gebhart/patrepeval huggingface dataset:
Ventricular tachycardia in ischemic heart disease substrates (2014)

Advances in the treatment of myocardial infarction (MI) have improved survival after ischemic cardiac injury. Post-infarct structural and functional remodeling results in electrophysiologic substrates at risk for monomorphic ventricular tachycardia (MMVT). Characterization of this substrate using a variety of clinical and investigative tools has improved our understanding of MMVT circuits, and has accelerated the development of device and catheter-based therapies aimed at identification and elimination of this arrhythmia. This review will discuss the central role of the ischemic heart disease substrate in the development MMVT. Electrophysiologic characterization of the post-infarct myocardium using bipolar electrogram amplitudes to delineate scar border zones will be reviewed. Functional electrogram determinants of reentrant circuits such as isolated late potentials will be discussed. Strategies for catheter ablation of reentrant ventricular tachycardia, including structural and functional targets will also be examined, as will the role of the epicardial mapping and ablation in the management of recurrent MMVT.
Liver cell transplantation. (2005)

Liver cell transplantation is an emerging procedure, consisting of infusing mature adult hepatocytes in the portal system of the recipient. It aims to correct inborn errors of liver metabolism, bridge unstable patients to transplantation, or even allow bridge to recovery in fulminant liver failure. The technique addresses ideally patients with inborn errors of metabolism, unstable but not sick enough for orthotopic transplantation. Best results have so far been obtained in metabolic diseases, such as urea cycle disorders, glycogenosis type I, Crigler Najjar, Refsum disease and factor VII deficiency. Cryopreserved hepatocytes can be used, allowing delay between cell isolation and patient's transplantation. The percentage of engraftment obtained can reach up 10%, with de novo expression of deficient enzyme activity. Better results of engraftment have been obtained in animal studies by different chemical or physical techniques, but not yet applied in humans. Because supply of human cells can be limited, research also aims to obtain transplantable cells from other sources, such as embryonic or adult stem cells, or liver progenitor cells that could be expanded in vitro. Careful progression in this field, and collaboration between centers are mandatory to validate further the technique for wider clinical use.
Mitochondrial respiratory chain disorders and the liver (1999)

Mitochondrial respiratory chain disorders are an established cause of liver failure in early childhood but they are probably under-diagnosed, partly due to under-recognition and partly due to the difficulty of investigation. It is particularly important to look for mitochondrial disorders if the liver disease presents with hypoglycaemia and lactic acidaemia or if it is accompanied by neurological, muscle or renal tubular abnormalities. Respiratory chain defects have been demonstrated in a number of patients who die of liver failure following severe epilepsy; this includes at least some cases of Alpers syndrome or 'progressive neuronal degeneration of childhood'. In mitochondrial liver disease, histology usually shows steatosis, often accompanied by fibrosis, cholestasis and loss of hepatocytes. Unless the clinical picture suggests a particular syndrome, such as Pearson syndrome, biochemical assays and histochemistry should be the initial investigations. Ideally, investigations should be carried out on liver as well as more standard tissues, such as muscle, since defects can be tissue-specific. Nuclear defects and mtDNA point mutations are probably responsible for many cases of mitochondrial liver disease but, as yet, the only identified molecular abnormalities are mtDNA rearrangements and mtDNA depletion. Treatment of mitochondrial liver disease is unsatisfactory. If the disease is confined to the liver, transplantation may be appropriate but in several patients transplantation has been followed by the appearance of disease in other organs, particularly the brain.
Experimental scheme for qubit and qutrit symmetric informationally complete positive operator-valued measurements using multiport devices (2012)

