gebhart/patrepeval huggingface dataset:
Reducing Mass Degeneracy in SAR by MS by Stable Isotopic Labeling (2001)

Mass spectrometry (MS) promises to be an invaluable tool for functional genomics, by supporting low-cost, high-throughput experiments. However, large-scale MS faces the potential problem of mass degeneracy--indistinguishable masses for multiple biopolymer fragments (e.g. from a limited proteolytic digest). This paper studies the tasks of planning and interpreting MS experiments that use selective isotopic labeling, thereby substantially reducing potential mass degeneracy. Our algorithms support an experimental-computational protocol called Structure-Activity Relation by Mass Spectrometry (SAR by MS), for elucidating the function of protein-DNA and protein-protein complexes. SAR by MS enzymatically cleaves a crosslinked complex and analyzes the resulting mass spectrum for mass peaks of hypothesized fragments. Depending on binding mode, some cleavage sites will be shielded; the absence of anticipated peaks implicates corresponding fragments as either part of the interaction region or inaccessible due to conformational change upon binding. Thus different mass spectra provide evidence for different structure-activity relations. We address combinatorial and algorithmic questions in the areas of data analysis (constraining binding mode based on mass signature) and experiment planning (determining an isotopic labeling strategy to reduce mass degeneracy and aid data analysis). We explore the computational complexity of these problems, obtaining upper and lower bounds. We report experimental results from implementations of our algorithms.
Concise Review: Epigenetic Mechanisms Contribute to Pluripotency and Cell Lineage Determination of Embryonic Stem Cells (2006)

Epigenetic mechanisms, such as histone modifications and DNA methylation, have been shown to play a key role in the regulation of gene transcription. Results of recent studies indicate that a novel "bivalent" chromatin structure marks key developmental genes in embryonic stem cells (ESCs), wherein a number of untranscribed lineage-control genes, such as Sox1, Nkx2-2, Msx1, Irx3, and Pax3, are epigenetically modified with a unique combination of activating and repressive histone modifications that prime them for potential activation (or repression) upon cell lineage induction and differentiation. However, results of these studies also showed that a subset of lineage-control genes, such as Myf5 and Mash1, were not marked by these histone modifications, suggesting that distinct epigenetic mechanisms might exist for lineage-control genes in ESCs. In this review article, we summarize evidence regarding possible mechanisms that control these unique histone modifications at lineage-control gene loci in ESCs and consider their possible contribution to ESC pluripotency. In addition, we propose a novel "histone modification pulsing" model wherein individual pluripotent stem cells within the inner cell mass of blastocysts undergo transient asynchronous histone modifications at these developmental gene loci, thereby conferring differential responsiveness to environmental cues and morphogenic gradients important for cell lineage determination. Finally, we consider how these rapid histone modification exchanges become progressively more stable as ESCs undergo differentiation and maturation into specialized cell lineages.
RD Optimized Coding for Motion Vector Predictor Selection (2008)

The H.264/MPEG4-AVC video coding standard has achieved a higher coding efficiency compared to its predecessors. The significant bitrate reduction is mainly obtained by efficient motion compensation tools, as variable block sizes, multiple reference frames, 1/4-pel motion accuracy and powerful prediction modes (e.g., SKIP and DIRECT). These tools have contributed to an increased proportion of the motion information in the total bit- stream. To achieve the performance required by the future ITU-T challenge, namely to provide a codec with 50% bitrate reduction compared to the current H.264, the reduction of this motion information cost is essential. This paper proposes a competing framework for better motion vector coding and SKIP mode. The predictors for the SKIP mode and the motion vector predictors are optimally selected by a rate-distortion criterion. These methods take advantage from the use of the spatial and the temporal redundancies in the motion vector fields, where the simple spatial median usually fails. An adaptation of the temporal predictors according to the temporal distances between motion vector fields is also described for multiple reference frames and B-slices options. These two combined schemes lead to a systematic bitrate saving on Baseline and High profile, compared to an H.264/MPEG4-AVC standard codec, which reaches up to 45%.
Molecular cloning and structure of the human interleukin-5 gene. (1987)

