gebhart/patrepeval huggingface dataset:
Mitochondrial Function in Permeabilized Cardiomyocytes Is Largely Preserved in the Senescent Rat Myocardium (2012)

The aging heart is characterized by a progressive decline in contractile function and diastolic relaxation. Amongst the factors implicated in these changes is a progressive replacement fibrosis secondary to cardiomyocyte death, oxidative damage, and energetic deficit, each of which may be secondary to impaired mitochondrial function. Here, we performed an in-depth examination of mitochondrial function in saponin-permeabilized cardiomyocyte bundles, a preparation where all mitochondria are represented and their structure intact, from young adult (YA) and senescent (SEN) rats (n = 8 per group). When accounting for increased fibrosis (+19%, P<0.01) and proportional decrease in citrate synthase activity in the SEN myocardium (-23%, P<0.05), mitochondrial respiration and reactive oxygen species (H(2)O(2)) emission across a range of energized states was similar between age groups. Accordingly, the abundance of electron transport chain proteins was also unchanged. Likewise, except for CuZnSOD (-37%, P<0.05), the activity of antioxidant enzymes was unaltered with aging. Although time to mitochondrial permeability transition pore (mPTP) opening was decreased (-25%, P<0.05) in the SEN heart, suggesting sensitization to apoptotic stimuli, this was not associated with a difference in apoptotic index measured by ELISA. Collectively, our results suggest that the function of existing cardiac ventricular mitochondria is relatively preserved in SEN rat heart when measured in permeabilized cells.
Does weight loss prognosis depend on genetic make‐up? (2005)

The prevalence of obesity is rising throughout the world. Indeed, obesity has reached epidemic proportions in many developed and transition countries. Obesity is a complex disease with multifactorial origin, which in many cases appears as a polygenic condition affected by environmental factors. Treatment or prevention of obesity is necessary to reverse or avoid the onset of type 2 diabetes and other obesity-related diseases. Weight loss is a complex trait that depends on many environmental, behavioural and genetic influences. An effective programme for the management of overweight and obesity must take into account all of these factors. Individual responses to weight loss interventions vary widely and reliable predictors of successful slimming are poorly understood. The individual genetic make-up participating in energy expenditure regulation, appetite control, lipid metabolism and adipogenesis, have been reported to affect the risk of treatment failure in some subjects. In addition, the genotype could also help to predict the changes in lipid profile, cardiovascular risk factors and insulin sensitivity in response to weight loss. Herein, the current evidence from human studies that support the existence of a genetic component and the participation of different polymorphisms in the prognosis of weight loss induced by interventions leading to a negative energy balance are reviewed.
Bacteriophage therapy: an alternative to conventional antibiotics. (2003)

Bacteriophage therapy is an important alternative to antibiotics in the current era of multidrug resistant pathogens. We reviewed the studies that dealt with the therapeutic use of phages from 1966-1996 and few latest ongoing phage therapy projects via internet. Phages were used topically, orally or systemically in Polish and Soviet studies. The success rate found in these studies was 80-95% with few gastrointeslinal or allergic side effects. British studies also demonstrated significant efficacy of phages against Escherichia coli, Acinetobacter spp., Pseudomonas spp and Staphylococcus aureus. US studies dealt with improving the bioavailability of phage. Problems faced in these studies have also been discussed. In conclusion, phage therapy may prove as an important alternative to antibiotics for treating multidrug resistant pathogens.
How Bacteria Adhere to Brushy PEG Surfaces: Clinging to Flaws and Compressing the Brush (2012)

