gebhart/patrepeval huggingface dataset:
Antineoplastic agents 320: synthesis of a practical pancratistatin prodrug. (1995)

Owing to its sparingly soluble properties, the potential anticancer drug pancratistatin (1) resisted conventional drug formulation procedures and the synthesis of a water-soluble prodrug became necessary. That important objective for further pre-clinical development was met by devising a route to a disodium phosphate derivative (5). The key step in the synthesis of the phenolic phosphate was phosphorylation of 1,2,3,4-tetraacetoxy-pancratistatin (2) with dibenzyloxy(N,N-diisopropylamido)-phosphine. Subsequent oxidation with m-chloroperbenzoic acid afforded phosphate 4a. Hydrogenolysis of the benzyl esters followed by base-catalysed hydrolysis of the acetate groups led to the water-soluble prodrug 5 in high yield.
Methods and Statistics for Combining Motif Match Scores (1998)

Position-specific scoring matrices are useful for representing and searching for protein sequence motifs. A sequence family can often be described by a group of one or more motifs, and an effective search must combine the scores for matching a sequence to each of the motifs in the group. We describe three methods for combining match scores and estimating the statistical significance of the combined scores and evaluate the search quality (classification accuracy) and the accuracy of the estimate of statistical significance of each. The three methods are: 1) sum of scores, 2) sum of reduced variates, 3) product of score p-values. We show that method 3) is superior to the other two methods in both regards, and that combining motif scores indeed gives better search accuracy. The MAST sequence homology search algorithm utilizing the product of p-values scoring method is available for interactive use and downloading at URL http:/(/)www.sdsc.edu/MEME.
Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). (1994)

Alzheimer's disease is characterized by the presence of senile plaques comprised primarily of deposits of the beta-amyloid protein (A beta) derived from larger amyloid precursor proteins (APP). We have identified a cDNA that encodes a 751-amino acid APP-like protein (designated APLP2) from the mouse that, with exception of the A beta region, is highly homologous to APP. In situ hybridization and quantitative polymerase chain reaction reveal that APLP2 and APP mRNA are expressed in similar, if not identical, neuronal populations and at similar levels. APLP2 appears to mature through the same unusual secretory/cleavage pathway as APP. Furthermore, widely utilized antibodies generated against non-overlapping epitopes of APP do not discriminate between APP and APLP2. Although APLP2 cannot give rise to A beta, its near identity to APP outside the A beta domain confounds the interpretation of previous immunocytochemical and biochemical characterizations of APP biosynthesis and metabolism.
Purification and characterization of human H-ras proteins expressed in Escherichia coli. (1985)

The full-length normal and T24 mutant human H-ras proteins and two truncated derivatives of the T24 mutant were expressed efficiently in Escherichia coli. The proteins accumulated to 1 to 5% of total cellular protein, and each was specifically recognized by anti-ras monoclonal antibodies. The two full-length proteins as well as a carboxyl-terminal truncated derivative (deleted for 23 amino acid residues) were soluble upon cell lysis and were purified to 90% homogeneity without the use of denaturants. In contrast, an amino-terminal truncated ras derivative (deleted for 22 amino acid residues) required treatment with urea for its solubilization. The guanine nucleotide binding activity of these four proteins was assessed by a combination of ligand binding on proteins blots, immunoprecipitation, and standard filter binding procedures. The full-length proteins showed similar binding kinetics and a stoichiometry approaching 1 mol of GTP bound per mol of protein. The showed similar binding kinetics and a stoichiometry approaching 1 mol of GTP bound per mol of protein. The carboxyl-terminal truncated protein also bound GTP, but to a reduced extent, whereas the amino-terminal truncated protein did not have binding activity. Apparently, the carboxyl-terminal domain of ras, although important for transforming function, does not play a critical role in GTP binding.
Microlumbar discectomy: a conservative surgical approach to the virgin herniated lumbar disc. (1978)

