gebhart/patrepeval huggingface dataset:
Targeted transcriptional activation of silent oct4 pluripotency gene by combining designer TALEs and inhibition of epigenetic modifiers (2012)

Specific control of gene activity is a valuable tool to study and engineer cellular functions. Recent studies uncovered the potential of transcription activator-like effector (TALE) proteins that can be tailored to activate user-defined target genes. It remains however unclear whether and how epigenetic modifications interfere with TALE-mediated transcriptional activation. We studied the activity of five designer TALEs (dTALEs) targeting the oct4 pluripotency gene. In vitro assays showed that the five dTALEs that target distinct sites in the oct4 promoter had the expected DNA specificity and comparable affinities to their corresponding DNA targets. In contrast to their similar in vitro properties, transcriptional activation of oct4 by these distinct dTALEs varied up to 25-fold. While dTALEs efficiently upregulated transcription of the active oct4 promoter in embryonic stem cells (ESCs) they failed to activate the silenced oct4 promoter in ESC-derived neural stem cells (NSCs), indicating that as for endogenous transcription factors also dTALE activity is limited by repressive epigenetic mechanisms. We therefore targeted the activity of epigenetic modulators and found that chemical inhibition of histone deacetylases by valproic acid or DNA methyltransferases by 5-aza-2'-deoxycytidine facilitated dTALE-mediated activation of the epigenetically silenced oct4 promoter in NSCs. Notably, demethylation of the oct4 promoter occurred only if chemical inhibitors and dTALEs were applied together but not upon treatment with inhibitors or dTALEs only. These results show that dTALEs in combination with chemical manipulation of epigenetic modifiers facilitate targeted transcriptional activation of epigenetically silenced target genes.
Improved in vivo photoacoustic microscopy based on a virtual-detector concept (2006)

Recently an in vivo high-resolution backward-mode photoacoustic microscope was developed that shows potential for applications in dermatology and related cancer research. However, the limited depth of focus of the large-numerical-aperture (NA) ultrasonic lens employed in this system causes the image quality to deteriorate significantly in the out-of-focus region. To solve this problem, we devised and explored, for the first time to our knowledge, a virtual-detector-based synthetic-aperture focusing technique, combined with coherence weighting, for photoacoustic microscopy with such a large-NA transducer. Images of phantoms show that the proposed technique improves the -6 dB lateral resolution from 49-379 to 46-53 microm and increases the signal-to-noise ratio by up to 29 dB, depending on the distance from the ultrasonic focal point. In vivo experiments show that the technique also provides a clearer representation of the vascular distribution in the rat's scalp.
Ligand Binding Characteristics of CXCR4 Incorporated into Paramagnetic Proteoliposomes (2001)

The G protein-coupled receptor CXCR4 is a coreceptor, along with CD4, for the human immunodeficiency virus type 1 (HIV-1) and has been implicated in breast cancer metastasis. We studied the binding of the HIV-1 gp120 envelope glycoprotein (gp) to CXCR4 but found that the gp120s from CXCR4-using HIV-1 strains bound nonspecifically to several cell lines lacking human CXCR4 expression. Therefore, we constructed paramagnetic proteoliposomes (CXCR4-PMPLs) containing pure, native CXCR4. CXCR4-PMPLs specifically bound the natural ligand, SDF-1alpha, and the gp120s from CXCR4-using HIV-1 strains. Conformation-dependent anti-CXCR4 antibodies and the CXCR4 antagonist AMD3100 blocked HIV-1 gp120 binding to CXCR4-PMPLs. The gp120-CXCR4 interaction was blocked by anti-gp120 antibodies directed against the third variable (V3) loop and CD4-induced epitopes, structures that have also been implicated in the binding of gp120 to the other HIV-1 coreceptor, CCR5. Compared with the binding of R5 HIV-1 gp120s to CCR5, the gp120-CXCR4 interaction exhibited a lower affinity (K(d) = 200 nm) and was dependent upon prior CD4 binding, even at low temperature. Thus, although similar regions of X4 and R5 HIV-1 gp120s appear to be involved in binding CXCR4 and CCR5, respectively, differences exist in nonspecific binding to cell surfaces, affinity for the chemokine receptor, and CD4 dependence at low temperature.
Epithelial cytoskeletal framework and nuclear matrix-intermediate filament scaffold: three-dimensional organization and protein composition. (1984)

