gebhart/patrepeval huggingface dataset:
Structure‐antibacterial, antitumor and hemolytic activity relationships of cecropin A‐magainin 2 and cecropin A‐melittin hybrid peptides (1999)

In order to elucidate the structure-antibiotic activity relationship of cecropin A-magainin 2 and cecropin A-melittin hybrid peptides, several truncated peptides and the analogues with amino acid substitutions were synthesized and their antibacterial, antitumor and hemolytic activities of were examined. Cecropin A-magainin 2 hybrid analog, L16-CA(1-8)-MA(1-12) (termed as L-CA-MA in this study: KWKLFKKIGIGKFLHLAKKF-NH2), is known to have potent antibacterial and antitumor activity with less hemolytic activity. We found that the C-terminal region of L-CA-MA is more involved in the alpha-helical structure on cell membrane-like environment than N-terminal one by circular dichroism analysis. Deletion of the Gly-Ile-Gly sequence, the central hinge region of L-CA-MA, produced a considerable reduction in antitumor and hemolytic activity rather than an antibacterial one. The insertion of Pro, Gly-Ile or Gly-Pro in this hinge region of L-CA-MA caused retention of both antibacterial and antitumor activity while causing a significant decrease in hemolytic activity. However, the substitution with Gly-Pro-Gly instead of the Gly-Ile-Gly in CA(1-8)-MA(1-12), CA(1-8)-ME(1-12), CA(1-13)-MA(1-13) and CA(1-13)-ME(1-13) hybrids resulted in a drastic decrease in antibacterial, antitumor and hemolytic activity. The increase of hydrophobicity at position 16 in CA(1-8)-MA(1-12) by substituting Trp or Phe induced a significant increase in hemolytic activity without a considerable change in either antibacterial or antitumor activity. Therefore, these results suggested that the appropriate flexibility in the hinge region of CA-MA and CA-ME hybrid peptides and the appropriate hydrophobicity at position 16 in the hydrophobic region of CA (1-8)-MA(1-12) are important in potent antibacterial and antitumor activity with no hemolytic effect.
A chance for peace (2000)

The realisation of the African renaissance will require a rapid transformation of the status quo, which sees the arc of crisis on the continent stretching from Angola to the Upper Nile Basin. The Democratic Republic of Congo (DRC) lies at the vortex of the continent's conflict zone, with six neighbouring countries and at least three rebel groups having been drawn into what has become Africa's largest battlefield.
Flavonoid Biosynthesis. A Colorful Model for Genetics, Biochemistry, Cell Biology, and Biotechnology (2001)

The role of flavonoids as the major red, blue, and purple pigments in plants has gained these secondary products a great deal of attention over the years. From the first description of acid and base effects on plant pigments by Robert Boyle in 1664 to the characterization of structural and
In vivo induction of interleukin-12 mRNA expression after oral immunization with Salmonella dublin or the B subunit of Escherichia coli heat-labile enterotoxin (1995)

Mice orally immunized with Salmonella dublin EL23, a nonreverting, aromatic-dependent, histidine-requiring mutant transformed with a plasmid which carries a gene that codes for production of the B subunit of the heat-labile toxin (LT-B) of enterotoxigenic Escherichia coli, or with purified LT-B alone were compared for their ability to initiate expression of interleukin-12 (IL-12) mRNAs at mucosal sites. At 6 or 20 h following oral immunization, the Peyer's patches and mesenteric lymph nodes were removed, and polyadenylated mRNA was prepared from each tissue. Constitutive expression of an mRNA encoding the p35 subunit of IL-12 was observed in control as well as immunized mice. Conversely, expression of an mRNA encoding the p40 subunit of IL-12 was not detected in control animals but was dramatically upregulated in immunized mice. By using semiquantitative reverse transcription-PCR (RT-PCR) followed by competitive RT-PCR, differences in the magnitude of IL-12 p40 mRNA expression were quantified. Six hours after oral immunization with the Salmonella construct, mice had 12.1- and 8.4-fold increases in expression of IL-12 p40 mRNA in the Peyer's patches and mesenteric lymph nodes, respectively, compared with control mice receiving only saline. By 20 h, the pattern of increased mRNA expression was reversed, showing 2.5- and 17.6-fold increases in the Peyer's patches and mesenteric lymph nodes, respectively. Oral immunization with LT-B alone also stimulated IL-12 p40 mRNA expression, but to a lesser extent. The constitutive expression of IL-12 p35 mRNA at these mucosal sites coupled with a rapid and dramatic induction of IL-12 p40 mRNA following immunization with wild-type or attenuated strains of S. dublin is consistent with other investigations which support a role for IL-12 in modulating cell-mediated immune responses against intracellular pathogens.
SOS chromotest, a direct assay of induction of an SOS function in Escherichia coli K-12 to measure genotoxicity. (1982)

