gebhart/patrepeval huggingface dataset:
Monoclonal antibody-ricin A chain conjugate selectively cytotoxic for cells bearing the common acute lymphoblastic leukemia antigen. (1982)

The toxic subunit of ricin has been conjugated by a disulfide bound to a monoclonal murine antibody (J-5) specific for the common acute lymphoblastic leukemia antigen (CALLA) expressed on human lymphoblastic cells. Both the monoclonal antibody and ricin A chain retained their original biological activity after conjugation. The ricin A chain portion of this conjugate effectively inhibited protein synthesis in a cell-free rabbit reticulocyte lysate system. Its antibody-combining site attached to the membrane of CALLA-bearing cells, whereupon both components of the molecule, antibody and A chain, could be detected using fluorescein-labeled antibody probes directed against either mouse F(ab')2 or ricin A chain. This conjugate proved to be a potent cytotoxin for CALLA-positive Nalm-1 cells growing in vitro and produced 50% inhibition of proliferation at levels of 2 x 10(-10) M. In contrast, CALLA-negative cell lines were unaffected until levels of conjugate approached 10(-6) M. When tested for cytotoxic action on Nalm-1 cells, the composite conjugate molecule was at least 2000 times more effective than J-5 antibody alone, ricin A chain alone, or a noncovalent mixture of these components. Cytotoxicity of the conjugate could be blocked completely by addition of antibodies specific for either mouse immunoglobulin or ricin A chain. Direct comparison of the in vitro cytotoxicity of CALLA-directed univalent Fab versus bivalent F(ab')2 carriers of ricin A chain revealed 70-fold greater efficacy for the latter conjugate. This differential could not be accounted for by differences in A chain activity or binding affinity for the cell membrane but appeared related to the ability of the multivalent agent to induce modulation and internalization of CALLA determinants. No overt toxic effects were noted when the F(ab')2-A chain conjugate was administered i.v. to rabbits at levels as high as 20 mg/kg single injection or 5 mg/kg for 5 days. The unique specificity characteristics and high potency of this cytotoxic conjugate indicate that it has significant therapeutic potential for the treatment of CALLA-bearing human leukemias and lymphomas.
Clostridium difficile infection: pathophysiology and diagnosis. (1997)

Clostridium difficile is a relatively common enteric pathogen encountered most frequently in association with antibiotic use and as a nosocomial pathogen. Four factors dictate clinical expression: (1) acquisition of the organism from environmental sources or previous colonization; (2) distortion of the competing colonic flora by antibiotics; (3) toxin production; and (4) age-related susceptibility. Characteristics of clinical features include inflammatory diarrhea (cramps, fecal leukocytes, systemic response), endoscopic evidence of colitis or pseudomembranous colitis, and protein-losing enteropathy. The usual diagnostic tests are designed to detect toxin B with a tissue culture assay or toxin A with an enzyme immunoassay.
Lysyl Oxidase Activates the Transcription Activity of Human Collagene III Promoter (2000)

Lysyl oxidase is an extracellular enzyme that controls the maturation of collagen and elastin. Lysyl oxidase and collagen III often show similar expression patterns in fibrotic tissues. Therefore, we investigated the influence of lysyl oxidase overexpression on the promoter activity of human COL3A1 gene. Our results showed that when COS-7 cells overexpressed the mature form of lysyl oxidase, the activity of the human COL3A1 promoter was increased up to an average of 12 times when tested by luciferase reporter assay. The effect was specific, because other promoters were not affected. Moreover, lysyl oxidase effect was abolished by beta-aminopropionitrile, a specific inhibitor of its catalytic activity. Electrophoretic mobility shift assay showed a binding activity in the region from -101 to -77 that was significantly increased by lysyl oxidase overexpression. The binding was specifically competed by the cold probe, and the mutagenesis of this region abolished both the binding activity in gel retardation and lysyl oxidase stimulation of COL3A1 promoter in transfection experiments. We identified the binding activity as Ku antigen in its two components: Ku80 and Ku70. This study suggests a new coordinated mechanism by which lysyl oxidase might control the development of fibrosis.
Vacuolar H+-ATPase d2 Subunit (2005)

