gebhart/patrepeval huggingface dataset:
The Cholinergic Lesion of Alzheimer's Disease: Pivotal Factor or Side Show? (2004)

A profound loss of cortical cholinergic innervation is a nearly invariant feature of advanced Alzheimer's disease (AD). The temporal course of this lesion and its relationship to other aspects of the disease have not yet been fully clarified. Despite assertions to the contrary, a review of the evidence suggests that a perturbation of cholinergic innervation is likely to be present even in the very early stages of AD. This cholinergic lesion is unlikely to be a major determinant of the clinical symptoms or of the neuropathological lesions. Nonetheless, it almost certainly contributes to the severity of the cognitive and behavioral deficits, especially in the areas of memory and attention. The cholinergic lesion may also influence the progression of the neuropathological process through complex interactions with amyloidogenesis, tau phosphorylation and neuroplasticity.
Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody. (1994)

Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections.
Two‐dimensional proton NMR studies on poly(VPGVG) and its cyclic conformational correlate, cyclo(VPGVG)3 (1989)

Two-dimensional nuclear Overhauser enhancement (2D NOESY) data are reported for the polypentapeptide of elastin, poly(VPGVG), and the cyclopentadecapeptide, cyclo(VPGVG)3. In both, the repeating type II Pro2-Gly3 beta-turn can be derived from the NOE data, providing confirmation of many previous studies. In addition, other through-space connectivities are detailed that also compare favorably with previously determined crystal and solution structures for cyclo(VPGVG)3. Also, near identical data for the cyclopentadecapeptide and the polypentapeptide demonstrate the cyclic conformation-linear (helical) conformational correlate relationship between the two molecules. The 2D NOESY experiment is seen to be an effective means of establishing the presence or absence of a conformational relationship between a cyclic repeating sequence and its higher molecular weight linear counterpart. This is an approach of substantial practical value when developing the conformation of sequential polypeptides and when attempting to identify the presence of the conformation of a repeating peptide sequence within a more complex primary structure. Having established the basic conformational relationship between a cyclic conformation and its linear helical counterpart, cross peaks present in the linear helical structure that are not present in the cyclic conformational correlate can provide information on the interactions between adjacent turns of the helix. In this connection, a Val gamma CH3 in equilibrium Pro beta CH2 interaction is reported that can be the basis for determining the number of pentamers per turn of helix once it is determined whether it is dominantly the Val1 or Val4 gamma CH3 that is interacting with the Pro2 beta CH2.
Mutational analysis of a human immunodeficiency virus type 1 Tat protein transduction domain which is required for delivery of an exogenous protein into mammalian cells (2002)

The human immunodeficiency virus type 1 (HIV-1) Tat protein transduction domain (PTD), which contains a high proportion of arginine and lysine residues, is responsible for highly efficient protein transduction through the plasma membrane. To identify the role of the PTD sequence motif in transduction, various deletions and substitutions were introduced into the PTD. Tat-green fluorescent protein (GFP) fusion proteins, containing various lengths of the Tat PTD, were expressed and the extent of their transduction into mammalian cells was analysed by Western blot analysis and fluorescence microscopy. Deletion analysis of PTD mapped to a nine amino acid motif (residues 49-57: RKKRRQRRR) sufficient for transduction. Further deletion of this Tat basic domain either at the N terminus or at the C terminus significantly decreased transduction efficiency. The transduction efficiencies of GFPs fused to nine consecutive lysine (9Lys-GFP) or arginine (9Arg-GFP) residues were similar to that of Tat(49-57)-GFP. The transduced proteins localized to both the nucleus and the cytosol, as assessed by confocal microscopy and Western blot analysis of subcellular fractions from transduced cells. Thus, the availability of recombinant GFP fusion proteins facilitates the simple and specific identification of protein transduction mediated by these peptide sequences. The modified PTD sequences designed in this study may provide useful tools necessary for delivering therapeutic proteins/peptides into cells.
Endothelial cell phenotypes in the rheumatoid synovium: activated, angiogenic, apoptotic and leaky. (2004)