We present and evaluate the SOS chromotest, a bacterial test for detecting DNA-damaging agents. It is a colorimetric assay based on the induction by these agents of the SOS function sfiA, whose level of expression is monitored by means of a sfiA::lacZ operon fusion. The response is rapid (a few hours), and does not require survival of the tester strain. Dose-response curves for various chemicals include a linear region. The slope of this region is taken as a measure of the SOS inducing potency. Comparison for a number of substances of known genotoxicity of the SOS inducing potency determined in the SOS chromotest with the mutagenic potency determined in the Salmonella assay (mutatest) revealed a striking quantitative correlation over more than 7 orders of magnitude. The sensitivity of the SOS chromotest (lowest amount detected) is equal to that of the mutatest and generally 4-40 times higher than that of a phage induction assay (inductest). From a practical point of view our observations contribute to the validation of the SOS chromotest as a test for detecting genotoxins and in particular genotoxic carcinogens. From a theoretical standpoint the results suggest that mutagenic potency measured in the mutatest reflects the level of induction of an SOS function and that most genotoxins are inducers of the SOS response in bacteria.
A framework to support large-scale active applications (1996)

Many applications are emerging which share the characteristic of being active, i.e. driven by asynchronous run-time events. The application areas include multimedia, cooperative working (such as conferencing), intelligent agent architectures, active database and support for user mobility. Prototype active applications are often developed from scratch as monolithic entities and are thus inflexible. Platforms which offer generalized support only usually deal with one application class in isolation.The thesis of this work is that active applications have generic requirements of a supporting platform. Rather than building each application as a monolithic entity, they can be composed of inter-connected sub-components called active objects. These objects can be used interchangeably in a plug-and-play architecture. This encourages on-the-fly application development and assists fast prototyping.This paper is supported by our implementation of a prototype distributed active application support platform. Our software is used to provide examples throughout. Section 1 describes the application requirements which a platform must be able to support. Section 2 describes the model for composing applications. Section 3 describes how a distributed programming platform has been enhanced for run-time object support and to allow new active object classes to be constructed easily. Finally, section 4 concludes.
Modulation of the Immune System by Human Milk and Infant Formula Containing Nucleotides (1998)

Infant formula fortified with nucleotides enhanced H influenzae type b and diphtheria humoral antibody responses. Feeding human milk enhanced antibody responses to OPV. Dietary factors play a role in the antibody response of infants to immunization.
‘Side Locked’ Migraine and Trigeminal Autonomic Cephalgias: Evidence for Clinical Overlap (2003)

This paper will discuss evidence which supports a link between 'side locked' migraine (SLM) and the trigeminal autonomic cephalgias (TACs). Recent papers brought strictly unilateral primary headaches into focus, proposing new classification and discussing pathophysiological mechanisms. We reviewed those proposals and present evidence that SLM falls in between the well-defined TACs and side shifting migraine (SSM). It is difficult to differentiate SLM from the recently proposed headache subtype called hemicrania generis incerti (i.e. hemicrania continua unresponsive to indomethacin). We also present cases that may exemplify the considerations made in the paper.
Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1----3Gal epitope in primates. (1987)

