gebhart/patrepeval huggingface dataset:
The Prion Protein Knockout Mouse (2007)

The key pathogenic event in prion disease involves misfolding and aggregation of the cellular prion protein (PrP). Beyond this fundamental observation, the mechanism by which PrP misfolding in neurons leads to injury and death remains enigmatic. Prion toxicity may come about by perverting the normal function of PrP. If so, understanding the normal function of PrP may help to elucidate the molecular mechansim of prion disease. Ablation of the Prnp gene, which encodes PrP, was instrumental for determining that the continuous production of PrP is essential for replicating prion infectivity. Since the structure of PrP has not provided any hints to its possible function, and there is no obvious phenotype in PrP KO mice, studies of PrP function have often relied on intuition and serendipity. Here, we enumerate the multitude of phenotypes described in PrP deficient mice, many of which manifest themselves only upon physiological challenge. We discuss the pleiotropic phenotypes of PrP deficient mice in relation to the possible normal function of PrP. The critical question remains open: which of these phenotypes are primary effects of PrP deletion and what do they tell us about the function of PrP?
The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins (2004)

Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors.
An autoantibody inhibitory to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease (2002)

Mutations in the CLN3 gene are responsible for the neurodegenerative disorder Batten disease; however, the molecular basis of this disease remains unknown. In studying a mouse model for Batten disease, we report the presence of an autoantibody to glutamic acid decarboxylase (GAD65) in cln3-knockout mice serum that associates with brain tissue but is not present in sera or brain of normal mice. The autoantibody to GAD65 has the ability to inhibit the activity of glutamic acid decarboxylase. Furthermore, brains from cln3-knockout mice have decreased activity of glutamic acid decarboxylase as a result of the inhibition of this enzyme by the autoantibody, resulting in brain samples from cln3-knockout mice having elevated levels of glutamate as compared with normal. This elevated glutamate in the brain of cln3-knockout mice co-localizes with presynaptic markers. The decreased activity of GAD65 and increased levels of glutamate may have a causative role in astrocytic hypertrophy evident in cln3-knockout mice, and in altered expression of genes involved in the synthesis and utilization of glutamate that underlie a shift from synthesis to utilization of glutamate. An autoantibody to GAD65 is also present in sera of 20 out of 20 individuals tested who have Batten disease. Postmortem tissue shows decreased reactivity to an anti-GAD65 antibody that may be due to loss of GAD65-positive neurons or due to the reactive epitope being blocked by the presence of the autoantibody. We propose that an autoimmune response to GAD65 may contribute to a preferential loss of GABAergic neurons associated with Batten disease.
Secondary structure determination of the conserved 98-base sequence at the 3' terminus of hepatitis C virus genome RNA (1997)

The RNA genome of hepatitis C virus (HCV) terminates with a highly conserved 98-base sequence. Enzymatic and chemical approaches were used to define the secondary structure of this 3'-terminal element in RNA transcribed in vitro from cloned cDNA. Both approaches yielded data consistent with a stable stem-loop structure within the 3'-terminal 46 bases. In contrast, the 5' 52 nucleotides of this 98-base element appear to be less ordered and may exist in multiple conformations. Under the experimental conditions tested, interaction between the 3' 98 bases and upstream HCV sequences was not detected. These data provide valuable information for future experiments aimed at identifying host and/or viral proteins which interact with this highly conserved RNA element.
Biology of Fibrous Composites (1993)

This book, by a leading thinker with 30 years experience in the field, is the first devoted to fibrous composites in biology. It tackles a major unsolved problem in developmental biology - how does chemistry create architecture outside cells? Fibrous composites occur in all skeletal systems including plant cell walls, insect cuticles, moth eggshells, bone and cornea. They function like man-made fibreglass, with fibres set in a matrix. The fibrous molecules are long, extracellular and water-insoluble and to be effective they must be orientated strategically. The underlying hypothesis of this book is that the fibres are orientated by self-assembly just outside the cells during a mobile liquid crystalline phase prior to stabilization. The commonest orientations of the fibres are plywood laminates (orthogonal and helicoidal), and as parallel fibres. These may be imitated in vitro by liquid crystalline chemicals. The book takes an interdisciplinary approach and will be relevant to biologists, biochemists, biophysicists, material scientists and to liquid crystals chemists.
RSFQ TECHNOLOGY: PHYSICS AND DEVICES (2001)