We isolated the chromosomal gene for human interleukin-5 (IL-5) from human genomic libraries using a cloned human IL-5 cDNA as probe. Nucleotide sequence determination of the IL-5 gene and its flanking regions showed that the gene consisted of four exons and three introns. TATA-like and CAAT-like sequences reside 26 and 73 base pairs, respectively, upstream of the transcription initiation site identified by S1 mapping analysis. The 5'-flanking region of the IL-5 gene has sequences homologous with those of the corresponding regions of the genes for human granulocyte/macrophage colony-stimulating factor, murine IL-4, human interferon-gamma, and human IL-2. The intron-exon organization and location of the cysteine residue suggest that the IL-5 gene is phylogenetically related to the genes for the granulocyte/macrophage colony-stimulating factor, IL-4, and IL-2, although their amino acid sequences are not significantly conserved.
Recombinant Bone Morphogenetic Proteins: Novel Substances for Enhancing Bone Healing (1995)

Bone morphogenetic proteins (BMPs) are differentiative factors whose principal function is to induce transformation of undifferentiated mesenchymal cells into chondroblasts and osteoblasts in a dose-dependent manner. Bone morphogenetic proteins have been isolated postnatally in mammals from bone matrix, periosteal cells, mesenchymal cells of marrow stroma, tooth analagen, and cells of osteosarcoma and chondrosarcoma. Distribution in additional embryonic tissues implies a broader organogenic function. Bone morphogenetic proteins are the only differentiative factors able to singularly induce de novo bone formation in vitro and in vivo. Recombinant DNA technology allows their production in large and highly purified quantities. The BMPs' osteoinductive ability has been shown with a variety of carriers including collagens and polymers at heterotopic and orthotopic sites in a wide range of species. They are presently being readied for clinical use as alternatives to bone grafts. Other potential applications include use as pulp capping agents, promoters of implant osteointegration and soft tissue reunion with bone, treatments for nonadaptive bone disease, and implants for use with mitotically expanded skeletal stem cell populations. Errors in the genetic coding of BMPs may manifest as clinical disease entities.
Caco-2 cell permeability assays to measure drug absorption (2005)

Caco-2 cells are a human colon epithelial cancer cell line used as a model of human intestinal absorption of drugs and other compounds. When cultured as a monolayer, Caco-2 cells differentiate to form tight junctions between cells to serve as a model of paracellular movement of compounds across the monolayer. In addition, Caco-2 cells express transporter proteins, efflux proteins, and Phase II conjugation enzymes to model a variety of transcellular pathways as well as metabolic transformation of test substances. In many respects, the Caco-2 cell monolayer mimics the human intestinal epithelium. One of the functional differences between normal cells and Caco-2 cells is the lack of expression of the cytochrome P450 isozymes and in particular, CYP3A4, which is normally expressed at high levels in the intestine. However, Caco-2 cells may be induced to express higher levels of CYP3A4 by treatment with vitamin D3. Caco-2 cell monolayers are usually cultured on semipermeable plastic supports that may be fitted into the wells of multi-well culture plates. Test compounds are then added to either the apical or basolateral sides of the monolayer. After incubation for various lengths of time, aliquots of the buffer in opposite chambers are removed for the determination of the concentration of test compounds and the computation of the rates of permeability for each compound (called the apparent permeability coefficients). Although radiolabelled compounds were used in the original Caco-2 cells monolayer assays, radiolabelled compounds have been replaced in most laboratories by the use of liquid chromatography-mass spectrometry (LC-MS) and LC-tandem mass spectrometry (LC-MS-MS). Mass spectrometry not only eliminates the need for radiolabelled compounds, but permits the simultaneous measurement of multiple compounds. The measurement of multiple compounds per assay reduces the number of incubations that need to be carried out, thereby increasing the throughput of the experiments. Furthermore, LC-MS and LC-MS-MS add another dimension to Caco-2 assays by facilitating the investigation of the metabolism of compounds by Caco-2 cells.
Role of the cag‐pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis (2011)