Anti-Gal is a natural antibody, which constitutes as much as 1% of circulating IgG in humans and displays a distinct specificity for the structure Gal alpha 1----3Gal. This glycosidic structure has been found on various tissues of many nonprimate mammals. A comparative study of the occurrence of anti-Gal versus the expression of the Gal alpha 1----3Gal epitope was performed in primates, and a distinct evolutionary pattern was observed. Whereas anti-Gal was found to be present in Old World monkeys and apes in titers comparable to those in humans, its corresponding antigenic epitope is abundantly expressed on erythrocytes of New World monkeys. Immunostaining with anti-Gal of glycolipids from New World monkey erythrocytes indicated that the molecules to which anti-Gal binds are similar to those found in rabbit and bovine erythrocytes. These findings indicate that there is an evolutionary reciprocity between New World and Old World primates in the production of the Gal alpha 1----3Gal structure and the antibody that recognizes it. The expression of the Gal alpha 1----3Gal epitope was evolutionarily conserved in New World monkeys, but it was suppressed in ancestral lineages of Old World primates. The suppression of this epitope was accompanied by the production of anti-Gal. The observed in vivo binding of anti-Gal to human normal senescent and some pathologic erythrocytes implies that the Gal alpha 1----3Gal epitope is present in man in a cryptic form.
Carcinoembryonic antigen in patients with different cancers (1972)

Carcinoembryonic antigen (CEA) is a cancer-specific antigen described by Gold in 1965. It is a glycoprotein present in malignant entodermal tissues, in fetal colonic mucosa, and in the plasma of patients with gastrointestinal tract cancers. We have measured plasma CEA levels in 346 patients using a new procedure which detects an ion-sensitive antigenic site in the carcinoembryonic molecule. Levels in 39 of 48 patients with gastrointestinal tract cancer and 90 of 281 with nonentodermally derived malignancies were abnormal. Following successful therapy CEA level returns to normal (colon, four of four; neuroblastoma, three of three). The identity between the antigen measured in the present study and the carcinoembryonic antigen of Gold has not been established. The assay appears to be useful in the follow-up of patients with cancer and may eventually be of diagnostic value in the asymptomatic patient.
Responsiveness of rat substantia gelatinosa neurones to mechanical but not thermal stimuli revealed by in vivo patch‐clamp recording (1999)

1. Synaptic responses of 46 substantia gelatinosa (SG) neurones in the spinal dorsal horn to cutaneous mechanical and/or thermal stimuli were investigated in an in vivo rat preparation with whole-cell patch-clamp recordings. The clamped neurones were identified as being in the SG based on either their morphological features by intrasomatic injection of biocytin or the depth of the neurones from the surface of the spinal cord. 2. In all SG neurones examined where spontaneous EPSCs occurred, pinch (noxious) and air (innocuous) stimuli applied to the ipsilateral hindlimb elicited a barrage of EPSCs (some of which initiated an action potential under current-clamp conditions), which subsided just after cessation of the stimuli without any residual slow current (or after-discharge). The spontaneous and evoked EPSCs were reversibly abolished by a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, CNQX (20 microM). 3. Noxious (>= 45 C) or innocuous (<= 40 C) thermal stimuli did not elicit any synaptic responses in all 18 SG neurones tested which were sensitive to mechanical stimuli. Noxious cold stimulation (<= 10 C) also failed to produce any responses (n = 6). 4. It is concluded that both noxious and innocuous mechanical information to SG neurones are transmitted primarily by activation of non-NMDA receptors, probably without any involvement of slow synaptic transmission, and that thermal information is conveyed to areas of the dorsal horn other than SG.
Docking unbound proteins using shape complementarity, desolvation, and electrostatics (2002)

A comprehensive docking study was performed on 27 distinct protein-protein complexes. For 13 test systems, docking was performed with the unbound X-ray structures of both the receptor and the ligand. For the remaining systems, the unbound X-ray structure of only molecule was available; therefore the bound structure for the other molecule was used. Our method optimizes desolvation, shape complementarity, and electrostatics using a Fast Fourier Transform algorithm. A global search in the rotational and translational space without any knowledge of the binding sites was performed for all proteins except nine antibodies recognizing antigens. For these antibodies, we docked their well-characterized binding site-the complementarity-determining region defined without information of the antigen-to the entire surface of the antigen. For 24 systems, we were able to find near-native ligand orientations (interface C(alpha) root mean square deviation less than 2.5 A from the crystal complex) among the top 2,000 choices. For three systems, our algorithm could identify the correct complex structure unambiguously. For 13 other complexes, we either ranked a near-native structure in the top 20 or obtained 20 or more near-native structures in the top 2,000 or both. The key feature of our algorithm is the use of target functions that are highly tolerant to conformational changes upon binding. If combined with a post-processing method, our algorithm may provide a general solution to the unbound docking problem. Our program, called ZDOCK, is freely available to academic users (http://zlab.bu.edu/~rong/dock/).
CuH in a Bottle: A Convenient Reagent for Asymmetric Hydrosilylations (2005)

