gebhart/patrepeval huggingface dataset:
A comparison of eukaryotic viral 5′-leader sequences as enhancers of mRNA expressionin vivo (1987)

The 5'-untranslated leader sequences of several plant RNA viruses, and a portion of the 5'-leader of an animal retrovirus, were tested for their ability to enhance expression of contiguous open reading frames for chloramphenicol acetyltransferase (CAT) or beta-glucuronidase (GUS) in tobacco mesophyll protoplasts, Escherichia coli and oocytes of Xenopus laevis. Translation of capped or uncapped transcripts was substantially enhanced in almost all systems by the leader sequence of either the U1 or SPS strain of TMV. All leader sequences, except that of TYMV, stimulated expression of 5'-capped GUS mRNA with the native prokaryotic initiation codon context, in electroporated protoplasts. Only the TMV leaders enhanced translation of uncapped GUS mRNAs in protoplasts and increased expression of uncapped CAT mRNA in microinjected X. laevis oocytes. In oocytes, the TYMV leader sequence was inhibitory. In transformed E. coli, the TMV-U1 leader enhanced expression of both the native and eukaryotic context forms of GUS mRNA about 7.5-fold, despite the absence of a Shine-Dalgarno region in any of the transcripts. The absolute levels of GUS activity were all about 6-fold higher with mRNAs containing the native initiation codon context. In E. coli, the leaders of AlMV RNA4 and TYMV were moderately stimulatory whereas those of BMV RNA3, RSV and the SPS strain of TMV enhanced GUS expression by only 2- to 3-fold.
Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy. (1992)

Angiogenesis, the growth of blood capillaries, is regulated by soluble growth factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic mitogens act over large distances to initiate capillary growth whereas changes in ECM govern whether individual cells will grow, differentiate, or involute in response to these stimuli in the local tissue microenvironment. Analysis of this local control mechanism has revealed that ECM molecules switch capillary endothelial cells between differentiation and growth by both binding specific transmembrane integrin receptors and physically resisting cell-generated mechanical loads that are applied to these receptors. Control of capillary endothelial cell form and function therefore may be exerted by altering the mechanical properties of the ECM as well as its chemical composition. Understanding of this mechanochemical control mechanism has led to the development of new angiogenesis inhibitors that may be useful for the treatment of cancer.
Privatizing Infrastructure : Capital Market Pressures and Management Incentives (1996)

The authors propose a number of privatization rules to ensure that management will improve after privatization. Governments should ensure that the privatized sector has several firms operating in industries that are local natural monopolies, so that if one operator goes bankrupt, another can readily take over. Governments should also permit concentrated ownership and foreign ownership, and profits should not be guaranteed through regulation.
Biosynthetic incorporation of unnatural sialic acids into polysialic acid on neural cells (2000)

In this study we demonstrate that polysialyltransferases are capable of accepting unnatural substrates in terminally differentiated human neurons. Polysialyltransferases catalyze the glycosylation of the neural cell adhesion molecule (NCAM) with polysialic acid (PSA). The unnatural sialic acid analog, N-levulinoyl sialic acid (SiaLev), was incorporated into cell surface glycoconjugates including PSA by the incubation of cultured neurons with the metabolic precursor N-levulinoylmannosamine (ManLev). The ketone group within the levulinoyl side chain of SiaLev was then used as a chemical handle for detection using a biotin probe. The incorporation of SiaLev residues into PSA was demonstrated by protection from sialidases that can cleave natural sialic acids but not those bearing unnatural N-acyl groups. The presence of SiaLev groups on the neuronal cell surface did not impede neurite outgrowth or significantly affect the distribution of PSA on neuronal compartments. Since PSA is important in neural plasticity and development, this mechanism for modulating PSA structure might be useful for functional studies.
New Twists on Nucleic Acids (1994)

The structures and physical properties of oligonucleotide duplexes depend strongly on the limited conformational flexibility of (deoxy)ribose-phosphodiester linkages and the sugar. Molecular mechanics and NMR spectroscopy have been employed to understand and predict alterations in sugar pucker and conformation resulting from replacement of oxygen, hydrogen, and carbon in the sugar with other heteroatoms. Studies on model monomer, dimer, and longer single stranded nucleosides are correlated with data on duplex stability obtained from oligomers incorporating 2′, 3′, and 4′-modified sugars to establish a set of guidelines for the types of alterations that can be tolerated within oligonucleotide duplexes. The results suggest that increased affinity of an antisense oligomer for a complementary RNA target can be achieved by decreasing the entropie motion of the sugar while maintaining a preorganized structure with an RNA-like conformation.
Rhythms of the Brain (2006)

