gebhart/patrepeval huggingface dataset:
Isolation of a Mutant Arabidopsis Plant That Lacks N-Acetyl Glucosaminyl Transferase I and Is Unable to Synthesize Golgi-Modified Complex N-Linked Glycans (1993)

The complex asparagine-linked glycans of plant glycoproteins, characterized by the presence of beta 1-->2 xylose and alpha 1-->3 fucose residues, are derived from typical mannose9(N-acetylglucosamine)2 (Man9GlcNAc2) N-linked glycans through the activity of a series of glycosidases and glycosyl transferases in the Golgi apparatus. By screening leaf extracts with an antiserum against complex glycans, we isolated a mutant of Arabidopsis thaliana that is blocked in the conversion of high-manne to complex glycans. In callus tissues derived from the mutant plants, all glycans bind to concanavalin A. These glycans can be released by treatment with endoglycosidase H, and the majority has the same size as Man5GlcNAc1 glycans. In the presence of deoxymannojirimycin, an inhibitor of mannosidase I, the mutant cells synthesize Man9GlcNAc2 and Man8GlcNAc2 glycans, suggesting that the biochemical lesion in the mutant is not in the biosynthesis of high-mannose glycans in the endoplasmic reticulum but in their modification in the Golgi. Direct enzyme assays of cell extracts show that the mutant cells lack N-acetyl glucosaminyl transferase I, the first enzyme in the pathway of complex glycan biosynthesis. The mutant plants are able to complete their development normally under several environmental conditions, suggesting that complex glycans are not essential for normal developmental processes. By crossing the complex-glycan-deficient strain of A. thaliana with a transgenic strain that expresses the glycoprotein phytohemagglutinin, we obtained a unique strain that synthesizes phytohemagglutinin with two high-mannose glycans, instead of one high-mannose and one complex glycan.
Fluorescence indicates a calcium-dependent interaction between the lipopeptide antibiotic LY 146032 and phospholipid membranes (1988)

LY146032 is one of the A21978C family of calcium-dependent antibiotics. This paper reports on its interactions with membranes as studied by its intrinsic fluorescence. The Trp residue was found to have a low fluorescence yield because of Förster-type energy transfer to the kynurenine residue (Kyn) (epsilon = 5000 at 364 nm). However, the Kyn fluorescence (lambda max = 465 nm in H2O) was a sensitive probe of the membrane interactions, and it was used in steady-state fluorescence measurements including fluorescence polarization anisotropy. Initial binding of the peptide to phospholipid vesicles occurs in calcium-free solutions. When calcium is added, the resulting 10-fold fluorescent enhancement and 15-nm blue shift show that it causes the antibiotic to penetrate further into the lipid bilayer. Calcium is bound with an association constant of 151 M-1, while a phospholipid titration in the presence of calcium gave an association constant of 5 x 10(3) M-1 for egg phosphatidylcholine. Magnesium and cadmium cause very slight fluorescence enhancements, but a more significant effect is caused by the trivalent lanthanide ions. Analysis of these data indicates that the calcium-selective site is on the peptide and that ion binding to the phospholipid headgroups has a secondary role. Comparison with the divalent cation dependent antibiotics bacitracin and amphomycin shows that LY146032 has a quite different activity and that a calcium-dependent membrane interaction could account for results obtained in vivo.
Molecular basis of β-amyloid oligomer recognition with a conformational antibody fragment (2012)

