gebhart/patrepeval huggingface dataset:
The Lymphochip: A Specialized cDNA Microarray for the Genomic-scale Analysis of Gene Expression in Normal and Malignant Lymphocytes (1999)

Immunologists have a long tradition of dissecting thecellular components of the immune system based on theexpression of cell surface markers. Because of the easewith which immune cell subsets can be identified andsorted using these markers, the immune system is one ofthe best-understood differentiation systems in mammalian biology. Despite this success, the known lymphoid subsets are defined by using only a handful of theapproximately 100,000 genes in the mammalian genome.Recently, methods have been developed that offer a genomic-scale analysis of gene expression, and we have begun to view the immune system from this new perspective. Two technical advances have enabled this genomicview of biology: high throughput sequencing of cDNA libraries for gene discovery (Adams et al. 1992) and microarray technology for genomic-scale quantitation ofgene expression (Schena et al. 1995, 1996; Lockhart et al.1996; Shalon et al. 1996). These two technologies are intimately coupled, since microarray technology can onlymeasure the expression of genes for which a sequenceand/or a physical clone exists. In this paper, we summarize our work combining these two methodologies to understand the gene expression program of normal B-lymphocyte differentiation and its relationship to the geneexpression profiles of human B-cell malignancies...
5-Methyltetrahydrofolate, the Active Form of Folic Acid, Restores Endothelial Function in Familial Hypercholesterolemia (1998)

These results show that the active form of folic acid restores in vivo endothelial function in FH. It is suggested from our in vitro experiments that this effect is due to reduced catabolism of NO.
A novel engineered meganuclease induces homologous recombination in yeast and mammalian cells (2003)

Homologous gene targeting is the ultimate tool for reverse genetics, but its use is often limited by low efficiency. In a number of recent studies, site- specific DNA double-strand breaks (DSBs) have been used to induce efficient gene targeting. Engineering highly specific, dedicated DNA endonucleases is the key to a wider usage of this technology. In this study, we present two novel, chimeric meganucleases, derived from homing endonucleases. The first one is able to induce recombination in yeast and mammalian cells, whereas the second cleaves a novel (chosen) DNA target site. These results are a first step toward the generation of custom endonucleases for the purpose of targeted genome engineering.
Homogeneous plate based antibody internalization assay using pH sensor fluorescent dye (2016)

Receptor-mediated antibody internalization is a key mechanism underlying several anti-cancer antibody therapeutics. Delivering highly toxic drugs to cancer cells, as in the case of antibody drug conjugates (ADCs), efficient removal of surface receptors from cancer cells and changing the pharmacokinetics profile of the antibody drugs are some of key ways that internalization impacts the therapeutic efficacy of the antibodies. Over the years, several techniques have been used to study antibody internalization including radiolabels, fluorescent microscopy, flow cytometry and cellular toxicity assays. While these methods allow analysis of internalization, they have limitations including a multistep process and limited throughput and are generally endpoint assays. Here, we present a new homogeneous method that enables time and concentration dependent measurements of antibody internalization. The method uses a new hydrophilic and bright pH sensor dye (pHAb dye), which is not fluorescent at neutral pH but becomes highly fluorescent at acidic pH. For receptor mediated antibody internalization studies, antibodies against receptors are conjugated with the pHAb dye and incubated with the cells expressing the receptors. Upon binding to the receptor, the dyes conjugated to the antibody are not fluorescent because of the neutral pH of the media, but upon internalization and trafficking into endosomal and lysosomal vesicles the pH drops and dyes become fluorescent. The enabling attributes of the pHAb dyes are the hydrophilic nature to minimize antibody aggregation and bright fluorescence at acidic pH which allows development of simple plate based assays using a fluorescent reader. Using two different therapeutic antibodies--Trastuzumab (anti-HER2) and Cetuximab (anti-EGFR)--we show labeling with pHAb dye using amine and thiol chemistries and impact of chemistry and dye to antibody ration on internalization. We finally present two new approaches using the pHAb dye, which will be beneficial for screening a large number of antibody samples during early monoclonal development phase.
Epidermal Growth Factor in the Treatment of Diabetic Foot Ulcers: An Update (2012)