Microlumbar discectomy is an extremely conservative microsurgical procedure for the treatment of the virgin herniated lumbar disc. The technique has been utilized in 530 patients over a 5 1/2-year period, and features no laminectomy or curettement of the disc space. Preservation of extradural fat and blunt perforation of the annulus fibrosus, rather than scalpel incision, appear to minimize reherniations and adhesion reactions. Operating time has averaged 37 minutes and postoperative stay 3.1 days during the past 36 months (46% of these were compensation cases). In this series, a satisfactory result is defined as those patients who remain economically productive and physically comfortable at the time of followup. Satisfactory results were achieved in 91% of patients after one procedure.
The CGTCA sequence motif is essential for biological activity of the vasoactive intestinal peptide gene cAMP-regulated enhancer. (1988)

cAMP-regulated transcription of the human vasoactive intestinal peptide gene is dependent upon a 17-base-pair DNA element located 70 base pairs upstream from the transcriptional initiation site. This element is similar to sequences in other genes known to be regulated by cAMP and to sequences in several viral enhancers. We have demonstrated that the vasoactive intestinal peptide regulatory element is an enhancer that depends upon the integrity of two CGTCA sequence motifs for biological activity. Mutations in either of the CGTCA motifs diminish the ability of the element to respond to cAMP. Enhancers containing the CGTCA motif from the somatostatin and adenovirus genes compete for binding of nuclear proteins from C6 glioma and PC12 cells to the vasoactive intestinal peptide enhancer, suggesting that CGTCA-containing enhancers interact with similar transacting factors.
Vampire Bat Salivary Plasminogen Activator (Desmoteplase) Inhibits Tissue-Type Plasminogen Activator-Induced Potentiation of Excitotoxic Injury (2005)

Background and Purpose— In contrast to tissue-type plasminogen activator (tPA), vampire bat ( Desmodus rotundus ) salivary plasminogen activator (desmoteplase [DSPA]) does not promote excitotoxic injury when injected directly into the brain. We have compared the excitotoxic effects of intravenously delivered tPA and DSPA and determined whether DSPA can antagonize the neurotoxic and calcium enhancing effects of tPA. Methods— The brain striatal region of wild-type c57 Black 6 mice was stereotaxically injected with N-methyl- d -Aspartate (NMDA); 24 hour later, mice received an intravenous injection of tPA or DSPA (10 mg/kg) and lesion size was assessed after 24 hours. Cell death and calcium mobilization studies were performed using cultures of primary murine cortical neurons. Results— NMDA-mediated injury was increased after intravenous administration of tPA, whereas no additional toxicity was seen after administration of DSPA. Unlike DSPA, tPA enhanced NMDA-induced cell death and the NMDA-mediated increase in intracellular calcium levels in vitro. Moreover, the enhancing effects of tPA were blocked by DSPA. Conclusions— Intravenous administration of tPA promotes excitotoxic injury, raising the possibility that leakage of tPA from the vasculature into the parenchyma contributes to brain damage. The lack of such toxicity by DSPA further encourages its use as a thrombolytic agent in the treatment of ischemic stroke.
Specific Binding of a Synthetic Peptide Derived from an Antibody Complementarity Determining Region to Phosphatidylserine (1995)

We have established a series of monoclonal antibodies that bind to phosphatidylserine (PS). One mAb, PS4A7, showed a strict specificity for PS and distinguished the stereospecific configuration of its serine moiety. We determined the amino acid sequences of the heavy and light chain variable regions of PS4A7, and examined the reactivity of the synthetic peptides corresponding to the complementarity determining region (CDR) of the mAb with phospholipids. We found that a 12-amino acid synthetic peptide corresponding to the third CDR of the heavy chain (amino acid residues 93-102, referred to as CDR3-H) bound specifically to PS. Although the affinity of the peptide to PS was markedly lower, the peptide was shown to bind to 1,2-diacyl-sn-glycero-3-phospho-L-serine (PS), but not to 1,2-diacyl-sn-glycero-3-phospho-D-serine, showing a similar specificity to that of PS4A7. The specific binding of the CDR3-H peptide to PS was confirmed by ELISA and TLC-immunostaining assay. The interaction between the CDR3-H peptide and water-soluble PS-derivatives was investigated by inhibition of the ELISA. PS effectively inhibited the binding and phosphoserine showed a weak but significant inhibition, but no appreciable inhibition was observed with serine. These observations suggest that the CDR3-H peptide plays a major role in the interaction of PS4A7 with the phosphoserine residue of the PS molecule.
RNA-guided DNA insertion with CRISPR-associated transposases (2019)

