gebhart/patrepeval huggingface dataset:
Bacteriophage selection against a plasmid-encoded sex apparatus leads to the loss of antibiotic-resistance plasmids (2011)

Antibiotic-resistance genes are often carried by conjugative plasmids, which spread within and between bacterial species. It has long been recognized that some viruses of bacteria (bacteriophage; phage) have evolved to infect and kill plasmid-harbouring cells. This raises a question: can phages cause the loss of plasmid-associated antibiotic resistance by selecting for plasmid-free bacteria, or can bacteria or plasmids evolve resistance to phages in other ways? Here, we show that multiple antibiotic-resistance genes containing plasmids are stably maintained in both Escherichia coli and Salmonella enterica in the absence of phages, while plasmid-dependent phage PRD1 causes a dramatic reduction in the frequency of antibiotic-resistant bacteria. The loss of antibiotic resistance in cells initially harbouring RP4 plasmid was shown to result from evolution of phage resistance where bacterial cells expelled their plasmid (and hence the suitable receptor for phages). Phages also selected for a low frequency of plasmid-containing, phage-resistant bacteria, presumably as a result of modification of the plasmid-encoded receptor. However, these double-resistant mutants had a growth cost compared with phage-resistant but antibiotic-susceptible mutants and were unable to conjugate. These results suggest that bacteriophages could play a significant role in restricting the spread of plasmid-encoded antibiotic resistance.
Charged and Hydrophobic Surfaces on the A Chain of Shiga-Like Toxin 1 Recognize the C-Terminal Domain of Ribosomal Stalk Proteins (2012)

Shiga-like toxins are ribosome-inactivating proteins (RIP) produced by pathogenic E. coli strains that are responsible for hemorrhagic colitis and hemolytic uremic syndrome. The catalytic A(1) chain of Shiga-like toxin 1 (SLT-1), a representative RIP, first docks onto a conserved peptide SD[D/E]DMGFGLFD located at the C-terminus of all three eukaryotic ribosomal stalk proteins and halts protein synthesis through the depurination of an adenine base in the sarcin-ricin loop of 28S rRNA. Here, we report that the A(1) chain of SLT-1 rapidly binds to and dissociates from the C-terminal peptide with a monomeric dissociation constant of 13 µM. An alanine scan performed on the conserved peptide revealed that the SLT-1 A(1) chain interacts with the anionic tripeptide DDD and the hydrophobic tetrapeptide motif FGLF within its sequence. Based on these 2 peptide motifs, SLT-1 A(1) variants were generated that displayed decreased affinities for the stalk protein C-terminus and also correlated with reduced ribosome-inactivating activities in relation to the wild-type A(1) chain. The toxin-peptide interaction and subsequent toxicity were shown to be mediated by cationic and hydrophobic docking surfaces on the SLT-1 catalytic domain. These docking surfaces are located on the opposite face of the catalytic cleft and suggest that the docking of the A(1) chain to SDDDMGFGLFD may reorient its catalytic domain to face its RNA substrate. More importantly, both the delineated A(1) chain ribosomal docking surfaces and the ribosomal peptide itself represent a target and a scaffold, respectively, for the design of generic inhibitors to block the action of RIPs.
Tissue-Specific Splicing and Functions of the Drosophila Transcription Factor Grainyhead (1997)

Grainyhead belongs to a recently identified group of transcription factors which share a 250-amino-acid domain required for binding to DNA and a carboxy-terminal dimerization domain. The activities of Grainyhead and other members of the family appear to be modulated so that they can participate in different developmental processes. We have examined the structure and function of mRNAs from the Drosophila grainyhead gene and demonstrated that alternate splicing is responsible for generating a neuroblast-specific isoform of the protein. A mutation which abolishes this isoform results in pupal and adult lethality. Reporter genes containing different Grainyhead binding sites exhibit tissue-specific patterns of expression that correlate with the Grainyhead isoforms, suggesting that the alternate splicing serves to alter the repertoire of target genes controlled in the neuroblasts.
Integration Challenges for Low Dielectric Constant Materials (2001)