Management of diabetic foot ulcers remains a rather challenging task. Epidermal growth factor (EGF) plays a central role in wound healing. It acts on epithelial cells and fibroblasts promoting restoration of damaged epithelium. However, its bioavailability is impaired in chronic diabetic foot ulcers. Current evidence suggests that application of human recombinant EGF in addition to standard treatment is able to achieve both partial and complete healing and to prevent foot amputations. Its efficacy has been tested at various concentrations and by various administration routes (topical application and intralesional injection). Intralesional injection has better availability on the deep wound layers, but pain at the injection site is a common complaint. Generally, adverse events have been minor to mild. Finally, numerous issues need to be further clarified before widespread use of EGF becomes possible in everyday practice. Such issues include optimal dosage and administration route, characteristics of the ulcers most likely to heal (severity and ischemic/neuropathic or both), and cost-effectiveness.
Docosahexaenoic acid promotes differentiation of developing photoreceptors in culture. (1998)

The advancement in differentiation selectively elicited by 22:6 correlates with the fact that 22:6 n-3, but none of the other fatty acids, delays significantly the onset of apoptosis in photoreceptors in culture. The synthesis of 22:6-containing phospholipid molecules could be required for the proper localization of opsin. This could contribute to furthering the differentiation of photoreceptors, preventing their apoptosis, and extending their survival.
Multiple aromatic side chains within a disordered structure are critical for transcription and transforming activity of EWS family oncoproteins (2007)

Chromosomal translocations involving the N-terminal approximately 250 residues of the Ewings sarcoma (EWS) oncogene produce a group of EWS fusion proteins (EFPs) that cause several distinct human cancers. EFPs are potent transcriptional activators and interact with other proteins required for mRNA biogenesis, indicating that EFPs induce tumorigenesis by perturbing gene expression. Although EFPs were discovered more than a decade ago, molecular analysis has been greatly hindered by the repetitive EWS activation domain (EAD) structure, containing multiple degenerate hexapeptide repeats (consensus SYGQQS) with a conserved tyrosine residue. By exploiting total gene synthesis, we have been able to systematically mutagenize the EAD and determine the effect on transcriptional activation by EWS/ATF1 and cellular transformation by EWS/Fli1. In both assays, we find the following requirements for EAD function. First, multiple tyrosine residues are essential. Second, phenylalanine can effectively substitute for tyrosine, showing that an aromatic ring can confer EAD function in the absence of tyrosine phosphorylation. Third, there is little requirement for specific peptide sequences and, thus, overall sequence composition (and not the degenerate hexapeptide repeat) confers EAD activity. Consistent with the above findings, we also report that the EAD is intrinsically disordered. However, a sensitive computational predictor of natural protein disorder (PONDR VL3) identifies potential molecular recognition features that are tyrosine-dependent and that correlate well with EAD function. In summary we have uncovered several molecular features of the EAD that will impact future studies of the broader EFP family and molecular recognition by complex intrinsically disordered proteins.
Effects of Cardiopulmonary Bypass on Renal Perfusion, Filtration, and Oxygenation in Patients Undergoing Cardiac Surgery (2016)

Cardiopulmonary bypass impairs renal oxygenation due to renal vasoconstriction and hemodilution during and after cardiopulmonary bypass, accompanied by increased release of a tubular injury marker.
Realization of All-Optical Flip-Flop Using Directionally Coupled Bistable Laser Diode (2004)

A novel all-optical flip-flop device has been realized using a directionally-coupled bistable laser diode (DC-BLD). We have fabricated the DC-BLD by a conventional fabrication technique of LDs. To separate the adjacent electrodes of the directional coupler, an oblique electron-beam evaporation technique was developed. By this self-align process, the two adjacent waveguides of the directional coupler were electrically isolated without employing any additional lithography step. Using the fabricated DC-BLD, all-optical flip-flop has been demonstrated due to the nonlinear effects of the saturable absorber and the directional coupler. The flip-flop operation has been achieved with sufficiently small input optical power level around 0 dBm.
Increased expression of MCM5 is significantly associated with aggressive progression and poor prognosis of oral squamous cell carcinoma (2013)