Rapid Single-Flux-Quantum (RSFQ) logic, based on the representation of digital bits by single quanta of magnetic flux in superconducting loops, may combine several-hundred-GHz speed with extremely low power dissipation (close to 10 -18 Joule/bit) and very simple fabrication technology. The drawbacks of this technology include the necessity of deep (liquid-helium-level) cooling of RSFQ circuits and the rudimentary level of the currently available fabrication and testing facilities. The objective of this paper is to review RSFQ device physics and also discuss in brief the prospects of future development of this technology in the light of the tradeoff between its advantages and handicaps.
Niobium Tunable Microwave Filter (2009)

A superconductor bandpass filter with tunable central frequency in the range of 2-3.5 GHz has been implemented using superconducting quantum interference devices (SQUIDs). The filter is designed using two pi-network resonators connected by a transmission line. Both resonators have a SQUID inductor with a tuning range of 65-200 pH, controlled by current magnetically coupled to the SQUIDs. Over a frequency tunability of 1.5 GHz, the filter has a mid-band insertion loss of 0.5-3.0 dB and corresponding maximum unloaded quality factor of 40. Due to the presence of active elements, tunability of the filter depends on the power of the microwave signal. A maximum power of -52 dBm corresponds to a frequency tuning range of 15%. Spectral measurements by controlling the central frequency of the filter with variable pulsewidth shows that the filter can be tuned at a rate of 120 GHz/mus.
Efficacy of GM-CSF-producing Tumor Vaccine after Docetaxel Chemotherapy in Mice Bearing Established Lewis Lung Carcinoma (2006)

In this report, we evaluated the efficacy of a GM-CSF-producing tumor vaccine given before and after docetaxel in mice bearing established lung tumors. Mice bearing established 3LL tumors were treated with docetaxel and tumor vaccines transduced with either control or GM-CSF adenoviral vectors. Docetaxel (5-20 mg/kg) treatment alone had only a minimal effect on growth of established 3LL tumors in vivo, although docetaxel was cytotoxic to 3LL cells in vitro. When mice bearing established 3LL tumors were pretreated with docetaxel followed by vaccination with irradiated GM-CSF- transduced 3LL tumor cells, significant tumor regression and prolonged survival were observed compared with chemotherapy alone. Delaying docetaxel treatment until after tumor vaccination abrogated the vaccine's anti-tumor effects. Mice that survived treatment were able to resist a lethal rechallenge of 3LL tumor cells. Memory CTL specific for an epitope (MUT-1) derived from 3LL were detected in surviving mice. Docetaxel induced a mild lymphodepletion in mice, both CD4 and CD8 subsets were reduced in LN and spleens. Interestingly, docetaxel also diminished the number of memory CD8+ T cells (CD122+) and possible CD4+ CD25+ Foxp3+ natural Treg cells. Docetaxel treatment did not affect antigen-driven proliferation of naive T cells but significantly promoted survival of activated T cells. Thus, augmentation of vaccine induced antitumor immunity in docetaxel-treated mice primarily due to the enhanced survival of antigen-experienced T cells.
Nanoparticle‐Induced Phase Transitions in Diblock‐Copolymer Films (2005)

Films of a symmetric A–B diblock copolymer and A-coated Au nanoparticles cast from a selective solvent for A develop a lamellar surface layer. The surface layers have a low volume fraction of nanoparticles in the A lamellae atop a substrate layer of B cylinders/spheres in an A matrix containing a larger volume fraction of nanoparticles (see Figure). This arrangement thus induces an order–order transition between block-copolymer phases as their concentration is increased.
Multimedia as value enabler for decision making in virtual enterprises (2002)