This study examined the compression of solvated polymer brushes on bioengineered surfaces during the initial stages of Staphylococcus Aureus (S. aureus) adhesion from gentle flow. A series of PEG [poly(ethylene glycol)] brushes, 7 to 17 nm in height and completely non-adhesive to proteins and bacteria, were modified by the incorporation of sparse isolated ~10 nm cationic polymer "patches" at their bases. These nanoscale regions, which lacked PEG tethers, were electrostatically attractive towards negative bacteria or proteins. S. aureus drawn to the interface by multiple adhesive patches compressed the PEG brush in the remaining contact region. The observed onset of bacterial or fibrinogen capture with increases in patch content was compared with calculations. Balancing the attraction energy (proportional to the number of patches engaging a bacterium during capture) against steric forces (calculated using the Alexander-DeGennes treatment) provided perspective on the brush compression. The results were consistent with a bacteria-surface gap on the order of the Debye length in these studies. In this limit of strong brush compression, structural features (height, persistence length) of the brush were unimportant so that osmotic pressure dominated the steric repulsion. Thus, the dominant factor for bacterial repulsion was the mass of PEG in the brush. This result explains empirical reports in the literature that identify the total PEG content of a brush as a criteria for prevention of bioadhesion, independent of tether length and spacing, within a reasonable range for those parameters. Bacterial capture was also compared to that of protein capture. It was found, surprisingly, that the patchy brushes were more protein-than bacteria-resistant. S. aureus adhesion driven by patches within otherwise protein-resistant PEG brushes was explained by the bacteria's greater tendency to compress large areas of brush to interact with many patches. By contrast, proteins are thought to penetrate the brush at a few sites of PEO-free patches. The finding provides a mechanism for the literature reports that in-vitro protein resistance is a poor predictor of in-vitro implant failure related to cell-surface adhesion.
Molecular Targets of Antiviral Therapy (1989)

THE development of specific antiviral drugs that are minimally toxic to normal cells has ushered in a new era of antiviral therapy. The advent of this therapy is especially timely in the light of the threat to the lives of immunocompromised patients from cytomegalovirus infection,1 , 2 the increasing morbidity of recurrent genital herpes simplex infection,3 and most notably, the rising epidemic of the acquired immunodeficiency syndrome (AIDS), a lethal retroviral infection caused by human immunodeficiency virus type 1 (HIV-1).4 In theory, antiviral drugs work by interacting directly with the virus, with a viral-encoded enzyme or other protein, or with a cellular . . .
Blind separation of a dynamic image source from superimposed reflections (2005)

We consider the problem of recovering a moving visual scene recorded through a semi-reflective device, and extend the Sparse Component Analysis (SCA) method to three-dimensional data sources, using two different mixtures of the dynamic image source and the superimposed reflection, recorded at different polarizations, without having any a-priori knowledge about the structure and/or the statistics of the sources, or of the mixing matrix. We first apply our method on a simple physical example of separation of dynamic reflections, such as video signals recorded through the windshield of a car. In this example the required assumptions of linearity and stationarity are valid. A more interesting application deals with dynamic scenarios recorded from aircrafts or satellites, where it is desirable to extract a clear landscape view by separating it from a thin semi-transparent layers of clouds superimposed on the desired dynamic image. This is a more complex problem, since the mixtures are not stationary in space and the mixing coefficients vary in the presence of clouds. Further, the mixtures are not strictly linear and involve also multiplicative and convolutive components. We apply the 3D-SCA method in simulations of linearly mixed moving landscape contaminated by clouds.
Actin microfilaments play a critical role in endocytosis at the apical but not the basolateral surface of polarized epithelial cells. (1993)