The more advanced an integrated circuit becomes, the more stringent are the demands for certain properties of a dielectric or insulating material. In addition, it is essential that the layer maintains its specific electrical, physical and chemical properties after incorporation in the device structure and during subsequent processing. Due to temperature budget constraints and the accelerated decrease of feature sizes below 0.25 μm one can no longer rely on traditional choices but has to search for alternatives, both for low and high permittivity replacements. In this article we survey currently used low dielectric constant materials and future trends for microelectronic applications. Modern semiconductor circuit interconnection techniques now focus on the integration of copper-based thin film metallization and low dielectric constant (low-κ) insulating thin films using a strategy known as damascene processing. The objective of this approach is the optimization of information processing speed in the circuit by minimizing resistive and capacitive delays resulting from the electrical field interactions between adjacent conductors.
Compiling data parallel programs to message passing programs for massively parallel MIMD systems (2002)

The currently dominant message-passing programming paradigm for MIMD systems is difficult to use and error prone. One approach that avoids explicit communication is the data-parallel programming model. This model stands for a single thread of control, global name space, and loosely synchronous parallel computation. It is easy to use and data-parallel programs usually scale very well. Based on the experiences of an existing compilation system for data-parallel Fortran programs it is shown how to design such a compilation system and which optimization techniques are required to make data-parallel programs competitive with their handwritten counterparts using message-passing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Low bias electron cyclotron resonance plasma etching of GaN, AlN, and InN (1994)

Highly anisotropic dry etching of GaN, AlN, and InN was obtained at low dc self-bias in electron cyclotron resonance Cl2/H2 or CH4/H2/Ar discharges. The Cl2/H2 chemistry produces etch rates of ∼1100 Å min−1 for AlN and ∼700 Å min−1 for GaN at −150 V and 1 mTorr for high microwave powers (1000 W), while the CH4/H2/Ar mixture etches InN at ∼350 Å min−1 at −250 V under similar conditions. The surfaces of the III-V nitrides remain stoichiometric without requiring a wet-etch cleanup. The microwave enhancement of the discharges produces these practical etch rates, the highest reported for the nitrides, while keeping the dc bias relatively low. These low pressure, low bias conditions are well suited to pattern transfer processes in device fabrication.
Construction and Screening of Antigen Targeted Immune Yeast Surface Display Antibody Libraries (2008)

These protocols describe a yeast surface display-based process for the rapid selection of antibodies from immunized mice, eliminating the need for creating and screening hybridoma fusions. A yeast surface display library of single-chain antibody fragments (scFvs) is created from antigen-binding B cells from the splenocytes of immunized mice. The antigen targeted library is then screened for antigen specific scFv by magnetic-activated cell sorting (MACS) and fluorescence-activated cell sorting (FACS). Library construction and screening can be accomplished in as little as 2 weeks, resulting in a panel of scFvs specific for the target antigen.
An immunoglobulin-like antigen in human cell lines and sera of cancer patients. (1992)

Different sera from cancer patients were tested for the presence of C1-GMA, an antigen described by us, which was shared by HeLa-like human cell lines and gastric mucosa. Using the immunodiffusion test, dot-blotting and electrophoresis followed by immunoblotting, we failed to reveal the antigen in the sera of patients. However, an Ig-like 56-60 kD antigen was found in the sera of patients with ovary and stomach carcinoma and lymphoid tumors. The Ig-like antigen was also revealed in 2 out of 5 tested human cell lines of non-leukocyte origin (HEp-2 and E16-B).
Fluorescent neoglycolipids (2000)

