gebhart/patrepeval huggingface dataset:
scFv multimers of the anti-neuraminidase antibody NC10: length of the linker between VH and VL domains dictates precisely the transition between diabodies and triabodies (1999)

Single-chain Fv antibody fragments (scFvs) incorporate a polypeptide linker to tether the VH and VL domains together. An scFv molecule with a linker 5-12 residues long cannot fold into a functional Fv domain and instead associates with a second scFv molecule to form a bivalent dimer (diabody). Direct ligation of VH and VL domains further restricts association and forces three scFv molecules to associate into a trivalent trimer (triabody). We have defined the effect of linker length on scFv association by constructing a series of scFvs from anti-neuraminidase antibody NC10 in which the linker varied from one to four glycine residues. NC10 scFv molecules containing linkers of three and four residues showed a strong preference for dimer formation (diabodies), whereas a linker length of one or two glycine residues prevented the formation of diabodies and directed scFv association into trimers (triabodies). The data suggest a relatively strict transition from dimer (diabody) to trimer (triabody) upon reduction of the linker length from three to two glycine residues. Modelling studies are consistent with three residues as the minimum linker length compatible with diabody formation. Electron microscope images of complexes formed between the NC10 scFv multimers and an anti-idiotype Fab' showed that the dimer was bivalent for antigen binding and the trimer was trivalent.
N-acetylaspartylglutamate activates cyclic AMP-coupled metabotropic glutamate receptors in cerebellar astrocytes (1998)

N-Acetylaspartylglutamate (NAAG) is the most prevalent peptide in the mammalian nervous system. NAAG meets the traditional criteria of a neurotransmitter, including localization in synaptic vesicles, depolarization-induced release, low potency activation of some N-methyl-D-aspartate receptors, and highly selective activation of a cAMP-coupled metabotropic glutamate receptor (mGluR) with potency approaching that of glutamate. The peptide is present in cultured cortical glia in high concentration and is hydrolyzed by cell surface peptidase activity. In the present work, we tested the hypothesis that NAAG selectively activates a subclass of metabotropic receptors on cultured rat cerebellar glia, primarily astrocytes. These glial cells express mRNA for mGluR subtypes 1, 3, 4, 5, 6, 7, and 8. We were not able to detect message for mGluR2 in these cells using the reverse transcriptase-polymerase chain reaction. Cerebellar glia responded to NAAG, glutamate, and trans-ACPD with a decrease in forskolin-stimulated cAMP formation. AP4, an agonist of the group III receptors mGluR4, mGluR6, mGluR7, and mGluR8, had little or no effect on stimulated cAMP levels. Treatment with low micromolar NAAG significantly increased uptake of radioactive thymidine by cultured astrocytes through activation of metabotropic glutamate receptors. Antagonists of group II mGluRs prevented the decrease in cAMP and the increase in uptake of thymidine by NAAG. Cultured cerebellar astrocytes expressed 20 pmol NAAG per mg protein, a value that is at least 30-fold lower than that expressed by mixed glial cultures prepared from mouse cortex. We conclude that cerebellar astrocytes respond to NAAG via the mGluR3 receptor and that the peptide may selectively activate this receptor subtype in astrocytes following release from neurons or glia.
Up‐regulation of hippocampal glutamate transport during chronic treatment with sodium valproate (2001)

Excessive glutamatergic neurotransmission has been implicated in some neurodegenerative disorders. It would be of value to know whether glutamate transport, which terminates the glutamate signal, can be up-regulated pharmacologically. Here we show that chronic treatment of rats with the anti-epileptic drug sodium valproate (200 mg or 400 mg/kg bodyweight, twice per day for 90 days) leads to a dose-dependent increase in hippocampal glutamate uptake capacity as measured by uptake of [(3)H]glutamate into proteoliposomes. The level of glutamate transporters EAAT1 and EAAT2 in hippocampus also increased dose-dependently. No effect of sodium valproate on glutamate transport was seen in frontal or parietal cortices or in cerebellum. The hippocampal levels of glial fibrillary acidic protein and glutamine synthetase were unaffected by valproate treatment, whereas the levels of synapsin I and phosphate-activated glutaminase were reduced by valproate treatment, suggesting that the increase in glutamate transporters was not caused by astrocytosis or increased synaptogenesis. A direct effect of sodium valproate on the glutamate transporters could be excluded. The results show that hippocampal glutamate transport is an accessible target for pharmacological intervention and that sodium valproate may have a role in the treatment of excitotoxic states in the hippocampus.
Creating Periodic Three-Dimensional Structures by Multibeam Interference of Visible Laser (2002)

