gebhart/patrepeval huggingface dataset:
Cytosolic Catechols Inhibit α-Synuclein Aggregation and Facilitate the Formation of Intracellular Soluble Oligomeric Intermediates (2006)

Aberrant aggregation of alpha-synuclein (alpha-syn) to form fibrils and insoluble aggregates has been implicated in the pathogenic processes of many neurodegenerative diseases. Despite the dramatic effects of dopamine in inhibiting the formation of alpha-syn fibrils by stabilization of oligomeric intermediates in cell-free systems, no studies have examined the effects of intracellular dopamine on alpha-syn aggregation. To study this process and its association with neurodegeneration, intracellular catechol levels were increased to various levels by expressing different forms of tyrosine hydroxylase, in cells induced to form alpha-syn aggregates. The increase in the steady-state dopamine levels inhibited the formation of alpha-syn aggregates and induced the formation of innocuous oligomeric intermediates. Analysis of transgenic mice expressing the disease-associated A53T mutant alpha-syn revealed the presence of oligomeric alpha-syn in nondegenerating dopaminergic neurons that do contain insoluble alpha-syn. These data indicate that intraneuronal dopamine levels can be a major modulator of alpha-syn aggregation and inclusion formation, with important implications on the selective degeneration of these neurons in Parkinson's disease.
Enzyme structure and mechanism (1977)

This is the second edition of this biological reference aimed at undergraduates and graduates. The book covers the structure and mechanism of enzymes, creating a guide to the current understanding of enzymology.
Targeted antigen presentation using crosslinked antibody heteroaggregates. (1987)

We have targeted protein antigens to antigen-presenting cells in vitro by using antibody heteroaggregates containing an antibody against a protein antigen covalently crosslinked to an antibody against a target structure on the surface of the antigen-presenting cells. Antigen presentation was assessed by measurement of lymphokine released by antigen-specific T cell hybridomas. Depending on the experimental conditions, the crosslinked antibodies decreased the amount of antigen required to give a response by the hybridomas by factors of 10(2) to 10(3). Enhanced presentation occurred when antigen was targeted to MHC class I and class II molecules, surface immunoglobulin, or Fc gamma receptors on the surface of the murine B cell lymphoma-hybridoma, TA3. An enhancement of antigen presentation also occurred when antigen was targeted to surface IgD, or class I and class II MHC molecules on murine splenic B cells, and when antigen was targeted to class I and class II molecules on irradiated adherent spleen cells. No response was seen when antigen was targeted to Fc gamma R on B cells or adherent spleen cells. The ability of each crosslinked antibody to enhance presentation paralleled the total amount of each that bound to the surface of the antigen-presenting cells. Antigen presentation, mediated by crosslinked antibody, was antigen-specific and I-A restricted. The presentation of one antigen by using crosslinked antibody did not result in enhanced presentation of a second, bystander antigen. These results suggest that a novel means of stimulating immune responses may be possible in vivo, by targeting antigen to surface structures on antigen-presenting cells.
Directed Ring-Opening of 1,5-Dioxaspiro[3.2]hexanes:  Selective Formation of 2,2-Disubstituted Oxetanes (2003)

1,5-Dioxaspiro[3.2]hexanes undergo ring-opening reactions with many heteroatom nucleophiles to provide alpha-substituted-beta'-hydroxy ketones. However, certain Lewis acidic nucleophiles provide 2,2-disubstituted oxetanes. Herein, the results of reactions of 3-phenyl-1,5-dioxaspiro[3.2]hexane with a variety of nitrogen-containing heteroaromatic bases are reported. There appears to be a correlation between the pK(a) of the nucleophile and the reaction outcome with more acidic nucleophiles providing 2,2-disubstituted oxetanes. Moreover, the mode of ring opening can be directed toward the substituted oxetane by the addition of a Lewis acid. These results are rationalized by calculation of stationary points on the potential energy surfaces for the various possible reaction pathways using ab initio molecular orbital methods.
Identification of a Novel Pyridoxal 5‘-Phosphate Binding Site in Adenosylcobalamin-Dependent Lysine 5,6-Aminomutase from Porphyromonas gingivalis (2002)

