gebhart/patrepeval huggingface dataset:
Electrophysiologic Characteristics of a Pulsed Iontophoretic Drug-Delivery System in Coronary Arteries (1997)

This study evaluated the electrophysiologic effects of a pulsed iontophoretic drug-delivery system when used in the coronary arteries. Prevention of acute thrombosis and restenosis after intravascular procedures may be enhanced by high concentrations of therapeutic agents within the vessel wall. A new intravascular drug-delivery system uses iontophoresis to maximize local tissue concentrations of drug. However, the electrophysiologic effects of such a system in coronary arteries are unknown. An iontophoretic membrane balloon-tipped catheter was placed fluoroscopically in the mid left anterior descending coronary artery of 10 anesthetized dogs. Strength-duration curves and effective refractory period (ERP) were initially determined. Threshold for capture was assessed at pulse widths of 0.5, 1.0, 2.0, 4.0, and 8.0 ms. Capture occurred at 4.9 +/- 0.9, 3.4 +/- 0.5, 2.6 +/- 0.5, 1.6 +/- 0.2, and 1.2 +/- 0.2 mA, respectively. The ERP was 169 +/- 6 ms (4.0-ms pulses at twice threshold). Then square-wave pulses for iontophoresis were R-wave synchronized and delivered at 50 and 75% of the ERP with the balloon inflated to 1 atm. Output was increased until significant arrhythmias occurred [premature beats > 10/min, supraventricular tachycardia (SVT), ventricular tachycardia (VT), ventricular fibrillation (VF)], by using sequential steps of 1, 5, 10, 15, and 20 mA. Highest average outputs achieved without an arrhythmia were 14.1 +/- 2.5 and 4.9 +/- 2.0 mA at 50 and 75% of ERP, respectively (p < 0.05). High-grade arrhythmias (pulseless VT or VF) occurred in three of four animals studied before use of a frequency limiter, which allowed current delivery only at intervals > 400 ms (thus inhibiting current activation during premature beats). No further VT or VF occurred in the remaining six animals, except for one episode of nonsustained VT (11 beats). An R-wave synchronized iontophoretic field with a response-frequency limiter can be safely used within the canine coronary arterial system at 50% of ERP with moderate outputs (5-10 mA). Increasing the stimulus duration to 75% of ERP increases arrhythmogenesis but is tolerated at lower output levels (< 5 mA).
Selective Blockade of MicroRNA Processing by Lin28 (2008)

MicroRNAs (miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri-miRNAs) is blocked posttranscriptionally in embryonic stem cells, embryonal carcinoma cells, and primary tumors. Here we show that Lin28, a developmentally regulated RNA binding protein, selectively blocks the processing of pri-let-7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we found that Lin28 is necessary and sufficient for blocking Microprocessor-mediated cleavage of pri-let-7 miRNAs. Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers.
Computer methods to locate signals in nucleic acid sequences (1984)

This paper describes computer methods for locating signals in nucleic acid sequences. The signals include ribosome binding sites, promoter sequences and splice junctions. The methods are of use both to those trying to interpret the function of newly determined sequences and to those studying the molecular mechanisms involved in the recognition of these special signal sequences.
Adaptive Analog Nonlinear Algorithms and Circuits for Improving Signal Quality in the Presence of Technogenic Interference (2013)

We introduce algorithms and conceptual circuits for Nonlinear Differential Limiters (NDLs), and outline a methodology for their use to mitigate in-band noise and interference, especially that of technogenic (man-made) origin, affecting various real, complex, and/or vector signals of interest, and limiting the performance of the affected devices and services. At any given frequency, a linear filter affects both the noise and the signal of interest proportionally, and when a linear filter is used to suppress the interference outside of the passband of interest, the resulting signal quality is invariant to the type of the amplitude distribution of the interfering signal, as long as the total power and the spectral composition of the interference remain unchanged. Such a linear filter can be converted into an NDL by introducing an appropriately chosen feedback-based nonlinearity into the response of the filter, and the NDL may reduce the spectral density of particular types of interferences in the signal passband without significantly affecting the signal of interest. As a result, the signal quality can be improved in excess of that achievable by the respective linear filter. The behavior of an NDL filter and its degree of nonlinearity is controlled by a single parameter in a manner that enables significantly better overall suppression of the noise compared to the respective linear filter, especially when the noise contains components of technogenic origin. Adaptive configurations of NDLs are similarly controlled by a single parameter, and are suitable for improving quality of non-stationary signals under time-varying noise conditions. NDLs are designed to be fully compatible with existing linear devices and systems, and to be used as an enhancement, or as a low-cost alternative, to the state-of-art interference mitigation methods.
A Specific Region of 37 Amino Acid Residues in the SPRY (B30.2) Domain of African Green Monkey TRIM5α Determines Species-Specific Restriction of Simian Immunodeficiency Virus SIVmac Infection (2005)