The ubiquitous multisubunit vacuolar-type proton pump (H+- or V-ATPase) is essential for acidification of diverse intracellular compartments. It is also present in specialized forms at the plasma membrane of intercalated cells in the distal nephron, where it is required for urine acidification, and in osteoclasts, playing an important role in bone resorption by acid secretion across the ruffled border membrane. It was reported previously that, in human, several of the renal pump's constituent subunits are encoded by genes that are different from those that are ubiquitously expressed. These paralogous proteins may be important in differential functions, targeting or regulation of H+-ATPases. They include the d subunit, where d1 is ubiquitous whereas d2 has a limited tissue expression. This article reports on an investigation of d2. It was first confirmed that in mouse, as in human, kidney and bone are two of the main sites of d2 mRNA expression. d2 mRNA and protein appear later during nephrogenesis than does the ubiquitously expressed E1 subunit. Mouse nephron-segment reverse transcription-PCR revealed detectable mRNA in all segments except thin limb of Henle's loop and distal convoluted tubule. However, with the use of a novel d2-specific antibody, high-intensity d2 staining was observed only in intercalated cells of the collecting duct in fresh-frozen human kidney, where it co-localized with the a4 subunit in the characteristic plasma membrane-enhanced pattern. In human bone, d2 co-localized with the a3 subunit in osteoclasts. This different subunit association in different tissues emphasizes the possibility of the H+-ATPase as a future therapeutic target.
Multiplexed Protein Quantitation in Saccharomyces cerevisiae Using Amine-reactive Isobaric Tagging Reagents (2004)

We describe here a multiplexed protein quantitation strategy that provides relative and absolute measurements of proteins in complex mixtures. At the core of this methodology is a multiplexed set of isobaric reagents that yield amine-derivatized peptides. The derivatized peptides are indistinguishable in MS, but exhibit intense low-mass MS/MS signature ions that support quantitation. In this study, we have examined the global protein expression of a wild-type yeast strain and the isogenic upf1Delta and xrn1Delta mutant strains that are defective in the nonsense-mediated mRNA decay and the general 5' to 3' decay pathways, respectively. We also demonstrate the use of 4-fold multiplexing to enable relative protein measurements simultaneously with determination of absolute levels of a target protein using synthetic isobaric peptide standards. We find that inactivation of Upf1p and Xrn1p causes common as well as unique effects on protein expression.
Mechanics of noncoplanar mesh design for stretchable electronic circuits (2009)

A noncoplanar mesh design that enables electronic systems to achieve large, reversible levels stretchability (&amp;gt;100%) is studied theoretically and experimentally. The design uses semiconductor device islands and buckled thin interconnects on elastometric substrates. A mechanics model is established to understand the underlying physics and to guide the design of such systems. The predicted buckle amplitude agrees well with experiments within 5.5% error without any parameter fitting. The results also give the maximum strains in the interconnects and the islands, as well as the overall system stretchability and compressibility.
Postnatal development of the murine cerebellar cortex: formation and early dispersal of basket, stellate and Golgi neurons (2006)

The cerebellar cortex consists of a small set of neuronal cell types interconnected in a highly stereotyped way. While the development of cerebellar cortical projection neurons, i.e. Purkinje cells, and that of granule cells has been elucidated in considerable detail, that of cerebellar cortical inhibitory interneurons is still rather fragmentarily understood. Here, we use mice expressing green fluorescent protein (GFP) from the Pax2 locus to analyse the ontogenesis of these cells. Numbers of Pax2-positive inhibitory interneuronal precursors increase following a classical sigmoidal growth curve to yield a total of some 905.000 +/- 77.000 cells. Maximal cell increase occurs at about postnatal day (P)5.4, and some 75% of all inhibitory interneurons are generated prior to P7. Conjoint analysis of the developmental accruement of Pax2-GFP-positive cells and their cell cycle distribution reveals that, at least at P0 and P3, the numerical increase of these cells results primarily from proliferation of a Pax2-negative precursor population and suggests that Pax2 expression begins at or around the final mitosis. Following their terminal mitosis, inhibitory cerebellar cortical interneurons go through a protracted quiescent phase in which they maintain expression of the cell cycle marker Ki-67. During this phase, they translocate into the nascent molecular layer, where they stall next to premigratory granule cell precursors without penetrating this population of cells. These observations provide a quantitative description of cerebellar cortical inhibitory interneuron genesis and early differentiation, and define Pax2 as a marker expressed in basket and stellate cells, from around their final mitosis to their incipient histogenetic integration.
Delivery systems for molecular vaccination. (2000)