Oligomers are intermediates of the β-amyloid (Aβ) peptide fibrillogenic pathway and are putative pathogenic culprits in Alzheimer’s disease (AD). Here we report the biotechnological generation and biochemical characterization of an oligomer-specific antibody fragment, KW1. KW1 not only discriminates between oligomers and other Aβ conformations, such as fibrils or disaggregated peptide; it also differentiates between different types of Aβ oligomers, such as those formed by Aβ (1–40) and Aβ (1–42) peptide. This high selectivity of binding contrasts sharply with many other conformational antibodies that interact with a large number of structurally analogous but sequentially different antigens. X-ray crystallography, NMR spectroscopy, and peptide array measurements imply that KW1 recognizes oligomers through a hydrophobic and significantly aromatic surface motif that includes Aβ residues 18–20. KW1-positive oligomers occur in human AD brain samples and induce synaptic dysfunctions in living brain tissues. Bivalent KW1 potently neutralizes this effect and interferes with Aβ assembly. By altering a specific step of the fibrillogenic cascade, it prevents the formation of mature Aβ fibrils and induces the accumulation of nonfibrillar aggregates. Our data illuminate significant mechanistic differences in oligomeric and fibril recognition and suggest the considerable potential of KW1 in future studies to detect or inhibit specific types of Aβ conformers.
Parallel resetting of arterial baroreflex control of renal and cardiac sympathetic nerve activities during upright tilt in rabbits (2010)

Since humans are under ceaseless orthostatic stress, the mechanisms to maintain arterial pressure (AP) against gravitational fluid shift are important. As one mechanism, it was reported that upright tilt reset baroreflex control of renal sympathetic nerve activity (SNA) to a higher SNA in anesthetized rabbits. In the present study, we tested the hypothesis that upright tilt causes a parallel resetting of baroreflex control of renal and cardiac SNAs in anesthetized rabbits. In anesthetized rabbits (n = 8, vagotomized and aortic denervated) with 0 degrees supine and 60 degrees upright tilt postures, renal and cardiac SNAs were simultaneously recorded while isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg. Upright tilt shifted the reverse-sigmoidal curve of the CSP-SNA relationship to higher SNA similarly in renal and cardiac SNAs. Although upright tilt increased the maximal gain, the response range and the minimum value of SNA, the curves were almost superimposable in these SNAs regardless of postures. Scatter plotting of cardiac SNA over renal SNA during the stepwise changes in CSP was close to the line of identity in 0 degrees supine and 60 degrees upright tilt postures. In addition, upright tilt also shifted the reverse-sigmoidal curve of the CSP-heart rate relationship to a higher heart rate, with increases in the maximal gain and the response range. In conclusion, upright posture caused a resetting of arterial baroreflex control of SNA similarly in renal and cardiac SNAs in anesthetized rabbits.
Age-related effects on the number of human lymphocytes in culture initially responding to an antigenic stimulus. (1982)

Lymphocyte transformation responses to the antigen streptokinase-streptodornase were evaluated in a group of 14 healthy elderly subjects by enumeration of antigen-responsive cells, first-generation responding lymphocytes and progeny generated per responding cell. Peak lymphocyte transformation responses to the antigen were diminished in the elderly subjects when compared to a group of young adult subjects. Antigen-responsive cells were found by limiting-dilution analysis to be significantly decreased in the elderly subjects (geometric means of antigen-responsive cells per 10(5) mononuclear cells = 4.35 in the elderly versus 14.79 in the younger group, P less than 0.001). The number of cells recruited into the first-generation lymphocyte response per antigen-responsive cell were equivalent in the two groups. Also, the proliferation into progeny of each first-generation lymphocyte was of the same magnitude for the elderly and young subjects within the six to eight cell divisions required for this response. Therefore, in this system the diminished total lymphocyte transformation responses to the antigen streptokinase-streptodornase of cells from elderly humans can be accounted for by a reduction in the number of lymphocytes initially responsive to the antigen.
Non-invasive Intracranial Pressure estimation using Support Vector Machine (2010)

Intracranial Pressure (ICP) measurements are of great importance for the diagnosis, monitoring and treatment of many vascular brain disturbances. The standard measurement of the ICP is performed invasively by the perforation of the cranial scalp in the presence of traumatic brain injury (TBI). Measuring the ICP in a noninvasive way is relevant for a great number of pathologies where the invasive measurement represents a high risk. The method proposed in this paper uses the Arterial Blood Pressure (ABP) and the Cerebral Blood Flow Velocity (CBFV) - which may be obtained by means of non-invasive methods - to estimate the ICP. A non-linear Support Vector Machine was used and reached a low error between the real ICP signal and the estimated one, allowing an on-line implementation of the ICP estimation, with an adequate temporal resolution.
Su-11248 Sugen. (2004)