Human immunodeficiency virus type 1 (HIV-1) efficiently enters cells of Old World monkeys but encounters a block before reverse transcription. This restriction is mediated by a dominant repressive factor. Recently, a member of the tripartite motif (TRIM) family proteins, TRIM5alpha, was identified as a blocking factor in a rhesus macaque cDNA library. Among Old World monkey cell lines, the African green monkey kidney cell line CV1 is highly resistant to not only HIV-1 but also simian immunodeficiency virus SIVmac infection. We analyzed TRIM5alpha of CV1 cells and HSC-F cells, a T-cell line from a cynomolgus monkey, and found that both CV1- and HSC-F-TRIM5alphas could inhibit CD4-dependent HIV-1 infection, as well as vesicular stomatitis virus glycoprotein-mediated infection. CV1-TRIM5alpha could also inhibit SIVmac infection, whereas HSC-F-TRIM5alpha could not. In the SPRY (B30.2) domain of CV1-TRIM5alpha, there was a 20-amino-acid duplication that was not present in HSC-F-TRIM5alpha. A chimeric TRIM5alpha containing 37 amino acid residues from CV1-TRIM5alpha, which spanned the 20-amino-acid duplication, in the background of HSC-F-TRIM5alpha fully gained the ability to inhibit SIVmac infection. Conversely, the mutant CV1-TRIM5alpha lacking the 20-amino-acid duplication completely lost the ability to restrict SIVmac infection. These findings clearly indicated that a specific region of 37 amino acid residues in the SPRY domain of CV1-TRIM5alpha contained a determinant of species-specific restriction of SIVmac.
The temporomandibular joint: magnetic resonance imaging using surface coils. (1985)

A total of 115 temporomandibular joints (TMJ) in 67 patients were examined by high resolution magnetic resonance (MR) using a surface coil. Five millimeter sections were imaged using a two-dimensional multisection acquisition. Findings of MR examinations were correlated with findings of conventional radiographic and clinical examinations. Surgical confirmation was available in 15 patients. MR definition of soft-tissue structures including the meniscus is superior to that of conventional imaging methods. Bony detail is comparable. MR is an excellent method for the primary diagnostic evaluation of TMJ abnormalities.
GaAs cleaning with a hydrogen radical beam gun in an ultrahigh-vacuum system (1988)

GaAs surface cleaning prior to molecular-beam epitaxy (MBE) using a new hydrogen radical beam produced by an electron cyclotron resonance plasma in an ultrahigh-vacuum system is investigated. Residual oxygen and carbon on the GaAs surface after cleaning are monitored in situ with Auger electron spectroscopy. Oxygen and carbon, which are hard to remove by conventional thermal cleaning, can be removed by hydrogen radical (H*) beam irradiation at a substrate temperature of &amp;lt;400 °C. It is verified that the plasma-dissociated radicals are much more reactive in the gas phase–solid phase surface chemical interaction than the nondischarged molecules. Ga and As stoichiometry is kept after H* beam cleaning. Good crystallinity is obtained according to reflection high-energy elecron diffraction. By carrier concentration measurement at the interface between the cleaned surface and the in situ MBE-regrown layer, it is found that H* beam cleaning reduces the interface state concentration. This cleaning technique makes clean GaAs surfaces available for MBE pretreatment.
Therapeutic murine monoclonal antibodies developed for individual cancer patients. (1989)