Lysine 5,6-aminomutase (5,6-LAM) catalyzes the interconversion of D-lysine with 2,5-diaminohexanoate and of L-beta-lysine with 3,5-diaminohexanoate. The coenzymes for 5,6-LAM are adenosylcobalamin (AdoCbl) and pyridoxal 5'-phosphate (PLP). In the proposed chemical mechanism, AdoCbl initiates the formation of substrate radicals, and PLP facilitates the radical rearrangement by forming an external aldimine linkage with the epsilon-amino group of a substrate, either D-lysine or L-beta-lysine. In the resting enzyme, an internal aldimine between PLP and an essential lysine in the active site facilitates productive PLP binding and catalysis. We present here biochemical, biophysical, and site-directed mutagenesis experiments, which document the existence of an essential lysine residue in the active site of 5,6-LAM from Porphyromonas gingivalis. Reduction of 5,6-LAM with NaBH(4) rapidly inactivates the enzyme and shifts the electronic absorption band from 420 to 325 nm. This is characteristic of the reduction of an aldimine linkage between the carbonyl group of PLP and the epsilon-amino group of a lysine residue. The reduced peptide was identified by Q-TOF/MS and further confirmed by Q-TOF/MS/MS sequencing. We show that lysine 144 in the small subunit of 5,6-LAM is the essential lysine residue. Lysine 144(beta) is separated by only 11 amino acids from histidine 133(beta), which forms a part of the "base-off"-AdoCbl binding motif. The sequence of the novel PLP-binding motif is conserved in 5,6-LAM from Clostridium sticklandii and P. gingivalis, and it is distinct from all known PLP-binding motifs. Mutation of lysine 144(beta) to glutamine led to K144Q(beta)-5,6-LAM, which displayed no enzymatic activity and no absorption band corresponding to an internal PLP-aldamine. In summary, we introduce a novel PLP-binding motif, the first to be discovered in an AdoCbl-dependent enzyme.
Non-reciprocal transceivers in OFDM/SDMA systems: Impact and mitigation (2004)

Channel reciprocity is needed in SDMA or MIMO downlink pre-filtering when the channel knowledge is acquired in the uplink. We first show analytically that the non-reciprocity of the base station analog hardware, which is part of the channel, introduces a very high level of multi-user interference and quantify the effect of the non-reciprocity by means of simulations. We then propose a novel calibration technique at the base station that enables to compensate for the non-reciprocity and reduce the MUI to a negligible value while having a low implementation cost.
AS/400 Security in a Client/Server Environment (1995)

MANAGEMENT The Assault System Values User Profiles Object Management Communication Management Client/Server Issues Object States and Domains Impact of Altered Objects Program Validation Values The Core War IMPLEMENTATION Physical Security System Values Designing Profiles Authority Management Backup and Recovery AUDITING System Values User Profiles Resource Usage Audit Soul of a Hacker Appendix Bibliography Index.
In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of β-thalassemia (2008)

Gene therapy for beta-thalassemia requires stable transfer of a beta-globin gene into hematopoietic stem cells (HSCs) and high and regulated hemoglobin expression in the erythroblastic progeny. We developed an erythroid-specific lentiviral vector driving the expression of the human beta-globin gene from a minimal promoter/enhancer element containing two hypersensitive sites from the beta-globin locus control region. Transplantation of transduced HSCs into thalassemic mice leads to stable and long-term correction of anemia with all red blood cells expressing the transgene. A frequency of 30-50% of transduced HSCs, harboring an average vector copy number per cell of 1, was sufficient to fully correct the thalassemic phenotype. In the mouse model of Cooley's anemia transplantation of transduced cells rescues lethality, leading to either a normal or a thalassemia intermedia phenotype. We show that genetically corrected erythroblasts undergo in vivo selection with preferential survival of progenitors harboring proviral integrations in genome sites more favorable to high levels of vector-derived expression. These data provide a rationale for a gene therapy approach to beta-thalassemia based on partially myeloablative transplantation protocols.
Comparative Effects of Moxifloxacin and Clarithromycin on the Normal Intestinal Microflora (2000)

