gebhart/patrepeval huggingface dataset:
Antagonism of Immunostimulatory CpG-Oligodeoxynucleotides by Quinacrine, Chloroquine, and Structurally Related Compounds (1998)

Phosphorothioate oligodeoxynucleotides containing CpG (CpG-ODN) activate immune responses. We report that quinacrine, chloroquine, and structurally related compounds completely inhibit the antiapoptotic effect of CpG-ODN on WEHI 231 murine B lymphoma cells and inhibit CpG-ODN-induced secretion of IL-6 by WEHI 231. They also inhibit IL-6 synthesis and thymidine uptake by human unfractionated PBMC induced by CpG-ODN. The compounds did not inhibit LPS-induced responses. Half-maximal inhibition required 10 nM quinacrine or 100 nM chloroquine. Inhibition was noncompetitive with respect to CpG-ODN. Quinine, quinidine, and primaquine were much less powerful. Quinacrine was effective even when added after the CpG-ODN. Near-toxic concentrations of ammonia plus bafilomycin A1 (used to inhibit vesicular acidification) did not reduce the efficacy of the quinacrine, but the effects of both quinacrine and chloroquine were enhanced by inhibition of the multidrug resistance efflux pump by verapamil. Agents that bind to DNA, including propidium iodide, Hoechst dye 33258, and coralyne chloride did not inhibit CpG-ODN effect, nor did 4-bromophenacyl bromide, an inhibitor of phospholipase A2. Examination of the structure-activity relationship of seventy 4-aminoquinoline and 9-aminoacridine analogues reveals that increased activity was conferred by bulky hydrophobic substituents on positions 2 and 6 of the quinoline nucleus. No correlation was found between published antimalarial activity and ability to block CpG-ODN-induced effects. These results are discussed in the light of the ability of quinacrine and chloroquine to induce remission of rheumatoid arthritis and lupus erythematosus.
The identity of Bossiaea strigillosa Benth. (Fabaceae: Tribe Bossiaeeae) (2001)

Bossiaea strigillosa Benth. is a synonym of Pultenaea rotundifolia (Turcz.) Benth. A lectotype is selected for B. strigillosa.
Medical treatment of cholestatic liver diseases: From pathobiology to pharmacological targets (2006)

Bile secretion is dependent on the coordinated functions of a number of hepatobiliary transport systems. Cholestasis may be caused by an impairment of bile secretion, an obstruction of bile flow or a combination of the two. The common consequence of all forms of cholestasis is retention of bile acids and other potentially toxic compounds in the hepatocytes leading to apoptosis or necrosis of hepatocytes and eventually to chronic cholestatic liver disease. In certain cholestatic disorders there is also leakage of bile acids into the peribiliary space causing portal inflammation and fibrosis. The following pharmacological targets for treatment of intrahepatic cholestasis can be identified: stimulation of orthograde biliary secretion and retrograde secretion of bile acids and other toxic cholephils into the systemic circulation for excretion via the kidneys to reduce their retention in the hepatocytes; stimulation of the metabolism of hydrophobic bile acids and other toxic compounds to more hydrophilic, less toxic metabolites; protection of injured cholangiocytes against toxic effects of bile; inhibition of apoptosis caused by elevated levels of cytotoxic bile acids; inhibition of fibrosis caused by leakage of bile acids into the peribiliary space. The clinical results of ursodeoxcholic acid therapy of primary biliary cirrhosis may be regarded as the first success of this strategy.
The Thread & Cut Method: Syntheses of Molecular Knot Precursors (2008)

Abstract A novel approach to molecular knots is described. This method may allow access to smaller and more complex knots. Two knot precursors, 1a and 1b , are efficiently prepared in overall yields of 9.6 % and 8.7 %, respectively. The convergent six‐step syntheses utilize Fréchet‐type etherifications, alkyne/azide click cycloadditions, and bis‐macrolactonizations.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)
Production of disulfide-bonded proteins in Escherichia coli (2011)