The purpose of this work was to create antibodies that are highly specific to epitopes on the surface of patient tumor cells that, when added together as a "cocktail," bind to greater than 99% of the patient's tumor cells. We describe the rationale and the methods used to develop new murine hybridomas that secrete monoclonal antibodies reactive with surface markers expressed on breast, lung, colon, kidney, islet cell, and miscellaneous carcinomas and melanoma. A rapid immunofluorescence method (cell concentration fluorescence immunoassay) is also described that has been developed to rapidly screen culture supernatants on viable patient tumor cells, tumor cell lines, or peripheral blood cells. We report the development of one breast, five colon, and three melanoma, three nephroma, and two pancreatic islet cell carcinoma antibodies. The breast antibody binds to 75% of the breast tumors tested thus far and to the same percentage of colon tumors as do the five colon antibodies, 77-85%. The melanoma antibodies described react with 90-100% of the melanoma and prostate cancers tested. The total process of creating the hybridomas and screening the antibodies for potential clinical usefulness has taken from 6 to 9 months to complete, including testing normal tissue reactivity by immunohistochemistry and production of gram quantities of monoclonal antibodies from ascites.
Coarctation of the aorta: natural history and outcome after surgical treatment (1999)

Coarctation of the aorta (Figure 1) accounts for approximately 5% of all congenital heart disease and is found at necropsy in up to 1:1550 patients.1 It is approximately three times more common in males.2 The traditional classification into infantile (preductal) and adult (postductal) types is now regarded as too simplistic, since many patients with preductal lesions do not present until adulthood.3 A spectrum of lesions is now recognized, and it is only those with the most severe obstruction (e.g. aortic arch atresia or interruption) or associated cardiac defects who invariably present in infancy. Most other cases are now identified at routine medical examination. Otherwise, age at presentation is related to the severity rather than the site of obstruction, as a result of cardiac failure or occasionally cerebrovascular accident (CVA), aortic dissection, or endocarditis.



 Figure 1. 
Chest radiograph demonstrating severe rib notching, prominence of the left subclavian artery, and cardiomegaly in an adult with juxtaductal aortic coarctation.



Coarctation of the aorta was not regularly diagnosed clinically until after 1933.4 Details of the natural history of aortic coarctation are therefore incomplete, being largely derived from hospital post-mortem records and selected case series prior to 1945, at which time operative repair was introduced. The first and largest post-mortem series was published by Abbott5 in 1928, who collated findings from all 200 previously documented cases over the age of 2 years, dating from the first report of aortic coarctation by Paris6 in 1791. Reifenstein, Levine and Goss7 subsequently reported 104 further cases from the literature dating from 1928 to 1947. The median age of death for all 304 cases was 31 years, and 76% of deaths were attributed to complications of the aortic coarctation.8 Cardiac failure accounted for 26% of deaths, at a mean age of 37 years. … 

Dr N.P. Jenkins, Department of Cardiology, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT
Enhanced allele-specific PCR discrimination in SNP genotyping using 3? locked nucleic acid (LNA) primers (2003)

The specificity and reliability of locked nucleic acid (LNA) substitution at the 3' position of allele-specific PCR (AS-PCR) primers for SNP detection was investigated in direct comparison to DNA primers. Both plasmid and human genomic DNA templates were examined in this study. All possible DNA and 3' LNA mismatch combinations were tested in triplicate with the plasmid target. LNA primers yield consistently low amounts of mismatch products with all base combinations, whereas certain mismatches with DNA primers generate strong false positive amplicons. Amplified human SNP alleles within the cystic fibrosis (CFTR) gene were analyzed in AS-PCR by gel analysis and real-time fluorescence generation. A 3' LNA residue in the primer at the SNP site improves allelic discrimination and functions under a wide window of PCR conditions. We demonstrate increased AS-PCR specificity with comparable sensitivity using 3' LNA primers in gel electrophoresis and real-time detection experiments. This increase in AS-PCR discrimination with 3' LNA primers should facilitate the use of this simple, rapid, and inexpensive technique for SNP genotyping applications.
Optimistic active learning using mutual information (2007)