Madin-Darby canine kidney (MDCK) cells grow as differentiated, epithelial colonies that display tissue-like organization. We examined the structural elements underlying the colony morphology in situ using three consecutive extractions that produce well-defined fractions for both microscopy and biochemical analysis. First, soluble proteins and phospholipid were removed with Triton X-100 in a physiological buffer. The resulting skeletal framework retained nuclei, dense cytoplasmic filament networks, intercellular junctional complexes, and apical microvillar structures. Scanning electron microscopy showed that the apical cell morphology is largely unaltered by detergent extraction. Residual desmosomes, as can be seen in thin sections, were also well-preserved. The skeletal framework was visualized in three dimensions as an unembedded whole mount that revealed the filament networks that were masked in Epon-embedded thin sections of the same preparation. The topography of cytoskeletal filaments was relatively constant throughout the epithelial sheet, particularly across intercellular borders. This ordering of epithelial skeletal filaments across contiguous cell boundaries was in sharp contrast to the more independent organization of networks in autonomous cells such as fibroblasts. Further extraction removed the proteins of the salt-labile cytoskeleton and the chromatin as separate fractions, and left the nuclear matrix-intermediate filament (NM-IF) scaffold. The NM-IF contained only 5% of total cellular protein, but whole mount transmission electron microscopy and immunofluorescence showed that this scaffold was organized as in the intact epithelium. Immunoblots demonstrate that vimentin, cytokeratins, desmosomal proteins, and a 52,000-mol-wt nuclear matrix protein were found almost exclusively in the NM-IF scaffold. Vimentin was largely perinuclear while the cytokeratins were localized at the cell borders. The 52,000-mol-wt nuclear matrix protein was confined to the chromatin-depleted matrix and the desmosomal proteins were observed in punctate polygonal arrays at intercellular junctions. The filaments of the NM-IF were seen to be interconnected, via the desmosomes, over the entire epithelial colony. The differentiated epithelial morphology was reflected in both the cytoskeletal framework and the NM-IF scaffold.
Polymerase Chain Reaction and Transcription Using Locked Nucleic Acid Nucleotide Triphosphates (2008)

Polymerase chain reaction amplification of a locked nucleic acid (LNA)-modified DNA strand and transcription reactions using LNA-A nucleoside 5'-triphosphate were successfully accomplished with DNA and RNA polymerases.
Biodegradable poly(lactic acid) and poly(lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties (1990)

Poly(lactic acid) [PLA] and its co-polymers with glycolic acid [PLCG] have been known to be biodegradable and histocompatible for the past 20 years. Their physico-chemical and biological properties have been found suitable, in many instances, for sustaining drug release in vivo for days or months. Several dosage forms for parenteral administration have been investigated using these polymers and a microencapsulation technique is chosen frequently for its unique properties. There are a limited number of published papers concerning preparation and characterization of PLA or PLCG microcapsules, possibly because of commercial unavailability and difficulties in the synthesis of reproducible batches of these polymers. However, microcapsules can be made using different traditional and non-traditional techniques containing core materials ranging from biological proteins to synthetic drugs. An attempt is made here to review problems associated with the different microencapsulation techniques using PLA or PLCG. In vivo and in vitro drug release from these microcapsules is also reviewed.
Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease (2010)

Fibroblast growth factors (FGFs) are a family of structurally related polypeptides that are essential for embryonic development and that function postnatally as homoeostatic factors, in the response to injury, in the regulation of electrical excitability of cells and as hormones that regulate metabolism. In humans, FGF signalling is involved in developmental, neoplastic, metabolic and neurological diseases. Fgfs have been identified in metazoans but not in unicellular organisms. In vertebrates, FGFs can be classified as having intracrine, paracrine and endocrine functions. Paracrine and endocrine FGFs act via cell-surface FGF receptors (FGFRs); while, intracrine FGFs act independent of FGFRs. The evolutionary history of the Fgf family indicates that an intracrine Fgf is the likely ancestor of the Fgf family. During metazoan evolution, the Fgf family expanded in two phases, after the separation of protostomes and deuterostomes and in the evolution of early vertebrates. These expansions enabled FGFs to acquire diverse actions and functions.
ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial (2015)