A second generation of lipid-linked oligosaccharide probes, fluorescent neoglycolipids, has been designed and synthesized for ligand discovery within highly complex mixtures of oligosaccharides. The aminolipid 1,2-dihexadecyl-sn-glycero-3-phosphoethanolamine (DHPE), which has been used extensively to generate neoglycolipids for biological and structural studies, has been modified to incorporate a fluorescent label, anthracene. This new lipid reagent, N-aminoacetyl-N-(9-anthracenylmethyl)-1, 2-dihexadecyl-sn-glycero-3-phosphoethanolamine (ADHP), synthesized from anthracenaldehyde and DHPE gives an intense fluorescence under UV light. Fluorescent neoglycolipids derived from a variety of neutral and acidic oligosaccharides by conjugation to ADHP, by reductive amination, can be detected and quantified by spectrophotometry and scanning densitometry, and resolved by TLC and HPLC with subpicomole detection. Antigenicities of the ADHP-neoglycolipids are well retained, and picomole levels can be detected using monoclonal carbohydrate sequence-specific antibodies. Among O-glycans from an ovarian cystadenoma mucin, isomeric oligosaccharide sequences, sialyl-Lea- and sialyl-Lex-active, could be resolved by HPLC as fluorescent neoglycolipids, and sequenced by liquid secondary-ion mass spectrometry. Thus the neoglycolipid technology now uniquely combines high sensitivity of immuno-detection with a comparable sensitivity of chemical detection. Principles are thus established for a streamlined technology whereby an oligosaccharide population is carried through ligand detection and ligand isolation steps, and sequence determination by mass spectrometry, enzymatic sequencing and other state-of-the-art technologies for carbohydrate analysis.
Plasma HDL Levels Highly Correlate With Cognitive Function in Exceptional Longevity (2002)

These data demonstrate that cognitive dysfunction in centenarians is associated with a progressive decline in plasma HDL concentrations. This underscores the protective effects of increased plasma HDL and its role in maintaining superior cognition in longevity.
Epac: A New cAMP-Binding Protein in Support of Glucagon-Like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic β-Cell (2004)

Recently published studies of islet cell function reveal unexpected features of glucagon-like peptide-1 (GLP-1) receptor-mediated signal transduction in the pancreatic beta-cell. Although GLP-1 is established to be a cAMP-elevating agent, these studies demonstrate that protein kinase A (PKA) is not the only cAMP-binding protein by which GLP-1 acts. Instead, an alternative cAMP signaling mechanism has been described, one in which GLP-1 activates cAMP-binding proteins designated as cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs, also known as Epac). Two variants of Epac (Epac1 and Epac2) are expressed in beta-cells, and downregulation of Epac function diminishes stimulatory effects of GLP-1 on beta-cell Ca(2+) signaling and insulin secretion. Of particular note are new reports demonstrating that Epac couples beta-cell cAMP production to the stimulation of fast Ca(2+)-dependent exocytosis. It is also reported that Epac mediates the cAMP-dependent mobilization of Ca(2+) from intracellular Ca(2+) stores. This is a process of Ca(2+)-induced Ca(2+) release (CICR), and it generates an increase of [Ca(2+)](i) that may serve as a direct stimulus for mitochondrial ATP production and secretory granule exocytosis. This article summarizes new findings concerning GLP-1 receptor-mediated signal transduction and seeks to define the relative importance of Epac and PKA to beta-cell stimulus-secretion coupling.
Enantioselective Synthesis of Janus Kinase Inhibitor INCB018424 via an Organocatalytic Aza-Michael Reaction (2009)

An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.
A Nonparametric Estimate of a Multivariate Density Function (1965)

Let $x_1, \cdots, x_n$ be independent observations on a $p$-dimensional random variable $X = (X_1, \cdots, X_p)$ with absolutely continuous distribution function $F(x_1, \cdots, x_p)$. An observation $x_i$ on $X$ is $x_i = (x_{1i}, \cdots, x_{pi})$. The problem considered here is the estimation of the probability density function $f(x_1, \cdots, x_p)$ at a point $z = (z_1, \cdots, z_p)$ where $f$ is positive and continuous. An estimator is proposed and consistency is shown. The problem of estimating a probability density function has only recently begun to receive attention in the literature. Several authors [Rosenblatt (1956), Whittle (1958), Parzen (1962), and Watson and Leadbetter (1963)] have considered estimating a univariate density function. In addition, Fix and Hodges (1951) were concerned with density estimation in connection with nonparametric discrimination. Cacoullos (1964) generalized Parzen's work to the multivariate case. The work in this paper arose out of work on the nonparametric discrimination problem.
The biosynthesis of the chromophore of phycocyanin. Pathway of reduction of biliverdin to phycocyanobilin (1989)