The increased expression of MCM5 protein begins at the oral pre-cancerous stage. The higher expression of MCM5 protein is significantly associated with the aggressive progression and poor prognosis of OSCC.
Enzyme replacement therapy decreases hypergammaglobulinemia in Gaucher's disease. (1998)

We report the effects of enzyme replacement therapy in a patient with Gaucher's disease associated with a monoclonal gammopathy. Alglucerase induces a linear decline in immunoglobulin and beta 2-microglobulin levels. This observation suggests that this treatment decreases the chronic antigenic stimulation commonly found in Gaucher's disease.
Utrophin deficiency worsens cardiac contractile dysfunction present in dystrophin-deficient mdx mice (2005)

The loss of dystrophin in patients with Duchenne muscular dystrophy (DMD) causes devastating skeletal muscle degeneration and cardiomyopathy. Dystrophin-deficient (mdx) mice have a much milder phenotype, whereas double knockout (DKO) mice lacking both dystrophin and its homolog, utrophin, exhibit the clinical signs observed in DMD patients. We have previously shown that DKO and mdx mice have similar severities of histological features of cardiomyopathy, but no contractile functional measurements of DKO heart have ever been carried out. To investigate whether DKO mice display cardiac dysfunction at the tissue level, contractile response of the myocardium was tested in small, unbranched, ultrathin, right ventricular muscles. Under near physiological conditions, peak isometric active developed tension (F(dev), in mN/mm2) at a stimulation frequency of 4 Hz was depressed in DKO mice (15.3 +/- 3.7, n = 8) compared with mdx mice (24.2 +/- 5.4, n = 7), which in turn were depressed compared with wild-type (WT) control mice (33.2 +/- 4.5, n = 7). This reduced Fdev was also observed at frequencies within the murine physiological range; at 12 Hz, Fdev was (in mN/mm2) 11.4 +/- 1.8 in DKO, 14.5 +/- 4.2 in mdx, and 28.8 +/- 5.4 in WT mice. The depression of Fdev was observed over the entire frequency range of 4-14 Hz and was significant between DKO versus mdx mice, as well as between DKO or mdx mice versus WT mice. Under beta-adrenergic stimulation (1 micromol/l isoproterenol), Fdev in DKO preparations was only (in mN/mm2) 14.7 +/- 5.1 compared with 30.9 +/- 8.9 in mdx and 41.0 +/- 4.9 in WT mice. These data show that cardiac contractile dysfunction of mdx mice is generally worsened in mice also lacking utrophin.
Continuous positive airway pressure for asthma: not a big stretch? (2007)

Obesity increases the risk of both asthma and obstructive sleep apnoea (OSA). By compromising upper airway anatomy, obesity contributes to compromised pharyngeal mechanics and the development of OSA. The mechanisms for how obesity contributes to the development of asthma are less well understood. The association between obesity and asthma, however, is undeniable and to date over 30 articles have shown a relationship between the two 1, 2. Obesity has effects on both inflammation and airway mechanics, which may be important in asthma. For example, obesity has been associated with increased inflammatory cytokines and adipokines 3. The role of leptin, a hormone that decreases appetite and increases metabolism, has been of particular interest in obesity and asthma. Obese subjects have increased levels of leptin, suggesting leptin resistance, at least at the level of hypothalamic appetite regulation. Leptin has been found to be pro-inflammatory and in animal models it may increase airway hyperresponsiveness 4, 5.