Disulfide bonds are covalent bonds formed post-translationally by the oxidation of a pair of cysteines. A disulfide bond can serve structural, catalytic, and signaling roles. However, there is an inherent problem to the process of disulfide bond formation: mis-pairing of cysteines can cause misfolding, aggregation and ultimately result in low yields during protein production. Recent developments in the understanding of the mechanisms involved in the formation of disulfide bonds have allowed the research community to engineer and develop methods to produce multi-disulfide-bonded proteins to high yields. This review attempts to highlight the mechanisms responsible for disulfide bond formation in Escherichia coli, both in its native periplasmic compartment in wild-type strains and in the genetically modified cytoplasm of engineered strains. The purpose of this review is to familiarize the researcher with the biological principles involved in the formation of disulfide-bonded proteins with the hope of guiding the scientist in choosing the optimum expression system.
IL-2 and IL-15 Each Mediate De Novo Induction of FOXP3 Expression in Human Tumor Antigen-specific CD8 T Cells (2007)

Although FOXP3 is primarily expressed by regulatory CD4 T cells (Treg) in vivo, polyclonal activation of human CD8 T cells can result in the expression of FOXP3 in a fraction of CD8 T cells. However, the cellular lineage and mechanism of FOXP3 induction in CD8 T cells remain unclear. Here, we demonstrate that interleukin-2 (IL-2) induces FOXP3 expression in OKT3-stimulated or antigen-stimulated CD8 T cells, indicating that FOXP3 expression is neither limited to a unique subset of CD8 T cells nor dependent on the mode of T-cell receptor stimulation. In the absence of IL-2, antigen stimulation resulted in T-cell activation and acquisition of effector function without induction of FOXP3, indicating that acquisition of effector function is independent of induction of FOXP3 expression in CD8 T cells. Interestingly, IL-15, but not IL-7 or IL-21, also led to de novo induction of FOXP3 in antigen-specific CD8 T cells, suggesting that signaling by IL-2/IL-15Rbeta chain is pivotal for induction of FOXP3 in human CD8 T cells. These findings indicate that induction of FOXP3 is intrinsic to CD8 T cells that are activated in the presence of IL-2 or IL-15, and in vitro-induced expression of FOXP3 cannot be simply interpreted as an indicator of Treg activity or activation marker.
Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer (2012)

Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to the lack of disease-specific biomarkers that could afford early and accurate diagnosis. With a recombinant antibody microarray platform, targeting mainly immunoregulatory proteins, we screened sera from 148 patients with pancreatic cancer, chronic pancreatitis, autoimmune pancreatitis (AIP), and healthy controls (N). Serum biomarker signatures were derived from training cohorts and the predictive power was evaluated using independent test cohorts. The results identified serum portraits distinguishing pancreatic cancer from N [receiver operating characteristics area under the curve (AUC) of 0.95], chronic pancreatitis (0.86), and AIP (0.99). Importantly, a 25-serum biomarker signature discriminating pancreatic cancer from the combined group of N, chronic pancreatitis, and AIP was determined. This signature exhibited a high diagnostic potential (AUC of 0.88). In summary, we present the first prevalidated, multiplexed serum biomarker signature for diagnosis of pancreatic cancer that may improve diagnosis and prevention in premalignant diseases and in screening of high-risk individuals.
Artificial Neural Networks in the Diagnosis and Prognosis of Prostate Cancer: A Pilot Study (1994)

There is controversy about how prostate cancer screening tests should best be used because of the false-negative and false-positive results. There also is controversy about prostate cancer treatment because of errors in tumor staging, uncertainty about treatment efficacy and the variable natural history of the disease. We sought to determine in a pilot study whether artificial neural networks would be helpful to predict biopsy results in men with abnormal screening test(s) and to predict treatment outcome after radical prostatectomy. To predict biopsy results, we extracted data from a prostate specific antigen (PSA) based screening study data base in 1,787 men with a serum PSA concentration of more than 4.0 ng./ml. (approximately 40% of the men also had suspicious findings on digital rectal examination). To predict cancer recurrence after radical prostatectomy, we extracted data from a random sample of 240 patients selected from a data base of men who had undergone radical prostatectomy. The neural network predicted the biopsy result with 87% overall accuracy, and its output threshold could be adjusted to achieve the desired tradeoff between sensitivity and specificity. It also predicted tumor recurrence with 90% overall accuracy. We conclude that trained neural networks may be useful in decision making for prostate cancer patients.
Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD) 3‐tTF (2013)