Decision making in organizations, as contrasted with virtual enterprises, is based on physical, communicating, functional departments. The twin technologies of computing and communication, and the need for management problem-solving expertise have made it necessary to have a virtual enabler for effective decision making in enterprise processes. This paper brings out value-added aspects of multimedia technology in decision making and describes the Multimedia Architecture for Decision Processes (MADP), which can be used at the strategic, tactical and operational levels of enterprises. The study was applied to the financial analysis of mergers and acquisition decisions, and to equipment diagnosis.
Driving the citizen-oriented information on the electronic highway (2002)

The paper outlines the design and ongoing development of the Citizen Information Network (CIN) which makes information available to meet the growing demands from citizens for better information about public administration services and self-organized initiatives as well as for better communication among citizens about community affairs. Multimedia technology offers new opportunities but there are complex problems to solve, in particular with regard to data structure and data logistics, and interactive user interface design for casual users. The CIN enables users to get information comprised of text, photos, pictures, voice, and video elements in a multimedia kiosk, to search for the required information via a full-text retrieval from the frequently updated database. Original features of the approach of Bremen concern a public-private partnership and cost-sharing between a tourist and a citizen information system as well as a technical open client server architecture. The creation of such a system is a software and organization development process.
Distinct regulation of interleukin‐17 in human T helper lymphocytes (2007)

The present data demonstrate the differential regulation of IL-17 and RORgammat expression in human CD4+ T cells compared with murine cells. Optimal conditions for the development of IL-17-producing T cells from murine naive precursors are ineffective in human T cells. Conversely, IL-23 promoted the generation of human Th17 cells but was also a very potent inducer of other proinflammatory cytokines. These findings may have important implications in the pathogenesis of human autoimmunity as compared with mouse models.
Fractionation of subsets of BFU-E from normal human bone marrow: responsiveness to erythropoietin, human placental-conditioned medium, or granulocyte-macrophage colony-stimulating factor (1988)

Normal human bone marrow mononuclear cells were fractionated by differential adherence, immunomagnetic separation, and fluorescence- activated cell sorting (FACS). The resultant fractionated cells were cultured in semisolid medium to monitor the presence of BFU-E, Mix-CFC, and nonerythroid CFC. Two populations of cells were recovered on the basis of binding by the monoclonal antibody (MoAb) RFB-1. One of these populations contained BFU-E that were stimulated only by erythropoietin (Epo), whereas the second population contained BFU-E responsive to Epo, Epo and recombinant human granulocyte-macrophage colony-stimulating factor (rHGM-CSF), or Epo and human placental-conditioned medium (HPCM). Prior enrichment of clonogenic cells by removal of adherent and Leu-M3+ve, Leu-4+ve, Leu-7+ve, B1+ve, WEMG1+ve, and Glycophorin A+ve cells, followed by FACS fractionation on the basis of RFB-1 binding, consistently resulted in recoveries of BFU-E, Mix-CFC, and nonerythroid CFC of greater than 100% (up to 800%). These procedures also resulted in enrichment of up to 200-fold and frequencies of 1:6 for BFU-E, 1:5 for CFC, and 1:130 for Mix-CFC.
Tissue Localization of Perfused Endothelial Cell IGF Binding Protein is Markedly Altered by Association with IGF-I (1990)