Bottled for freshness: [{(R)-DTBM-segphos}CuH] (see formula; DTBM=3,5-di-tert-butyl-4-methoxy) generated in situ represents the first reported copper hydride reagent that can be stored and used over time without loss of activity in several types of asymmetric hydrosilylation reactions.
Regulated Nuclear Localization of the Varicella‐Zoster Virus Major Regulatory Protein, IE62 (1998)

The major transcriptional regulatory protein encoded by varicella-zoster virus (VZV), IE62, accumulates within the nucleus of transfected and VZV-infected cells. Data are presented to show that nuclear localization of IE62 is dependent upon charged amino acids mapping to residues 677-685 of the 1310 residue protein. Furthermore, coexpression of VZV open-reading frame (ORF) 66 with IE62 results in the accumulation of cytoplasmic forms of IE62, suggesting that the ORF 66 protein can override the IE62 nuclear localization signal. Consistent with this, cytoplasmic forms of IE62 were detected in VZV-infected cells at late but not immediate early times after infection. The ORF 66 protein, a putative protein kinase, did not affect nuclear localization of other proteins, and IE62 nuclear localization was not affected by coexpression with VZV ORF 47, another putative kinase. These results suggest that IE62 nuclear functions may be specifically regulated by the VZV ORF 66 protein.
GRIK4/KA1 protein expression in human brain and correlation with bipolar disorder risk variant status (2011)

The kainate class of ionotropic glutamate receptors is involved in the regulation of neuronal transmission and synaptic plasticity. Previously we reported that a deletion variant within the gene GRIK4, which encodes the KA1 kainate receptor subunit, was associated with a reduced risk of bipolar disorder and increased GRIK4 mRNA abundance. Using a high resolution immunohistochemistry technique, we characterized KA1 protein localization in human brain and performed a genotype-protein expression correlation study. KA1 was expressed in specific populations of neuronal cells in the cerebellum and all layers of the frontal and parahippocampal cortices. In the hippocampus, strong KA1 expression was observed in the stratum pyramidale and stratum lucidum of CA3 and CA2, in cell processes in CA1, in the neuropil of the CA4 region, in polymorphic cells including mossy fiber neurons in the hilus, and dentate gyrus (DG) granule cells. Mean counts of KA1 positive DG granule cells, hippocampal CA3 pyramidal cells, and layer 1 of the frontal cortex were significantly increased in subjects with the deletion allele (P = 0.0005, 0.018, and 0.0058, respectively) compared to subjects homozygous for the insertion. Neuronal expression levels in all regions quantified were higher in the deletion group. These results support our hypothesis that the deletion allele affords protection against bipolar disorder through increased KA1 protein abundance in neuronal cells. Biological mechanisms which may contribute to this protective effect include KA1 involvement in adult hippocampal neurogenesis, HPA axis activation, or plasticity processes affecting neuronal circuitry.
Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase (1995)

The level of genetic variation of human immunodeficiency virus type 1 (HIV-1), a member of the lentivirus genus of the Retroviridae family, is high relative to that of retroviruses in some other genera. The high error rates of purified HIV-1 reverse transcriptase in cell-free systems suggest an explanation for this high genetic variation. To test whether the in vivo rate of mutation during reverse transcription of HIV-1 is as high as predicted by cell-free studies, and therefore higher than that rates of mutation of retroviruses in other genera, we developed an in vivo assay for detecting forward mutations in HIV-1, using the lacZ alpha peptide gene as a reporter for mutations. This system allows the rates and types of mutations that occur during a single cycle of replication to be studied. We found that the forward mutation rate for HIV-1 was 3.4 x 10(-5) mutations per bp per cycle. Base substitution mutations predominated; G-to-A transition mutations were the most common base substitution. The in vivo mutation rates for HIV-1 are three and seven times higher than those previously reported for two other retroviruses, spleen necrosis virus and bovine leukemia virus, respectively. In contrast, our calculated in vivo mutation rate for HIV-1 is about 20-fold lower than the error rate of purified HIV-1 reverse transcriptase, with the same target sequence. This finding indicates that HIV-1 reverse transcription in vivo is not as error prone as predicted from the fidelity of purified reverse transcriptase in cell-free studies. Our data suggest that the fidelity of purified HIV-1 reverse transcriptase may not accurately reflect the level of genetic variation in a natural infection.
Clearance Rate and Effect on Renal Function of Stroma-Free Hemoglobin Following Renal Ischemia (1972)