An “active learning system ” will sequentially decide which unlabeled instance to label, with the goal of efficiently gathering the information necessary to produce a good classifier. Some such systems greedily select the next instance based only on properties of that instance and the few currently labeled points — e.g., selecting the one closest to the current classification boundary. Unfortunately, these approaches ignore the valuable information contained in the other unlabeled instances, which can help identify a good classifier much faster. For the previous approaches that do exploit this unlabeled data, this information is mostly used in a conservative way. One common property of the approaches in the literature is that the active learner sticks to one single query selection criterion in the whole process. We propose a system, MM+M, that selects the query instance that is able to provide the maximum conditional mutual information about the labels of the unlabeled instances, given the labeled data, in an optimistic way. This approach implicitly exploits the discriminative partition information contained in the unlabeled data. Instead of using one selection criterion, MM+M also employs a simple on-line method that changes its selection rule when it encounters an “unexpected label”. Our empirical results demonstrate that this new approach works effectively. 1
Autotomy following peripheral nerve lesions: experimental anesthesia dolorosa (1979)

(1) When hindlimb peripheral nerves are cut across in rats and mice, there is a tendency for the animal to attack the anaesthetic limb. We have called this attack "autotomy". In this paper we describe the time course and degree of autotomy following various types of nerve injury. (2) Four different types of lesion were applied to the sciatic nerve of rats. The most serious autotomy was produced by section of the nerve and encapsulation of its cut end in a polythene tube. Section followed by immediate resuturing also produced serious autotomy. Simple ligation of the nerve end was followed by less autotomy than encapsulation or cut and resuture. A crush lesion caused only minimal attack. (3) Section of the saphenous branch of the femoral nerve produced no autotomy. However, if the saphenous and sciatic nerves were ligated at the same time so that the entire foot became anaesthetic there was a great increase of autotomy over that seen when the sciatic nerve alone was ligated. This increase with the double lesion occurred even if the saphenous nerve was ligated more than 100 days after the sciatic nerve had been cut. (4) Mice showed autotomy very similar to that seen in rats but the onset was somewhat faster. (5) Reasons are given to propose that autotomy is triggered by an abnormal afferent barrage generated in the cut end of the nerve. Autotomy from peripheral nerve lesions is a different phenomenon from that seen after dorsal root section. Autotomy occurs under conditions which produce anaesthesia dolorosa in man. This simple model may be suitable for studies of the prevention of irritations originating from chronic lesions of peripheral nerves.
Part VI. Nonpeptide angiotensin II receptor antagonists: N-[(benzyloxy)benzyl]imidazoles and related compounds as potent antihypertensives (1990)

A series of compounds has been synthesized and demonstrated to be antagonists of the angiotensin II (AII) receptor. These compounds are structurally related to the N-(benzamidobenzyl)imidazoles and extend the scope of this new class of nonpeptide AII antagonists. It has been found that the amide linkage (X = NHCO) in the N-(benzamidobenzyl)imidazoles can be replaced successfully by a variety of groups (X = single bond, O, S, CO, OCH2, CH = CH, NHCONH); linkers of 0-1 atoms in length are most effective. When administered intravenously to awake renal hypertensive rats, these compounds are potent antihypertensives.
Long-Term Effects of Vitamin E, Vitamin C, and Combined Supplementation on Urinary 7-Hydro-8-Oxo-2′-Deoxyguanosine, Serum Cholesterol Oxidation Products, and Oxidation Resistance of Lipids in Nondepleted Men (2000)

We studied the long-term effects of vitamins E and C and their combination on lipid peroxidation in vivo and in vitro. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) trial is a double-masked placebo-controlled randomized clinical trial to study the effects of vitamin C (500 mg of slow release ascorbate per day), vitamin E (182 mg of RRR-alpha-tocopherol acetate per day), and the combination of both antioxidants. Lipid peroxidation measurements were carried out for 48 male participants at entry and at 12 and 36 months. Compared with placebo, vitamin E and the vitamin combination increased plasma lipid-standardized alpha-tocopherol during the first 12 months by 68.2% and 65.2% (P:<0. 001 for both), respectively, and reduced serum 7beta-hydroxycholesterol by 50.4% (P:=0.013) and 44.0% (P:=0.041), respectively. The net change of lipid standardized alpha-tocopherol was 63.8% after 36 months of vitamin E supplementation and 43.3% for the combination. Vitamin C supplementation elevated plasma total ascorbate level by 30.1% (P:=0.043) in 12 months and by 91.1% (P:=0. 001) in 36 months. Neither vitamin E, vitamin C, nor the combination influenced the urinary excretion rate of 7-hydro-8-oxo-2'-deoxyguanosine or the antioxidative capacity of plasma. Vitamin E and the combination of vitamins E and C enhanced the oxidation resistance of isolated lipoproteins and total serum lipids. Our data indicate that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation in vitro and in vivo, whereas a relatively high dose of vitamin C alone does not.
tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors (2005)