The functional polymorphism rs10245483 differentially affects remission and side effect outcomes depending on the antidepressant. The predictive power of the SNP for response or side effects was not lessened by the presence of cognitive impairment.
Genetic Modification of Carbon Catabolite Repression in Trichoderma reesei for Improved Protein Production (2009)

The cellulase and hemicellulase genes of the filamentous fungus Trichoderma reesei have been shown to be under carbon catabolite repression mediated by the regulatory gene cre1. In this study, strains were constructed in which the cre1 gene was either completely removed or replaced by a truncated mutant variant, cre1-1, found previously in the Rut-C30 mutant strain with enhanced enzyme production capability. The T. reesei transformants with either deletion or truncation of cre1 had clearly altered colony morphology compared with the parental strains, forming smaller colonies and fewer aerial hyphae and spores. Liquid cultures in a medium with glucose as a carbon source showed that the transformants were derepressed in cellulase and hemicellulase production. Interestingly, they also produced significantly elevated levels of these hydrolytic enzymes in fermentations carried out in a medium inducing the hydrolase genes. This suggests that cre1 acts as a modulator of cellulase and hemicellulase gene expression under both noninducing and inducing conditions. There was no phenotypic difference between the Deltacre1 and cre1-1 mutant strains in any of the experiments done, indicating that the cre1-1 gene is practically a null allele. The results of this work indicate that cre1 is a valid target gene in strain engineering for improved enzyme production in T. reesei.
Majorana fermions in strongly interacting helical liquids (2011)

Majorana fermions were proposed to occur at edges and interfaces of gapped one-dimensional systems where phases with different topological character meet due to an interplay of spin-orbit coupling, proximity-induced superconductivity and external magnetic fields. Here we investigate the effect of strong particle interactions and show that a helical liquid offers a mechanism that protects the very existence of Majorana edge states: whereas moderate interactions close the proximity gap that supports the edge states, in helical liquids the gap reopens due to two-particle processes. However, gapless fermionic excitations occur at spatial proximity to the Majorana states at interfaces and may jeopardize their long-term Majorana coherence.
Cardiac actin is the major actin gene product in skeletal muscle cell differentiation in vitro. (1984)

We examined the expression of alpha-skeletal, alpha-cardiac, and beta- and gamma-cytoskeletal actin genes in a mouse skeletal muscle cell line (C2C12) during differentiation in vitro. Using isotype-specific cDNA probes, we showed that the alpha-skeletal actin mRNA pool reached only 15% of the level reached in adult skeletal muscle and required several days to attain this peak, which was then stably maintained. However, these cells accumulated a pool of alpha-cardiac actin six times higher than the alpha-skeletal actin mRNA peak within 24 h of the initiation of differentiation. After cells had been cultured for an additional 3 days, this pool declined to 10% of its peak level. In contrast, over 95% of the actin mRNA in adult skeletal muscle coded for alpha-actin. This suggests that C2C12 cells express a pattern of sarcomeric actin genes typical of either muscle development or regeneration and distinct from that seen in mature, adult tissue. Concurrently in the course of differentiation the beta- and gamma-cytoskeletal actin mRNA pools decreased to less than 10% of their levels in proliferating cells. The decreases in beta- and gamma-cytoskeletal actin mRNAs are apparently not coordinately regulated.
Identification of mammalian noggin and its expression in the adult nervous system (1995)

The multiple roles of noggin during dorsal fate specification in Xenopus embryos, together with noggin's ability to directly induce neural tissue, inspired an effort to determine whether a similar molecule exists in mammals. Here we describe the identification of human and rat noggin and explore their expression patterns; we also localize the human NOGGIN gene to chromosome 17q22, and the mouse gene to a syntenic region of chromosome 11. Mammalian noggin is remarkably similar in its sequence to Xenopus noggin, and is similarly active in induction assays performed on Xenopus embryo tissues. In the adult mammal, noggin is most notably expressed in particular regions of the nervous system, such as the tufted cells of the olfactory bulb, the piriform cortex of the brain, and the Purkinje cells of the cerebellum, suggesting that one of the earliest acting neural inducers also has important roles in the adult nervous system.
Molecular biology and biochemistry of the natriuretic peptide system. I (1992)