Perfused endothelial cell IGF binding proteins (ECBP) have been previously demonstrated to leave the microcirculation of the rat heart and distribute primarily in connective tissue elements of the heart. In the present study, ECBP have been crosslinked to IGF-I and the biologically inactive [1-27,gly4,38-70]-hlGF-I, an analog of IGF-I lacking the type I IGF receptor domain. The crosslinked ECBPs were perfused through the isolated rat heart and their tissue distributions determined. Both [ECBP-Analog] and [ECBP-IGF-I] left the microcirculation of the heart. [ECBP-Analog] preferentially localized in connective tissue elements with a muscle:connective tissue ratio of approximately 1:6, similar to the tissue distribution of perfused ECBP. In contrast, the [ECBP-IGF-I] complexes localized in cardiac muscle with a muscle to connective tissue ratio of approximately 3:1, virtually identical to the tissue distribution of IGF-I when the IGF-I is perfused through the heart in the absence of any binding proteins. We conclude that 1) ECBP in the presence of IGF will cross capillary boundaries and 2) the tissue distribution of [ECBP-IGF-I] is dictated by the IGF-I molecule.
Survival of Mycobacterium tuberculosis in Host Macrophages Involves Resistance to Apoptosis Dependent upon Induction of Antiapoptotic Bcl-2 Family Member Mcl-1 (2003)

Mcl-1 protein expression was found to be up-regulated during infection with virulent Mycobacterium tuberculosis strain H37Rv. Mcl-1 induction in THP-1 cells was optimal at a multiplicity of infection of 0.8-1.2 bacilli per macrophage and was independent of opsonin coating of the bacteria. Mcl-1 expression was elevated as early as 4 h, peaked at 5.8-fold above control cells at 24 h, and remained elevated at 48 h after infection. In THP-1 cells, mMcl-1 mRNA was induced by infection with live H37Rv but not with attenuated M. tuberculosis strain H37Ra, heat-killed H37Rv, or latex beads. In THP-1 cells and monocyte-derived macrophages (MDMs), Mcl-1 protein was induced by infection with live H37Rv but not with attenuated M. tuberculosis strain H37Ra, heat-killed H37Rv, or latex beads. Treatment of uninfected, H37Ra-infected, and H37Rv-infected THP-1 cells and MDMs with antisense oligonucleotides to mcl-1 reduced Mcl-1 expression by >84%. This resulted in an increase in apoptosis of both MDMs and THP-1 cells that were infected with H37Rv, but not cells that were uninfected or infected with H37Ra. Increased apoptosis correlated with a decrease in M. tuberculosis CFUs recovered from antisense-treated, H37Rv-infected cells at 4 and 7 days after infection. In contrast, CFU recoveries from sense-treated, H37Rv-infected cells or from antisense- or sense-treated, H37Ra-infected cells were unchanged from controls. Thus, the antiapoptotic effect of the induction of Mcl-1 expression in H37Rv-infected macrophages promotes the survival of virulent M. tuberculosis.
Involvement of the epidermal growth factor receptor in epithelial repair in asthma (2000)

Epithelial damage and airway remodeling are consistent features of bronchial asthma and are correlated with disease chronicity, severity, and bronchial hyperreactivity. To examine the mechanisms that control bronchial epithelial repair, we investigated expression of the epidermal growth factor receptor (c-erbB1, EGFR) in asthmatic bronchial mucosa and studied repair responses in vitro. In biopsies from asthmatic subjects, areas of epithelial damage were frequently observed and exhibited strong EGFR immunostaining. EGFR expression was also high in morphologically intact asthmatic epithelium. Using image analysis, EGFR immunoreactivity (% of total epithelial area, median (range) was found to increase from 9.4 (4.1-20.4) in normal subjects (n=10) to 18.4 (9.3-28.9) in mild asthmatics (P<0.01, n=13) and 25.4 (15.4-31.8) in severe asthmatics (P<0.00, n=5). Epithelial EGFR immunoreactivity remained elevated in patients treated with corticosteroids and was positively correlated with subepithelial reticular membrane thickening. Using 16HBE 14o- bronchial epithelial cells, we found that EGF accelerated repair of scrape-wounded monolayers and that the EGFR-selective inhibitor, tyrphostin AG1478, inhibited both EGF-stimulated and basal wound closure whereas dexamethasone was without effect. Intrinsic activation of the EGFR was confirmed by analysis of tyrosine phosphorylated proteins, which revealed a rapid, damage-induced phosphorylation of the EGFR, irrespective of the presence of exogenous EGF. To assess the relationship between EGFR-mediated repair and tissue remodeling, release of the profibrogenic mediator TGF-beta2 was also measured. Scrape wounding increased release of TGF-beta2 from epithelial monolayers and EGF had no additional stimulatory effect. However, when repair was retarded with AG1478, the amount of TGF-beta2 increased significantly. These data indicate that the EGFR may play an important role in bronchial epithelial repair in asthma and that impairment of this function may augment airway remodeling.
Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats. Characterization and mode of action. (1987)