Studies of mechanisms in the brain that allow complicated things to happen in a coordinated fashion have produced some of the most spectacular discoveries in neuroscience. This book provides support for the idea that spontaneous neuron activity, far from being mere noise, is actually the source of our cognitive abilities. It looks at the co-evolution of structure and function in the mammalian brain, illustrating how self-emerged oscillatory timing is the brains fundamental organizer of neuronal information. The small world-like connectivity of the cerebral cortex allows for global computation on multiple spatial and temporal scales. The perpetual interactions among the multiple network oscillators keep cortical systems in a highly sensitive metastable state and provide energy-efficient synchronizing mechanisms via weak links. In a sequence of cycles, this book travels from the physics of oscillations through neuronal assembly organization to complex cognitive processing and memory storage.
Arylamine N-acetyltransferase-1 is highly expressed in breast cancers and conveys enhanced growth and resistance to etoposide in vitro. (2003)

Comparative two-dimensional proteome analysis was used to identify proteins differentially expressed in multiple clinical normal and breast cancer tissues. One protein, the expression of which was elevated in invasive ductal and lobular breast carcinomas when compared with normal breast tissue, was arylamine N-acetyltransferase-1 (NAT-1), a Phase II drug-metabolizing enzyme. NAT-1 overexpression in clinical breast cancers was confirmed at the mRNA level and immunohistochemical analysis of NAT-1 in 108 breast cancer donors demonstrated a strong association of NAT-1 staining with estrogen receptor-positive tumors. Analysis of the effect of active NAT-1 overexpression in a normal luminal epithelial-derived cell line demonstrated enhanced growth properties and etoposide resistance relative to control cells. Thus, NAT-1 may not only play a role in the development of cancers through enhanced mutagenesis but may also contribute to the resistance of some cancers to cytotoxic drugs.
SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile (2002)

We have identified a novel short synthetic SRIF peptidomimetic, which exhibits high affinity binding to four of the five human SRIF receptor subtypes and has potent, long lasting inhibitory effects on GH and IGF-I release. Therefore SOM230 is a promising development candidate for effective GH and IGF-I inhibition and is currently under evaluation in phase 1 clinical trials.
Respiratory Syncytial Virus Affects Pulmonary Function in BALB/c Mice (1998)

BALB/c mice inoculated intranasally with respiratory syncytial virus (RSV) were studied in a whole-body plethysmograph to determine if signs of respiratory illness similar to those observed in human infants could be detected. Also, responsiveness to methacholine was assessed. RSV-infected mice showed significantly higher respiratory rates than did controls (409.2 vs. 305.2 breaths/min, P < .0001). Significantly increased airway responsiveness to methacholine was noted, infected mice responding to a 100-fold lower dose than controls (P = .003). Together, these data provide the first objective evidence of respiratory illness in the mouse model of RSV infection, which enhances the value of this model for evaluating effects of vaccines, antivirals, and other drugs acting on respiratory tract disease caused by RSV.
La Red de Salud Mental y de Adicciones del Institut d'Assistència Sanitària (IAS) de Girona: una visión desde la gestión (2012)

This article describes how the Institut d'Assitencia Sanitaria public company that provides health services of the Generalitat de Catalunya, has been shaping the mental health network in the counties of Girona from a management perspective.
We review briefly the history from a perspective of mental health nursing based design to improve the quality of life for users. lt is described as through business modernization, with the introduction of management systems based on planning, quality care processes and set up an integrated network of mental health treatment focused on user proximity. It also describes the different devices and Community Hospital (CSM Adults, Children and Youth, Department of Rehabilitation, Drug Centers, esidential resources, and labor resources) that make up the current network. Delimit the two basic network principles: continuity of care and comprehensive treatment of the user, and then show a series of results and proVide a cost analysis of the mental health network of the province of Girona.
Interaction between the CD45 antigen and phytohemagglutinin. Inhibitory effect on the lectininduced T cell proliferation by anti‐CD45 monoclonal antibody (1987)