RELIHAN, MICHAEL M.D.; OLSEN, RAYMOND E. D.V.M., Ph.D.; LITWIN, MARTIN S. M.D. Author Information
AMP Deaminase Inhibitors. 2. Initial Discovery of a Non-Nucleotide Transition-State Inhibitor Series (2000)

A series of N3-substituted coformycin aglycon analogues are described that inhibit adenosine 5'-monophosphate deaminase (AMPDA) or adenosine deaminase (ADA). The key steps involved in the preparation of these compounds are (1) treating the sodium salt of 6, 7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one (4) with an alkyl bromide or an alkyl mesylate to generate the N3-alkylated compound 5 and (2) reducing 5 with NaBH(4). Selective inhibition of AMPDA was realized when the N3-substituent contained a carboxylic acid moiety. For example, compound 7b which has a hexanoic acid side chain inhibited AMPDA with a K(i) = 4.2 microM and ADA with a K(i) = 280 microM. Substitution of large lipophilic groups alpha to the carboxylate provided a moderate potency increase with maintained selectivity as exemplified by the alpha-benzyl analogue 7j (AMPDA K(i) = 0.41 microM and ADA K(i) > 1000 microM). These compounds, as well as others described in this series of papers, are the first compounds suitable for testing whether selective inhibition of AMPDA can protect tissue from ischemic damage by increasing local adenosine concentrations at the site of injury and/or by minimizing adenylate loss.
Drillstring Design Optimization for High-Angle Wells (1989)

ABSTRACT Drill string design for high angle wells should be optimized for all required functions of the drill string. Optimum drill string design requires a thorough review of well design and objectives in order to rank in importance the demands of a drill string. Practical considerations for drill string design for high angle wells and systematic approaches to the design process are presented.
PTH elevates inositol polyphosphates and diacylglycerol in a rat osteoblast-like cell line (1988)

Parathyroid hormone (PTH)-stimulated signal transduction through mechanisms alternate to adenosine 3',5'-cyclic monophosphate (cAMP) production were studied in UMR 106-01 cells, a cell line with an osteoblastic phenotype. PTH produced transient, dose-related increases in cytosolic calcium [( Ca2+]i), inositol trisphosphates, and diacylglycerol (DAG). Both inositol 1,4,5-trisphosphate (Ins-1,4,5P3) and inositol 1,3,4-trisphosphate (Ins-1,3,4P3) production were rapidly stimulated by PTH. Consistent with the production of Ins-1,3,4P3, rapid stimulation of late eluting inositol tetrakisphosphate was observed. The effects on the inositol phosphates were induced rapidly, consistent with roles as signals for changes in [Ca2+]i. In saponin-permeabilized UMR 106-01 cells, Ins-1,4,5P3 stimulated 45Ca release from a nonmitochondrial intracellular pool. Thus the hypothesis that PTH-stimulated Ins-1,4,5P3 production initiates Ca2+ release and contributes to transient elevations of [Ca2+]i is supported. Pretreatment of UMR 106-01 cells with pertussis toxin had no effect on PTH stimulation of inositol phosphates. Pertussis toxin reduced PTH-stimulated elevations of [Ca2+]i, but cAMP analogues had an even greater effect than pertussis toxin. These data suggest that stimulation of cAMP production during PTH stimulation may negatively affect production of rises in [Ca2+]i during PTH stimulation. The inactivation of the inhibitory G protein of adenylate cyclase by pertussis toxin could explain its action similar to cAMP analogues. Cyclic nucleotides diminish the effects of PTH on [Ca2+]i, probably interacting on a biochemical step subsequent to or independent of Ins-1,4,5P3 release.