gebhart/patrepeval huggingface dataset:
Novel Insights into the Bovine Polled Phenotype and Horn Ontogenesis in Bovidae (2013)

Despite massive research efforts, the molecular etiology of bovine polledness and the developmental pathways involved in horn ontogenesis are still poorly understood. In a recent article, we provided evidence for the existence of at least two different alleles at the Polled locus and identified candidate mutations for each of them. None of these mutations was located in known coding or regulatory regions, thus adding to the complexity of understanding the molecular basis of polledness. We confirm previous results here and exhaustively identify the causative mutation for the Celtic allele (PC) and four candidate mutations for the Friesian allele (PF). We describe a previously unreported eyelash-and-eyelid phenotype associated with regular polledness, and present unique histological and gene expression data on bovine horn bud differentiation in fetuses affected by three different horn defect syndromes, as well as in wild-type controls. We propose the ectopic expression of a lincRNA in PC/p horn buds as a probable cause of horn bud agenesis. In addition, we provide evidence for an involvement of OLIG2, FOXL2 and RXFP2 in horn bud differentiation, and draw a first link between bovine, ovine and caprine Polled loci. Our results represent a first and important step in understanding the genetic pathways and key process involved in horn bud differentiation in Bovidae.
View‐dependent dynamics of articulated bodies (2008)

Abstract We propose a method for view‐dependent simplification of articulated‐body dynamics, which enables an automatic trade‐off between visual precision and computational efficiency. We begin by discussing the problem of simplifying the simulation based on visual criteria, and show that it raises a number of challenging questions. We then focus on articulated‐body dynamics simulation, and propose a semi‐predictive approach which relies on a combination of exact, a priori error metrics computations, and visibility estimations. We suggest several variants of semi‐predictive metrics based on hierarchical data structures and the use of graphics hardware, and discuss their relative merits in terms of computational efficiency and precision. Finally, we present several benchmarks and demonstrate how our view‐dependent articulated‐body dynamics method allows an animator (or a physics engine) to finely tune the visual quality and obtain potentially significant speed‐ups during interactive or off‐line simulations. Copyright © 2008 John Wiley &amp; Sons, Ltd.
Reversible, fluorescence-based optical sensor for hydrogen peroxide (2007)

The preparation and characterisation are described of a robust, reversible, hydrogen peroxide optical sensor, based on the fluorescent quenching of the dye ion-pair [Ru(bpy)(3)(2+)(Ph(4)B(-))(2)], by O(2) produced by the catalytic breakdown of H(2)O(2), utilizing the inorganic catalyst RuO(2).xH(2)O. The main feature of this system is the one-pot formulation of a coating ink that, when dried, forms an active single-layer fluorescence-based H(2)O(2) sensor, demonstrably capable of detecting H(2)O(2) over the range of 0.01 to 1 M, with a relative standard deviation of ca. 4% and a calculated lower limit of detection of 0.1 mM. These sensors are sterilisable, using dry-heat, and stable when stored over 40 days, without exhibiting any loss in sensitivity or response characteristics.
Histotoxicity of Cyanoacrylate Tissue Adhesives: A Comparative Study (1990)

Cyanoacrylate derivatives have been used as surgical adhesives for many years. Shorter-chain derivatives (methyl- and ethyl-cyanoacrylate) have proved to be histotoxic. Longer-chain derivatives (butyl- and isobutyl-cyanoacrylate) are much less histotoxic. Many surgeons continue to use ethyl-2-cyanoacrylate (Krazy Glue) despite the availability of a less toxic derivative, butyl-2-cyanoacrylate (Histoacryl). In this study, the histotoxicity and bone graft-cartilage binding ability of Krazy Glue and Histoacryl were compared. Bone grafts harvested from the anterior wall of the maxillary sinus were placed in a subcutaneous pocket and glued to auricular cartilage in the rabbit. Krazy Glue and Histoacryl were used in opposite ears, harvesting specimens at 1, 2, 4, 12, 24, and 48 weeks. The Krazy Glue-treated ears developed seromas with histologic evidence of acute inflammation, tissue necrosis, and chronic foreign body giant cell reaction. The Histoacryl-treated ears showed mild acute inflammation and mild foreign body giant cell reaction. The Krazy Glue was completely degraded within 12 months, while some Histoacryl was still present at 1 year. Histoacryl had minimal histotoxic effect and good bone graft-cartilage binding ability, whereas Krazy Glue demonstrated severe histotoxicity.
Tau Aggregates: Toxic, Inert, or Protective Species? (2008)