Helicobacter pylori is a very successful human-specific bacterium worldwide. Infections of the stomach with this pathogen can induce pathologies, including chronic gastritis, peptic ulcers and even gastric cancer. Highly virulent H. pylori strains encode the cytotoxin-associated gene (cag)-pathogenicity island, which expresses a type IV secretion system (T4SS). This T4SS forms a syringe-like pilus structure for the injection of virulence factors such as the CagA effector protein into host target cells. This is achieved by a number of T4SS proteins, including CagI, CagL, CagY and CagA, which by itself binds the host cell integrin member β(1) followed by delivery of CagA across the host cell membrane. A role of CagA interaction with phosphatidylserine has also been shown to be important for the injection process. After delivery, CagA becomes phosphorylated by oncogenic tyrosine kinases and mimics a host cell factor for the activation or inactivation of some specific intracellular signalling pathways. We review recent progress aiming to characterize the CagA-dependent and CagA-independent signalling capabilities of the T4SS, which include the induction of membrane dynamics, disruption of cell-cell junctions and actin-cytoskeletal rearrangements, as well as pro-inflammatory, cell cycle-related and anti-apoptotic transcriptional responses. The contribution of these signalling pathways to pathogenesis during H. pylori infections is discussed.
Synthesis and Properties of New Fluorescein-Labeled Oligonucleotides (1995)

Abstract 2,4-Dinitroaniline is an efficient intramolecular fluorescence-quencher for fluorescein - labeled oligonucleotides and interacts with the heterocyclic bases on duplex formation. Consequently, intramolecular fluorescence quenching is disturbed in double labeled oligonucleotides of this type, and fluorescein shows strong fluorescence in a duplex form. There is a substential increase of the fluorescence-quantum yield when the marker and quencher is attached to a single guanosine residue. Two kinds of doubly labeled oligonucleotides have been synthesized, using the NPE/NPEOC strategy.
Skin Concentrations of Topically Applied Substances in Reconstructed Human Epidermis (RHE) Compared with Human Skin Using in vivo Confocal Raman Microscopy (2015)

Detailed knowledge about the skin concentration of topically applied substances is important to understand their local pharmacological activity. In particular since in vitro models of reconstructed human epidermis are increasingly used as models for diseased skin. In general, diffusion cell experiments are performed to determine the diffusion flux of test substances through either skin models or excised skin both from humans and animals. Local concentrations of the test substances within the skin are then calculated applying diffusion laws and suitable boundary conditions. In this study we used a direct approach to reveal the local concentrations of test substances within skin using confocal Raman microscopy. This non-invasive method can also be applied in vivo and therefore we directly compared in vivo concentrations with those obtained from commercially available reconstructed human epidermis (RHE). Hydrophilic and lipophilic test substances with log Pow from -0.07 to 5.91 were topically applied on human skin in vivo and RHE from SkinEthic was used as the commercial skin model. Local concentration profiles in the stratum corneum (SC) showed substantial differences between the RHE model and the in vivo situation. Differences between RHE models and human skin in vivo were also observed in their molecular composition, in particular in terms of their water profile, lipid content and the presence of natural moisturizing factor (NMF). Confocal Raman is shown to be a powerful non-invasive method for qualitative and quantitative comparative studies between RHE models and human skin in vivo. This method can also be applied to validate RHE models for future use in clinical studies.
Flow cytometric analysis of neural stem cells in the developing and adult mouse brain (2002)

Despite recent progress in the neural stem cell biology, their cellular characteristics have not been described well. We investigated various characteristics of neural stem cells (NSCs) in vivo during CNS development, using FACS to identify the NSCs. We first examined stage-dependent changes in the physical parameters, using forward scatter (FSC) and side scatter (SSC) profiles, of NSCs from the developing striatum, where they appear to be active throughout the life of mammals. NSCs were divided into several fractions according to their FSC/SSC profile. With development, their number decreased in the FSC(high) fractions but increased in the FSC(low)/SSC(high) fraction, whereas NSCs were significantly concentrated in the fraction containing the largest cells (about 20 microm in diameter) at any stage, which were mostly the cells with the highest nestin-enhancer activity. Furthermore, we demonstrated that, at all stages examined, the "side population" (SP), defined as the Hoechst 33342 low/negative fraction, which is known to be a stem cell-enriched population in bone marrow, was also enriched for Notch1-positive immature neural cells (about 60%) from the developing striatum. However, these immature SP cells were not detected in the large-cell fraction, however, but were concentrated instead in the FSC(low/mid) fractions. FACS analysis showed that SP cells from adults were included to some extent in the CD24(low)/PNA(low) fraction, where NSCs were greatly concentrated. Collectively, the characteristics of NSCs were not uniform and changed developmentally.
Image analysis and three‐dimensional modelling of pores in soil aggregates (1991)