CRISPR-Cas nucleases are powerful tools for manipulating nucleic acids; however, targeted insertion of DNA remains a challenge, as it requires host cell repair machinery. Here we characterize a CRISPR-associated transposase from cyanobacteria <i>Scytonema hofmanni</i> (ShCAST) that consists of Tn7-like transposase subunits and the type V-K CRISPR effector (Cas12k). ShCAST catalyzes RNA-guided DNA transposition by unidirectionally inserting segments of DNA 60 to 66 base pairs downstream of the protospacer. ShCAST integrates DNA into targeted sites in the <i>Escherichia coli</i> genome with frequencies of up to 80% without positive selection. This work expands our understanding of the functional diversity of CRISPR-Cas systems and establishes a paradigm for precision DNA insertion.
Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation (1991)

Two genes encode Fc gamma RIII (CD16), a low affinity FcR for IgG. CD16-I is expressed as a phosphatidylinositol glycan-anchored membrane glycoprotein on neutrophils, whereas CD16-II is a transmembrane-linked glycoprotein on NK cells. Membrane anchoring is determined by codon 203. Site-directed mutation of codon 203 and transient expression of these cDNA in COS-7 cells indicated that Phe, Ile, Leu, and Val permit transmembrane expression, whereas Ser, Thr, Tyr, Asn, Gly, Ala, Asp and Lys enable phosphatidylinositol-glycan attachment. Thus, the involvement of amino acid 203 in membrane anchoring cannot be explained simply on the basis of size, charge, or polarity of the amino acid side groups at this site. Efficient expression of CD16-II in COS-7 cells requires co-transfection with either CD3 zeta or Fc epsilon RI-gamma. Truncation of the cytoplasmic segment of CD16 failed to affect association with CD3 zeta. CD3 zeta and Fc epsilon RI-gamma with truncated cytoplasmic segments were also able to facilitate membrane expression of CD16-II, implicating the transmembrane segments as the interaction site between CD16-II and CD3 zeta or Fc epsilon RI-gamma. Prior studies have suggested that the acidic residue in the CD3 zeta transmembrane segment may be important for the association of CD3 zeta complexes. Although site-directed mutation of CD3 zeta-Asp36 to Glu, Leu, or Val retained the ability to permit membrane expression of CD16-II, quantitatively the wild-type CD3 zeta-Asp36 provided optimal levels of expression, consistent with conservation of this amino acid in mouse and human CD3 zeta.
Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice (2016)

Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer's disease (AD). Cell culture and animal studies showed that tau fibrils can undergo cell-to-cell transmission and seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated in models overexpressing tau. In this study, we found that intracerebral inoculation of tau fibrils purified from AD brains (AD-tau), but not synthetic tau fibrils, resulted in the formation of abundant tau inclusions in anatomically connected brain regions in nontransgenic mice. Recombinant human tau seeded by AD-tau revealed unique conformational features that are distinct from synthetic tau fibrils, which could underlie the differential potency in seeding physiological levels of tau to aggregate. Therefore, our study establishes a mouse model of sporadic tauopathies and points to important differences between tau fibrils that are generated artificially and authentic ones that develop in AD brains.
Significant correlations between severe fatty liver and risk factors for metabolic syndrome (2006)

The presence of severe fatty liver by US correlated significantly with the prevalence and degree of hypertension, abnormal glucose and triglyceride metabolism. Patients with severe fatty liver could be at an increased risk of atherosclerotic cardiovascular disease and should be screened regularly for metabolic disorders. The physician may also evaluate ALT and hepatic fat content by US in patients with metabolic syndrome. Evaluating the severity of fatty liver by US may be useful because it correlates with the status of hyperinsulinemia, the risks of developing cardiovascular disease, and the threshold for oxidative stress.
Extracting phosphor‐scattered photons to improve white LED efficiency (2005)