Alzheimer's disease brains are characterized by extracellular aggregates of the amyloid-beta peptide and intracellular neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein. The role of aggregated tau in neurodegeneration is still controversial, as evidence point to either a toxic or protective role in the disease. Here, we will first examine tau aggregation and its putative roles in Alzheimer's disease. We will then review the findings concerning different species of tau and their potential toxicity.
Real-time phase-resolved optical coherence tomography and optical Doppler tomography (2002)

We have developed a novel real-time phase-resolved optical coherence tomography (OCT) and optical Doppler tomography (ODT) system using optical Hilbert transformation. By combining circularly polarized reference and linearly polarized sample signals, in-phase and quadrature interference components are produced in separate channels and treated as the real and imaginary parts of a complex signal to obtain the phase information directly. Using a resonant scanner at an axial scanning speed of 4 kHz in the reference arm of the interferometer, both structure and blood flow velocity images with 200 axial scans can be acquired at 20 frames per second with high sensitivity and large dynamic range. Real-time videos of in vivo blood flow in the chick chorioallantoic membrane using this interferometer are presented.
Implication of Serine Residues 271, 273, and 275 in the Human Immunodeficiency Virus Type 1 Cofactor Activity of Lens Epithelium-Derived Growth Factor/p75 (2009)

Lens epithelium-derived growth factor (LEDGF)/p75 is a cellular cofactor for HIV-1 DNA integration. It is well established that the simultaneous binding of LEDGF/p75 to chromatin and to HIV-1 integrase is required for its cofactor activity. However, the exact molecular mechanism of LEDGF/p75 in HIV-1 integration is not yet completely understood. Our hypothesis is that evolutionarily conserved regions in LEDGF/p75 exposed to solvent and harboring posttranslational modifications may be involved in its HIV-1 cofactor activity. Therefore, a panel of LEDGF/p75 deletion mutants targeting these protein regions were evaluated for their HIV-1 cofactor activity, chromatin binding, integrase interaction, and integrase-to-chromatin-tethering activity by using different cellular and biochemical approaches. The deletion of amino acids 267 to 281 reduced the cofactor activity of LEDGF/p75 to levels observed for chromatin-binding-defective mutants. This region contains a serine cluster (residues 271, 273, and 275) recurrently found to be phosphorylated in both human and mouse cells. Importantly, the conversion of these Ser residues to Ala was sufficient to impair the ability of LEDGF/p75 to mediate HIV-1 DNA integration, although these mutations did not alter chromatin binding, integrase binding, or the integrase-to-chromatin-tethering capability of LEDGF/p75. These results clearly indicated that serine residues 271, 273, and 275 influence the HIV-1 cofactor activity of integrase-to-chromatin-tethering-competent LEDGF/p75.
Growth Promotion by Homocysteic Acid (1976)

Homocysteic acid, H03SCH2CH2CHNH2CO2H, promotes growth of hypophysectomized rats, assayed by observation of increased thickness of epiphyseal cartilage of the tibia and by observation of tail growth. Doses of homocysteic acid as low as 1 microgram per day for 4 days in the tibia assay and 2.5 milligrams per kilogram per day for 5 weeks in the tail assay were effective in promoting growth. Serum somatomedin activity, determined by the porcine cartilage disk assay, was also increased by homocysteic acid. These findings relate an area of sulfur amino acid metabolism to the physiological action of growth hormone, accelerated growth in homocystinuria, initiation of arteriosclerosis, and control of cellular growth.
Replication and Nested Transactions in the Eden Distributed System (1986)

