gebhart/patrepeval huggingface dataset:
Autosomal Dominant Polycystic Kidney Disease: Early Diagnosis and Consideration of Pathogenesis (1980)

Renal function studies and excretory urograms were performed for 16 asymptomatic subjects at risk for polycystic kidney disease (PKD). The subjects represented five unrelated families, and ranged in age from 11 to 26 years. Fourteen subjects with normal excretory urograms underwent percutaneous renal biopsy. An additional renal biopsy specimen was obtained at the time of nephrectomy from a subject who had PKD. In four of the 14 subjects who had biopsies, PKD was documented about three years later by excretory urograms with nephrotomograms, renal radionuclide imaging, and gray-scale ultrasonography. Light-microscopic findings of dilated distal and collecting tubules suggested early manifestations of PKD in the renal biopsy specimens from five of the 14 subjects. In three of these five subjects, but also in one of nine subjects without light-microscopic changes of tubular dilatation, PKD was documented three years later. By electron microscopy, no differences in fine structural details were seen between specimens with and without tubular dilation observed by light microscopy, except for splitting of the lamina densa of the glomerular capillary basement membrane, which was present in only two specimens with light-microscopic changes of tubular dilation from subjects with PKD documented three years later, and in the nephrectomy specimen. Renal function studies were normal for 14 subjects, including four who had documented PKD. These data suggest that lightmicroscopic changes of tubular dilatation (seen in five of the 14 specimens, including three from the four restudied subjects in whom PKD was documented three years later) and electronmicroscopic changes of lamina densa splitting (seen only in two specimens with light-microscopic changes of tubular dilatation from subjects with PKD documented three years later and in the nephrectomy specimen), may be the earliest recognizable histologic changes in the carriers of the abnormal gene for PKD. However, because in the early stages of PKD these histologic changes may not be diffusely distributed, we do not advocate renal biopsy, but would suggest excretory urograms (with nephrotomography), radionuclide imaging, or gray-scale ultrasonography as the initial diagnostic procedures.
Forward Chemical Genetics: Library Scaffold Design (2004)

With the unraveling of the entire human genome, it has become imperative to understand the function of the gene products, proteins. Within the past several years, chemical genetics has gained recognition as a powerful approach to study protein function by using small molecules as gene knock-out or knock-in mimics. Forward chemical genetics is a three-step process; the design and synthesis of a small molecule library represents the first step followed secondly by the search for novel phenotypes and then by isolation and identification of target protein(s). This review will focus on the first step, the design of the scaffold for small molecule libraries. It will also examine the connection between the choice of a scaffold and the propensity of that library to demonstrate enhanced biological activity when tested in certain cellular systems.
Herpes Simplex Virus Glycoproteins gD and gE/gI Serve Essential but Redundant Functions during Acquisition of the Virion Envelope in the Cytoplasm (2003)

The late stages of assembly of herpes simplex virus (HSV) and other herpesviruses are not well understood. Acquisition of the final virion envelope apparently involves interactions between viral nucleocapsids coated with tegument proteins and the cytoplasmic domains of membrane glycoproteins. This promotes budding of virus particles into cytoplasmic vesicles derived from the trans-Golgi network or endosomes. The identities of viral membrane glycoproteins and tegument proteins involved in these processes are not well known. Here, we report that HSV mutants lacking two viral glycoproteins, gD and gE, accumulated large numbers of unenveloped nucleocapsids in the cytoplasm. These aggregated capsids were immersed in an electron-dense layer that appeared to be tegument. Few or no enveloped virions were observed. More subtle defects were observed with an HSV unable to express gD and gI. A triple mutant lacking gD, gE, and gI exhibited more severe defects in envelopment. We concluded that HSV gD and the gE/gI heterodimeric complex act in a redundant fashion to anchor the virion envelope onto tegument-coated capsids. In the absence of either one of these HSV glycoproteins, envelopment proceeds; however, without both gD and gE, or gE/gI, there is profound inhibition of cytoplasmic envelopment.
Membrane and surface interactions of Alzheimer’s Aβ peptide – insights into the mechanism of cytotoxicity (2011)

Alzheimer's disease is the most common form of dementia and its pathological hallmarks include the loss of neurones through cell death, as well as the accumulation of amyloid fibres in the form of extracellular neuritic plaques. Amyloid fibrils are composed of the amyloid-β peptide (Aβ), which is known to assemble to form 'toxic' oligomers that may be central to disease pathology. Aβ is produced by cleavage from the amyloid precursor protein within the transmembrane region, and the cleaved peptide may retain some membrane affinity. It has been shown that Aβ is capable of specifically binding to phospholipid membranes with a relatively high affinity, and that modulation of the composition of the membrane can alter both membrane-amyloid interactions and toxicity. Various biomimetic membrane models have been used (e.g. lipid vesicles in solution and tethered lipid bilayers) to examine the binding and interactions between Aβ and the membrane surfaces, as well as the resulting permeation. Oligomeric Aβ has been observed to bind more avidly to membranes and cause greater permeation than fibrillar Aβ. We review some of the recent advances in studying Aβ-membrane interactions and discuss their implications with respect to understanding the causes of Alzheimer's disease.
The electrophile counterattack response: Protection against neoplasia and toxicity (1993)