It is crucial for various quantum information processing tasks that the state of a quantum system can be determined reliably and efficiently from general quantum measurements. One important class of measurements for this purpose is symmetric informationally complete positive operator-valued measurements (SIC-POVMs). SIC-POVMs have the advantage of providing an unbiased estimator for the quantum state with the minimal number of outcomes needed for full tomography. By virtue of Naimark's dilation theorem, any POVM can always be realized with a suitable coupling between the system and an auxiliary system and by performing a projective measurement on the joint system. In practice, finding the appropriate coupling is rather nontrivial. Here we propose an experimental design for directly implementing SIC-POVMs using multiport devices and path-encoded qubits and qutrits, the utility of which has recently been demonstrated by several experimental groups around the world. Furthermore, we describe how these multiports can be attained in practice with an integrated photonic system composed of nested linear optical elements.
Two-site enzyme immunoassay of cholesteryl ester transfer protein with monoclonal and oligoclonal antibodies. (1994)

We developed a sandwich-type enzyme immunoassay to measure cholesteryl ester transfer protein (CETP) mass in human plasma. A specific monoclonal antibody (TP-4) that recognizes an epitope located in the C-terminal domain was used for antigen capture and an anti-CETP peptide antibody directed against the 290-306 residue was used for detection. Bound antibodies were revealed with an antibody-peroxidase conjugate specific for rabbit IgG. The presence of 10 mL/L Triton X-100 in the incubation buffer increased antigen exposure of CETP in plasma. The curves for CETP in standard plasma and partially purified CETP were parallel. This technique is rapid (results within 6 h), accurate, precise (mean intra- and interassay CVs 3.6% and 8.4%, respectively), and simple to perform. Assay sensitivity is at microgram concentrations, with a working range of 20-200 micrograms/L. In 40 normolipidemic healthy subjects, the mean CETP concentration in plasma was 1.1 +/- 0.4 mg/L. A strong correlation between CETP concentration and CETP activity (r = 0.91, n = 42) was observed. In plasma, the bulk of CETP was found in high-density lipoprotein fractions. Therefore, this assay may be a useful tool for investigations of CETP and its significance in relevant diseases.
A new 2D segmentation method based on dynamic programming applied to computer aided detection in mammography (2004)

Mass segmentation plays a crucial role in computer-aided diagnosis (CAD) systems for classification of suspicious regions as normal, benign, or malignant. In this article we present a robust and automated segmentation technique--based on dynamic programming--to segment mass lesions from surrounding tissue. In addition, we propose an efficient algorithm to guarantee resulting contours to be closed. The segmentation method based on dynamic programming was quantitatively compared with two other automated segmentation methods (region growing and the discrete contour model) on a dataset of 1210 masses. For each mass an overlap criterion was calculated to determine the similarity with manual segmentation. The mean overlap percentage for dynamic programming was 0.69, for the other two methods 0.60 and 0.59, respectively. The difference in overlap percentage was statistically significant. To study the influence of the segmentation method on the performance of a CAD system two additional experiments were carried out. The first experiment studied the detection performance of the CAD system for the different segmentation methods. Free-response receiver operating characteristics analysis showed that the detection performance was nearly identical for the three segmentation methods. In the second experiment the ability of the classifier to discriminate between malignant and benign lesions was studied. For region based evaluation the area Az under the receiver operating characteristics curve was 0.74 for dynamic programming, 0.72 for the discrete contour model, and 0.67 for region growing. The difference in Az values obtained by the dynamic programming method and region growing was statistically significant. The differences between other methods were not significant.
Magnetization Transfer Magnetic Resonance Imaging (1996)