The later stages in the pathway of biosynthesis of phycocyanobilin, the chromophore of phycocyanin, were studied by using radiolabelled intermediates. Three possible pathways from biliverdin IX-alpha to phycocyanobilin were considered. 14C-labelled samples of key intermediates in two of the pathways, 3-vinyl-18-ethyl biliverdin IX-alpha and 3-ethyl-18-vinyl biliverdin IX-alpha, were synthesized chemically and were administered to cultures of Cyanidium caldarium that were actively synthesizing photosynthetic pigments in the light. Neither of these two compounds was apparently incorporated into the phycobiliprotein chromophore, suggesting that two of the three pathways were not operative. By elimination, the results imply that the third possible pathway, which involves phytochromobilin, the chromophore of phytochrome, represents the route for biosynthesis of phycocyanobilin. Unfortunately, since 14C-labelled phytochromobilin is not available, no direct proof of this pathway could be obtained. However, if correct, the present interpretation represents a unified pathway for biosynthesis of all plant bilins, via the intermediacy of phytochromobilin.
Characterization of a novel neuroglandular antigen (NGA) expressed on abnormal human melanocytes (1987)

Murine monoclonal antibodies (MAbs) were produced with reactivity to human malignant melanoma. Six MAbs, 3 of the IgGI (LS113, LS140, LS152) and 3 of the IgG2a (LS59, LS62, LS76) subclasses, were selected for their binding, with an identical pattern of reactivity, to a novel melanoma-associated antigen. As characterized by the enzyme-linked immunosorbent assay (ELISA), these MAbs were found to be positive on n-octyl-beta-D-glucopyranoside extracts of all 10 melanoma cell lines tested and on extracts of 22 metastatic melanoma tumors. The antibodies had minimal reaction with a panel of 14 normal adult tissue extracts. A degree of cross-reactivity was observed with 50% of 39 non-melanoma tumor extracts. The results obtained with the ELISA on cell line and tissue extracts were duplicated using the ABC method of peroxidase staining. The pattern of cross-reactivity, as demonstrated by the intense staining of paraffin-embedded and frozen tissue sections of normal, benign and malignant tissues, defines the recognized protein as a neuroglandular antigen (NGA). Immunoadsorbents made with the antibodies were used to purify the antigen shed from cultured melanomas. All 6 MAbs recognized this purified antigen while 5 other antimelanoma antibodies did not react with it. On gel electrophoresis this antigen is a highly glycosylated glycoprotein with a protein core of 21 kDa.
Interaction of cytosolic and plastidic nitrogen metabolism in plants (2002)

In angiosperms, the assimilation of ammonia resulting from nitrate reduction and from photorespiration depends on the operation of the plastidic GS/GOGAT cycle. The precursor for ammonia assimilation, 2-oxoglutarate, is synthesized in the mitochondria and in the cytosol. It is imported into the plastid by a 2-oxoglutarate/malate translocator (DiT1). In turn, the product of ammonia assimilation, glutamate, is exported from the plastids by a glutamate/malate translocator (DiT2). These transport processes link plastidic and cytosolic nitrogen metabolism and are essential for plant metabolism. DiT1 was purified to homogeneity from spinach chloroplast envelope membranes and identified as a protein with an apparent molecular mass of 45 kDa. Peptide sequences were obtained from the protein and the corresponding cDNA was cloned. The function of the DiT1 protein and its substrate specificity were confirmed by expression of the cDNA in yeast cells and functional reconstitution of the recombinant protein into liposomes. Recent advances in the molecular cloning of DiT2 and in the analysis of the in vivo function of DiT1 by antisense repression in transgenic tobacco plants will be discussed. In non-green tissues, the reducing equivalents required for glutamate formation by NADH-GOGAT are supplied by the oxidative pentose phosphate pathway. Glucose 6-phosphate, the immediate precursor of the oxidative pentose phosphate pathway is generated in the cytosol and imported into the plastids by the plastidic glucose 6-phosphate/phosphate translocator.
Allosteric inhibitors of telomerase: oligonucleotide N3'->P5' phosphoramidates (2002)