(RGD)₃-tTF may be a promising strategy for the treatment of colorectal cancer.
5-Modified-2′-dU and 2′-dC as Mutagenic Anti HIV-1 Proliferation Agents: Synthesis and Activity (2010)

With the goal of limiting HIV-1 proliferation by increasing the mutation rate of the viral genome, we synthesized a series of pyrimidine nucleoside analogues modified in position 5 of the aglycone moiety but unmodified on the sugar part. The synthetic strategies allow us to prepare the targeted compounds directly from commercially available nucleosides. All compounds were tested for their ability to reduce HIV-1 proliferation in cell culture. Two of them (5-hydroxymethyl-2'-dU (1c) and 5-hydroxymethyl-2'-dC (2c)) displayed a moderate antiviral activity in single passage experiments. The same two compounds plus two additional ones (5-carbamoyl-2'-dU (1a) and 5-carbamoylmethyl-2'-dU (1b)) were potent inhibitors of HIV-1 RT activity in serial passage assays, in which they induced a progressive loss of HIV-1 replication. In addition, viruses collected after seven passages in the presence of 1c and 2c replicated very poorly after withdrawal of these compounds, consistent with the accumulation of deleterious mutations in the HIV-1 genome.
A simple carbon-13 nuclear magnetic resonance spectroscopic method for distinguishing between open-chain and pseudoacid chlorides (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA simple carbon-13 nuclear magnetic resonance spectroscopic method for distinguishing between open-chain and pseudoacid chloridesWilliam J. Elliott and Josef FriedCite this: J. Org. Chem. 1978, 43, 13, 2708–2710Publication Date (Print):June 1, 1978Publication History Published online1 May 2002Published inissue 1 June 1978https://pubs.acs.org/doi/10.1021/jo00407a037https://doi.org/10.1021/jo00407a037research-articleACS PublicationsRequest reuse permissionsArticle Views229Altmetric-Citations10LEARN 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
Domain Organization and DNA-Induced Conformational Changes of an Archaeal Family B DNA Polymerase (1996)

Family B DNA polymerase from the thermoacidophilic archaeon Sulfolobus solfataricus (Sso DNA pol) is a monomer of about 100 kDa with two associated catalytic functions: 3'-5' exonuclease and DNA polymerase activities. The structure of this enzyme in the free and DNA-bound states was probed by limited proteolysis and fluorescence spectroscopy measurements. The results of partial trypsin proteolysis experiments on the recombinant Sso DNA pol pinpointed three major sites of protease sensitivity: near the N-terminus, within the center, and near the C-terminal end of the polypeptide chain. When partial trypsin digestion was carried out in the presence of either activated calf thymus DNA or primed M13mp18 single-stranded DNA, changes in cleavage pattern and in susceptibility to protease were detected. This phenomenon was dependent on the nucleic acid concentration and suggested the occurrence of DNA-induced conformational changes. These were also probed by steady-state fluorescence spectroscopy measurements using acrylamide as a quencher. Fine mapping of the DNA-specific cleavage sites allowed us to precisely locate the protein subdomains which were affected by these structural changes. Importantly, a specific proteolytic fragment of about 8 kDa was recovered after partial digestion of Sso DNA pol only in the presence of nucleic acid ligands. It was found to start at residues 392-394 and to span the protease-hypersensitive central region of the polypeptide chain. Its involvement in critical polymerase functions, such as substrate binding and/or enzyme processivity, was discussed. In addition, we found that controlled trypsin digestion of Sso DNA pol did not inactivate either polymerase or 3'-5' exonuclease activity concomitantly with the disappearance of full-sized enzyme. Activity gel analysis revealed that proteolytic products corresponding to the amino- and carboxyl-terminal halves of the enzyme retained 3'-5' exonuclease and DNA polymerase activity, respectively. These results are in line with the model of modular organization proposed for Sso DNA pol in a previous report.
InGaAs nano-pillar array formation on partially masked InP(111)B by selective area metal–organic vapour phase epitaxial growth for two-dimensional photonic crystal application (2003)