Exposure of rodents or their cells in culture to low doses of a wide variety of chemical agents, many of which are electrophiles, evokes a coordinated metabolic response that protects these systems against the toxicity (including mutagenicity and carcinogenicity) of higher doses of the same or other electrophiles. This response involves enhanced transcription of Phase 2 enzymes: glutathione transferases, NAD(P)H:quinone reductase, UDP-glucuronsyltransferases, and epoxide hydrolase, as well as the elevation of intracellular levels of reduced glutathione. We suggest that this cellular adaptation, which occurs in the liver and many peripheral tissues, be designated as the "Electrophile Counterattack" response. Seven families of highly diverse chemical agents that elicit this response include: oxidatively labile diphenols and quinones; Michael reaction acceptors (olefins conjugated to electron-withdrawing groups); isothiocyanates; organic hydroperoxides; vicinal dimercaptans; trivalent arsenicals; heavy metals (HgCl2, CdCl2) as well as mercury derivatives with high affinities for sulfhydryl groups; and 1,2-dithiole-3-thiones. An analysis of the molecular mechanisms of these enzyme inductions was carried out by transient expression in hepatoma cells of a plasmid containing a 41-bp enhancer element derived from the 5'-upstream region of the mouse glutathione transferase Ya gene, and the promoter region of this gene, linked to a human growth hormone reporter gene. The concentrations of 28 inducers (belonging to the seven chemical classes) required to double growth hormone production in this system spanned a range of four orders of magnitude and were closely and linearly correlated with the concentrations of the same compounds required to double the specific activity of quinone reductase in murine hepatoma cells. We therefore conclude that the regulation of these Phase 2 enzymes (and possibly also that of glutathione synthesis) by all of these inducers is mediated by the same enhancer element that contains AP-1-like sites. Similar enhancer sequences are present in the rat glutathione transferase Ya gene, and in the upstream regulatory regions of the quinone reductase genes of rat and human liver.
Competitive intelligence, software robots and the Internet: the NewsAlert prototype (2002)

The Internet offers managers and executives a vast array of untapped data that can be applied to issues of competitive intelligence. The exponential growth in the Internet has made it virtually impossible for managers and executives to track these data with even the best Windows-based Internet tools. What is required is a proactive system that automatically and routinely monitors Internet data for patterns of interest and only notifies the end user when these patterns appear. At the core of these systems are software robots. In this paper we explore a robot-based "detect and alert" system called NewsAlert that delivers Internet alerts to the desktops of managers and executives in the form of a personalized electronic newspaper.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mucosal addressin cell adhesion molecule-1: a structural and functional analysis demarcates the integrin binding motif (1996)

The leukocyte integrin receptor, alpha 4 beta 7, and the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) are postulated to be important in regulating lymphocyte trafficking to normal intestine. Here we provide the first description of MAdCAM-1 expression in inflamed intestine. Using mouse models of experimentally induced colitis, we show a concordant increase in MAdCAM-1 expression associated with increased cellular infiltrates in areas of intestinal inflammation. To understand more of the molecular nature of the interactions between MAdCAM-1 and its leukocyte ligand, the alpha 4 beta 7 integrin receptor, we have analyzed the structural and functional properties of chimeric recombinant MAdCAM-1 proteins in vitro. Using site-directed mutagenesis and molecular modeling, we demarcate the alpha 4 beta 7 binding motif as three linear residues within the C-D loop in the first domain of MAdCAM-1. Mutation of residue L40, D41, or T42 in the first domain completely abrogates alpha 4 beta 7+ cell binding and cellular activation. Mutagenesis of other residues in the first domain do not impact these functions. We have modeled peptides based on the predicted structure of the alpha 4 beta 7 integrin binding motif on MAdCAM-1 and are able to show specific and selective blocking of cell binding. These observations suggest that the amino acid residues LDT on MAdCAM-1 play a role in the interaction with alpha 4 beta 7 in cell adherence and cell activation.
Multi-Day Low Dose Ketamine Infusion for the Treatment ofComplex Regional Pain Syndrome (2005)

A four-hour ketamine infusion escalated from 40-80 mg over a 10-day period can result in a significant reduction of pain with increased mobility and a tendency to decreased autonomic dysregulation.
Global Epidemiology ofClostridium difficileInfection in 2010 (2010)

