the commercially available chimeric anti-EGFR antibody, cetuximab. Our refolding system could aid in the efficient optimization of other proteins with heterodimeric structure.
Methodology for Capturing Driver Eye Glance Behavior during In-Vehicle Secondary Tasks (2005)

Driving is a visual task; any driver behavior that takes the driver's visual attention from the driving environment is likely to increase the risk of a crash. Many new intelligent transportation systems telematics applications are now being installed in cars, and some of these may result in substantial degradation of visual attention. Accurately capturing driver eye glance behavior during the evaluation of these devices is critical to assessing the safety impact of engaging in secondary tasks while driving. The development of a methodology is reported; it reliably determines on-road and off-road eye glance duration by using video data collected during highway driving evaluation trials while drivers were engaged with secondary tasks. Human raters determined glance location and duration by detailed coding of the driver's eye movements on the videos. The raters agreed most of the time, but sufficient disagreement suggested that using the consensus of multiple raters significantly improved the reliability of the resulting eye glance data.
Temperature-induced reflectivity changes and activation of hydrogen sensitive optically thin palladium films on silicon oxide (1998)

The optical properties of several thin metal film palladium-silicon oxide structures are examined at room temperature before and after annealing to 200 °C and also at 90 °C—in all cases in the presence of hydrogen gas. Multicycling sample activation is shown to occur in the presence of hydrogen at room temperature with an increase in reflectivity on exposure to hydrogen, in contrast to thicker 80 Å films. The reflectivity change increases with increasing film thickness (1–10 Å). The surface activation at room temperature, before and after annealing to 200 °C, is compared with the performance at 90 °C, where it is shown that heat treatment strongly influences the behavior of the metal film.
Heterogeneity of human mast cells based on cytokine content (1995)

Human mast cells can be divided into two distinct phenotypes based on their content of neutral serine proteases, suggesting that they serve differing biologic and pathologic roles. Recently, it has been demonstrated that human mast cells are a source of several pleiotropic cytokines including IL-4, IL-5, IL-6, IL-8, and TNF-alpha, but not all mast cells contain all of these cytokines, suggesting that there is also functional heterogeneity with respect to cytokine expression. In this study, we have examined the relationship between mast cell neutral protease expression and cytokine content using immunohistochemistry. Bronchial mucosal biopsies from five normal subjects and five patients with allergic asthma, and nasal mucosal biopsies from five normal subjects and three patients with allergic rhinitis were embedded in glycol methacrylate. Sections (2 microns) were stained for IL-4, IL-5, and IL-6, adjacent to serial sections stained for tryptase and chymase. The distribution of cytokines among the tryptase+ chymase- mast cells (MCT) and tryptase+ chymase+ mast cells (MCTC) was examined by co-localization of cytokines to MCTC or MCT in serial sections using the camera-lucida. Although IL-4 was distributed among both mast cell phenotypes, it was expressed preferentially by the MCTC subset (overall 85% MCTC:15% MCT). In contrast, IL-5 and IL-6 were restricted almost exclusively to the MCT subset. Immunostaining of isolated skin mast cells (> 99% MCTC) supported these findings, with strong immunoreactivity present for IL-4 but very little for IL-5 or IL-6. These results indicate that in addition to exhibiting heterogeneity with respect to neutral protease content of the secretory granules, human mast cells are also heterogeneous with respect to cytokine content. This suggests that the biologic functions of MCTC and MCT cells differ as a result of their capacity to generate and release different cytokine profiles.
A quantitative in vivo mouse model used to assay inhibitors of tumor-induced angiogenesis. (1991)

An in vivo model of tumor-induced angiogenesis was used to monitor two known inhibitors of angiogenesis, protamine sulfate and the steroid tetrahydro S. Tumor cells entrapped in alginate beads were injected s.c. into mice. Blood vessel induction was measured by two quantitative methods: measurement of hemoglobin at the alginate pellet site, and pooling of radiolabeled RBC to the alginate pellet site. The two methods gave parallel results. Tetrahydro S with or without heparin inhibited blood vessel growth by 50%, and protamine sulfate inhibited blood vessel growth by 85%. These results were supported by gross morphology and histological analysis of the alginate pellet site.
Pests and pathogens: plant responses to foliar attack (1993)