Magnetic resonance imaging has traditionally used the T1 and T2 relaxation times and proton density (PD) of tissue water (hydrogen protons) to manipulate contrast. Magnetization transfer (MT) is a new form of tissue contrast based on the physical concept that tissues contain two or more separate populations of hydrogen protons: a highly mobile (free) hydrogen (water) pool, Hr, and an immobile (restricted) hydrogen pool, Hr, the latter being those protons bound to large macromolecular proteins and lipids, such as those found in such cellular membranes as myelin. Direct observation of the Hr magnetization pool is normally not possible because of its extremely short T2 time (< 200 microseconds). But saturation of the restricted pool will have a detectable effect on the mobile (free) proton pool. Saturation of the restricted pool decreases the signal of the free pool by transferring the restricted pool's saturation. Exchange of magnetization between the free and restricted hydrogen protons is a substantial mechanism for spin-lattice (T1) relaxation in tissues and the physical basis of MT. Through an appropriately designed pulse sequence, magnetization transfer contrast (MTC) can be produced. MT contrast is different from T1, T2, and PD, and it likely reflects the structural integrity of the tissue being imaged. A variety of clinically important uses of MT have emerged. In this clinical review of the neuroradiological applications of MT, we briefly review the physics of MT, the appearance of normal brain with MT, and the use of MT as a method of contrast enhancement/background suppression and in tissue characterization, such as evaluation of multiple sclerosis and other white-matter lesions and tumors. The role of MT in small-vessel visualization on three-dimensional time-of-flight magnetic resonance angiography and in head and neck disease and newer applications of MT are also elaborated.
Factors influencing isradipine and amlodipine binding to human plasma lipoproteins. (1994)

The objectives of this study were to determine the distribution of isradipine among individual plasma lipoproteins ex vivo in healthy volunteers (n = 8) and in hypercholesterolaemic patients (n = 12), and to investigate the mechanisms involved in the interaction of isradipine and amlodipine with isolated lipoprotein fractions in vitro. The distribution study ex vivo demonstrated the different relative affinity of isradipine for the plasma lipoproteins: high-density lipoprotein (HDL) > low-density lipoprotein (LDL) > very low-density lipoprotein (VLDL). Isradipine binding correlated linearly with the cholesterol levels in LDL and VLDL; however, binding to HDL did not correlate with the cholesterol level in this fraction. The total binding affinity of isradipine to isolated LDL was markedly higher compared with amlodipine; total binding affinity (nKa) of isradipine vs amlodipine was (1.60 +/- 0.08) x 10(7) l/mol vs (4.14 +/- 0.33) x 10(6) l/mol, respectively. Binding to HDL was also higher with isradipine --nKa = (1.04 +/- 0.04) x 10(5) l/mol--compared with that of amlodipine: nKa = (3.82 +/- 0.18) x 10(4) l/mol. There was no significant competitive binding effect of cyclosporin A (CyA) on isradipine binding to individual lipoprotein fractions. It is likely that, in addition to the structure of surface apoproteins, the factors determining the interaction of calcium antagonists with plasma lipoproteins also include the plasma level of each lipoprotein fraction as well as the lipophilicity of the drug.
Dynamic reconfiguration to support concurrent applications (2002)

The proposed dynamically reconfigurable system can support multiple applications running concurrently. An FPGA resource manager is developed to allocate and de-allocate FPGA resources and to pre-load FPGA configuration files. For each individual application, different tasks that require FPGA resources are represented as a flow graph which is made available to the resource manager so as to enable efficient resource management and pre-loading. The impact of supporting concurrency and pre-loading in reducing application execution time is demonstrated.
Arthritis-inducing ability of a synthetic adjuvant, N-acetylmuramyl peptides, and bacterial disaccharide peptides related to different oil vehicles and their composition (1980)

A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), failed to produce polyarthritis with a wide dose range in a water-in-oil emulsion of mineral oil such as liquid paraffin, Drakeol, or heavy mineral oil. MDP, however, produced moderate to severe arthritis with almost 100% incidence in a water-in-oil emulsion made up of Difco incomplete adjuvant, which consists of Bavol F as an oil vehicle and Arlacel A as an emulsifier. N-acetylmuramyl-L-alanyl-L-isoglutamine did not produce arthritis, whereas 4,6-diacetyl-MDP produced the disease. Bacterial peptidoglycans, such as disaccharide peptides which were N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelyl-D-alanine and N-acetylglucosaminyl-6,o-acetyl-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelyl-D-alanine, also produced polyarthritis with low incidence in Difco oil but not in the other mineral oils described above. MDP and bacterial disaccharide peptides were able to produce the disease even in the latter mineral oil only when the concentration of Arlacel A was increased from 15% to 20 to 30% in the oil. We concluded that one of the minimal essential structures responsible for development of this disease is MDP, although the role of the oil vehicle remained uncertain, and there is no direct correlation between granulona formation and arthritogenicity of MDP.
Toll receptors and sepsis (2001)