Vaccination is one of the medical success stories of the 20th century, however, there are many diseases for which no prophylactic regimes are available. A major hindrance that has prevented the development of effective mass immunization programs is the inability to induce an appropriate, protective, immune response. For example, for vaccines against intracellular pathogens there is a requirement for cell-mediated immunity as characterized by cytolytic T-lymphocyte activity. However, such a response can be extremely difficult to elicit, especially those employing recombinant, soluble protein subunits. This deficiency is due to the inability of these antigens to access the machinery of the appropriate antigen-processing pathway. Following an improved understanding of the mechanisms underlying such processing, as well as the realization that delivery systems can affect, quantitatively and qualitatively, the resulting immune response, the last decade has witnessed an intense research effort in this field. In this article we will review the major developments in the area of antigen delivery as related to vaccination.
Diagnosis and treatment of overactive bladder. (2005)

Overactive bladder is a very common condition, affecting an estimated 50 to 100 million people worldwide. More than 90% of women with overactive bladder have no recognizable pathology. Several risk factors have been recognized for overactive bladder syndrome and incontinence including age, diabetes, Caucasian race, and hormone replacement therapy. The gold standard for diagnosing detrusor overactivity is multichannel urethrocystometry, although single channel cystometry or even simple cystometry may be used. A variety of interventions are available for the treatment of the overactive bladder syndrome. These include behavioral interventions, pelvic floor electrical stimulation, electromagnetic innervation, neuromodulation, intravesical instillations and injections, operative bladder augmentation, and pharmacotherapy. In any therapy for overactive bladder symptoms, expectations play a pivotal role in success or failure, and communication between the healthcare provider and the patient is essential for setting and achieving treatment goals.
CD4 T cells activated in the mesenteric lymph node mediate gastrointestinal food allergy in mice (2007)

A localized Th2 milieu has been observed in the intestine of subjects with food allergic disorders; however, the role of T cells in the pathophysiology of these disorders remains poorly understood. Our aim was to examine sites of T cell activation in response to food challenge, identify potential factors responsible for T cell recruitment to the gut, and determine the role of T cells in disease. BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly fed with OVA to induce allergic diarrhea. Local cytokine and chemokine expressions were assessed by quantitative PCR, and cytokine secretion levels in the mesenteric lymph node (MLN) were determined by ELISA. Homing molecule expression was determined by flow cytometry, and the role of CD4(+) T cells in promoting disease was tested by adoptive transfer. Mice developed diarrhea associated with changes in epithelial ion transport, mast cell infiltration, intestinal IgE secretion, and local upregulation of Th2 cytokines and the Th2 chemokines CCL1, CCL17, and CCL22 in the small intestine. T cell activation occurred in the MLN before symptom onset, and a single feed of OVA induced T cell proliferation, alpha(4)beta(7) upregulation, and CD62L downregulation. Cells from the MLN, including purified CD4(+) T cells, were able to transfer allergic diarrhea to naive mice. A gut-homing phenotype induced in the MLN and selective upregulation of Th2 chemoattractants are likely important factors in the gastrointestinal recruitment of pathological Th2-skewed CD4(+) T cells in food allergy.
Regional blood flow during simulated diving in the conscious Weddell seal (1979)