From the Second Division, Department of Medicine, Kyoto University School of Medicine, Kyoto, Japan.
Top-down patterning of Zeolitic Imidazolate Framework composite thin films by deep X-ray lithography (2012)

For the first time a top-down process was used to control the spatial location of Metal-Organic Frameworks on a surface. Deep X-ray lithography was utilised to micropattern a Zeolitic Imidazolate Framework layer on a sol-gel surface, with exposure hardening the sol-gel by inducing crosslinking while leaving the frameworks intact.
Synthesis of Achiral Linker Reagents for Direct Labelling of Oligonucleotides On Solid Supports (1999)

Full experimental procedures for the synthesis of a series of new functional linker reagents (14-16) and solid supports (11-13) are reported. The achiral linker reagents and supports can be used for high yield incorporation of free amino groups, fluorescein or biotin into DNA oligomers.
Comparative effects of serotonergic agonists withvarying efficacy at the 5-HT1Areceptor on core body temperature: modification by the selective 5-HT1Areceptor antagonist WAY 100635 (1999)

A reduction in core body temperature is one of the characteristic consequences of 5-HT1A receptor activation in rodents. In this study, we characterized the hypothermic effects of four 5-HT1A receptor ligands with varying affinity and selectivity at the 5-HT1A receptor. 8-OH-DPAT and flesinoxan (full agonists); ipsapirone (selective partial agonist) and eltoprazine (non selective partial agonist), all induced a dose-dependent reduction in core body temperature, which was maximal 30 min subsequent to administration. This response differed quantitatively between the agonists, in both the extent and the duration of its effects. The selective 5-HT1A receptor antagonist WAY 100635 (0.15 mg/kg), attenuated the hypothermia induced by the partial agonists, ipsapirone (10 mg/kg) and eltoprazine (10 mg/kg). In contrast, the higher dose of WAY 100635 (1 mg/kg) antagonized the effects of all agonists. This study therefore further confirms the utility of hypothermia as a simple, robust in-vivo probe of 5-HT1A receptor function. This paradigm, which was enhanced by use of specific antagonists such as WAY 100635, may prove useful for the detection and characterization of novel 5-HT1A receptor ligands.
Learning Multiagent Communication with Backpropagation (2016)

Many tasks in AI require the collaboration of multiple agents. Typically, the communication protocol between agents is manually specified and not altered during training. In this paper we explore a simple neural model, called CommNet, that uses continuous communication for fully cooperative tasks. The model consists of multiple agents and the communication between them is learned alongside their policy. We apply this model to a diverse set of tasks, demonstrating the ability of the agents to learn to communicate amongst themselves, yielding improved performance over non-communicative agents and baselines. In some cases, it is possible to interpret the language devised by the agents, revealing simple but effective strategies for solving the task at hand.
Anti–HIV‐1 Activity of Weekly or Biweekly Treatment with Subcutaneous PRO 140, a CCR5 Monoclonal Antibody (2010)

ClinicalTrials.gov identifier: NCT00642707 .
A novel feature extraction method for epilepsy EEG signals based on robust generalized synchrony analysis (2013)

A feature extraction method for Epilepsy diagnosis is proposed in this paper, which can be incorporated in automatic/semi-automatic epilepsy diagnosis systems to improve diagnosis efficiency from multi-channel Electroencephalogram signals. This method calculates the Robust Generalized Synchrony between pairs of Electroencephalogram channels in the first step. Then six character parameters are extracted from the Robust Generalized Synchrony values for the whole brain and the sub-brain regions. A set of Electroencephalogram data including 20 normal objects and 20 epileptic patients in interictal states were used to test the proposed method The results demonstrate that these features are effective to differentiate between epilepsy patients and the normal objects with the p-values smaller than 0.01.
Defining intelligent network services in a multivendor distributed environment (2003)