We report on the selective area metal–organic vapour phase epitaxial growth of an InGaAs nano-pillar array on a partially masked InP(111)B substrate. This technique is very promising as a way to form semiconductor two-dimensional photonic crystals (2DPCs) suitable for infrared optical fibre communication. We successfully formed uniform hexagonal 2DPCs having vertical (110) facet sidewalls on 400 nm-pitch masked substrates. We observed vertical growth enhancement as well as the lateral overgrowth suppression for high aspect ratio InGaAs nano-pillar array formation under high growth-rate, long growth-time, and narrow window-opening conditions. We verified infrared emission from the InGaAs nano-pillar array by low-temperature photoluminescence measurement.
Registered Wide BGP Community Values (2016)

Communicating various routing policies via route tagging plays an
important role in external BGP peering relations. The most common tool
used today to attach various information about routes is realized with
the use of BGP communities. Such information is important for the
peering AS to perform some mutually agreed actions without the need to
maintain a separate offline database for each pair of prefix and an
associated with it requested set of action entries. This document
proposes to establish a new IANA maintained registry of most commonly
used Wide BGP Communities by network operators. Such public registry
will allow for easy refernece and clear interpretation of the actions
associated with received community values.
Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury (2008)

IL-18 function is neutralized in IL-18 binding protein transgenic (IL-18BP Tg) mice. First, we determined whether IL-18BP Tg mice are protected against ischemic acute kidney injury (AKI). Ischemic AKI was induced by bilateral renal pedicle clamping. IL-18BP Tg mice were functionally and histologically protected against ischemic AKI as determined by blood urea nitrogen, serum creatinine, and acute tubular necrosis score. We have demonstrated that the injurious effect of IL-18 in the kidney is independent of neutrophils and lymphocytes. Thus the effect of IL-18 inhibition on renal macrophage infiltration was determined. The number of macrophages was significantly reduced in IL-18BP Tg compared with wild-type kidneys. To determine the cytokines and chemokines that are dependent on IL-18, we performed flow cytometry based assays. Multiple chemokines/cytokines, IL-3, IL-6, IL-15, IL-18, leukemia inhibitory factor, macrophage colony-stimulating factor, macrophage inflammatory protein-2, granulocyte-macrophage colony-stimulating factor, and monocyte chemotactic protein-1 were significantly increased in AKI vs. sham kidneys. Only CXCL1 (also known as KC or IL-8) was significantly increased in AKI vs. sham kidneys and significantly reduced in IL-18BP Tg AKI vs. wild-type AKI kidneys. To determine whether macrophages are the source of CXCL1 in the kidney, we depleted macrophages with liposomal encapsulated clodronate. CXCL1 was significantly decreased in macrophage-depleted vs. control AKI mice. In summary, in ischemic AKI in mice, 1) IL-18BP Tg mice are functionally and histologically protected, 2) macrophage infiltration in the kidney and CXCL1 are significantly reduced in IL-18BP Tg mice, and 3) macrophage depletion significantly reduces CXCL1 in the kidney. In conclusion, protection against ischemic AKI in IL-18BP Tg mice is associated with less macrophage infiltration and less production of CXCL1 in the kidney.
Heat as a Ground Water Tracer (2005)