Face-centered cubiclike lattices with periods of 0.9 μm were created by interference of multiple visible laser beams on photosensitive epoxy. Defect-free porous structures were obtained in an area larger than 1 mm within seconds of exposure. The initiating system includes a xanthene dye as a photosensitizer and a diaryliodionium salt as a photoacid generator. An appropriate concentration of triethylamine is added as a neutralizer to eliminate nonzero background caused by partly nonparallel polarization of multiple beams.
The Properties of Human Fibrinogen Coagulum—Preliminary Report (1943)

No AccessJournal of Urology1 Apr 1943The Properties of Human Fibrinogen Coagulum—Preliminary Report1 John E. Dees, and Hilda Fox John E. DeesJohn E. Dees More articles by this author , and Hilda FoxHilda Fox More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)70580-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1943 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited BySherer J (2018) Cryoprecipitate Coagulum PyelolithotomyJournal of Urology, VOL. 123, NO. 5, (621-624), Online publication date: 1-May-1980.Marshall S (2018) Commercial Fibrinogen, Autogenous Plasma, Whole Blood and Cryoprecipitate for Coagulum Pyelolithotomy: A Comparative StudyJournal of Urology, VOL. 119, NO. 3, (310-311), Online publication date: 1-Mar-1978.Dees J (2018) Coagulum PyelolithotomyJournal of Urology, VOL. 73, NO. 3, (445-450), Online publication date: 1-Mar-1955.Moore T and Sweetser T (2018) Coagulum Pelviolithotomy; An Improved TechniqueJournal of Urology, VOL. 67, NO. 5, (579-584), Online publication date: 1-May-1952. Volume 49Issue 4April 1943Page: 503-511 Advertisement Copyright & Permissions© 1943 by The American Urological Association Education and Research, Inc.MetricsAuthor Information John E. Dees More articles by this author Hilda Fox More articles by this author Expand All Advertisement Loading ...
Chemical Sensing Using Sol-Gel Derived Planar Waveguides and Indicator Phases (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical Sensing Using Sol-Gel Derived Planar Waveguides and Indicator PhasesLin. Yang and S. Scott. SaavedraCite this: Anal. Chem. 1995, 67, 8, 1307–1314Publication Date (Print):April 15, 1995Publication History Published online1 May 2002Published inissue 15 April 1995https://pubs.acs.org/doi/10.1021/ac00104a002https://doi.org/10.1021/ac00104a002research-articleACS PublicationsRequest reuse permissionsArticle Views414Altmetric-Citations117LEARN 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
Asparagine Depletion Potentiates the Cytotoxic Effect of Chemotherapy against Brain Tumors (2014)

Findings have potential impact for providing adjuvant means to enhance brain tumor chemotherapy.
Long‐term effect of interferon alpha‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus‐related cirrhosis (2006)

We assessed the efficacy of interferon (IFN) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b (3 or 5 MU thrice weekly) and oral ribavirin (1,000-1,200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow-up period of 37 (12-63) months, HCC developed in 11 patients with non-SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan-Meier method also showed that old age (>or=60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Cox's regression analysis, non-SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.
Reformulated tenofovir gel for use as a dual compartment microbicide (2012)

Reducing the osmolality of the tenofovir gel resulted in improved epithelial integrity, which suggests better safety upon rectal use. The improved gel safety did not compromise drug release or anti-HIV-1 activity. These data support the use of this gel as a dual compartment microbicide.
A new approach to quantifying abundances of materials in multispectral images (2002)

The authors tested a new technique for mapping abundances of materials using multispectral images which they call Foreground-Background Analysis (FBA). The method maximizes the contrast between sets of foreground and background spectra while simultaneously minimizing the variability within these sets. Spectral variability introduces errors in the fractions (abundance) of endmembers when simple mixture models (2-5 endmembers) are applied to complex natural surfaces. FBA was tested using CCD-camera measurements of known materials in the laboratory and included variations in illumination geometry. Lower abundance uncertainties were obtained using FBA than with simple mixture models.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Studies of electron-transfer properties of salicylate hydroxylase from Pseudomonas cepacia and effects of salicylate and benzoate binding (1988)