The author presents the potential for synergism between silicon compilation used in the application specific integrated circuit (ASIC) design process, and the intelligent network service defining process, including creation, evaluation, and execution. The synergism is explored to solve the problem of switch programmability in future intelligent networks. A three-domain framework of the intelligent network service defining process in a distributed heterogeneous environment has been prototyped. The front-end of this framework includes the user interface, and the knowledge-based engineering environment (KEE) tool. A behavior-level intelligent network service description defined by objects and object classes is the input of the front-end process. The output of the front-end process is the KEE internal construct. Given the KEE internal construct, a service script translator (SST) written in LISP is used to generate the parameterized service/operation scripts in VXM formats. The SST is the back-end of the intelligent network service defining process. Service/operation scripts are used to control the execution of applications over a distributed heterogeneous network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Selective and Sensitive TNT Sensors Using Biomimetic Polydiacetylene-Coated CNT-FETs (2011)

Miniaturized smart sensors that can perform sensitive and selective real-time monitoring of target analytes are tremendously valuable for various sensing applications. We developed selective nanocoatings by combining trinitrotoluene (TNT) receptors bound to conjugated polydiacetylene (PDA) polymers with single-walled carbon nanotube field-effect transistors (SWNT-FET). Selective binding events between the TNT molecules and phage display derived TNT receptors were effectively transduced to sensitive SWNT-FET conductance sensors through the PDA coating layers. The resulting sensors exhibited an unprecedented 1 fM sensitivity toward TNT in real time, with excellent selectivity over various similar aromatic compounds. Our biomimetic receptor coating approach may be useful for the development of sensitive and selective micro- and nanoelectronic sensor devices for various other target analytes.
Surface Nuclear Magnetic Resonance over the Layered Conductive Earth (2004)

Abstract The numerical modeling of surface nuclear magnetic resonance (NMR) responses from stratified water saturated formation of finite conductivity involves two problems. One is the integration of Hankel transform of a rapid oscillating kernel function, and the other is the volume integration of surface NMR signal induced in receiver loop from the protons in the aquifers. In this paper, a direct numerical integration method is applied to the oscillating kernel function integration to obtain the radial and vertical components of the magnetic fields from large loop source, and then the spatial characteristics of the fields is analyzed. Based on these features, an ununiform space interval subdivision method is used to estimate the surface NMR response in the receiver loop in order to save computing time. The surface NMR responses from different conductive models are evaluated, and the influences of model conductivity, aquifer depth and its thickness, and loop size are studied. Numerical results show that the combination of direct numerical integration and ununiform space interval subdivision is feasible to get the surface NMR signal. And the conductivity of formations is the key to generate the phase of surface NMR signal. While other factors, such as groundwater depth, its thickness, and loop size, can make the amplitude and phase of the surface NMR response be greatly different.
Naturally-Occurring Cyclopeptides: Structures and Bioactivity (2006)

Cyclic peptides are a special bioactive group of compounds with interesting pharmacological and biochemical properties. Different natural sources are mentioned in this paper, but interest is focused on those cyclopeptides isolated from higher plants and higher fungi. Cyclopeptides occur in higher plant species, which belong to the following families: Annonaceae, Araliaceae, Asteraceae, Caryophyllaceae, Euphorbiaceae, Fabaceae, Labiatae, Linaceae, Olacaceae, Rhamnaceae, Rubiaceae, Rutaceae, Schizandraceae, Solanaceae, and Violaceae. Basidiomycetes is the group of higher fungi, which has shown to be rich in cyclopeptides, e.g., Amanita, Conocybe, Lepiota, Galerina, and Omphalotus species. Usually these compounds are associated to a toxic response in mammals, as well as to cytotoxic, insecticidal, antimalarial, estrogenic, sedative, nematicidal, antimicrobial, immunosuppressive, and enzyme-inhibitory activities. Structures are elucidated by chemical methods and spectroscopic techniques. Configurational and conformational analyses of some bioactive cyclopeptides are discussed. Conformational studies of the natural cyclopeptides and their derivatives are related to the stereochemical requirements for these bioactive compounds. Keywords: heterocyclopeptides, Phencyclopeptines, m-Ansa Compounds, Proline-rich Cyclic peptides, Amanita virosa