Plant versus pests and pathogens - an old story but the same story?, P.G. Ayres defoliation - do physiological and morphological responses lead to (over) compensation, A.H. Prins and H.J. Verkaar signals in the wounded plant, D.J. Bowles resistance - the role of the hypersensitive response and phytoalexins, R.N. Strange altered patterns of protein synthesis - their significance in defence and growth, M.T. Esquerre-Tugaye et al resistance and defence - the role of secondary plant substances, P.J. Edwards photosynthesis - cellular and tissue aspects in diseased leaves, J.D. Scholes beyond photosynthesis - the translocation and respiration of diseased leaves, J.F. Farrar partitioning to storage, re-growth and reproduction, N.D. Paul interaction of pests and pathogens on light interception, photosynthesis, growth rate and yield of field crops, W.A.H. Rossing et al constraints on the evolution of resistance to pests and pathogens, M.A. Parker.
The peritonitis dilemma: Better safe than sorry or wait for the cat to jump?* (2007)

Department of Surgery, University-Hospital Duesseldorf, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
Sympathectomy for Essential Hypertension (1952)

The successful treatment of essential hypertension remains one of the most difficult problems in medicine. Approximately 18 years have elapsed since extensive sympathectomy was first performed for essential hypertension. Extensive sympathectomy occasionally produces striking decrease in blood pressure of patients with essential hypertension; in many instances it fails to decrease blood pressure or modify the course of the disease. That which is most desired are some standards for preoperative selection of patients so that only patients who will be benefited by sympathectomy will be operated on. Unfortunately this apparently cannot be accomplished. The indications for sympathectomy remain at least partially uncertain and there is no agreement among those most experienced in the field of hypertension relative to the results of operation. There also are differences of opinion about the extensiveness of sympathectomy which is advisable. This paper indicates clearly differences of opinion among those most experienced in this field and emphasizes some of the points of agreement. It seems clear that additional technics of sympathectomy cannot be devised for the treatment of essential hypertension. There seems little doubt that sympathectomy would not be performed were adequate medical treatment available. This presentation gives the opinion of internists and surgeons who are particularly interested in hypertension and its treatment.
CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients (2016)

Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells, and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn't affect the viability of primary human T cells during the prolonged in vitro culture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-γ production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies.
Foam stability related to polymer permeability. I. Low molecular weight additives (1997)

In the production of polyethylene foams by extrusion with alkanes as a blowing agent, significant changes in the dimensions of extruded products are encountered. The dimensional stability of a foam with a structure of closed cells is improved by blending the polymer with small amounts of a low molecular weight additive. It is believed that the dimensional stability is related to the ratio of the blowing agent to air permeability. It is shown in this article that the additive reduces the blowing agent permeability more than it does the air permeability only if the additive has migrated to the surface of the polymer. The presence of the additive at the polymer surface has been confirmed by electron microscopy and infrared spectroscopy. The (partially) ordening of the additive at the surface, as shown with wide-angle X-ray diffraction, explains the low gas permeabilities of the additive compared to the corresponding permeabilities of polyethylene. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 65: 2679–2689, 1997
Engineering Three-Dimensional Pulmonary Tissue Constructs (2006)

In this paper, we report on engineering 3-D pulmonary tissue constructs in vitro. Primary isolates of murine embryonic day 18 fetal pulmonary cells (FPC) were comprised of a mixed population of epithelial, mesenchymal, and endothelial cells as assessed by immunohistochemistry and RT-PCR of 2-D cultures. The alveolar type II (AE2) cell phenotype in 2-D and 3-D cultures was confirmed by detection of SpC gene expression and presence of the gene product prosurfactant protein C. Three-dimensional constructs of FPC were generated utilizing Matrigel hydrogel and synthetic polymer scaffolds of poly-lactic-co-glycolic acid (PLGA) and poly-L-lactic-acid (PLLA) fabricated into porous foams and nanofibrous matrices, respectively. Three-dimensional Matrigel constructs contained alveolar forming units (AFU) comprised of cells displaying AE2 cellular ultrastructure while expressing the SpC gene and gene product. The addition of tissue-specific growth factors induced formation of branching, sacculated epithelial structures reminiscent of the distal lung architecture. Importantly, 3-D culture was necessary for inducing expression of the morphogenesis-associated distal epithelial gene fibroblast growth factor receptor 2 (FGFr2). PLGA foams and PLLA nanofiber scaffolds facilitated ingrowth of FPC, as evidenced by histology. However, these matrices did not support the survival of distal lung epithelial cells, despite the presence of tissue-specific growth factors. Our results may provide the first step on the long road toward engineering distal pulmonary tissue for augmenting and/or replacing dysfunctional native lung in diseases, such as neonatal pulmonary hypoplasia.