Twelve healthy male subjects age range 24-40 y participated in the investigation. The trial was divided into 2 35-d periods. The 2 treatment regimens were: (i) 1 x 400 mg moxifloxacin tablet in the morning and 1 placebo tablet in the evening for 7 d; and (ii) 1 x 500 mg clarithromycin tablet in the morning and 1 x 500 mg clarithromycin tablet in the evening for 7 d. Each subject received firstly I treatment regimen and secondly the other treatment regimen. The wash-out period was 6 weeks between the two treatment regimens. Moxifloxacin caused significant decreases of enterococci and enterobacteria during the administration period while the numbers of staphylococci, streptococci, Bacillus and Candida were not affected. No impact on peptostreptococci, lactobacilli, Veillonella, Bacteroides or fusobacteria was observed, while bifidobacteria and clostridia decreased during moxifloxacin administration. The microflora was normalized after 35 d. Clarithromycin caused significant reduction of Escherichia coli while the numbers of enterococci, Enterobacter, Citrobacter, Klebsiella and Pseudomonas increased markedly. No significant changes in the numbers of staphylococci, streptococci, Bacillus and Candida were noticed. In the anaerobic microflora bifidobacteria, lactobacilli and clostridia were suppressed, while no changes in peptostreptococci, Veillonella, Bacteroides and fusobacteria were found. The microflora was normalized in all volunteers after 35 d.
Optimal Acquisition Delay for Dynamic Contrast-Enhanced MRI of Hypervascular Hepatocellular Carcinoma (2009)

With the injection protocol used in this study, optimal acquisition delay-determined from abdominal aortic contrast arrival time to the middle of the k-space acquisition-for imaging of hypervascular hepatocellular carcinoma was 9-12, 21 or more, and 49 seconds for the early, late hepatic arterial, and portal venous phases.
Neocortical dynamic theory should be as simple as possible, but not simpler (2000)

EEG and synaptic action fields provide experimental and theoretical entry points into brain complexity. Such entry is distinguished from the core system of cell assemblies assumed to underlie cognitive processing. The global theory of synaptic action predicts several new properties of EEG, providing limited penetration into brain complexity.
Steroidal Heterocycles. VI.1 Formylation of A/B-cis 3-Ketosteroids.2 Preparation of 5β-Steroidal[3,2-c]pyrazoles (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteroidal Heterocycles. VI.1 Formylation of A/B-cis 3-Ketosteroids.2 Preparation of 5β-Steroidal[3,2-c]pyrazolesR. O. Clinton, Robert L. Clarke, F. W. Stonner, A. J. Manson, K. F. Jennings, and D. K. PhillipsCite this: J. Org. Chem. 1962, 27, 8, 2800–2807Publication Date (Print):August 1, 1962Publication History Published online1 May 2002Published inissue 1 August 1962https://pubs.acs.org/doi/10.1021/jo01055a022https://doi.org/10.1021/jo01055a022research-articleACS PublicationsRequest reuse permissionsArticle Views221Altmetric-Citations27LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Intravenous Immunoglobulin for the Treatment of Severe, Refractory, and Recurrent Clostridium difficile Diarrhea (2006)

Intravenous immunoglobulin may be effective for severe, refractory, or recurrent Clostridium difficile diarrhea after failed conventional treatment.
Acyl‐CoA dehydrogenases (2004)