Endothelial cells are active participants in chronic inflammatory diseases. These cells undergo phenotypic changes that can be characterised as activated, angiogenic, apoptotic and leaky. In the present review, these phenotypes are described in the context of human rheumatoid arthritis as the disease example. Endothelial cells become activated in rheumatoid arthritis pathophysiology, expressing adhesion molecules and presenting chemokines, leading to leukocyte migration from the blood into the tissue. Endothelial cell permeability increases, leading to oedema formation and swelling of the joints. These cells proliferate as part of the angiogenic response and there is also a net increase in the turnover of endothelial cells since the number of apoptotic endothelial cells increases. The endothelium expresses various cytokines, cytokine receptors and proteases that are involved in angiogenesis, proliferation and tissue degradation. Associated with these mechanisms is a change in the spectrum of genes expressed, some of which are relatively endothelial specific and others are widely expressed by other cells in the synovium. Better knowledge of molecular and functional changes occurring in endothelial cells during chronic inflammation may lead to the development of endothelium-targeted therapies for rheumatoid arthritis and other chronic inflammatory diseases.
Synthesis of oligodeoxyribonucleotides by a continuous-flow, solid-phase method using phosphotriester intermediates (1982)

A new composite polydimethylacrylacrylamide–kieselguhr support has been used in a continuous-flow assembly apparatus for the efficient solid-phase synthesis of an undeca- and a heptadeca-deoxyribonucleotide using phosphotriester intermediates.
Decreasing intradental nerve activity in the cat with potassium and divalent cations (1991)

Nerve activity was recorded from deep dentinal cavities in the canine teeth to assess the possible influence of potassium and divalent cations in decreasing this activity in hypersensitive teeth. The decreased activity after the topical application of 0.756 mol/l KCl to the cavity was primarily due to the cation. KCl elicited a biphasic response from intradental nerves, an initial transient excitatory response followed by a prolonged inhibitory period. During the inhibitory period 3 mol/l NaCl, an effective excitatory stimulus, failed to evoke intradental nerve activity. However, with time the response to 3 mol/l NaCl eventually recovered to its previous control level. Close, intra-arterial injection of KCl showed the same biphasic response and time-course of intradental nerve activity as with topical application. Therefore, whether KCl was applied topically or injected its effectiveness in altering the nerve activity was similar. Pretreatment of the dentinal cavity with CaCl2, MgCl2 or SrCl2 greatly reduced the response of intradental nerves to KCl. Therefore these divalent cations seem to have a depressant action on pulpal nerve fibres. The mechanism of action of KCl seems to be an alteration of K+ concentration immediately surrounding the intradental nerves which presumably depolarizes the nerve fibre membrane and elicits an initial firing of action potentials. Because of the persisting high levels of extracellular potassium a sustained depolarized state occurs that results in an inactivation of the action potential. Divalent cations appear to depress the excitability of the nerve cell membrane without altering membrane potential. Such ionic agents could be used in conjunction with KCl as a possible treatment for hypersensitive teeth.
Robust Fuel- and Time-Optimal Control of Uncertain Flexible Space Structures (2005)

The problem of computing open-loop, fuel- and timeoptimal control inputs for flexible space structures in the face of modeling uncertainty is investigated. Robustified, fuel- and time-optimal pulse sequences are obtained by solving a constrained optimization problem subject to robustness constraints. It is shown that "bang-off-bang" pulse sequences with a finite number of stitchings provide a practical tradeoff among the maneuvering time, fuel consumption, and performance robustness of uncertain flexible spacecraft.
Regulation and Functional Involvement of Macrophage Scavenger Receptor MARCO in Clearance of Bacteria In Vivo (1999)

The scavenger receptors expressed by macrophages are thought to play an important role in the immune response against bacteria by mediating binding and phagocytosis. A novel member of the class A scavenger receptor family, macrophage receptor with collagenous structure (MARCO), has recently been identified. In this study we have generated a panel of mAbs with specificities for different domains of this receptor. Two of those reacting with the C-terminal cysteine-rich domain block ligand binding of MARCO. The in vivo expression of this murine receptor is normally restricted to distinct populations of macrophages in the spleen and lymph nodes. During bacillus Calmette-Guérin (BCG) infection, during bacterial sepsis, or after the injection of purified LPS, however, the expression of MARCO is rapidly induced on macrophages in other tissues, including Kupffer cells in the liver. Using the mouse macrophage cell line J774.2, it was shown that LPS stimulation up-regulates surface expression of MARCO in a dose- and time-dependent fashion. The proinflammatory cytokines IL-1, IL-6, TNF-alpha, and IFN-gamma had little or no effect. Using inhibitory mAbs, the relevance of MARCO for the clearance of circulating bacteria in vivo was determined. Although the overall elimination of live Escherichia coli and Staphylococcus aureus from the blood did not appear to be affected by treatment with these Abs, the capturing of heat-killed bacteria by macrophages in the marginal zone areas of the spleen was clearly inhibited. This study suggests a role for MARCO in the host antibacterial defense.
Angiogenic Growth Factors: Autocrine and Paracrine Regulation of Survival in Hematologic Malignancies (2001)