Treatment with cytochalasin D, a drug that acts by inducing the depolymerization of the actin cytoskeleton, selectively blocked endocytosis of membrane bound and fluid phase markers from the apical surface of polarized MDCK cells without affecting the uptake from the basolateral surface. Thus, in MDCK cell transformants that express the VSV G protein, cytochalasin blocked the internalization of an anti-G mAb bound to apical G molecules, but did not reduce the uptake of antibody bound to the basolateral surface. The selective effect of cytochalasin D on apical endocytosis was also demonstrated by the failure of the drug to reduce the uptake of 125I-labeled transferrin, which occurs by receptor-mediated endocytosis, via clathrin-coated pits, almost exclusively from the basolateral surface. The actin cytoskeleton appears to play a critical role in adsorptive as well as fluid phase apical endocytic events, since treatment with cytochalasin D prevented the apical uptake of cationized ferritin, that occurs after the marker binds to the cell surface, as well as uptake of Lucifer yellow, a fluorescent soluble dye. Moreover, the drug efficiently blocked infection of the cells with influenza virus, when the viral inoculum was applied to the apical surface. On the other hand, it did not inhibit the basolateral uptake of Lucifer yellow, nor did it prevent infection with VSV from the basolateral surface, or with influenza when this virus was applied to monolayers in which the formation of tight junctions had been prevented by depletion of calcium ions. EM demonstrated that cytochalasin D leads to an increase in the number of coated pits in the apical surface where it suppresses the pinching off of coated vesicles. In addition, in drug-treated cells cationized ferritin molecules that were bound to microvilli were not cleared from the microvillar surface, as is observed in untreated cells. These findings indicate that there is a fundamental difference in the process by which endocytic vesicles are formed at the two surfaces of polarized epithelial cells and that the integrity and/or the polymerization of actin filaments are required at the apical surface. Actin filaments in microvilli may be part of a mechanochemical motor that moves membrane components along the microvillar surface towards intermicrovillar spaces, or provides the force required for converting a membrane invagination or pit into an endocytic vesicle within the cytoplasm.
GSM fabric antenna for mobile phones integrated within clothing (2002)

Present day products utilize the mobile phone's relatively small built-in antenna. However the close proximity of the antenna to the user's body leads to extensive signal losses. Building the antenna into the clothing would allow a much larger antenna to be constructed that incorporates a large ground plane to isolate the user from the antenna's fields. Antenna construction using fabric technology enhances user comfort by permitting the antenna to be light, breathable and flexible. This paper describes how a fabric mobile phone antenna may be incorporated within a new range of garments.
Simple and Rapid HPLC of Quinine, Hydroxychloroquine, Chloroquine, and Desethylchloroquine in Serum, Whole Blood, and Filter Paper-Adsorbed Dry Blood (1994)

A simple high-performance liquid chromatographic assay for the measurement of quinine, hydroxychloroquine, chloroquine, and desethylchloroquine in small volumes (50-200 microL) of serum, whole blood, or filter paper-adsorbed dry blood was developed. The analytes are isolated by liquid-liquid extraction and chromatographed on a sulfophenylpropyl-modified silica column under isocratic conditions. The column effluent is monitored by fluorimetry (excitation wavelength, 215 nm; no emission filter). The limit of quantitation is 0.005-0.01 mg/L for chloroquine and hydroxychloroquine and 0.05 mg/L for quinine. No interference from other antimalarial drugs or other compounds commonly used has been observed. Quantitative results can be obtained within 1 hour of receipt of the sample.
Effective delivery of large genes to the retina by dual AAV vectors (2013)

Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, AAV's limited cargo capacity prevents its application to therapies of inherited retinal diseases due to mutations of genes over 5 kb, like Stargardt's disease (STGD) and Usher syndrome type IB (USH1B). Previous methods based on 'forced' packaging of large genes into AAV capsids may not be easily translated to the clinic due to the generation of genomes of heterogeneous size which raise safety concerns. Taking advantage of AAV's ability to concatemerize, we generated dual AAV vectors which reconstitute a large gene by either splicing (trans-splicing), homologous recombination (overlapping), or a combination of the two (hybrid). We found that dual trans-splicing and hybrid vectors transduce efficiently mouse and pig photoreceptors to levels that, albeit lower than those achieved with a single AAV, resulted in significant improvement of the retinal phenotype of mouse models of STGD and USH1B. Thus, dual AAV trans-splicing or hybrid vectors are an attractive strategy for gene therapy of retinal diseases that require delivery of large genes.
Amphotericin B selection of mutant Chinese hamster cells with defects in the receptor-mediated endocytosis of low density lipoprotein and cholesterol biosynthesis. (1983)