SUGEN is developing SU-11248, an orally active inhibitor of platelet-derived growth factor tyrosine kinase (TK) and other TK signaling pathways, as a potential anticancer agent. By October 2003, phase III trials for gastrointestinal stromal tumors and renal cell carcinoma were underway.
Directed Drug Delivery (1985)

This book is based on the proceedings of the symposium entitled "Di rected Drug Delivery: A Multidisciplinary Problem," which was held in Lawrence, Kansas on October 17-19, 1984. The purpose of the sy
Thrombopoietin and its receptor, the proto-oncogene c-mpl (1995)

For more than 30 years, researchers have sought an elusive humoral growth factor termed thrombopoietin that was a specific regulator of platelet production. In the past year a ligand for the cytokine receptor c-mpl was identified. The new cytokine, called Mpl ligand, thrombopoietin, or megakaryocyte growth and development factor, is a potent stimulator of megakaryocyte proliferation, maturation, and platelet production; its action is synergized by stem cell factor or interleukin-3. The cloning of thrombopoietin complementary DNA and large-scale protein production offer potential applications for the management of patients suffering from thrombocytopenia. Understanding of the molecular mechanisms regulating plasma levels of thrombopoietin might be fundamental to the elucidation of the pathogenesis of certain platelet disorders. Finally, thrombopoietin might ultimately enable the mass production of functional platelets for use in transfusion.
Microsoft Office 97 Professional (Mastering) (1996)

From the Publisher:
Mastering Microsoft Office 97 Professional Edition is a completely redesigned edition of our comprehensive guide to Microsoft's integrated software suite. Packed with new strategies for streamlining your work and sharing information, this is both a tutorial guide and an effective reference. It features our new Master's Reference section filled with quick, step-by-step answers to all your Office 97 questions, giving you double the learning power in one great book.
Lipopolysaccharide binds to and activates A<SUB>1</SUB> adenosine receptors on human pulmonary artery endothelial cells (2002)

Previously, it was reported that A(1) adenosine receptor antagonists prevent endotoxin-induced acute lung injury and pulmonary arterial endothelial cell damage. In competition radioligand binding experiments in membranes prepared from human pulmonary artery endothelial cells (PAECs), lipopolysaccharides (LPSs) of Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas aeruginosa displaced the binding of a selective A(1) adenosine receptor antagonist [(125)I]-BWA844U (IC(50) values: 195 ng/ml, 290 ng/ml, 602 ng/ml, and 693 ng/ml, respectively) in a dose-dependent, competitive manner. There was no displacement of this radioligand by enterotoxin (< or = 10 microg/ml), diphosphoryl lipid A (< or = 10 microg/ml), and glycolipids, monosialoganglioside (< or = 1 microg/ml), lactocerebroside (< or = 100 microg/ml), or NBD galactocerebroside (< or = 100 microg/ml). Based on calculated IC(50) values, LPS (E. coli, IC(50) 111 ng/ml) displaced the selective A(1) adenosine receptor agonist, [(3)H]-2-chloro, N(6)-cyclopentyladenosine (CCPA) in human PAECs with a potency profile, CCPA > LPS > 2-phenylaminoadenosine (CV 1808), a selective A(2) adenosine receptor agonist. The potency profile for displacement of the selective A(2a) adenosine receptor agonist [(3)H]-CGS 21680 was CV 1808 > CCPA. LPS (E. coli 0.1 pg/ml-10 microg/ml) did not displace [(3)H]-CGS 21680 binding. In human PAECs, IL-6 and TXA(2) release induced by LPS (0-1 microg/ml) or CCPA (0-1 microM) at high doses was significantly reduced by the selective A(1) adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1 microM). These data suggest that LPS binds to and activates A(1) adenosine receptors on human PAECs to induce the release of IL-6 and TXA(2). Activation of A(1) adenosine receptors on human PAECs by LPS, may contribute to the pathophysiology of acute lung injury associated with Gram-negative septicemia and endotoxemia.
Band offsets and deep defect distribution in hydrogenated amorphous silicon-crystalline silicon heterostructures (1989)