The past decade has been characterized by an epidemic of Clostridium difficile infection in North America and Europe that threatens to extend to the rest of the world. The epidemic is due in part to the emergence of a previously rare and now more lethal C. difficile strain variously named group BI, ribotype 027, and North American pulsed&#x2010;field gel electrophoresis type 1.
Interactions of lysozyme in guanidinium chloride solutions from static and dynamic light‐scattering measurements (2005)

The interactions of partially unfolded proteins provide insight into protein folding and protein aggregation. In this work, we studied partially unfolded hen egg lysozyme interactions in solutions containing up to 7 M guanidinium chloride (GdnHCl). The osmotic second virial coefficient (B(22)) of lysozyme was measured using static light scattering in GdnHCl aqueous solutions at 20 degrees C and pH 4.5. B(22) is positive in all solutions, indicating repulsive protein-protein interactions. At low GdnHCl concentrations, B(22) decreases with rising ionic strength: in the absence of GdnHCl, B(22) is 1.1 x 10(-3) mLmol/g(2), decreasing to 3.0 x 10(-5) mLmol/g(2) in the presence of 1 M GdnHCl. Lysozyme unfolds in solutions at GdnHCl concentrations higher than 3 M. Under such conditions, B(22) increases with ionic strength, reaching 8.0 x 10(-4) mLmol/g(2) at 6.5 M GdnHCl. Protein-protein hydrodynamic interactions were evaluated from concentration-dependent diffusivity measurements, obtained from dynamic light scattering. At moderate GdnHCl concentrations, lysozyme interparticle interactions are least repulsive and hydrodynamic interactions are least attractive. The lysozyme hydrodynamic radius was calculated from infinite-dilution diffusivity and did not change significantly during protein unfolding. Our results contribute toward better understanding of protein interactions of partially unfolded states in the presence of a denaturant; they may be helpful for the design of protein refolding processes that avoid protein aggregation.
Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. (1993)

In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.
Randomized Clustering Forests for Image Classification (2008)

Some of the most effective recent methods for content-based image classification work by quantizing image descriptors, and accumulating histograms of the resulting visual word codes. Large numbers of descriptors and large codebooks are required for good results and this becomes slow using k-means. We introduce Extremely Randomized Clustering Forests ensembles of randomly created clustering trees and show that they provide more accurate results, much faster training and testing, and good resistance to background clutter. Second, an efficient image classification method is proposed. It combines ERC-Forests and saliency maps very closely with the extraction of image information. For a given image, a classifier builds a saliency map online and uses it to classify the image. We show in several state-of-the-art image classification tasks that this method can speed up the classification process enormously. Finally, we show that the proposed ERC-Forests can also be used very successfully for learning distance between images. The distance computation algorithm consists of learning the characteristic differences between local descriptors sampled from pairs of same or different objects. These differences are vector quantized by ERC-Forests and the similarity measure is computed from this quantization. The similarity measure has been evaluated on four very different datasets and always outperforms the state-of-the-art competitive approaches.
Bacteriological and histopathological evaluation of guinea pigs after infection with Listeria monocytogenes (1977)

Randomly bred guinea pigs were infected with Listeria monocytogenes using the intracardial, intravenous and intraperitoneal routes of infection. Doses of Listeria ranged from 5 to 1,000 x the 50% lethal dose based on the 50% lethal dose for intracardially injected Listeria. A complete necropsy was performed on all animals that died after infection. Gross and microscopic examination of tissues revealed major pathological features which include myocarditis, edema and congestion with interstitial pneumonitis present in the lungs, and fatty hepatic changes with focal necrosis. For all or a majority of the animals, large numbers of Listeria were likewise recovered from these organs and from lymph nodes, spleen, kidneys, and adrenal gland tissue. Of the three routes of infection used, guinea pigs were most susceptible to Listeria injected via the intracardial route. The relatively high lethal dose of listeric for the quinea pig, however, suggests that the organism is a low-grade pathogen for this species.
Periodic structures in lipid monolayer phase transitions (1984)

Periodic patterns are observed when supported lipid monolayers doped with low concentrations of fluorescent lipid probes are observed with epi-fluorescence microscopy. Monolayers of dipalmitoyl phosphatidylcholine were examined on air-water interfaces and also on alkylated glass coverslips. The patterns are formed by periodic arrays of solid-phase lipid domains in equilibrium with fluid-phase lipid under specified conditions of temperature and two-dimensional lipid pressure. Electrostatic forces may stabilize the periodic ordering of the solid domains.
Cadherin-11 Provides Specific Cellular Adhesion between Fibroblast-like Synoviocytes (2004)