Hardware redundancy in distributed systems offers the potential for increased availability and performance, but this requires software support if the full potential is to be realized. We have designed and implemented two mechanisms for such support. The first provides crash-resistant resources, replicated transparently and consistently to increase the availability of distributed data. To update multiple copies despite down nodes, we have introduced the Regeneration method used in the implementation of a replicated system directory. Regeneration restores inaccessible copies elsewhere in the network, maintains the availability of resources, and adapts to configuration changes. The second mechanism is a systell1 supporting nested transactions, which can manage the complex failure modes in a distributed system, synchronize concurrent resource access internal to applications, and facilitate safe module composition. In the tree-structured nesting, each transaction has a Transaction Manager (TM), responsible for the concurrency control and crash recovery of its subtransactions. Many concurrency control and recovery techniques can be combined in this TM Tree design framework. We chose locking and versions for the first implementation. Using Eden objects and the replicated directory, our nested transactions provide consistent concurrent access 10 location-independent, crash- resistant resources. In summary, the principal contributions of this research are the Regeneration method and the TM Tree framework. Regeneration uses the separation of hardware repair from data restoration to increase replicated data availability. TM tree composes existing techniques to derive many difficult designs for nested transaction. Both have been proven in the design and implementation of actual systems.
New Unstable Variants of Green Fluorescent Protein for Studies of Transient Gene Expression in Bacteria (1998)

Use of the green fluorescent protein (Gfp) from the jellyfish Aequorea victoria is a powerful method for nondestructive in situ monitoring, since expression of green fluorescence does not require any substrate addition. To expand the use of Gfp as a reporter protein, new variants have been constructed by the addition of short peptide sequences to the C-terminal end of intact Gfp. This rendered the Gfp susceptible to the action of indigenous housekeeping proteases, resulting in protein variants with half-lives ranging from 40 min to a few hours when synthesized in Escherichia coli and Pseudomonas putida. The new Gfp variants should be useful for in situ studies of temporal gene expression.
Predicting the Hematopoietic Response to Recombinant Human Erythropoietin (Epoetin Alfa) in the Treatment of the Anemia of Cancer (1999)

Recombinant human erythropoietin (Epoetin alfa) is effective in increasing hemoglobin concentration and hematocrit, and in significantly reducing transfusion requirements in the majority of patients with either the anemia of chronic renal failure or chemotherapy-induced anemia of cancer. Identification of factors that could enable the clinician to predict individual patient hematological responses to Epoetin alfa therapy would be of great value. Changes in levels of serum transferrin receptor protein, hemoglobin, ferritin and reticulocyte count, following a short course of Epoetin alfa therapy, were useful markers for predicting later hematopoietic responses to Epoetin alfa. In addition, recent data suggest that low baseline erythropoietin levels, in association with increases of either &gt;0.5 g/dl in hemoglobin or ≥25% in circulating levels of transferrin receptor protein after 2 weeks of Epoetin alfa therapy, are highly predictive of a response (≥2 g/dl increase in hemoglobin) to Epoetin alfa. Progress has clearly been made in the development of predictive models that can identify those patients most likely to respond to Epoetin alfa by monitoring several specific hematological parameters at baseline and early in therapy. Future studies will focus on nonhematological measures of response, such as transfusion requirement and quality of life benefit.
Structural and Quantum Chemical Studies of 8-Aryl-sulfanyl Adenine Class Hsp90 Inhibitors (2006)