The pH dependence of the redox behavior of salicylate hydroxylase from Pseudomonas cepacia as well as the effects of salicylate, benzoate, and chloride binding is described. At pH 7.6 in 0.02 M potassium phosphate buffer E1(0')(EFl ox/EFl.-) is -0.150 V and E2(0')(EFl.-/EFl red H-) is -0.040 V versus the standard hydrogen electrode (SHE). A maximum of 5% of FAD anion semiquinone is thermodynamically stabilized under these conditions. However, in coulometric and dithionite titrations more semiquinone is kinetically formed, indicating slow transfer of the second electron. The potential/pH dependence is consistent with a two-electron, one-proton transfer. Upon salicylate binding the midpoint potential is shifted 0.020 V negative from -0.094 to -0.114 V vs SHE at pH 7.6. A maximum of 7% of the neutral semiquinone is stabilized both in potentiometric and coulometric titrations. This small potential shift indicates that the substrate is bound nearly to the same extent to all three oxidation states of the enzyme. It is clear that the substrate binding does not make the reduction of the flavin thermodynamically more favorable. In contrast to salicylate, the potential shift caused by the effector, benzoate, is much more significant. (A maximum potential shift of -0.07 V is calculated.) Benzoate binds most tightly to the oxidized form and is least tightly bound to the two-electron-reduced form of the enzyme. For the reduction of the free enzyme the transfer of the second electron or the transfer of the proton is rate limiting, as is shown by the kinetic formation of the anionic semiquinone.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification and characterization of cell wall-cell division gene clusters in pathogenic gram-positive cocci (1997)

Clusters of peptidoglycan biosynthesis and cell division genes (DCW genes) were identified and sequenced in two gram-positive cocci, Staphylococcus aureus and Enterococcus faecalis. The results indicated some similarities in organization compared with previously reported bacterial DCW gene clusters, including the presence of penicillin-binding proteins at the left ends and ftsA and ftsZ cell division genes at the right ends of the clusters. However, there were also some important differences, including the absence of several genes, the comparative sizes of the div1B and ftsQ genes, and a wide range of amino acid sequence similarities when the genes of the gram-positive cocci were translated and compared to bacterial homologs.
The Brain's Default Mode Network (2015)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its discovery was an unexpected consequence of brain-imaging studies first performed with positron emission tomography in which various novel, attention-demanding, and non-self-referential tasks were compared with quiet repose either with eyes closed or with simple visual fixation. The default mode network consistently decreases its activity when compared with activity during these relaxed nontask states. The discovery of the default mode network reignited a longstanding interest in the significance of the brain's ongoing or intrinsic activity. Presently, studies of the brain's intrinsic activity, popularly referred to as resting-state studies, have come to play a major role in studies of the human brain in health and disease. The brain's default mode network plays a central role in this work.
Sequences within the conserved cyclin box of human cyclin A are sufficient for binding to and activation of cdc2 kinase. (1993)

Cyclins are pivotal in the coordinate regulation of the cell cycle. By physical association, they are able to activate at least one of the cyclin-dependent kinases, cdc2. How this association between the catalytic moiety and cyclins leads to subsequent activation of the kinase remains unclear. In this report, we describe experiments to investigate this event at a physical level. Our approach was to map the regions required on the cyclin A molecule for interaction with cdc2. We have mapped the contact regions to two small noncontiguous stretches of amino acids, residues 189 to 241 and 275 to 320, both located within the conserved cyclin box domain of the protein. We have further shown that this region not only represents a contact site for cdc2 but apparently represents an intact functional domain with respect to cdc2 activation. This region alone is sufficient to stimulate maturation when injected into immature Xenopus laevis oocytes. This observation implies that events leading to the activation of cdc2 kinase can be mediated through small regions of the cyclin molecule that are located in the cyclin box. These regions contain some of the most highly conserved residues found between all the cyclin members so far identified. This suggests that the cyclin family members may have conserved a similar mechanism to bind and activate cyclin-dependent kinases.
Why don't we measure seismic signatures? (1991)