Heat carried by ground water serves as a tracer to identify surface water infiltration, flow through fractures, and flow patterns in ground water basins. Temperature measurements can be analyzed for recharge and discharge rates, the effects of surface warming, interchange with surface water, hydraulic conductivity of streambed sediments, and basin-scale permeability. Temperature data are also used in formal solutions of the inverse problem to estimate ground water flow and hydraulic conductivity. The fundamentals of using heat as a ground water tracer were published in the 1960s, but recent work has significantly expanded the application to a variety of hydrogeological settings. In recent work, temperature is used to delineate flows in the hyporheic zone, estimate submarine ground water discharge and depth to the salt-water interface, and in parameter estimation with coupled ground water and heat-flow models. While short reviews of selected work on heat as a ground water tracer can be found in a number of research papers, there is no critical synthesis of the larger body of work found in the hydrogeological literature. The purpose of this review paper is to fill that void and to show that ground water temperature data and associated analytical tools are currently underused and have not yet realized their full potential.
Structure and Variability of the a Sequence in the Genome of Human Cytomegalovirus (Towne Strain) (1987)

We have defined the boundaries of the a sequence from human cytomegalovirus (CMV) strain Towne, characterized internal variability and determined the position of the cleavage site used to generate genomic termini. The cleavage site is positioned a fixed distance from two stretches of sequence homology that have been observed near the ends of many herpesvirus genomes. Unlike a comparable region in CMV (AD169), the CMV (Towne) a sequence has a relatively low level of variability within the a sequence and its structure is stable through repeated virus passage.
A problem-based approach to clinical education in dietetics (2002)

\n\t\t\t\t\tDeveloping the clinical skills and knowledge of dietetic students provides a challenge for both universities and health care agencies. Deakin University has recently adopted a group learning model using problem-based learning to deliver the clinical component of the Master of Nutrition and Dietetics course. This approach was designed to enhance integration of clinical theory and practice, develop closer links between on-campus and off-campus learning environments and provide students with more active learning experiences. The impact of the new approach was evaluated using student questionnaires, academic and competency outcomes, and a focus group convened with hospital supervisors. The evaluation indicated that students generally thought that this method of learning had helped to integrate their basic knowledge with dietetic case management. There was no difference in academic scores from the previous year and an apparent reduction in the number of students requiring additional placement time to mee t competency standards. Hospital supervisors were supportive of the changes, although they had some reservations regarding the time and structure of clinical placements. As a result of this evaluation, recommendations for future development of the program include introducing problem-based learning to students earlier in their course, providing additional placement days during the block and increasing the amount of time dedicated to more complex topics. Based on the evaluation results obtained, this collaborative learning using a problem-based approach will continue to be used in the clinical education program at Deakin University. &lt;br /&gt;\n\t\t\t\t
Comparison of the Transcription Profile of Simian Parvovirus with That of the Human Erythrovirus B19 Reveals a Number of Unique Features (2004)

Simian parvovirus (SPV) is a member of the genus Erythrovirus and is closely related to the human parvovirus B19. Natural and experimental infection of monkeys with SPV resembles B19 infection of human. We report a detailed characterization of the viral RNAs and proteins generated following transfection of cloned SPV into COS cells and SPV infection of the human erythroid progenitor line UT-7/Epo-S1. SPV and B19 are 50% identical at the nucleotide level, and although their basic transcription and protein expression profiles were generally similar, there were also significant differences. SPV pre-mRNAs contain three introns, compared to two found for B19: an additional intron was found within the capsid-coding region. RNAs in which this intron was spliced were abundant and encoded the SPV 14-kDa protein (analogous to the B19 11-kDa protein), which initiated at an AUG in the exon preceding the third intron. Unlike B19, SPV RNAs were also spliced between the donor of the first intron and the acceptor of the second intron. The third intron was additionally spliced from a portion of these molecules; these mRNAs encoded the 14-kDa protein. A portion was not spliced further and encoded VP2. Like B19, SPV has a polyadenylation signal [AAUAAA (pA)p] in the middle of the genome, which directed efficient polyadenylation of both spliced and unspliced mRNAs (encoding a putative 10-kDa protein, analogous to the B19 7.5-kDa protein, and SPV NS1, respectively). The 14-kDa protein was localized to both in the nucleus and cytoplasm.