Telomerase is a ribonucleoprotein responsible for maintaining telomeres in nearly all eukaryotic cells. The enzyme is able to utilize a short segment of its RNA subunit as the template for the reverse transcription of d(TTAGGG) repeats onto the ends of human chromosomes. Transfection with telomerase was shown to confer immortality on several types of human cells. Moreover, telomerase activation appears to be one of the key events required for malignant transformation of normal cells. Inhibition of telomerase activity in transformed cells results in the cessation of cell proliferation in cultures and provides the rationale for the selection of telomerase as a target for anticancer therapy. Using oligonucleotide N3'-->P5' phosphoramidates (NPs) we have identified a region of the human telomerase RNA subunit (hTR) approximately 100 nt downstream from the template region whose structural integrity appears crucial for telomerase enzymatic activity. The oligonucleotides targeted to this segment of hTR are potent and specific inhibitors of telomerase activity in biochemical assays. Mutant telomerase, in which 3 nt of hTR were not complementary to a 15 nt NP, was found to be refractory to inhibition by that oligonucleotide. We also demonstrated that the binding of NP, oligonucleotides to this hTR allosteric site results in a marked decrease in the affinity of a telomerase substrate (single-stranded DNA primer) for the enzyme.
Magneto-optical Scattering from Multi-layer Magnetic and Dielectric Films (1965)

The problem of the scattering (reflection and transmission) of light by multi-layer magnetic and dielectric films is solved by means of 4 2 4 characteristic (transfer) matrices. The characteristic matrices are calculated for either w or k taken as gyrotropic (skew symmetric) tensors having off-diagonal elements characterized by the complex, dimensionless, parameters p and q, respectively. Solutions are given for the polar, longitudinal and transverse orientations between the magnetization, the light propagation vector and the reflecting surface. Useful general results include the similarity invariants of characteristic matrices and the precise specification of minimum-equivalent multi-layer structures. A salient feature of magneto-optical scattering is the transfer of energy from two otherwise non-interacting polarization modes, namely modes with H perpendicular or parallel to the incidence plane, respectively. The conversion efficiency (conversivity) depends on two factors: (1) ohmic loss in the magnetic film; (2) conversion matching. Ohmic loss can be reduced by placing the film on the surface of an electric mirror (tangential E = 0) in an optical standing wave. Conversion matching can be accomplished with dielectric films, somewhat analogous to the case of impedance matching. The need for the concept of conversion matching as distinct from impedance matching can be made clear by considering the general properties of a four terminal-pair (four port) network (junction), of which the magneto-optical scattering problem is an example. Such considerations show that a conversion impedance cannot be defined as a constant characterizing a given magnetic material.
Human IgG2 Antibodies against Epidermal Growth Factor Receptor Effectively Trigger Antibody-Dependent Cellular Cytotoxicity but, in Contrast to IgG1, Only by Cells of Myeloid Lineage (2009)

Ab-dependent cellular cytotoxicity (ADCC) is usually considered an important mechanism of action for immunotherapy with human IgG1 but not IgG2 Abs. The epidermal growth factor receptor (EGF-R) Ab panitumumab represents the only human IgG2 Ab approved for immunotherapy and inhibition of EGF-R signaling has been described as its principal mechanism of action. In this study, we investigated effector mechanisms of panitumumab compared with zalutumumab, an EGF-R Ab of the human IgG1 isotype. Notably, panitumumab was as effective as zalutumumab in recruiting ADCC by myeloid effector cells (i.e., neutrophils and monocytes) in contrast to NK cell-mediated ADCC, which was only induced by the IgG1 Ab. Neutrophil-mediated tumor cell killing could be stimulated by myeloid growth factors and was triggered via FcgammaRIIa. Panitumumab-mediated ADCC was significantly affected by the functional FcgammaRIIa-R131H polymorphism and was induced more effectively by neutrophils from FcgammaRIIa-131H homozygous donors than from -131R individuals. This polymorphism did not affect neutrophil ADCC induced by the IgG1 Ab zalutumumab. The in vivo activity of both Abs was assessed in two animal models: a high-dose model, in which signaling inhibition is a dominant mechanism of action, and a low-dose model, in which effector cell recruitment plays a prominent role. Zalutumumab was more effective than panitumumab in the high-dose model, reflecting its stronger ability to induce EGF-R downmodulation and growth inhibition. In the low-dose model, zalutumumab and panitumumab similarly prevented tumor growth. Thus, our results identify myeloid cell-mediated ADCC as a potent and additional mechanism of action for EGF-R-directed immunotherapy.