However, the pro-inflammatory effects of obesity are not the only way in which obesity contributes to the development of asthma. The effect of obesity on lung mechanics may be just as or even more important. With obesity, lung volumes (especially functional residual capacity; FRC) decrease as a result of increased abdominal and chest wall pressure. Since airway calibre is a function of lung volume 6, 7, obesity contributes to smaller airway calibre. Smaller airway calibre is likely to unload the airway smooth muscle, increase actin–myosin cross-bridging and allow for increased shortening when activated 8, 9. Deep breathing has been found to be a potent bronchodilator by periodically stretching the airway smooth muscle and disturbing actin–myosin attachments, making contractions less forceful …
Modulators of nicotinic acetylcholine receptors as analgesics. (2004)

The analgesic properties of nicotine have prompted attempts to develop compounds that specifically target nicotinic acetylcholine receptors (nAChRs) in the nervous system, with the beneficial effects of nicotine but without its side effects. Thus far, only nAChR agonists have been reported as being in development for pain, although nAChR antagonists could also have a potentially analgesic action. Various problems associated with the use of nAChR agonists as analgesics have been identified and measures suggested to overcome some of them. This review describes the nAChR agonists A-85380, tebanicline, ABT-366833, ABT-202, ABT-894, epibatidine analogs and SIB-1663, of which ABT-366833, ABT-202 and ABT-894 are currently undergoing development as pain therapeutics. In vivo studies of the pathomechanism of neuropathic pain indicate that targeting alpha3beta4 does not have a specific action on neuropathic pain, and that alpha3beta4 ligands cause side effects. On the other hand, alpha4beta2 receptors are specific for neuropathic pain, and ligands that bind preferentially to these receptors both effectively relieve pain and do not cause many adverse effects. This is the basis of the difference between the action of tebanicline, which binds with greater specificity to alpha3beta4 receptors, and ABT-366833, which binds more specifically to alpha4beta2 receptors.
Role of Toll-like receptor mediated signaling pathway in ischemic heart (2009)

Stimulation of TLRs by exogenous and endogenous ligands triggers expression of several genes that are involved in innate immune responses. Recently, a role of TLR4 in the myocardial response to injury separate from microbial pathogens has been examined in experimental studies. TLR4 deficient mice sustain significantly smaller infarctions compared with wild-type control mice given similar areas at risk. Levels of serum cytokines such as IL-1b, IL-6, and TNFa are increased after ischemia/reperfusion, but these responses are attenuated in TLR4 deficient mice compared to control mice. TLR2 signaling also importantly contributes to cardiac dysfunction following ischemia/reperfusion. MyD88, a key adaptor protein for TLR signaling, is responsible for the protective effects of TLR signaling inhibition in ischemia/reperfusion injury. TLR4 gene polymorphism (Asp299Gly) attenuates innate immune responsiveness, reduces the risk for coronary artery disease, and increases a chance of longevity. The innate immune system is clearly involved in the pathogenesis of cardiovascular diseases and could be a new therapeutic target.
Single Image Super-resolution Using Spatial Transformer Networks (2017)

Most of the previous models performed well for Single Image Super-Resolution (SISR). In these methods, the Low Resolution (LR) input image is amplified to the size of High Resolution (HR) through bicubic interpolation. However, bicubic interpolation can not represent the high frequency features of images with only one filter. Therefore, in this paper, we used a original framework which can effectively extract the feature maps from the input image space and transform to HR feature maps based on Spatial Transformer Networks (STN). In our STN-SR method, there are three kinds of parameters should be learned from the model: (i) a serial of filters to extract LR image feature maps; (ii)a local small network to learn parameters of the transformation <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\Gamma_{\theta}(G)$</tex> and (iii) the filter parameters to restore the HR patchs from the input HR feature maps through a restoring layer. Our model directly focus on the whole image, the proposed STN-SR method does not clip the image into many small size patches, and can use the image gobal message to rebuild more robust local texture. Compared to privious SR methods, the proposed STN-SR method can gain completely real image, while illustrating better edge and texture preservation performance.
A comparison of weight elimination methods for reducing complexity in neural networks (2003)

Three methods are examined for reducing complexity in potentially oversized networks. These consists of either removing redundant elements based on some measure of saliency, adding a further term to the cost function penalizing complexity, or observing the error on a further, validation set of examples, and then stopping training as soon as this performance begins to deteriorate. It was demonstrated on a series of simulation examples that all of these methods can significantly improve generalization, but their performance can prove to be domain dependent.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
From bench to bedside for gene-directed enzyme prodrug therapy of cancer (2005)