Changes in regional blood flow during simulated normobaric diving were studied in the conscious Antarctic Weddell seal (Leptonychotes weddelli) by injecting 25-microns radioactive microspheres into the left ventricle. Injections were performed before and 8--12 min after submersion of the head in iced seawater. Diving was associated with a fall in cardiac output from a mean control value of 39.8 +/- 10.2 to 5.6 +/- 3.4 l/min (mean +/- SD) and in heart rate from 52 +/- 15 to 15 +/- 4 beats/min. Blood flow to the splanchnic and peripheral vascular bed was reduced by more than 90%, cerebral blood flow was unchanged, right and left ventricular blood flow decreased by 85%, and adrenal blood flow decreased by 39%. The pulmonary fraction of the injected microsphere dose increased from 7.9 to 29.9% during diving. This may signify a large increase of peripheral arteriovenous shunting during the dive and/or increased bronchial artery blood flow. It is concluded that blood flow during diving is directed to organs and tissues according to their metabolic requirements.
A Familial Alzheimer's Disease Locus on Chromosome 1 (1995)

The Volga German kindreds are a group of seven related families with autosomal dominant early-onset Alzheimer's disease (AD). Linkage to known AD-related loci on chromosomes 21 and 14 has been excluded. Significant evidence for linkage to AD in these families was obtained with D1S479 and there was also positive evidence for linkage with other markers in the region. A 112-base pair allele of D1S479 co-segregated with the disease in five of seven families, which is consistent with a common genetic founder. This study demonstrates the presence of an AD locus on chromosome 1q31-42.
Triptolide: An inhibitor of a disintegrin and metalloproteinase 10 (ADAM10) in cancer cells (2009)

Triptolide, a diterpene triepoxide derived from Trypterygium wilfordii, is documented to have antitumor activity in a broad range of solid tumors and leukemia. The mechanisms that are involved in triptolide-mediated apoptosis or growth inhibition in cancer cells are not fully understood. We identified a disintegrin and metalloproteinase 10 (ADAM10) as a novel molecular target of triptolide using affinity chromatography and mass spectrometry. The identification was confirmed by western blot analysis using an anti-ADAM10 antibody. The expression of ADAM10 is enhanced in several tumors including leukemia and is involved in malignant cell growth and cancer progression. ADAM10 is a type 1 transmembrane glycoprotein that cleaves several plasma membrane proteins. We show that triptolide, at concentrations in the nM range, resulted in a significant decrease in ADAM10 expression followed by the appearance of ADAM10 cleaved product. Furthermore, triptolide reduced the viability of monocytic leukemic U937 cells. Triptolide treatment of MCF-7 breast cancer cells expressing ectopic ADAM10 or dominant negative ADAM10 (DN ADAM10) resulted in a decreased expression of ADAM10 with a concomitant increase in ADAM10 cleaved products. Moreover, siRNA-mediated knockdown of ADAM10 mRNA significantly affected the growth of MCF-7 cells. Interestingly, the combination of siRNA-mediated knockdown of ADAM10 mRNA expression and triptolide treatment lead to a further reduction in cell growth. Taken together, we provide evidence that ADAM10 is a novel target of triptolide, presenting a novel strategy to inhibit ADAM10 activity in tumorigenesis.
Large area x-ray and neutron imaging using three-dimensional arrays of microlenses (2004)

Linear arrays of biconcave microlenses have been shown to be capable of imaging small objects using either x rays or neutrons. Because these lenses have small apertures and finite lengths, they are limited in their field of view (FOV). To increase the FOV, we propose that two sets of three-dimensional arrays of these microlenses be used. The spacing of the microlenses is calculated to achieve a complete image with uniform brightness. General design criteria are discussed in situations where either a one-to-one image or a magnified image is required.
Drug Improvement of Cognition : Hope and Reality (1988)

Summary Recent research aimed at discovering and developing new drugs for diseases of cognition focuses heavily on Alzheimer’s disease and emphasizes mechanistic/biochemical approaches. Originally, research was based on a pragmatic search for compounds that would protect animals front disruptors of learning and memory. A series of compounds called nootropics do protect animals against these disruptions and offer hope that cognitive deficits may be amenable to pharmacological treatment. However, clinical development of these compounds is complicated by a number of factors. Among these is the poor correlation between animal models of cognitive loss and clinical disease states, a notable exception being the amnesic effects of benzodiazepines. Moreover, the inverted U-shaped dose-response function obtained in animal models and the lack of standard clinical outcome measures further complicate the development process. Tests that are beginning to gain acceptance as “standards” need to be characterized in terms of their validity, variability, and stability. There is a dearth of normative, especially longitudinal, data on cognitive decline. However, the great efforts being made in basic and applied research warrant cautious optimism.
Humanised IgG1 antibody variants targeting membrane-bound carcinoembryonic antigen by antibody-dependent cellular cytotoxicity and phagocytosis (2009)