Hsp90 chaperones play a critical role in modulating the activity of many cell signaling proteins and are an attractive target for anti-cancer therapeutics. We report here the structures of the water soluble 8-aryl-sulfanyl adenine class Hsp90 inhibitors, 1 (PU-H71) and 2 (PU-H64), in complex with the N-terminal domain of human Hsp90alpha. The conformation of 1 when bound to Hsp90 differs from previously reported 8-aryl adenine Hsp90 inhibitors including 3 (PU24FCl). While the binding mode for 3 places the 2'-halide of the 8-aryl group on top of the adenine ring, for 1 and 2, we show that the 2'-halide is rotated approximately 180 degrees away. This difference explains the opposing trends in Hsp90 inhibitory activity for the 2'-halo derivatives of the 3',4',5'-trimethoxy series where Cl > Br > I compared to the 4',5'-methylenedioxy series where I > Br > Cl. We also present quantum chemical calculations of 2 and its analogues that illuminate their basis for Hsp90 inhibition. The calculated conformation of 2 agreed well with the crystallographically observed conformations of 1 and 2. The predictive nature of the calculations has allowed the exploration of additional derivatives based on the 8-aryl adenine scaffold.
Receptor Tyrosine Kinase EphA5 Is a Functional Molecular Target in Human Lung Cancer (2015)

Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications.
Targeted insertion of exogenous DNA into the eukaryotic genome by the Cre recombinase. (1990)

Cre is a 38-kD protein from bacteriophage P1 that catalyzes site-specific recombination between 34-bp loxP sequences. Our previous work has shown that Cre can perform site-specific excisive recombination not only in prokaryotes, but also in eukaryotes such as yeast and cultured mammalian cells. In this work we show that intermolecular Cre-mediated recombination can specifically direct the integration of a loxP-containing circular DNA into a chromosomal loxP site, both in yeast and in mammalian cells. The resulting integrants are predominantly simple single-copy insertions. Cre-mediated recombination thus provides a simple way to direct single-copy site-specific integration of exogenous DNA into the eukaryotic genome.
Effect of Surface Composition on Electronic Structure, Stability, and Electrocatalytic Properties of Pt-Transition Metal Alloys:  Pt-Skin versus Pt-Skeleton Surfaces (2006)

The surface properties of PtM (M = Co, Ni, Fe) polycrystalline alloys are studied by utilizing Auger electron spectroscopy, low energy ion scattering spectroscopy, and ultraviolet photoemission spectroscopy. For each alloy initial surface characterization was done in an ultrahigh vacuum (UHV) system, and depending on preparation procedure it was possible to form surfaces with two different compositions. Due to surface segregation thermodynamics, annealed alloy surfaces form the outermost Pt-skin surface layer, which consists only platinum atoms, while the sputtered surfaces have the bulk ratio of alloying components. The measured valence band density of state spectra clearly shows the differences in electronic structures between Pt-skin and sputtered surfaces. Well-defined surfaces were hereafter transferred out from UHV and exposed to the acidic (electro)chemical environment. The electrochemical and post-electrochemical UHV surface characterizations revealed that Pt-skin surfaces are stable during and after immersion to an electrolyte. In contrast all sputtered surfaces formed Pt-skeleton outermost layers due to dissolution of transition metal atoms. Therefore, these three different near-surface compositions (Pt-skin, Pt-skeleton, and pure polycrystalline Pt) all having pure-Pt outermost layers are found to have different electronic structures, which originates from different arrangements of subsurface atoms of the alloying component. Modification in Pt electronic properties alters adsorption/catalytic properties of the corresponding bimetallic alloy. The most active systems for the electrochemical oxygen reduction reaction are established to be the Pt-skin near-surface composition, which also have the most shifted metallic d-band center position versus Fermi level.
Metal-Enhanced Fluorescence: Potential Applications in HTS (2003)

Metallic surfaces and particles can have dramatic effects on fluorescence, including localized excitation, increased quantum yields, increased photostability and increased distances for resonance energy transfer (RET), and directional emission. While all these effects have not yet been realized in a single system, metal-enhanced fluorescence promises to provide the next generation of high sensitivity fluorescence assays for low copy number detection of biochemical species.
The interferon‐α2b gene in Japanese patients with chronic viral hepatitis who developed antibodies after treatment with recombinant interferon‐α2a (1992)