Voltage filling pulse measurements taken on a-Si:H/c-Si heterostructure Schottky diode samples are used to examine the capture of electrons from the c-Si substrate into a-Si:H defect states. These measurements, along with the capacitance versus temperature spectra of these diodes, indicate a nearly zero conduction-band offset (50±50 meV). In addition, we have observed trapping of holes at the valence-band discontinuity ΔEv. A clear threshold for the subsequent optical release of these holes yields a value of ΔEv =0.58±0.02 eV. Our measurements also provide the energy and spatial distribution of deep defects within the a-Si:H layer and indicate a region of anomalously large defect density (1018 cm−3) within roughly 350 Å of the a-Si:H/c-Si interface.
The Pathogenesis and Treatment of ACNE (1990)

Acne is a follicular disorder of the skin occurring in specialized pilosebaceous units on the face and trunk. An abnormality of the keratinizing epithelium of these follicles, thought to be due to the action of sebum synthesized and secreted by the androgen-sensitive sebaceous glands, leads to inflammation induced by the follicular bacterium, Propionibacterium acnes. Therapy involves treatments that modify these pathogenic factors and includes drugs with antikeratinizing, antibacterial, and antiseborrheic actions.
인공피부모델과 사람, 돼지 피부의 피부흡수시험 비교 검증 연구 (2017)

This study was carried out in accordance with OECD guidelines on skin absorption test for the comparison of reconstructed human skin models, EFT-306™ and KeraSkinFT™ with human skin and pig skin. Three OECD standard compounds were used for penetration and absorption: Caffeine, benzoic acid and testosterone, all of which differ vastly in their lipophilicity. Reconstructed human skins were more permeable to low lipophilic compounds such as caffeine than human and pig skin. Differences became most obvious with KeraSkinFT™ showing a relatively weak penetration barrier on caffeine. EFT-306™ and KeraSkinFT™ both showed similar penetration patterns in the case of lipophilic compounds, benzoic acid and testosterone compared with human and pig skins. High correlation was observed on the penetration flux between the reconstructed human skin models and human and pig skin, even though different penetration rates existed. The reconstructed human skin models can be regarded as generally useful on lipophilic compounds for in-vitro penetration studies.
Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors. (1993)

In an effort to investigate the role of creatine kinase and its substrates in malignancy we have tested the effect of cyclocreatine [1-carboxymethyl-2-iminoimidazolidine (CCr)] on the growth of tumor cells in vitro and in vivo. CCr is phosphorylated by creatine kinase to yield a synthetic phosphagen [(N-phosphorylcyclocreatine (CCr approximately P)] with thermodynamic and kinetic properties distinct from those of creatine phosphate. We show that CCr accumulates as CCr approximately P in tumor cells expressing a high level of creatine kinase, and that the accumulation of this phosphagen is detrimental to tumor cell growth. Tumor cell lines expressing a low level of creatine kinase accumulate much less CCr approximately P, and consequently are growth inhibited only at higher concentrations of CCr. When these resistant cells are transfected with a creatine kinase B expression vector, they express creatine kinase, accumulate CCr approximately P, and are growth inhibited. In vivo, in nude mouse xenografts, the rate of growth of a high creatine kinase expressing tumor cell line is inhibited in animals fed 1% CCr. Our results indicate that CCr inhibits the growth of tumor cells in vitro and in vivo.
High-Throughput, Lysis-free Screening for Sulfatase Activity Using Escherichia coli Autodisplay in Microdroplets (2018)