The effect of oral administration of vanadate, in normalizing blood glucose levels of streptozotocin-treated rats (ST-rats), is further characterized and its mode of action is determined. We have examined the effects of two orally administered doses of sodium metavanadate. High concentrations of orally administered vanadate (0.8 mg/ml in drinking water) reduced blood glucose levels within 2-4 days of application and led to the appearance of hypoglycemia in test animals. Lower concentrations of vanadate (0.2 mg/ml in drinking water) also lowered blood glucose levels within 4 days, but did not lead to hypoglycemia for at least 3 weeks. These effects of vanadate were found to be reversible; hyperglycemia recurred within 2 days after removal of vanadate from the drinking water. In streptozotocin-treated rats receiving low vanadate treatment, circulating levels of vanadate were about 0.8 microgram/ml after 3 weeks of treatment. These rats became anabolic, while rats receiving high vanadate treatment remained catabolic. Subsequent to vanadate treatment, adipocytes derived from ST-rats responded to lower insulin concentrations. In addition, vanadate treatment lowered the increased insulin binding capacity of liver plasma membranes derived from ST-rats. Insulin binding capacity under these conditions approached that of control non-ST-rats. Basal rates of hexose uptake in muscle and liver tissues were doubled in vanadate-treated ST-rats. It is concluded that the oral administration of vanadate leads to normoglycemia by stimulating glucose uptake. Treatment with "low vanadate" leads to the formation of a stable anabolic and normoglycemic state in ST-rats and appears to restore insulin responsiveness of target tissues, without apparent signs of toxicity. Vanadate treatment did not impair either kidney or liver function, as assayed by the measurement of serum urea, creatinine, and glutamic-oxaloacetic transaminase.
Progress toward the clinical application of patient-specific pluripotent stem cells (2010)

Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of somatic cells through the exogenous expression of transcription factors. These cells, just like embryonic stem cells, are likely to have a major impact on regenerative medicine, because they self-renew and retain the potential to be differentiated into all cell types of the human body. In this Review, we describe the current state of iPS cell technology, including approaches by which they are generated and what is known about their biology, and discuss the potential applications of these cells for disease modeling, drug discovery, and, eventually, cell replacement therapy.
DETERMINANTS OF PHOTOSENSITIZATION BY PURPURINS (1989)

Studies were carried out on two purpurins, NT2 and an analog, Sn.NT2H2. Both are photosensitizers, but the latter is substantially more effective against neoplastic cells in vivo. These hydrophobic dyes can be solubilized via Cremophor EL emulsions. We found both dyes to be approximately equitoxic to murine leukemia L1210 cells in culture, in terms of intracellular concentrations. But uptake of NT2 was 10-fold less efficient than Sn.NT2H2, i.e. a 10-fold higher extracellular level of NT2 was needed to produce an equitoxic response. Fluorescence measurements indicate that NT2 partitions to a very hydrophobic intracellular environments; its phototoxicity was related to inhibition of biosynthesis of DNA. In contrast, SN.NT2H2 was accumulated at more hydrophilic loci (the apparent dielectric constant is consistent with a membrane interface) and mediated photodamage at sites of membrane transport.
Simple decision rules for classifying human cancers from gene expression profiles (2005)

actan@jhu.edu.