This paper describes a rapid and efficient two-step procedure for the isolation of mutant cells with defects in receptor-mediated endocytosis. The procedure takes advantage of two fungal metabolites, compactin (ML236B), a potent inhibitor of cholesterol biosynthesis, and amphotericin B, a polyene antibiotic that forms toxic complexes with sterols in membranes. Mutagen-treated Chinese hamster ovary cells were preincubated overnight in a medium containing mevalonate, low density lipoprotein (LDL), and compactin (Mev/LDL/Com). At the end of the preincubation period, wild-type cells were cholesterol replete while mutant cells that could not utilize the cholesterol in LDL were cholesterol deficient. Subsequent incubation with amphotericin B for 6 hr killed most of the wild-type cells. After a second round of Mev/LDL/Com-amphotericin B selection, endocytosis-defective clones appeared at a frequency of approximately equal to 2.6 X 10(-5). Some of these clones expressed LDL receptor-defective phenotypes and fell into one of two previously defined classes of mutation. Sensitivity of the mutants to infection by vesicular stomatitis virus suggested that the mutations do not disrupt the coated pit-coated vesicle pathway of endocytosis. Minor modifications in the Mev/LDL/Com-amphotericin B selection permit the isolation of cholesterol auxotrophs and might allow the isolation of conditional-lethal mutations. Because LDL can be coupled to ligands that bind to receptors other than the LDL receptor, Mev/LDL/Com-amphotericin B selection may permit the isolation of mutant cells with defects that specifically disrupt other endocytic pathways.
Altered proteolytic cleavage of human growth hormone as a result of deamidation. (1981)

The major desamido form of human growth hormone (hGH) results from deamidation of asparagine 152. Peptide mapping and amino acid sequencing were used in the identification. This desamido form (hGHAsp152) could be produced by incubation of the undeamidated hormone in an alkaline medium. Another minor deamidated form which contained glutamic acid at 137 (hGHGlu137) also was identified in preparations of hGH. This form was not produced by alkaline treatment of hGH. Limited hydrolysis of hGH with subtilisin produced two cleaved forms, one with cleavages at positions 139 and 149 and another with cleavages at 139 and 146. hGHAsp152 underwent only one type of modification, cleavage at positions 139 and 146. Hydrolysis of hGHGlu137 resulted in cleavages in the region of 139 to 149 identical with those noted with hGH, but in addition, proteolysis had occurred in the region of 95 to 127, an area where hGH was not attacked by subtilisin. That Glu at 137 modified cleavage points was also indicated by the greater resistance of hGHGlu137 to hydrolysis by subtilisin as compared to hGH. The results demonstrate that deamidation can alter points of proteolytic cleavage. If proteolytic processing of hGH is found to be of physiologic significance, deamidation may be a way of directing specific cleavages.
TGF-β antagonists: Why suppress a tumor suppressor? (2002)

Tumor metastasis is the major determinant of cancer patient survival.This ultimate phase in tumorigenesis depends on the ability of a tumor cell to invade the stroma, migrate in and out of blood or lymphatic vessels, and survive and re-establish itself at a secondary site.A large number of papers have provided strong evidence for a role of TGF- in tumor invasion and/or metastasis (1-6).Now, two papers in this issue of the JCI highlight this clinically significant action of TGF- in tumorigenesis and provide very encouraging results regarding both the efficacy and the low toxicity of a soluble TGF- receptor antagonist that effectively reduces tumor spread (7, 8).
Topical Anesthesia of the Skin by Liposome-Encapsulated Tetracaine (1988)

The potential of a liposomal local anesthetic formulation to provide topical anesthesia of the intact skin was investigated. Tetracaine base 0.5% was encapsulated into multilamellar phospholipid vesicles. The topical anesthetic effects of the liposomal and a control (Pontocaine cream) preparation were evaluated by pinprick technique in adult volunteers. Liposomal tetracaine-produced anesthesia, which lasted at least 4 hours after 1 hour application under occlusion. Pontocaine cream was ineffective. The liposomal formulation appeared to be suitable to provide long lasting anesthesia of the skin with low drug concentration.
A new fault location technique for two- and three-terminal lines (1992)