Recent research has focused on the role of angiogenic growth factors and their ability to mediate tumor growth and metastases, both in solid tumors and in hematologic malignancies. The bone marrow microenvironment is the setting for a wealth of complex interactions that include cell-to-cell contacts as well as secretion of and response to soluble factors. Abundant evidence supports the role of basic fibroblast growth factor (bFGF) in contributing to the dysregulation of apoptosis that is the hallmark of chronic lymphocytic leukemia (CLL). In fact, CLL cells themselves express bFGF; intracellular levels of this cytokine correlate with clinical CLL stage. Other stromal factors mediate the inhibition of apoptosis in CLL as well, suggesting that strategies to block the responses of CLL cells to these factors may represent effective therapies. More broadly, the class of agents known as angiogenesis inhibitors may offer important advantages with respect to the treatment of numerous types of malignancies. Currently, a number of clinical trials are under way to evaluate the clinical potential of several different angiogenesis inhibitors in several hematologic neoplasms.
Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR. (1996)

RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 microM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytanic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with Ki values of 4 microM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways.
First-in-Human Study Testing a New Radioenhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas (2016)

<b>Purpose:</b> This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS).<b>Experimental Design:</b> Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion.<b>Results:</b> Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6-40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22% increase); median percentage of residual viable tumor cells was 26% (range, 10%-90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible.<b>Conclusions:</b> A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed. <i>Clin Cancer Res; 23(4); 908-17. ©2016 AACR</i>.
Seismic monitoring of diffraction images for detection of local heterogeneities (1998)

Abstract Diffracted waves contain valuable information regarding both the structure and composition of the media they are in. In seismic data processing, however, these waves are usually regarded as noise. In this paper, we present an attempt to use scattered/diffracted waves for the detection of local heterogeneities. The method is based on the detection of diffracted waves by concentrating the signal amplitudes from diffracting points on the seismic section. This is done using a correlation procedure that enhances the amplitude of the seismic signal at the location of the diffractors on the common-diffraction-point section (D-section). The new local time correction for diffraction traveltime curve parameterization is based on the radius of curvature of the diffracted wavefront and near-surface velocity. We use the idea of seismic monitoring for detection and delineating local objects which may occur within the subsurface resulting from human activity or fast geological processes. The method consists of continuous repetition of seismic experiments above an investigated area, constructing D-sections, and comparing the images obtained.
Astrocytes promote process outgrowth by adult human oligodendrocytes in vitro through interaction between bFGF and astrocyte extracellular matrix (1996)

Cell-cell interactions regulate many important functions within the central nervous system. In this report, we demonstrate that process outgrowth by adult human oligodendrocytes (OLs) in vitro, an early event of myelinogenesis in vivo, is promoted by astrocytes. To elucidate the mechanisms by which astrocytes might exert this effect, we tested several growth factors known to be produced by astrocytes and found that only basic fibroblast growth factor (bFGF) could enhance process extension by the OL. In correspondence, the treatment of astrocytes with a neutralizing antibody to bFGF decreased their effects in promoting oligodendroglial process outgrowth. The potency of bFGF, however, was only one-third that of astrocytes, and since bFGF did not synergize with other soluble growth factors, we investigated the potential facilitatory role of the extracellular matrix (ECM) deposited by astrocytes. The astrocyte ECM was found to be a promoter of oligodendroglial process extension, and significantly, bFGF synergized with astrocyte ECM to match the potency of live astrocytes. The astrocyte ECM was found in Western blot analyses to contain fibronectin, vitronectin, and laminin. These purified ECM components, as well as heparan sulfate proteoglycan, did not promote oligodendroglial process extension by themselves, although laminin and fibronectin potentiated the effects of bFGF. We conclude that process outgrowth by OLs is guided by astrocytes; the mechanism of the astrocyte effect appears to be due to the combination of bFGF and an unidentified ECM component. © 1996 Wiley-Liss, Inc.
Cloned mouse ribonucleotide reductase subunit M1 cDNA reveals amino acid sequence homology with Escherichia coli and herpesvirus ribonucleotide reductases. (1985)