DNA was extracted from leucocytes of 23 Japanese patients with chronic viral hepatitis who received treatment with recombinant interferon-alpha 2a (IFN-alpha 2a) and nine healthy controls, as well as eight human cell lines of Caucasian or African origin. A part of the gene encoding IFN-alpha 2 was amplified by polymerase chain reaction and the sequence of nucleotides 1-231 was determined. Interferon-alpha 2a, -alpha 2b and -alpha 2c genes were tested for in five clones each from a patient or control, or a cell line, based on adenine or guanine at nucleotide positions 68 and 101. The IFN-alpha 2b gene was detected in all 160 clones from 23 Japanese patients and nine controls, but the IFN-alpha 2a or -alpha 2c gene was not found in any. Of five cell lines derived from Caucasians, four exhibited only the IFN-alpha 2b gene, while the remaining one exhibited both IFN-alpha 2a and -alpha 2b genes. Of three cell lines derived from Africans, one each showed only the IFN-alpha 2b or -alpha 2c gene, and the remaining one both IFN-alpha 2b and -alpha 2c genes. The 23 patients with the IFN-alpha 2b gene and chronic viral hepatitis included 10 who developed antibodies against IFN after treatment with recombinant IFN-alpha 2a. These results indicated a distinct geographical distribution of the three IFN-alpha 2 genes, and suggested the use of a recombinant IFN-alpha 2 preparation in agreement with the IFN-alpha 2 gene possessed by the recipient to avoid antibody responses.
The C‐type lectin‐like domain superfamily (2005)

The superfamily of proteins containing C-type lectin-like domains (CTLDs) is a large group of extracellular Metazoan proteins with diverse functions. The CTLD structure has a characteristic double-loop ('loop-in-a-loop') stabilized by two highly conserved disulfide bridges located at the bases of the loops, as well as a set of conserved hydrophobic and polar interactions. The second loop, called the long loop region, is structurally and evolutionarily flexible, and is involved in Ca2+-dependent carbohydrate binding and interaction with other ligands. This loop is completely absent in a subset of CTLDs, which we refer to as compact CTLDs; these include the Link/PTR domain and bacterial CTLDs. CTLD-containing proteins (CTLDcps) were originally classified into seven groups based on their overall domain structure. Analyses of the superfamily representation in several completely sequenced genomes have added 10 new groups to the classification, and shown that it is applicable only to vertebrate CTLDcps; despite the abundance of CTLDcps in the invertebrate genomes studied, the domain architectures of these proteins do not match those of the vertebrate groups. Ca2+-dependent carbohydrate binding is the most common CTLD function in vertebrates, and apparently the ancestral one, as suggested by the many humoral defense CTLDcps characterized in insects and other invertebrates. However, many CTLDs have evolved to specifically recognize protein, lipid and inorganic ligands, including the vertebrate clade-specific snake venoms, and fish antifreeze and bird egg-shell proteins. Recent studies highlight the functional versatility of this protein superfamily and the CTLD scaffold, and suggest further interesting discoveries have yet to be made.
Caveolin-1, caveolae, and glioblastoma (2012)

Glioblastoma multiforme (GBM) is the most common malignant brain tumor and is characterized by high invasiveness, poor prognosis, and limited therapeutic options. Biochemical and morphological experiments have shown the presence of caveolae in glioblastoma cells. Caveolae are flask-shaped plasma membrane subdomains that play trafficking, mechanosensing, and signaling roles. Caveolin-1 is a membrane protein that participates in the formation of caveolae and binds a multitude of signaling proteins, compartmentalizing them in caveolae and often directly regulating their activity via binding to its scaffolding domain. Caveolin-1 has been proposed to behave either as a tumor suppressor or as an ongogene depending on the tumor type and progress. This review discusses the existing information on the expression and function of caveolin-1 and caveolae in GBM and the role of this organelle and its defining protein on cellular signaling, growth, and invasiveness of GBM. We further analyze the available data suggesting caveolin-1 could be a target in GBM therapy.