Abstract There are three related problems with our approach to signature deconvolution. First, there is a confusion among geophysicists about the basis of the convolutional model itself, which leads to doubts about the value of measurements of the source signature. Secondly, it is not generally recognized that statistical methods of wavelet estimation are unreliable. Thirdly, many explorationists are unaware that it is practical in many cases to make meaningful measurements of the source signature.The convolutional model of the reflection seismogram applies only for a point source, and is the convolution of the source signature with the impulse response of the earth, of Green's function, which contains all possible arrivals, including reflections, refractions, multiples and diffractions. Stabilized deconvolution of the data with a known band-limited signature is straightforward. The signature can be obtained by independent measurements, as described in the literature. The recovery of the elastic layer parameters from the band-limited impulse response of the earth, after removal of the source signature by deconvolution, is the problem of inversion, and is not discussed in this paper.The theory of wave propagation does not support the commonly held view that a reflection seismogram can be regarded as a convolution of a wavelet with the series of normal-incidence primary reflection coefficients. This is true of both prestack and poststack data. Poststack seismic inversion schemes, based on this model, that use well logs to extract the wavelet for predicting lateral variations in lithology away from the wells, rely on the wavelet to be laterally invariant. Even if there is perfect shot-to-shot repeatability, this model must yield a different wavelet at every well, and therefore the extracted wavelet does vary laterally. These schemes are therefore self-contradictory and, in the worst cases, their results are likely to be worthless.Published methods for determining the source signature from measurements for the land vibrator, marine seismic source arrays, and dynamite on land are summarized. None of these methods appears to be in use. A Vibroseis example is included to show that the signal transmitted into the ground by the vibrators does not closely resemble the predetermined sweep, as is normally assumed. The transmitted signal could be determined in processing from measurements of the vibrator behaviour that are made in production for vibrator control, if only these measurements were recorded. Normally they are not. Instead of using measurements to determine the signature, the exploration industry relies on wavelet estimation methods that depend on both a model and statistical assumptions that have no theoretical justification.
Nucleotide sequence of the colicin B activity gene cba: consensus pentapeptide among TonB-dependent colicins and receptors (1987)

Colicin B formed by Escherichia coli kills sensitive bacteria by dissipating the membrane potential through channel formation. The nucleotide sequence of the structural gene (cba) which encodes colicin B and of the upstream region was determined. A polypeptide consisting of 511 amino acids was deduced from the open reading frame. The active colicin had a molecular weight of 54,742. The carboxy-terminal amino acid sequence showed striking homology to the corresponding channel-forming region of colicin A. Of 216 amino acids, 57% were identical and an additional 19% were homologous. In this part 66% of the nucleotides were identical in the colicin A and B genes. This region contained a sequence of 48 hydrophobic amino acids. Sequence homology to the other channel-forming colicins, E1 and I, was less pronounced. A homologous pentapeptide was detected in colicins B, M, and I whose uptake required TonB protein function. The same consensus sequence was found in all outer membrane proteins involved in the TonB-dependent uptake of iron siderophores and of vitamin B12. Upstream of cba a sequence comprising 294 nucleotides was identical to the sequence upstream of the structural gene of colicin E1, with the exception of 43 single-nucleotide replacements, additions, or deletions. Apparently, the region upstream of colicins B and E1 and the channel-forming sequences of colicins A and B have a common origin.
The use of diaminopurine to investigate structural properties of nucleic acids and molecular recognition between ligands and DNA (1998)

2,6-Diaminopurine (DAP) is an analogue of adenine which can be converted to nucleotides that serve as substrates for incorporation into nucleic acids by polymerases in place of (d)AMP. It pairs with thymidine (or uracil), engaging in three hydrogen bonds of the Watson-Crick type. The result of DAP incorporation is to add considerable stability to the double helix and to impart other structural features, such as an altered groove width and disruption of the normal spine of hydration. DNA containing DAP may or may not be recognized by restriction endonucleases; RNA containing DAP may not engage in normal splicing. The DAP.T pair affects the local flexibility of DNA and impedes the interaction with helix bending proteins. By providing a non-canonical hydrogen bond donor in the minor groove and/or blocking access to the floor of that groove it strongly affects interactions with small molecules such as antibiotics and anticancer drugs. Examples which illustrate altered recognition of nucleotide sequences in DAP-containing DNA are presented: changed sites of cutting by bleomycin, photocleavage by uranyl nitrate and footprinting with mithramycin. Using DNA in which both A-->DAP and G-->Inosine substitutions have been made it is possible to assess precisely the role of the purine 2-amino group in ligand-DNA recognition.
Clinical Implications of Gene Dosage and Gene Expression Patterns in Diploid Breast Carcinoma (2010)

Taken together, our findings suggest that the dysregulated genes identified here are critical for breast cancer initiation and progression, and could be used as novel therapeutic targets for drug development to complement classical clinicopathologic features.