Cadherins are integral membrane proteins expressed in tissue-restricted patterns that mediate homophilic intercellular adhesion. During development, they orchestrate tissue morphogenesis and, in the adult, they determine tissue integrity and architecture. The synovial lining is a condensation of fibroblast-like synoviocytes (FLS) and macrophages one to three cells thick. These cells are embedded within the extracellular matrix, but the structure is neither an epithelium nor an endothelium. Previously, the basis for organization of the synovium into a tissue was unknown. Here, we cloned cadherin-11 from human rheumatoid arthritis (RA)-derived FLS. We developed L cell transfectants expressing cadherin-11, cadherin-11 fusion proteins, and anti-cadherin-11 mAb. Cadherin-11 was found to be expressed mainly in the synovial lining by immunohistologic staining of human synovium. FLS adhered to cadherin-11-Fc, and transfection of cadherin-11 conferred the formation of tissue-like sheets and lining-like structures upon fibroblasts in vitro. These findings support a key role for cadherin-11 in the specific adhesion of FLS and in synovial tissue organization and behavior in health and RA.
Preclinical evaluation of a bispecific low‐molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer (2014)

The heterodimeric molecule is a promising agent for PET imaging of primary and recurrent prostate cancer covering two receptor entities which might lead to an improved diagnostic sensitivity and therapeutic efficiency.
Migrating neural crest cells in the trunk of the avian embryo are multipotent (1991)

Trunk neural crest cells migrate extensively and give rise to diverse cell types, including cells of the sensory and autonomic nervous systems. Previously, we demonstrated that many premigratory trunk neural crest cells give rise to descendants with distinct phenotypes in multiple neural crest derivatives. The results are consistent with the idea that neural crest cells are multipotent prior to their emigration from the neural tube and become restricted in phenotype after leaving the neural tube either during their migration or at their sites of localization. Here, we test the developmental potential of migrating trunk neural crest cells by microinjecting a vital dye, lysinated rhodamine dextran (LRD), into individual cells as they migrate through the somite. By two days after injection, the LRD-labelled clones contained from 2 to 67 cells, which were distributed unilaterally in all embryos. Most clones were confined to a single segment, though a few contributed to sympathetic ganglia over two segments. A majority of the clones gave rise to cells in multiple neural crest derivatives. Individual migrating neural crest cells gave rise to both sensory and sympathetic neurons (neurofilament-positive), as well as cells with the morphological characteristics of Schwann cells, and other non-neuronal cells (both neurofilament-negative). Even those clones contributing to only one neural crest derivative often contained both neurofilament-positive and neurofilament-negative cells. Our data demonstrate that migrating trunk neural crest cells can be multipotent, giving rise to cells in multiple neural crest derivatives, and contributing to both neuronal and non-neuronal elements within a given derivative.(ABSTRACT TRUNCATED AT 250 WORDS)
Co-localization of aortic apolipoprotein B and chondroitin sulfate in an injury model of atherosclerosis. (1993)

In vitro, chondroitin sulfate (CS) proteoglycans (PGs) bind with high-affinity lipoproteins (LPs) containing apolipoprotein B (apo B), and cultured monocytes incubated with LP-PG complexes transform into foam cells (FCs). Consequently, arterial PGs are thought to contribute to the accumulation of LPs in atherosclerotic lesions, but their in vivo interaction has yet to be demonstrated. Balloon catheterization of rabbit aorta modifies the normal aortic distribution of endogenous LPs containing apo B, and determines their accumulation in normocholesterolemic conditions. The distribution of aortic CS-PGs parallels that of apoB within the neointima of injured aortas and might contribute to a favorable environment for LP sequestration within the lesions. To visualize the in situ relationship between apo B and CS-PG, we performed experiments for double detection by immunofluorescence and by post-embedding electron microscope immunogold. The results indicated that the colocalization of endogenous LPs containing apo B and of the large intimal CS-PGs in advanced lesions developed under the regenerated endothelium. At the ultrastructural level, frequent associations were visualized in the extracellular space and in relation to FCs. The close spatial relation between CS-PG and apo B inside the aortic lesions seems to support the hypothesis of their in situ interaction and of a simultaneous cellular uptake, and may be related to the development of both extracellular lipid deposits and the formation of FCs in atherogenesis.
Lensless coherent imaging by phase retrieval with an illumination pattern constraint (2006)

It is often possible to reduce the requirements on an imaging system by placing greater demands either on an illumination system or on post-detection processing of the data collected by the system. An extreme example of this is a system with no receiver optics whatsoever. By illuminating an object or scene with coherent light having a shaped illumination pattern, the receiver can be a simple detector array with no imaging optics, detecting the speckle intensity pattern reflected from the object; an image of the object can be reconstructed by a phase retrieval algorithm.