SUMMARY Three cross‐sections of soil aggregates (2–5 mm diameter) were digitized at 5 μm resolution from montages (× 100) of scanning electron micrographs to produce binary images representing the soil pores and soil matrix. A three‐dimensional random Boolean process was chosen as a model of the soil pores and matrix. The soil matrix was simulated by randomly positioned, overlapping spheres with radii drawn from an exponential distribution. Simulation of a 1 mm cube of one soil aggregate showed that all but 0.1 % of the pore space was connected to the exterior, although only 50% appeared to be connected to the exterior in a cross‐sectional image. Pore spaces able to accommodate different sizes of microorganisms were also investigated. For example, a protozoan with a cross‐sectional diameter of 20 μm could be accommodated in 17% of the pores in a 1 mm 3 soil cube, although only 11 % of the pores would be accessible to those protozoa on the exterior of the cube.
Stem and Progenitor Cells: Origins, Phenotypes, Lineage Commitments, and Transdifferentiations (2001)

Multipotent stem cells are clonal cells that self-renew as well as differentiate to regenerate adult tissues. Whereas stem cells and their fates are known by unique genetic marker studies, the fate and function of these cells are best studied by their prospective isolation. This review is about the properties of various highly purified tissue-specific multipotent stem cells and purified oligolineage progenitors. We contend that unless the stem or progenitor cells in question have been purified to near homogeneity, one cannot know whether their generation of expected (or unexpected) progeny is a property of a known cell type. It is interesting that in the hematopoietic system the only long-term self-renewing cells in the stem and progenitors pool are the hematopoietic stem cells. This fact is discussed in the context of normal and leukemic hematopoiesis.
Formation and morphology of InAs/GaAs heterointerfaces (1992)

The synthesis of perfect InAs/GaAs heterostructures by conventional solid-source molecular-beam epitaxy is achieved by a growth approach that employs the modulation of growth temperature during the interface formation. Details of the evolution of the growth front during interface formation are probed by in situ reflection high-energy electron diffraction. The nucleation of InAs on GaAs occurs layer by layer for the first two monolayers. At this stage, the InAs film wets the underlying GaAs; i.e., a continuous coverage of the substrate is thermodynamically preferred. Thus, allowing the growth front to relax towards the equilibrium state minimizes the step density on the surface. During overgrowth of the InAs film with GaAs, a fraction of the deposited In segregates on the growing surface. This In floating layer is desorbed prior to overgrowth by a heating cycle, which prevents its incorporation into the GaAs capping layer. The resulting exceptional degree of crystalline perfection of the InAs/GaAs heterostructures is confirmed by double-crystal x-ray diffraction patterns of multilayer structures which are essentially indistinguishable from the theoretical pattern predicted by the dynamical diffraction theory. The atomic configuration at the InAs/GaAs interfaces is studied by high-resolution electron microscopy. Extensive image simulations provide reliable quantitative information on layer thickness and interface configuration. Lattice images of InAs films having thickness in excess of two monolayers reveal that both interfaces are structurally equivalent. Fluctuations of the interfaces are restricted to monoatomic steps. The atomic-scale morphology of these highly strained interfaces compares favorably with that of GaAs/${\mathrm{Al}}_{\mathit{x}}$${\mathrm{Ga}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$As heterointerfaces. The crucial point for obtaining this structural perfection is the flashoff of the In floating layer prior to GaAs overgrowth.
Genome‐wide array‐based comparative genomic hybridization of ocular marginal zone B cell lymphoma: Comparison with pulmonary and nodal marginal zone B cell lymphoma (2007)