Abstract White light‐emitting diode (LED) luminous efficacy must improve significantly if LEDs are to become useful for general lighting. Phosphors commonly used in white LEDs backscatter more than half of the down‐converted light, of which a significant portion is eventually lost within the package, thus reducing the overall efficacy. This letter describes an experi‐mental study that shows by placing the phosphor away from the die, the backscattered photons can be extracted and the ef‐ficacy can be significantly increased. At low currents, the lu‐minous efficacy exceeded 80 lm/W. (© 2005 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Chabot: retrieval from a relational database of images (1995)

Selecting from a large, expanding collection of images requires carefully chosen search criteria. We present an approach that integrates a relational database retrieval system with a color analysis technique. The Chabot project was initiated at our university to study storage and retrieval of a vast collection of digitized images. These images are from the State of California Department of Water Resources. The goal was to integrate a relational database retrieval system with content analysis techniques that would give our querying system a better method for handling images. Our simple color analysis method, if used in conjunction with other search criteria, improves our ability to retrieve images efficiently. The best result is obtained when text-based search criteria are combined with content-based criteria and when a coarse granularity is used for content analysis.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein. (1989)

The principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) is located in the external envelope protein, gp120, and has previously been mapped to a 24-amino acid-long sequence (denoted RP135). We show here that deletion of this sequence renders the envelope unable to elicit neutralizing antibodies. In addition, using synthetic peptide fragments of RP135, we have mapped the neutralizing determinant to 8 amino acids and found that a peptide of this size elicits neutralizing antibodies. This sequence contains a central Gly-Pro-Gly that is generally conserved between different HIV-1 isolates and is flanked by amino acids that differ from isolate to isolate. Antibodies elicited by peptides from one isolate do not neutralize two different isolates, and a hybrid peptide, consisting of amino acid sequences from two isolates, elicits neutralizing antibodies to both isolates. By using a mixture of peptides of this domain or a mixture of such hybrid peptides the type-specificity of the neutralizing antibody response to this determinant can perhaps be overcome.
The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function (1997)

We have recently shown that the adenovirus type 5 E4orf6 protein interacts with the cellular tumor suppressor protein p53 and blocks p53 transcriptional functions. Here we report that the E4orf6 protein can promote focus formation of primary rodent epithelial cells in cooperation with adenovirus E1A and E1A plus E1B proteins. The E4orf6 protein can also inhibit p53-mediated suppression of E1A plus E1B-19kDa-induced focus formation. Mutant analysis of the E4orf6 protein demonstrates that these activities correlate with the ability of the adenovirus protein to relieve transcriptional repression mediated by the carboxyl-terminal region of p53 in transient transfection assays. We further demonstrate that expression of wild-type E4orf6 correlates with a dramatic reduction of p53 steady-state levels in transformed rat cells. Our data demonstrate that adenovirus type 5 encodes two different proteins, E1B-55kDa and E4orf6, that bind to p53 and contribute to transformation by modulating p53 transcriptional functions.
Multimodal Compact Bilinear Pooling for Visual Question Answering and Visual Grounding (2016)

Modeling textual or visual information with vector representations trained from large language or visual datasets has been successfully explored in recent years. However, tasks such as visual question answering require combining these vector representations with each other. Approaches to multimodal pooling include element-wise product or sum, as well as concatenation of the visual and textual representations. We hypothesize that these methods are not as expressive as an outer product of the visual and textual vectors. As the outer product is typically infeasible due to its high dimensionality, we instead propose utilizing Multimodal Compact Bilinear pooling (MCB) to efficiently and expressively combine multimodal features. We extensively evaluate MCB on the visual question answering and grounding tasks. We consistently show the benefit of MCB over ablations without MCB. For visual question answering, we present an architecture which uses MCB twice, once for predicting attention over spatial features and again to combine the attended representation with the question representation. This model outperforms the state-of-the-art on the Visual7W dataset and the VQA challenge.
Multifold enhancement of the thermoelectric figure of merit in p-type BaBiTe3 by pressure tuning (2001)