The greatly enhanced in vitro ADCC activity of the glycoengineered version of hPR1A3 is likely to be clinically beneficial.
Assessing Identity, Phenotype, and Fate of Endothelial Progenitor Cells (2008)

From the paradigm shifting observations of Harvey, Malpighi, and van Leeuwenhoek, blood vessels have become recognized as distinct and dynamic tissue entities that merge with the heart to form a closed circulatory system.1 Vessel structures are comprised predominantly of a luminal layer of endothelial cells that is surrounded by some form of basement membrane, and mural cells (pericytes or vascular smooth muscle cells) that make up the vessel wall. In larger more complex vessel structures the vessel wall is composed of a complex interwoven matrix with nerve components. Understanding the cellular and molecular basis for the formation, remodeling, repair, and regeneration of the vasculature have been and continue to be popular areas for investigation.&#13;\n&#13;\nThe endothelium has become a particularly scrutinized cell population with the recognition that these cells may play important roles in maintaining vascular homeostasis and in the pathogenesis of a variety of diseases.2 Although it has been known for several decades that some shed or extruded endothelial cells enter the circulation as apparent contaminants in the human blood stream,3 only more recent technologies have permitted the identification of not only senescent sloughed endothelial cells,4 but also endothelial progenitor cells (EPCs), which have been purported to represent a normal component of the formed elements of circulating blood5 and play roles in disease pathogenesis.6–9 Most citations refer to an article published in 1997 in which Asahara and colleagues isolated, characterized, and examined the in vivo function of putative EPCs from human peripheral blood as a major impetus for generating interest in the field.10 This seminal article presented some evidence to consider emergence of a new paradigm for the process of neovascularization in the form of postnatal vasculogenesis. Since publication of that article, interest in circulating endothelial cells, and particularly EPCs, has soared, and one merely has to type the keyword search terms, endothelial progenitor cell, to recover more than 8984 articles including 1347 review articles in PubMed (as of June 2008).&#13;\n&#13;\nWhat can we possibly add in the form of another EPC review that will be considered of significant value for the reader? We will attempt to review some of the early article in the field and reflect on how information in those articles was gradually derivatized into perhaps more conflicting rather than unifying concepts. We will also attempt to concisely address some of the important determinants and principles that are now leading to a new understanding of what functionally constitutes an EPC and outline some of the current measures used to identify, enumerate, and quantify these cells. Finally, we give our opinion of the best definition for an EPC based on some comparative analyses performed primarily in human subjects.
Griffiths singularities and magnetoresistive manganites (2003)

The large, so-called colossal magnetoresistivity of doped ${\mathrm{LaMnO}}_{3}$ has attracted considerable attention, but is only one unusual feature of the ferromagnetic transition in these compounds. We examine in this paper the progression of magnetic and thermodynamic behavior as the transition temperature is made to vary from 360 K to 218 K by changing the divalent dopant. Single crystals of ${\mathrm{La}}_{0.7}{\mathrm{Sr}}_{0.3}{\mathrm{MnO}}_{3},$ as is well known, show modest magnetoresistivity and conventional critical behavior. ${\mathrm{La}}_{0.66}{\mathrm{Pb}}_{0.34}{\mathrm{MnO}}_{3},$ and to an even greater extent, ${\mathrm{La}}_{0.7}{\mathrm{Ca}}_{0.3}{\mathrm{MnO}}_{3},$ have unusual magnetic properties extending more than 100 K above the transition. We treat the properties of the latter samples in the context of a Griffiths phase in which the transition temperature is depressed from its maximum value ${T}_{G}$ by random bond-angle bending.