Toll-like receptors are a family of receptors that recognize components of bacteria and induce a proinflammatory response by cells, including macrophages and endothelial cells. Ten human Toll receptors differing in their specificity for microbial components have been cloned. They respond to various components, including lipopolysaccharide of Gram-negative bacteria, lipopeptides of Gram-positive cell walls, bacterial DNA, and flagella. Some Toll-like receptors require the cooperation of an adapter protein. Toll-like receptor 4 function requires the presence of the protein MD2. Recently, it has been shown that Toll-like receptors function cooperatively to increase the specificity of response to a given microbe. Human polymorphisms of Toll-like receptor genes have been discovered and are associated with hyporesponsiveness to bacterial components.
Analysis of Ig VH region genes encoding IgE antibodies in splenic B lymphocytes of a patient with asthma. (1995)

Abstract An atopic patient with hypersensitivity against house dust mite died as a result of an asthmatic attack. A portion of the spleen was obtained and was used to analyze the spectrum of Ig heavy chain V regions involved in encoding IgE Abs. A nested PCR technique generated 14 cloned VH sequences that had distinct CDR3 regions; 5 of 14 were derived from the minor VH5 family, and the remainder derived from the larger families, VH3 (6 of 14) and VH4 (3 of 14). One of the VH3-derived sequences was present as a repeated sequence in three clones. A control PCR with the same VH primers in combination with JH primers yielded only 1 of 13 sequences from VH5, indicating preferential VH5 usage only for IgE. Analysis of VH5-C epsilon sequences revealed usage of a single gene, DP73, with extensive mutations and several "hot spots" containing common replacement amino acids. However, there was no concentration of replacement mutations in the CDRs, which conventionally would indicate a role for Ag selection. The VH3 and VH4 genes in combination with C epsilon also harbored extensive somatic mutations. From these findings in splenic B lymphocytes, and those of a previous study of blood lymphocytes, it seems that preferential usage of VH5 genes and extensive somatic hypermutation are characteristic of B cells synthesizing IgE in patients with allergic disease.
p38α MAPK and Type I Inhibitors: Binding Site Analysis and Use of Target Ensembles in Virtual Screening (2015)

Mitogen-activated protein kinase p38α plays an essential role in the regulation of pro-inflammatory signaling, and selective blockade of this kinase could be efficacious in many pathological processes. Despite considerable research efforts focused on the discovery and development of p38α MAPK inhibitors, no drug targeting this protein has been approved for clinical use so far. We herein analyze the available crystal structures of p38α MAPK in complex with ATP competitive type I inhibitors, getting insights into ATP binding site conformation and its influence on automated molecular docking results. The use of target ensembles, rather than single conformations, resulted in a performance improvement in both the ability to reproduce experimental bound conformations and the capability of mining active molecules from compound libraries. The information gathered from this study can be exploited in structure-based drug discovery programs having as the ultimate aim the identification of novel p38α MAPK type I inhibitors.
Biological conversion of carbon monoxide: rich syngas or waste gases to bioethanol (2011)

