gebhart/patrepeval huggingface dataset:
Adenylate cyclase toxin from Bordetella pertussis produces ion conductance across artificial lipid bilayers in a calcium- and polarity-dependent manner. (1994)

Adenylate cyclase toxin (AC toxin) from Bordetella pertussis enters target cells to produce supraphysiologic levels of cAMP and, by a cAMP-independent process, is hemolytic. In the present study, we show for the first time that this toxin also produces ion-permeable, cation-selective pores in phospholipid bilayers. The resulting membrane conductance is absolutely calcium-dependent, as are the intoxication and hemolytic activities. It is strongly affected by the polarity and magnitude of the membrane potential and enhanced by the presence of negatively charged phospholipid. AC toxins from two mutants, BPDE386 and BPD377, which are defective in toxin activity, produce little or no conductance. Finally, evaluation of the current-voltage relationships and the concentration dependence of pore formation and of hemolysis reveal a greater than 3rd power dependence, suggesting that a multimer of AC toxin, probably consisting of three or more holotoxin molecules, is involved in pore formation.
Expression of deletion constructs of bovine β-1, 4-galactosyltransferase in Escherichia coli: importance of Cysl34 for its activity (1993)

Bovine beta-1,4-galactosyltransferase (beta-1,4-GT; EC 2.4.1.90) belongs to the glycosyltransferase family and as such shares a general topology: an N-terminal cytoplasmic tail, a signal anchor followed by a stem region and a catalytic domain at the C-terminal end of the protein. cDNA constructs of the N-terminal deleted forms of beta-1,4-GT were prepared in pGEX-2T vector and expressed in E. coli as glutathione-S-transferase (GST) fusion proteins. Recombinant proteins accumulated within inclusion bodies as insoluble aggregates that were solubilized in 5 M guanidine HCl and required an 'oxido-shuffling' reagent for regeneration of the enzyme activity. The recombinant beta-1,4-GT, devoid of the GST domain, has 30-85% of the sp. act. of bovine milk beta-1,4-GT with apparent Kms for N-acetylglucosamine and UDP-galactose similar to those of milk enzyme. Deletion analyses show that both beta-1,4-GT and lactose synthetase activities remain intact even in the absence of the first 129 residues (pGT-d129). The activities are lost when either deletions extend up to residue 142 (pGT-d142) or Cys134 is mutated to Ser (pGT-d129C134S). These results suggest that the formation of a disulfide bond involving Cys134 holds the protein in a conformation that is required for enzymatic activity.
Photolytic manipulation of Ca2+ and the time course of slow, Ca(2+)‐activated K+ current in rat hippocampal neurones. (1994)

1. Experiments were performed on hippocampal CA1 pyramidal cells to investigate the time course of a slow, Ca(2+)-activated K+ current that follows a burst of action potentials. At a temperature of 27-30 degrees C, this current rises to a peak 200-400 ms following the cessation of Ca2+ entry before decaying to baseline in 4-8s. 2. Intracellular recordings were made using electrodes containing the photolabile calcium buffers nitr-5 or DM-nitrophen loaded appropriately with Ca2+. Under these conditions, photolysis of the compound using an ultraviolet flashlamp caused an instantanous increase in cytoplasmic Ca2+ throughout the cell. The response to flash photolysis was a membrane hyperpolarization with an onset limited by the membrane time constant. Multiple (up to twenty) flash responses could be generated. 3. The postspike slow after-hyperpolarization (AHP) and flash-induced hyperpolarizations showed a common sensitivity to the beta-adrenergic receptor agonist isoprenaline. 4. Following a burst of spikes, the current underlying an AHP in progress could be terminated or reduced by photolysis-induced production of calcium buffer from diazo-4 within the cell. This action was rapid (within the setting time of the flash artifact, i.e. < 10 ms) despite the fact that the manipulation occurred 400-500 ms following the end of Ca2+ entry. 5. Partial block of the slow AHP by buffer production was accompanied by an increase in the time to peak of the event. 6. The time to peak of the slow AHP could also be manipulated by experiments which altered the spatial distribution of Ca2+ entry, such as production of calcium spikes or dendritic depolarization by glutamate in the presence of tetrodotoxin. 7. The Ca(2+)-dependent K+ current responsible for the slow AHP responds immediately to increase or decreases in cytoplasmic Ca2+. It seems likely, therefore, that the slow AHP is controlled solely by changes in free Ca2+ and that the time course is governed by the redistribution of cytoplasmic Ca2+ following activity-induced entry through voltage- or receptor-operated channels.
Influence of Thermal Annealing on GaN Buffer Layers and the Property of Subsequent GaN Layers Grown by Metalorganic Chemical Vapor Deposition (1999)