The genetic changes in marginal zone B cell lymphomas (MZBCL) vary according to the anatomical region. This study aimed to investigate genomic aberrations in ocular MZBCL and to compare them with those of tumors from other anatomical sites. The study population comprised 24 cases of primary ocular MZBCL, 11 pulmonary MZBCL, and seven nodal MZBCL. For array CGH, fresh tumor tissues were analyzed with a genome-wide scanning array containing 2,304 BAC/PAC clones which cover the whole human genome at a resolution of 1.3 Mb. FISH analysis for MALT1 gene alteration was performed for ocular and nodal MZBCL and RT-PCR for the detection of API2-MALT1 transcripts was performed for pulmonary MZBCL. The recurrent genomic alterations in ocular MZBCL were losses of chromosome bands 6q23.3 (9/24, 38%), 7q36.3 (2/24, 8%), and 13q34 (2/24, 8%), and gains of chromosomes 3 (9/24, 38%), and 15 (4/24, 16%), and chromosome arms 18q (4/24, 16%), and 6p (2/24, 8%). The t(11;18)(q21;q21) was not detected. The genomic alterations of pulmonary MZBCL included recurrent loss of 18q21 (2/11, 19%). A t(11;18)(q21;q21) fusion transcript was detected in five out of eight cases (63%). Nodal MZBCL showed neither recurrent genome alterations nor any change in MALT1 gene copy number. In conclusion, the array CGH profile of ocular MZBCL is distinct from those of pulmonary and nodal MZBCL. Deletion of chromosome band 6q23.3 in ocular MZBCL is a novel finding and may constitute a crucial genetic alteration in the pathogenesis of ocular MZBCL.
Breast cancer stem cells revealed (2003)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Inhibition of Cytomegalovirus Late Antigens by Phosphonoformate (1979)

Phosphonoformate (PFA) at a concentration of 500 muM and higher completely inhibited the replication of cytomegalovirus (CMV) in cell culture. 50% inhibition was obtained at a concentration of muM PFA. Early nuclear CMV antigens appeared uninhibited, but the formation of nuclear inclusion bodies, late cytoplasmic antigens, Fc-receptors and CPE were all inhibited by PFA. No visible cell toxicity was noted at the PFA concentrations and exposure times used.
Metabotropic Glutamate Receptor-Mediated Cell Signaling Pathways Are Altered in a Mouse Model of Huntington's Disease (2010)

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein (Htt). Group I metabotropic glutamate receptors (mGluRs) are coupled to G(alphaq) and play an important role in neuronal survival. We have previously demonstrated that mGluRs interact with Htt. Here we used striatal neuronal primary cultures and acute striatal slices to demonstrate that mGluR-mediated signaling pathways are altered in a presymptomatic mouse model of HD (Hdh(Q111/Q111)), as compared to those of control mice (Hdh(Q20/Q20)). mGluR1/5-mediated inositol phosphate (InsP) formation is desensitized in striatal slices from Hdh(Q111/Q111) mice and this desensitization is PKC-mediated. Despite of decreased InsP formation, (S)-3,5-dihydroxylphenylglycine (DHPG)-mediated Ca(2+) release is higher in Hdh(Q111/Q111) than in Hdh(Q20/Q20) neurons. Furthermore, mGluR1/5-stimulated AKT and extracellular signal-regulated kinase (ERK) activation is altered in Hdh(Q111/Q111) mice. Basal AKT activation is higher in Hdh(Q111/Q111) neurons and this increase is mGluR5 dependent. Moreover, mGluR5 activation leads to higher levels of ERK activation in Hdh(Q111/Q111) than in Hdh(Q20/Q20) striatum. PKC inhibition not only brings Hdh(Q111/Q111) DHPG-stimulated InsP formation to Hdh(Q20/Q20) levels, but also causes an increase in neuronal cell death in Hdh(Q111/Q111) neurons. However, PKC inhibition does not modify neuronal cell death in Hdh(Q20/Q20) neurons, suggesting that PKC-mediated desensitization of mGluR1/5 in Hdh(Q111/Q111) mice might be protective in HD. Together, these data indicate that group I mGluR-mediated signaling pathways are altered in HD and that these cell signaling adaptations could be important for striatal neurons survival.
Human T cell gamma chain joining regions and T cell development. (1987)

We have cloned and sequenced two homologous J regions of the T cell gamma gene and localized one 5' of each constant region. They have been numbered J gamma 1.1 and J gamma 2.1; other J regions have been renamed in a similar manner. Southern blot analysis suggests that there is comparatively more rearrangement to these J regions in thymocytes than peripheral blood T cells. We propose that either there is gamma-chain gene rearrangement first to J gamma 1.1 or 2.1 and then to J gamma 1.3 or 2.3, or there is selected cell death of thymic T cells bearing a J gamma 1.1 or 2.1 rearrangement.