A method for the computation of fault location in two- and three-terminal high voltage lines is presented. It is based on digital computation of the three-phase current and voltage 60/50 Hz phasors at the line terminals. The method is independent of fault type and insensitive to source impedance variation or fault resistance. Furthermore, it considers the synchronization errors in sampling the current and voltage waveforms at the different line terminals. The method can be used online following the operation of digital relays or offline using data transferred to a central processor from digital transient recording apparatus. The authors start with a two-terminal line to explain the principles and then present the technique for a three-terminal line. The technique was first tested using data obtained from a steady-state fault analysis program to evaluate the convergence, observability, and uniqueness of the solution. The technique was then tested using EMPT-generated transient data. The test results show the high accuracy of the technique.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Arylamine N-acetyltransferase activities in human breast cancer tissues. (2001)

N-Acetyltransferase activities were determined in tumor (12 malignant and 6 benign) and control (non-cancerous) breast tissues from 18 female patients. The activities of matched 12 malignant tumor and control tissue cytosols showed 6 rapid, 4 intermediate and 2 slow acetylators based on p-aminobenzoic acid (NAT1) and sulfamethazine (NAT2) as substrates. Compared to the activities of slow acetylators, the rapid acetylators exhibited mean apparent Vmax values about 5- and 50-fold greater for p-aminobenzoic acid and sulfamethazine, respectively. No correlation was observed between the blood and breast tissue N-acetyltransferase (NAT1 and NAT2) activities. When the mean apparent N-acetyltransferase activities of the malignant and benign breast tumor tissues were compared, the results showed an increased activity for both p-aminobenzoic acid (PABA) and sulfamethazine (SMZ) acetylation in the malignant tissues compared to benign ones, and also control tissues showed lower activities compared to tumor tissues. Moreover, the mean NAT2 activity was about 2-fold greater in the malignant tissues when compared to NAT1 activity.
Towards a Definition of Intractable Headache for Use in Clinical Practice and Trials (2006)

peer reviewed
Spatial‐Temporal progress of peripheral nerve regeneration within a silicone chamber: Parameters for a bioassay (1983)

The spatial-temporal progress of peripheral nerve regeneration across a 10-mm gap within a silicone chamber was examined with the light and electron microscope at 2-mm intervals. A coaxial, fibrin matrix was observed at 1 week with a proximal-distal narrowing that extended beyond the midpoint of the chamber. At 2 weeks, Schwann cells, fibroblasts, and endothelial cells had migrated into the matrix from both nerve stumps. There was a delay of 7-14 days after nerve transection and chamber implantation before regenerating axons appeared in the chamber. At 2 weeks, nonmyelinated axons were seen only in the proximal 1-5 mm of the chamber in association with Schwann cells. Axons reached the distal stump by 3 weeks and a proximal-distal gradient of myelination was observed. These observations define the parameters of a morphologic assay for regeneration in this chamber model which can be used to investigate cellular and molecular mechanisms underlying the success of peripheral nerve regeneration.
Crystal Structures of the FAK Kinase in Complex with TAE226 and Related Bis-Anilino Pyrimidine Inhibitors Reveal a Helical DFG Conformation (2008)

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase required for cell migration, proliferation and survival. FAK overexpression has been documented in diverse human cancers and is associated with a poor clinical outcome. Recently, a novel bis-anilino pyrimidine inhibitor, TAE226, was reported to efficiently inhibit FAK signaling, arrest tumor growth and invasion and prolong the life of mice with glioma or ovarian tumor implants. Here we describe the crystal structures of the FAK kinase bound to TAE226 and three related bis-anilino pyrimidine compounds. TAE226 induces a conformation of the N-terminal portion of the kinase activation loop that is only observed in FAK, but is distinct from the conformation in both the active and inactive states of the kinase. This conformation appears to require a glycine immediately N-terminal to the "DFG motif", which adopts a helical conformation stabilized by interactions with TAE226. The presence of a glycine residue in this position contributes to the specificity of TAE226 and related compounds for FAK. Our work highlights the fact that kinases can access conformational space that is not necessarily utilized for their native catalytic regulation, and that such conformations can explain and be exploited for inhibitor specificity.