We have investigated the influence of low-temperature buffer layer deposition conditions, such as thickness and thermal annealing time, on the properties of the high-temperature GaN growth layer. The surface morphology of the buffer layer after thermal annealing at 1040°C depends on both the thickness of the buffer layer and the annealing time. When a thick buffer layer was used, large trapezoidal growth nuclei were formed after annealing, which led to the poor crystallinity of the GaN growth layer. On the other hand, when a thin buffer layer or a fully annealed thick buffer layer was used, small growth nuclei having a relatively small misorientation were formed, which led to good crystallinity of GaN growth layer. Thus, the thermal annealing time must be optimized, taking the thickness of the buffer layer into the consideration.
Antibody-complement-mediated cytotoxicity is enhanced by ribosome-inactivating proteins. (1985)

The antibody-mediated cytotoxicity of complement can be increased by the ribosome-inactivating proteins gelonin and PAP-S. Treatment of human lymphoid cells that express CALLA with an anti-CALLA monoclonal antibody, J5, and then with rabbit complement, leaves about 6% of the cells alive. The same treatment in the presence of a sublethal concentration of gelonin or PAP-S leaves only about 0.02 and 0.3% of the cells alive respectively. This synergistic effect has potential implications for the in vitro elimination of malignant cells or of immunocompetent cells from bone marrow before its transplantation.
[Expression and significance of VCAM-1 in subjects with allergic inflammation of respiratory tract]. (2009)

This study shows that upregulation of VCAM results in generalized airway inflammation in patients with allergic rhinitis.
SEN1, a positive effector of tRNA-splicing endonuclease in Saccharomyces cerevisiae. (1992)

The SEN1 gene, which is essential for growth in the yeast Saccharomyces cerevisiae, is required for endonucleolytic cleavage of introns from all 10 families of precursor tRNAs. A mutation in SEN1 conferring temperature-sensitive lethality also causes in vivo accumulation of pre-tRNAs and a deficiency of in vitro endonuclease activity. Biochemical evidence suggests that the gene product may be one of several components of a nuclear-localized splicing complex. We have cloned the SEN1 gene and characterized the SEN1 mRNA, the SEN1 gene product, the temperature-sensitive sen1-1 mutation, and three SEN1 null alleles. The SEN1 gene corresponds to a 6,336-bp open reading frame coding for a 2,112-amino-acid protein (molecular mass, 239 kDa). Using antisera directed against the C-terminal end of SEN1, we detect a protein corresponding to the predicted molecular weight of SEN1. The SEN1 protein contains a leucine zipper motif, consensus elements for nucleoside triphosphate binding, and a potential nuclear localization signal sequence. The carboxy-terminal 1,214 amino acids of the SEN1 protein are essential for growth, whereas the amino-terminal 898 amino acids are dispensable. A sequence of approximately 500 amino acids located in the essential region of SEN1 has significant similarity to the yeast UPF1 gene product, which is involved in mRNA turnover, and the mouse Mov-10 gene product, whose function is unknown. The mutation that creates the temperature-sensitive sen1-1 allele is located within this 500-amino-acid region, and it causes a substitution for an amino acid that is conserved in all three proteins.
The Effects of Pharmacologic Agents for Type 2 Diabetes Mellitus on Body Weight (2008)

Type 2 diabetes mellitus and obesity share a pathogenic relationship, and both have rapidly increased in prevalence over the past decade. This review evaluates the effects of antidiabetes therapies on weight and glycemic control in the type 2 diabetes mellitus population. A PubMed search was conducted to identify randomized controlled trials that reported the weight effects of antidiabetes treatments. The search focused on the newer incretin-based therapies, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. Antiobesity drugs and treatment options potentially available to patients with type 2 diabetes mellitus, including bariatric surgery, were also examined. Most of the established antidiabetes therapies (eg, sulfonylureas, thiazolidinediones) promote weight gain, thereby exacerbating insulin resistance and glucose intolerance. Dipeptidyl peptidase-4 inhibitors exhibit a weight-neutral profile, however, and GLP-1 receptor agonists (eg, exenatide, liraglutide) have achieved significant body weight reductions in spite of improved glycemic control, which is often accompanied by weight gain. Antiobesity drugs, such as orlistat and sibutramine, are effective weight-lowering agents in patients with type 2 diabetes mellitus, but safety and tolerability concerns may limit their use. Bariatric surgery in obese patients is associated with improved glycemic values and decreased mortality. Clinical evidence substantiating the weight-neutral effects of DPP-4 inhibitors and the weight-loss effects of GLP-1 agonists is promising, offering an expansion of therapeutic options for overweight and obese patients with type 2 diabetes mellitus. Evidence on the clinical utility of antiobesity drugs is more equivocal, and more data are needed to evaluate the safety and tolerability of these agents.
Aiding the detection of fake accounts in large scale social online services (2012)