Abstract Directed evolution of enzymes toward improved catalytic performance has become a powerful tool in protein engineering. To be effective, a directed evolution campaign requires the use of high-throughput screening. In this study we describe the development of a high-throughput lysis-free procedure to screen for improved sulfatase activity by combining microdroplet-based single-variant activity sorting with E. coli autodisplay. For the first step in a 4-step screening procedure we quantitatively screened &gt;10 5 variants of the homodimeric arylsulfatase from Silicibacter pomeroyi ( Sp AS1), displayed on the E. coli cell surface, for improved sulfatase activity using fluorescence activated droplet sorting. Display of the sulfatase variants on living E. coli cells ensured the continuous linkage of genotype and phenotype during droplet sorting and allowed for direct recovery by simple regrowth of the sorted cells. The use of autodisplay on living cells simplified and reduced the degree of liquid handling during all steps in the screening procedure to the single event of simply mixing substrate and cells. The percentage of apparent improved variants was enriched &gt;10-fold as a result of droplet sorting. We ultimately identified 25 Sp AS1-variants with improved performance toward 4-nitrophenyl sulfate (up to 6.2-fold) and/or fluorescein disulfate (up to 30-fold). In Sp AS1 variants with improved performance toward the bulky fluorescein disulfate, many of the beneficial mutations occur in residues that form hydrogen bonds between α-helices in the C-terminal oligomerization region, suggesting a non-trivial, previously unknown role for the dimer interface in shaping the substrate binding site of Sp AS1. Table of contents graphic
Correction: Performance of Swabs, Lavage, and Diluents to Quantify Biomarkers of Female Genital Tract Soluble Mucosal Mediators (2012)

Background: Measurement of immune mediators and antimicrobial activity in female genital tract secretions may provide biomarkers predictive of risk for HIV-1 acquisition and surrogate markers of microbicide safety. However, optimal methods for sample collection do not exist. This study compared collection methods.
Neuroprotective strategy for Alzheimer disease: intranasal administration of a fatty neuropeptide. (1996)

Neurodegenerative diseases, in which neuronal cell disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearyl-norleucine17]VIP ([St-Nle17]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The beta-amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the beta-amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade. These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain.
Detection of Aspergillus species DNA in bronchoalveolar lavage samples by competitive PCR (1995)

A competitive PCR assay involving the use of bronchoalveolar lavage (BAL) samples for the diagnosis of invasive pulmonary aspergillosis (IPA) was developed. For this purpose, a 1-kb mitochondrial DNA fragment of Aspergillus fumigatus was sequenced. The primers used allowed amplification of A. fumigatus, A. flavus, A. terreus, and A. niger DNAs but not DNAs of other fungi and yeasts. BAL samples from 55 consecutively enrolled patients were tested. Three samples were excluded because of failure of correct amplification of the internal competitive control. Of 28 immunocompromised patients, 6 were PCR positive; 3 died of IPA and their BAL cultures yielded A. fumigatus; and 3 were culture negative and did not develop IPA. Of 15 human immunodeficiency virus-positive patients and 9 immunocompetent patients, 5 and 4, respectively, were both PCR positive and culture negative, and none developed aspergillosis. Thus, PCR confirmed IPA in three patients but gave positive results for 25% (12 of 49) of the patients who did not develop aspergillosis. The predictive value of PCR-positive results seems low for patients at risk for aspergillosis. Moreover, the risk of contamination of reaction buffers or biological samples with Aspergillus conidia seems high and has to be weighed in regard to the potential diagnostic benefit of PCR testing as a routine procedure.
Evidence of neuronal oxidative damage in Alzheimer's disease. (1996)

Oxidative stress has been proposed as a pathogenetic mechanism in Alzheimer's disease. One mechanism of oxidative damage is the nitration of tyrosine residues in proteins, mediated by peroxynitrite breakdown. Peroxynitrite, a reaction product of nitric oxide and superoxide radicals, has been implicated in N-methyl-D-aspartate receptor-mediated excitotoxic damage. Reported evidence of oxidative stress in Alzheimer's disease includes increased iron, alterations in protective enzymes, and markers of oxidative damage to proteins and lipids. In this report, we demonstrate the presence of nitrotyrosine in neurofibrillary tangles of Alzheimer's disease. Nitrotyrosine was not detected in controls lacking neurofibrillary tangles. Immunolabeling was demonstrated to be specific nitrotyrosine in a series of control experiments. These observations link oxidative stress with a key pathological lesion of Alzheimer's disease, the neurofibrillary tangle, and demonstrate a pathogenetic mechanism in common with the other major neurodegenerative diseases of aging, Parkinson's disease and amyotrophic lateral sclerosis. These findings further implicate nitric oxide expression and excitotoxicity in the pathogenesis of cell death in Alzheimer's disease.