TP53 is the most frequently mutated tumor suppressor gene in human cancer, with nearly 50% of all tumors exhibiting a loss-of-function mutation. To further elucidate the genetic pathways involving TP53 and cancer, we have exploited the zebrafish, a powerful vertebrate model system that is amenable to whole-genome forward-genetic analysis and synthetic-lethal screens. Zebrafish lines harboring missense mutations in the tp53 DNA-binding domain were identified by using a target-selected mutagenesis strategy. Homozygous mutant fish from two of these lines were viable and exhibited mutations similar to those found in human cancers (tp53(N168K) and tp53(M214K)). Although homozygous tp53(N168K) mutants were temperature-sensitive and suppressed radiation-induced apoptosis only at 37 degrees C, cells in the tp53(M214K) embryos failed to undergo apoptosis in response to gamma radiation at both 28 and 37 degrees C. Unlike wild-type control embryos, irradiated tp53(M214K) embryos also failed to up-regulate p21 and did not arrest at the G(1)/S checkpoint. Beginning at 8.5 months of age, 28% of tp53(M214K) mutant fish developed malignant peripheral nerve sheath tumors. In addition to providing a model for studying the molecular pathogenic pathways of malignant peripheral nerve sheath tumors, these mutant zebrafish lines provide a unique platform for modifier screens to identify genetic mutations or small molecules that affect tp53-related pathways, including apoptosis, cell-cycle delay, and tumor suppression.
A transcriptionally amplified DNA probe assay with ligatable probes and immunochemical detection (1993)

Transcriptionally amplified DNA probes are valuable tools in the development of sensitive nucleic acid-based diagnostic assays. Here we describe a model assay using a novel oligonucleotide hairpin probe that encodes a T7 RNA polymerase promoter. The hairpin probe and an adjacently hybridizing biotinylated capture probe were hybridized to target DNA and the duplex was captured onto streptavidin-coated magnetic particles. After ligation of the immobilized probes, which served to maintain specificity, the hairpin probe was transcribed by T7 RNA polymerase. The amplified RNA product was hybridized to the capture probe and bound to the streptavidin-coated magnetic particles. The immobilized heteroduplex was detected with an antibody-alkaline phosphatase conjugate specific for DNA:RNA hybrids, and the chemiluminescent substrate adamantyl-1,2-dioxetane phenyl phosphate. Ten attomoles of target DNA could be detected in a background of 5 micrograms of unrelated DNA. The chemiluminescent immunoassay was as sensitive as radioactive detection of specific product after gel electrophoresis.
Metal-free Cross-Dehydrogenative Coupling of HN-azoles with α-C(sp3)-H Amides via C–H Activation and Its Mechanistic and Application Studies (2016)

A metal-free one step coupling reaction between various N-azole rings and diverse α-C(sp<sup>3</sup>)-H containing amides has been developed under oxidative reaction conditions. Commercially available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide (TBHP), under neat reaction condition, efficiently catalyzed the coupling. Various azole types, such as 1H-benzotriazoles, 1H-1,2,3-triazoles, 1H-1,2,4-triazoles, 1H-tetrazoles, 1H-pyrazoles, and 1H-benzimidazoles, and α-C(sp<sup>3</sup>)-H containing amides, such as N,N-dimethylacetamide, N,N-dimethylbenzamide, N-methylacetamide, N,N-diethylacetamide, N-methylpyrrolidine, and pyrrolidine-2-one, were successfully employed for the coupling. A series of designed and controlled experiments were also performed in order to study the involvement of the different intermediates. Based on the evidence, a plausible mechanism is also proposed. These novel, simple, rapid, attractive, and straightforward transformations open the way of the construction of novel highly functionalized N-azoles via direct covalent N-H bond transformations onto N-C bonds. This approach allows to the synthesis of complex molecules requiring number of steps using classical synthetic ways. In addition, the range of α-C(sp<sup>3</sup>)-H containing amide substrates is virtually unlimited highlighting the potential value of this simple system for the construction of complex heterocyclic molecules, such as fused azoles derivatives.