Users increasingly rely on the trustworthiness of the information exposed on Online Social Networks (OSNs). In addition, OSN providers base their business models on the marketability of this information. However, OSNs suffer from abuse in the form of the creation of fake accounts, which do not correspond to real humans. Fakes can introduce spam, manipulate online rating, or exploit knowledge extracted from the network. OSN operators currently expend significant resources to detect, manually verify, and shut down fake accounts. Tuenti, the largest OSN in Spain, dedicates 14 full-time employees in that task alone, incurring a significant monetary cost. Such a task has yet to be successfully automated because of the difficulty in reliably capturing the diverse behavior of fake and real OSN profiles. We introduce a new tool in the hands of OSN operators, which we call SybilRank. It relies on social graph properties to rank users according to their perceived likelihood of being fake (Sybils). SybilRank is computationally efficient and can scale to graphs with hundreds of millions of nodes, as demonstrated by our Hadoop prototype. We deployed SybilRank in Tuenti’s operation center. We found that ∼90 % of the 200K accounts that SybilRank designated as most likely to be fake, actually warranted suspension. On the other hand, with Tuenti’s current user-report-based approach only ∼5 % of the inspected accounts are indeed fake. 1
Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum. (1991)

Merozoite surface antigen MSA-2 of the human parasite Plasmodium falciparum is being considered for the development of a malaria vaccine. The antigen is polymorphic, and specific monoclonal antibodies differentiate five serological variants of MSA-2 among 25 parasite isolates. The variants are grouped into two major serogroups, A and B. Genes encoding two different variants from serogroup A have been sequenced, and their DNA together with deduced amino acid sequences were compared with sequences encoded by other alleles. The comparison shows that the serological classification reflects differences in DNA sequences and deduced primary structure of MSA-2 variants and serogroups. Thus, the overall homologies of DNA and amino acid sequences are over 95% among variants in the same serogroup. In contrast, similarities between the group A variants and a group B variant are only 70 and 64% for DNA and amino acid sequences, respectively. We propose that the MSA-2 protein is encoded by two highly divergent groups of alleles, with limited additional polymorphism displayed within each group.
Increased salt concentration reversibly destabilizes p53 quaternary structure and sequence-specific DNA binding (1994)

Growth suppression by p53 correlates with sequence-specific DNA binding and is determined by tertiary and quaternary protein structures. Exposure to 300 mM NaCl did not affect p53 tertiary structure, but dissociated high-molecular-mass complexes with concomitant loss of specific DNA binding. Both effects were reversible. We conclude that high salt can reversibly destabilize the quaternary structure of p53 that is most efficient for sequence-specific DNA binding.
Design and evaluation of a compiler algorithm for prefetching (1992)

article Free Access Share on Design and evaluation of a compiler algorithm for prefetching Authors: Todd C. Mowry View Profile , Monica S. Lam View Profile , Anoop Gupta View Profile Authors Info & Claims ACM SIGPLAN NoticesVolume 27Issue 9Sept. 1992 pp 62–73https://doi.org/10.1145/143371.143488Online:01 September 1992Publication History 632citation2,091DownloadsMetricsTotal Citations632Total Downloads2,091Last 12 Months203Last 6 weeks38 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
A close-to-capacity dirty paper coding scheme (2005)

The "writing on dirty paper"-channel model offers an information-theoretic framework for precoding techniques for canceling arbitrary interference known at the transmitter. It indicates that lossless precoding is theoretically possible at any signal-to-noise ratio (SNR), and thus dirty-paper coding may serve as a basic building block in both single-user and multiuser communication systems. We design an end-to-end coding realization of a system materializing a significant portion of the promised gains. We employ multidimensional quantization based on trellis shaping at the transmitter. Coset decoding is implemented at the receiver using "virtual bits." Combined with iterative decoding of capacity-approaching codes we achieve an improvement of 2dB over the best scalar quantization scheme. Code design is done using the EXIT chart technique.
Total synthesis of furanocembranolides. 3. A concise convergent route to acerosolide (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of furanocembranolides. 3. A concise convergent route to acerosolideLeo A. Paquette and Peter C. AstlesCite this: J. Org. Chem. 1993, 58, 1, 165–169Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/jo00053a031https://doi.org/10.1021/jo00053a031research-articleACS PublicationsRequest reuse permissionsArticle Views954Altmetric-Citations60LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
The potential role of amyloid in the pathogenesis of age-related macular degeneration (2005)

Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid beta (Abeta) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Abeta on cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted mice, which leads to an increased deposition Abeta. The results showed that Abeta treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Abeta-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene-disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Abeta reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD.
Using the FASTA Program to Search Protein and DNA Sequence Databases (2003)

As this volume illustrates, computers have become an integral tool in the analysis of DNA and protein sequence data. One of the most popular applications of computers in modern molecular biology is to characterize newly determined sequences by searching DNA and protein sequence databases. The FASTA* program (,) is widely used for such searches, because it is fast, sensitive, and readily available. FASTA is available as part of a package of programs that construct local and global sequence alignments. This chapter will describe a number of simple applications of FASTA and other programs in the FASTA package. This chapter focuses on the steps required to run the programs, rather than on the interpretation of the results of a FASTA search. For a more complete description of FASTA and related programs for identifying distantly related DNA and protein sequences, for evaluating the statistical significance of sequence similarities, and for identifying similar structures in DNA and protein sequences see ref. .
SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes (2019)

The SARS (severe acute respiratory syndrome) outbreak was caused by a coronavirus (CoV) named the SARS-CoV. SARS pathology is propagated both by direct cytotoxic effects of the virus and aberrant activation of the innate immune response. Here, we identify several mechanisms by which a SARS-CoV open reading frame (ORF) activates intracellular stress pathways and targets the innate immune response. We show that ORF8b forms insoluble intracellular aggregates dependent on a valine at residue 77. Aggregated ORF8b induces endoplasmic reticulum (ER) stress, lysosomal damage, and subsequent activation of the master regulator of the autophagy and lysosome machinery, Transcription factor EB (TFEB). ORF8b causes cell death in epithelial cells, which is partially rescued by reducing its ability to aggregate. In macrophages, ORF8b robustly activates the NLRP3 inflammasome by providing a potent signal 2 required for activation. Mechanistically, ORF8b interacts directly with the Leucine Rich Repeat domain of NLRP3 and localizes with NLRP3 and ASC in cytosolic dot-like structures. ORF8b triggers cell death consistent with pyroptotic cell death in macrophages. While in those cells lacking NLRP3 accumulating ORF8b cytosolic aggregates cause ER stress, mitochondrial dysfunction, and caspase-independent cell death.
The complete amino acid sequence of human fibroblast interferon as deduced using synthetic oligodeoxyribonucleotide primers of reverse transcriptase (1980)

Using synthetic oligodeoxyribonucleotides to prime the transcription of interferon mRNA and cDNA, we recently determined the mRNA sequence coding for the 47 amino-terminal amino acids of mature human fibroblast interferon (1). From this sequence, we have now synthesised an oligodeoxyribonucleotide that is homologous with the mRNA sequence coding for amino acids 42-45 and used it as a primer to selectively transcribe an interferon cDNA template. The sequence of the newly synthesised DNA predicted the sequence of amino acids 48-109 in the interferon polypeptide. By repeating this process with one more primer, we have determined the complete amino acid sequence of mature human fibroblast interferon, a polypeptide of 166 amino acids.
Effect of Inhibitor of Tumor Necrosis Factor‐α and Oxatomide on Immune Mediated Otitis Media (2006)

Transtympanic administration of sTNF RI and oxatomide appears to suppress the development of immune-mediated MEE.
New patternable dielectric and optical materials for MCM-L/D- and o/e-MCM-packaging (1997)

Photopatternable inorganic-organic copolymers (ormocers, or organically modified ceramics) with negative resist behaviour have been developed and tested as thin film materials for electrical and/or optical packaging purposes, e.g. MCM-L/D and optoelectronic MCM packaging. Good processability in combination with a much lower post-curing temperature (120/spl deg/C-170/spl deg/C) than alternative materials such as polyimide and benzocyclobutene enables the use of low cost glass fiber reinforced polymer substrates such as FR-4 and BT. The good electrical, optical and other properties are presented and discussed. The process and tentative design-rules for multilayer MCM-L/Ds are described and some test-vehicles are presented, emphasizing the versatility and low-cost potential of the new materials.
Long‐term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment (2012)

Ten years of imiglucerase treatment results in sustainable improvements in all GD1 parameters.