Abstract Bioconversion of syngas/waste gas components to produce ethanol appears to be a promising alternative compared to the existing chemical techniques. Recently, several laboratory‐scale studies have demonstrated the use of acetogens that have the ability to convert various syngas components (CO, CO 2 , and H 2 ) to multicarbon compounds, such as acetate, butyrate, butanol, lactate, and ethanol, in which ethanol is often produced as a minor end‐product. This bioconversion process has several advantages, such as its high specificity, the fact that it does not require a highly specific H 2 /CO ratio, and that biocatalysts are less susceptible to metal poisoning. Furthermore, this process occurs under mild temperature and pressure and does not require any costly pre‐treatment of the feed gas or costly metal catalysts, making the process superior over the conventional chemical catalytic conversion process. The main challenge faced for commercializing this technology is the poor aqueous solubility of the gaseous substrates (mainly CO and H 2 ). In this paper, a critical review of CO‐rich gas fermentation to produce ethanol has been analyzed systematically and published results have been compared. Special emphasis has been given to understand the microbial aspects of the conversion process, by highlighting the role of different micro‐organisms used, pathways, and parameters affecting the bioconversion. An analysis of the process fundamentals of various bioreactors used for the biological conversion of CO‐rich gases, mainly syngas to ethanol, has been made and reported in this paper. Various challenges faced by the syngas fermentation process for commercialization and future research requirements are also discussed. © 2011 Society of Chemical Industry and John Wiley &amp; Sons, Ltd
Augmentation of Melanoma-Specific Gene Expression Using a Tandem Melanocyte-Specific Enhancer Results in Increased Cytotoxicity of the Purine Nucleoside Phosphorylase Gene in Melanoma (1999)

The lineage-specific human tyrosinase promoter has been used to successfully target gene expression at the transcriptional level to melanoma cells. The tyrosinase promoter, alone and in combination with a single, or a dual, tandem melanocyte-specific enhancer, was used to regulate expression of the firefly luciferase reporter gene. Transient transfections of these tissue-specific luciferase constructs in human and murine melanoma (Pmel, B16mel) and colon carcinoma (WiDr, MC38) cell lines resulted in melanoma-specific luciferase expression that was amplified 5- and 500-fold with the addition of a single or double enhancer, respectively, to the tyrosinase promoter. When the double enhancer-promoter construct expressed the highly toxic Escherichia coli purine nucleoside phosphorylase (PNP) gene, transfection of the same cell lines followed by administration of the prodrug 6-methyl purine deoxyriboside (6-MPDR) at a concentration of 50 microM caused melanoma-specific in vitro cell killing. Within 5 days after prodrug administration methylthiazol-tetrazolium (MTT) cytotoxicity assays showed that only 15 and 9% of Pmel and B16mel cells, respectively, remained viable compared with controls. This effect was highly specific, as 90 and 96% of WiDr and MC38 colon carcinoma cells remained viable 5 days after identical treatment. This effect was a direct result of increased tissue-specific conversion of 6-MPDR to the toxic metabolite 6-methylpurine (6-MP), as documented by HPLC analysis of culture supernatants. These results show that the dual tandem melanocyte-specific enhancer provides powerful amplification of the transcriptional targeting of gene expression afforded by use of the tyrosinase promoter. This amplification translates into increased, highly specific cytotoxicity to melanoma by the PNP/6-MPDR enzyme/prodrug system and, therefore, has potential efficacy in the use of gene therapy for the treatment of metastatic melanoma.
Studies on bleomycin (1967)

Bleomycin A, which is a complex of water-soluble peptides produced by a Streptomyces, inhibits DNA synthesis in intact cells of E. coli and HeLa cells and also inhibits Ehrlich carcinoma and Sarcoma 180. When it is injected, it distributes in lung and skin at higher concentration than in blood and kidney. In dogs a large dose caused liver damage which was reversible but, when a lower dose was injected twice weekly, toxic signs appeared; the signs—inflammation of the foot pad and loss of hair—disappeared after cessation of the injection. It gave curative effect on a skin cancer in a dog. The authors conclude that the effect on skin cancer was due to the high concentration in skin.
Interface engineering of highly efficient perovskite solar cells (2014)

Advancing perovskite solar cell technologies toward their theoretical power conversion efficiency (PCE) requires delicate control over the carrier dynamics throughout the entire device. By controlling the formation of the perovskite layer and careful choices of other materials, we suppressed carrier recombination in the absorber, facilitated carrier injection into the carrier transport layers, and maintained good carrier extraction at the electrodes. When measured via reverse bias scan, cell PCE is typically boosted to 16.6% on average, with the highest efficiency of ~19.3% in a planar geometry without antireflective coating. The fabrication of our perovskite solar cells was conducted in air and from solution at low temperatures, which should simplify manufacturing of large-area perovskite devices that are inexpensive and perform at high levels.