We have isolated and sequenced overlapping cDNA clones containing the entire coding region of mouse ribonucleotide reductase subunit M1. The coding region comprises 2.4 kilobases and predicts a polypeptide of 792 amino acids (Mr 90,234) which shows striking homology with ribonucleotide reductases from Escherichia coli and the herpesviruses, Epstein-Barr virus and herpes simplex virus. The homologies reveal three domains: an N-terminal domain common to the mammalian and bacterial enzymes, a C-terminal domain common to the mammalian and viral ribonucleotide reductases, and a central domain common to all three. We speculate on the functional basis of this conservation.
RHD positive haplotypes in D negative Europeans (2001)

The results of this study allowed to devise an improved RHD genotyping strategy, the false-positive rate of which was lower than 1:10,000. The number of characterized RHD positive antigen D negative and Del alleles was more than doubled and their population frequencies in Europe were defined.
Comparison of autofluorescence and iodine staining for detection of Isospora belli in feces. (2002)

To evaluate the sensitivity of autofluorescence for detection of Isospora oocysts, wet preparations of 192 stool samples from patients with chronic diarrhea were examined by fluorescence microscopy and by light microscopy after iodine staining used for routine screening for ova and parasites. Silicon-chambered glass coverslips were used for fluorescence microscopy. Isospora oocysts were detected in 46 iodine-stained concentrated stool samples; 91 samples were positive by autofluorescence. According to the maximum likelihood estimates, examination by fluorescence (95.7%; 95% confidence interval [CI], 85.2-99.5) was significantly more sensitive than iodine staining (48.4%; 95% CI, 37.7-59.1). Examination for autofluorescence is a simple, highly sensitive, inexpensive, and easily applicable method to detect Isospora spp. oocysts in feces.
A Component Library Management System and Browser (1993)

John Granacki, Zia Iqbal and Tauseef KaziUSC/Information Sciences Institute4676 Admiralty WayMarina del Rey, CA 90292310.822.1511AbstractThis report describes a component library management system (LMS) that is implementedwith the OCT database. The LMS consists of a user-extensible component library and, abrowser that enables the user to search through component lists with the help of a graphicaluser interface. The LMS provides a query mechanism that allows the user to search forcomponents by attributes and quickly identify parts that meet a design requirement. TheLMS also provides a link between the browser and FAST (an ARPA-sponsored electronicparts broker) procurement data, so that designers can automatically generate electronicorders for parts to FAST.Although commercial library browsing tools exist (such as Cah-ners Computer-Aided Product Selection CAPS), these tools cannot process the componentdata or generate procurement requests. In this report we discuss the trade-offs betweenrelational database systems and object oriented database system for implementing the LMSand describe the use of OCT in our implementation. We also present a ﬂexible and extensi-ble browser datastructure that has been created for rapid on-line access of the OCT compo-nent library information. Finally, we identify the limitations of the current implementationand propose some possible solutions and future work.
The route of ethanol formation in Zymomonas mobilis (1966)

1. Enzymic evidence supporting the operation of the Entner-Doudoroff pathway in the anaerobic conversion of glucose into ethanol and carbon dioxide by Zymomonas mobilis is presented. 2. Cell extracts catalysed the formation of equimolar amounts of pyruvate and glyceraldehyde 3-phosphate from 6-phosphogluconate. Evidence that 3-deoxy-2-oxo-6-phosphogluconate is an intermediate in this conversion was obtained. 3. Cell extracts of the organism contained the following enzymes: glucose 6-phosphate dehydrogenase (active with NAD and NADP), ethanol dehydrogenase (active with NAD), glyceraldehyde 3-phosphate dehydrogenase (active with NAD), hexokinase, gluconokinase, glucose dehydrogenase and pyruvate decarboxylase. Extracts also catalysed the overall conversion of glycerate 3-phosphate into pyruvate in the presence of ADP. 4. Gluconate dehydrogenase, fructose 1,6-diphosphate aldolase and NAD-NADP transhydrogenase were not detected. 5. It is suggested that NAD is the physiological electron carrier in the balanced oxidation-reduction involved in ethanol formation.