Acyl-CoA dehydrogenases constitute a family of flavoproteins that catalyze the alpha,beta-dehydrogenation of fatty acid acyl-CoA conjugates. While they differ widely in their specificity, they share the same basic chemical mechanism of alpha,beta-dehydrogenation. Medium chain acyl-CoA dehydrogenase is probably the best-studied member of the class and serves as a model for the study of catalytic mechanisms. Based on medium chain acyl-CoA dehydrogenase we discuss the main factors that bring about catalysis, promote specificity and determine the selective transfer of electrons to electron transferring flavoprotein. The mechanism of alpha,beta-dehydrogenation is viewed as a process in which the substrate alphaC-H and betaC-H bonds are ruptured concertedly, the first hydrogen being removed by the active center base Glu376-COO- as an H+, the second being transferred as a hydride to the flavin N(5) position. Hereby the pKa of the substrate alphaC-H is lowered from > 20 to approximately 8 by the effect of specific hydrogen bonds. Concomitantly, the pKa of Glu376-COO- is also raised to 8-9 due to the decrease in polarity brought about by substrate binding. The kinetic sequence of medium chain acyl-CoA dehydrogenase is rather complex and involves several intermediates. A prominent one is the molecular complex of reduced enzyme with the enoyl-CoA product that is characterized by an intense charge transfer absorption and serves as the point of transfer of electrons to the electron transferring flavoprotein. These views are also discussed in the context of the accompanying paper on the three-dimensional properties of acyl-CoA dehydrogenases.
Effects of steroid hormones and peptide growth factors on protooncogene c-fos expression in human breast cancer cells. (1988)

To investigate if the estrogen control of the tumorigenic phenotype of breast cancer cells was mediated through activation of the c-fos protooncogene, we examined the expression of this oncogene in MCF-7 cells. In cells synchronized by double thymidine blockade, the peptide growth factors transforming growth factor alpha and epidermal growth factor increased c-fos mRNA levels 6-fold above controls after 30 min of treatment. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, increased c-fos mRNA levels 4- to 5-fold above control. 17 beta-Estradiol, a growth stimulator, increased c-fos mRNA levels less than 2-fold above control levels, while progesterone, vitamin D3, dihydrotestosterone, and dexamethasone had little effect on c-fos mRNA levels. In contrast, 17 beta-estradiol treatment initially diminished the c-myc RNA level after 30 min of treatment and resulted in an elevation of c-myc by 2.5 h after initiation of treatment. We conclude that c-fos induction in these cells is growth related and accompanies stimulation by transforming growth factor alpha and epidermal growth factor. 17 beta-Estradiol, on the other hand, induced much smaller increases in c-fos mRNA levels, suggesting an alternative or more complex mechanism of cellular stimulation.
Evaluation of the Cepheid GeneXpertR system for detecting Bacillus anthracis (2006)

The GeneXpert is the only platform currently available that is capable of both nucleic acid purification and real-time PCR detection enclosed within a single system. Further, all sample manipulations are automated, thus reducing errors associated with manual processing.
Guidelines for predicting lesion size at common endocardial locations during radio-frequency ablation (2001)

We used the finite element method to study the effect of radio-frequency (RF) catheter ablation on tissue heating and lesion formation at different intracardiac sites exposed to different regional blood velocities. We examined the effect of application of RF current in temperature- and power-controlled mode above and beneath the mitral valve annulus where the regional blood velocities are high and low respectively. We found that for temperature-controlled ablation, more power was delivered to maintain the preset tip temperature at sites of high local blood velocity than at sites of low local blood velocity. This induced more tissue heating and larger lesion volumes than ablations at low velocity regions. In contrast, for power-controlled ablation, tissue heating was less at sites of high compared with low local blood velocity for the same RF power setting. This resulted in smaller lesion volumes at sites of low local velocity. Our numerical analyzes showed that during temperature-controlled ablation at 60 degrees C, the lesion volumes at sites above and underneath the mitral valve were comparable when the duration of RF current application was 10 s. When the duration of RF application was extended to 60 s and 120 s, lesion volumes were 33.3% and 49.4% larger above the mitral valve than underneath the mitral valve. Also, with temperature-controlled ablation, tip temperature settings of 70 degrees C or greater were associated with a risk of tissue overheating during long ablations at high local blood velocity sites. In power-controlled ablation (20 W), the lesion volume formed underneath the mitral valve was 165.7% larger than the lesion volume above the mitral valve after 10 s of ablation. We summarized the guidelines for energy application at low and high flow regions.
Mitochondria in neurodegenerative apoptosis: An opportunity for therapy? (1998)