As in the combinatorial approach to materials discovery, pressure tuning allows the phase space of interaction parameters that determine materials’ properties to be explored more rapidly than by traditional means. Both the thermoelectric power and electrical conductivity of BaBiTe3 are found to increase upon compression. As a result there is a dramatic increase in the dimensionless thermoelectric figure of merit ZT from ∼0.1 to ∼0.8. We suggest a mechanism for the enhancement involving an electronic topological transition. Such transitions can be induced both by means of pressure tuning and alloying, offering a potential route to reproducing the pressure induced improved behavior reported here by chemical means.
Human T cell-dependent B cell differentiation induced by staphylococcal superantigens. (1994)

Microbial superantigens (SAgs), by virtue of their binding to TCR V beta elements on T cells and to class II MHC molecules on accessory cells (AC), trigger T cell activation. Although anti-CD3 mAb (which also trigger T cell activation via surface CD3/TCR) can readily induce T cell-dependent B cell differentiation in unmanipulated PBMC cultures, induction of Ig production in SAg-stimulated cultures has usually required special manipulation of the T cells, such as irradiating them or treating them with mitomycin C. We now demonstrate that eight different staphylococcal SAgs, typically at concentrations 10- to 100-fold lower than those required for proliferation, can each trigger unmanipulated peripheral blood and tonsil T cells to drive polyclonal B cell differentiation. Such SAg-induced T cell-dependent generation of Ig-secreting cells (IgSC) requires T cells and B cells only and occurs in the absence of monocytes as long as there are adequate numbers of B cells to serve as (DR+) AC. Physical contact among T cells, responder B cells, and AC (when different from the responder B cells) is required. The fusion protein CTLA4Ig inhibits SAg-induced IgSC generation in a dose-dependent fashion, whereas a control fusion protein has no such effect. In contrast, CTLA4Ig has, at best, only modest effects on SAg-induced T cell proliferation, indicating that CD28 (CTLA4)/B7 (B7-like) interactions play a more prominent role in SAg-induced IgSC generation than in SAg-induced T cell proliferation. These results establish SAg-induced T cell-dependent B cell differentiation as a useful model for T cell/B cell interactions, inasmuch as no other cell types are necessary for successful B cell differentiation; these results also demonstrate the importance of CD28 (CTLA4)/B7 (B7-like)-dependent mechanisms in this process.
Codon Compression Algorithms for Saturation Mutagenesis (2014)

Saturation mutagenesis is employed in protein engineering and genome-editing efforts to generate libraries that span amino acid design space. Traditionally, this is accomplished by using degenerate/compressed codons such as NNK (N = A/C/G/T, K = G/T), which covers all amino acids and one stop codon. These solutions suffer from two types of redundancy: (a) different codons for the same amino acid lead to bias, and (b) wild type amino acid is included within the library. These redundancies increase library size and downstream screening efforts. Here, we present a dynamic approach to compress codons for any desired list of amino acids, taking into account codon usage. This results in a unique codon collection for every amino acid to be mutated, with the desired redundancy level. Finally, we demonstrate that this approach can be used to design precise oligo libraries amendable to recombineering and CRISPR-based genome editing to obtain a diverse population with high efficiency.
An Attempt to Construct the Stroma of Cornea Using Primary Cultured Corneal Cells (2007)

The number of patients currently awaiting corneal transplantation has resulted in the need to develop an artificial corneal replacement. In this study, we aimed to construct the corneal stroma using non-transformed corneal cells and a perfusion cell culture method. Corneal cells isolated from chicken embryos or rabbit and were embedded in the alkaline solubilized collagen gels crosslinked by TSG (Pentaerythritol polyethyleneglycol ether tetrasuccinimidyl glutarate). During culture, the majority of cells migrated from inside of the gel. The chicken and rabbit cells changed their morphology and stratified structures were constructed within the gels. These microstructures were similar to the natural corneal tissue. TEM analysis was performed to confirm the nano-microstructure of the constructs. Contrary to expectation, the cornea-like nanostructure of collagen fibrils was not observed within the gels. Further study including for example, such as the addition of dynamic stress or co-culture with endothelial cells, are therefore required in order to produce artificial constructs with the same superstructure as natural corneal tissue.