Gene therapy of cancer offers the possibility of a targeted treatment that destroys tumors and metastases, but not normal tissues. In gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, the gene encoding an enzyme is delivered to tumor cells, followed by administration of a prodrug, which is converted locally to a cytotoxin by the enzyme. The producer cells as well as surrounding bystanders are subsequently killed. Promising results have meant that suicide gene therapy has reached multicenter phase III clinical trials. This review will discuss the development, efficiency, mode of action and pharmacokinetics of seven GDEPT systems in vitro and in vivo. We will review the latest data of those systems in clinical trials (herpes simplex virus thymidine kinase/gancyclovir, bacterial cytosine deaminase/5-fluorocytosine, bacterial nitroreductase/CB1954 and cytochrome P450/cyclophosphamide), as well as the development of more recent and experimental systems which are not yet in clinical trials (P450 reductase/tirapazamine, carboxypeptidase/CMDA, horseradish peroxidase/indole-3-acetic acid or paracetamol and others).
Combined implicit or explicit integration steps for hybrid simulation (2007)

Abstract Explicit integration procedures have been widely adapted and applied to hybrid simulations of the seismic response of structures due to their simplicity. However, these procedures are only conditionally stable and have limited recent applications of hybrid simulations to simple structural models with few degrees of freedom. A novel integration procedure is proposed herein, in which a fully implicit formulation is applied to solve the equation of motion for the hybrid model, but defaults to an explicit or noniterative formulation in steps that fail to converge. The advantages to this approach are the ensured continuity of the simulation and the reduced accumulation of errors that occur during consecutive explicit steps that may lead to instability. The implicit procedure is applied by loading the experimental substructures beyond the expected displacement for the current step, then using the displacements and forces measured through the load path in the iterative implicit scheme. This approach captures the instantaneous behaviour of experimental substructures without physically imposing iterations. Numerical and experimental simulations demonstrate the effectiveness of the proposed integration scheme for multi‐degree‐of‐freedom models, especially in utilization of longer time steps that exceed stability limits of explicit methods, prevention of excitation of higher modes, and testing of stiff systems. Copyright © 2007 John Wiley &amp; Sons, Ltd.
Multimodal photo annotation and retrieval on a mobile phone (2008)

Mobile phones are becoming multimedia devices. It is common to observe users capturing photos and videos on their mobile phones on a regular basis. As the amount of digital multimedia content expands, it becomes increasingly difficult to find specific images in the device. In this paper, we present a multimodal and mobile image retrieval prototype named MAMI (Multimodal Automatic Mobile Indexing). It allows users to annotate, index and search for digital photos on their phones via speech or image input. Speech annotations can be added at the time of capturing photos or at a later time. Additional metadata such as location, user identification, date and time of capture is stored in the phone automatically. A key advantage of MAMI is tha it is implemented as a stand-alone application which runs in real-time on the phone. Therefore, users can search for photos in their personal archives without the need of connectivity to a server. In this paper, we compare multimodal and monomodal approaches for image retrieval and we propose a novel algorithm named the Multimodal Redundancy Reduction (MR2) Algorithm. In addition to describing in detail the proposed approaches, we present our experimental results and compare the retrieval accuracy of monomodal versus multimodal algorithms.
Nearly 100% internal phosphorescence efficiency in an organic light-emitting device (2001)

We demonstrate very high efficiency electrophosphorescence in organic light-emitting devices employing a phosphorescent molecule doped into a wide energy gap host. Using bis(2-phenylpyridine)iridium(III) acetylacetonate [(ppy)2Ir(acac)] doped into 3-phenyl-4(1′-naphthyl)-5-phenyl-1,2,4-triazole, a maximum external quantum efficiency of (19.0±1.0)% and luminous power efficiency of (60±5) lm/W are achieved. The calculated internal quantum efficiency of (87±7)% is supported by the observed absence of thermally activated nonradiative loss in the photoluminescent efficiency of (ppy)2Ir(acac). Thus, very high external quantum efficiencies are due to the nearly 100% internal phosphorescence efficiency of (ppy)2Ir(acac) coupled with balanced hole and electron injection, and triplet exciton confinement within the light-emitting layer.