Apoptotic cell death has been shown to constitute the terminal process in some neurodegenerative diseases, notably Alzheimer's disease and Parkinson's disease (PD). A decrease in mitochondrial membrane potential (delta psiM) causing opening of the permeability transition pore (PTP) in mitochondrial membranes has been implicated as a critical effector of apoptosis in a variety of non-neural cells. Opening of the PTP leads to the release of so-called apoptosis initiation factors that induce the degradative events of apoptosis, such as nuclear chromatin condensation and DNA fragmentation. We have extended those findings to a neuronal model of apoptosis caused by trophic withdrawal, by showing that a decrease in delta psiM is an early event occurring 2 to 6 hours before the degradative events of apoptosis. A deficiency in mitochondrial complex I activity has been demonstrated in the substantia nigra of postmortem brains and several peripheral tissues obtained from PD patients. Because delta psiM is generated by the pumping of protons out across the inner mitochondrial membrane at the mitochondrial complexes, particularly complex I, we hypothesized that the decrease in complex activity could result in a decrease in delta psiM that would render PD substantia nigra neurons vulnerable to apoptosis. In preliminary studies, we have found a decrease in delta psiM in fibroblasts obtained from some PD patients. If a decrease in delta psiM consequent on decreased complex activity is an intrinsic defect in some PD patients, it would open a number of new avenues for the reduction of neuronal apoptosis in PD. The oncoprotein BCL-2 and the scavenger protein SOD-1 have been shown to reduce apoptosis by facilitating closure of the PTP. A number of agents have been shown to maintain BCL-2 and/or SOD-1 synthesis in damaged nerve cells and thereby reduce apoptosis. Other agents, such as cyclosporin A and some benzodiazepine receptor-binding agents, have been found to act directly on the PTP to reduce apoptosis. Accordingly, agents that maintain delta psiM and PTP closure may offer new and effective means of treating neurodegenerative apoptosis.
[Effect of total flavones of Hippophae rhamnoides L. on sympathetic activity in hypertension]. (2001)

The results suggest that TFH does not alter the sympathetic activity in treatment of hypertension and the inhibitory effect of TFH on sympathetic activity after supine isometric exercise may provide clinical benefits.
Wnt-3a and Dvl Induce Neurite Retraction by Activating Rho-Associated Kinase (2004)

Dvl is a key protein that transmits the Wnt signal to the canonical beta-catenin pathway and the noncanonical planar cell polarity (PCP) pathway. We studied the roles of Rho-associated kinase (Rho-kinase), which is activated by Dvl in the PCP pathway of mammalian cells. The expression of Dvl-1, Wnt-1, or Wnt-3a activated Rho-kinase in COS cells, and this activation was inhibited by the Rho-binding domain of Rho-kinase. The expression of Dvl-1 in PC12 cells activated Rho and inhibited nerve growth factor (NGF)-induced neurite outgrowth. This inhibition was reversed by a Rho-kinase inhibitor but not by a c-Jun N-terminal kinase inhibitor. Dvl-1 also inhibited serum starvation-dependent neurite outgrowth of N1E-115 cells, and expression of the Rho-binding domain of Rho-kinase reversed this inhibitory activity of Dvl-1. Dvl-1 mutants that did not activate Rho-kinase did not inhibit the neurite outgrowth of N1E-115 cells. Furthermore, the purified Wnt-3a protein activated Rho-kinase and inhibited the NGF-dependent neurite outgrowth of PC12 cells. Wnt-3a-dependent neurite retraction was also prevented by a Rho-kinase inhibitor and a Dvl-1 mutant that suppresses Wnt-3a-dependent activation of Rho-kinase. These results suggest that Wnt-3a and Dvl regulate neurite formation through Rho-kinase and that PC12 and N1E-115 cells are useful for analyzing the PCP pathway.