Immunoprecipitation studies from 125I-labeled T cells, previously activated with the lectin phytohemagglutinin (PHA) from Phaseolus vulgaris, showed a preferential association between the CD45 glycoprotein family containing members of 220, 205, 190 and 180 kDa, and a protein of 33 kDa. This 33-kDa protein, with an identical molecular mass as PHA, was not associated with other highly expressed molecules such as class I histocompatibility antigens (HLA-A,B,C), transferrin receptor, CDw44 and CD11a. Further immunoprecipitation analysis from peripheral blood lymphocytes incubated with 125I-labeled PHA confirmed the identification of the CD45-associated 33-kDa protein as the lectin PHA. These results prompted us to analyze the possible involvement of the CD45 molecules in the T cell activation process induced by PHA. Thus, two monoclonal antibodies specific for CD45 antigens were able to inhibit the T cell proliferation induced by the lectin. This inhibitory ability was exerted by affecting both the interleukin 2 production and the interleukin 2 receptor expression.
Visualization of Nucleic Acids (1995)

The Classic Methods of Nucleic Acid Visualization for Light Microscopy, J.-M. Exbrayat Imaging Nucleic Acids with Scanning Probe Microscopes, W.M. Heckl and A. Engel The Spreading of Nucleic Acids, E. Delain and E. Le Cam DNA in Its Aqueous Environment, A. Leforestier and J. Dubochet Ultrastructural Cytochemistry, M. Derenzini In Situ Detection of Nucleic Acids by the Nuclease-Gold Method, C. Cheniclet, S. Garzon, and M. Bendayan Ultrastructural Detection of Nucleic Acids by Immunocytology, M. Thiry Visualization of DNA in Living Cells: Cytometric Approaches, S. Paillasson, J.M. Millot, M. Manfait, and X. Ronot Dynamical Study of Nucleic Acids by Autoradiography, Thomas, Cavalier, Gouranton Molecular Biological Techniques Used in the Visualization of Nucleic Acids, C. Perrett In Situ Hybridization on Chromosomes: Clinical Applications, J. Chiesa and J.P. Bureau Ultrastructural In Situ Hybridization on Chromosomes, M. Wu Detection of Nucleic Acid Sequences on Whole Cells with or without Genomic Amplification, G. Lizard, Y. Chardonnet, and D. Schmitt In Situ Hybridization for Electron Microscopy, G. Morel, D. Le Guellec, H. Mertani, and A. Trembleau Nonisotopic In Situ Hybridization: A Powerful Tool for Diagnosis of Viral Infection in Routine Pathology, P. Brousset, G. Daste, D. Roda, and J. Selves Visualization and Identification of Viral Nucleic Acids, F. Puvion-Dutilleul Ultrastructural Detection of Nucleic Acid in the Glomerular Basement Membrane of Lupus Nephritis, D. Malide and M. Bendayan Nucleic Acids-Ligand Interactions, E. Le Cam and E. Delain
Vegard’s law (1991)

Vegard's law is an approximate empirical rule which holds that a linear relation exists, at constant temperature, between the crystal lattice constant of an alloy and the concentrations of the constituent elements. Applications of a density-functional theory of nonuniform fluid mixtures to the fluid-solid transition of simple binary mixtures of hard spheres demonstrates the importance of relative atomic sizes in determining lattice constants and suggests that for sufficiently small disparities in atomic size Vegard's law may also hold along the fluid-solid coexistence curve.
T-bet acts as a powerful adjuvant in Ag85B DNA‑based vaccination against tuberculosis (2012)

Owing to the limitations of traditional Bacillus Calmette-Guerin vaccines and the low efficacy of DNA vaccines expressing single antigens of Mycobacterium tuberculosis, there is a pressing requirement for adjuvants capable of strengthing the immunogenicity and effectiveness of these vaccines against tuberculosis (TB). T-bet (TBX21) is a transcription factor, which controls the optimal development of type-1 immune responses responsible for the potent protection of vaccines against TB. However, little is known about the efficiency of the TB vaccine combined with T-bet. In this study, we report an approach to intensify the immunogenicity of Ag85B DNA-based vaccines using T-bet as an adjuvant. Balb/c mice were immunized by 3 intramuscular inoculations with pcDNA3.1-FLAG-T-bet in combination with pcDNA3.1-FLAG-Ag85B, and the immune responses were compared with those induced by vaccination with Ag85B DNA alone. We found that pcDNA3.1-T-bet-Ag85B not only induced evidently higher IgG2a antibody responses, but also increased the production of interferon-γ (IFN-γ) and interleukin (IL)-2 with the concomitant repression of IL-4 and IL-10 compared with pcDNA3.1-Ag85B alone or the empty vector. Thus, plasmid DNA coding for T-bet enhanced Ag85B-specific immune responses and shifted them to a predominant Th1-type immune response. In conclusion, T-bet is an efficacious Th1-inducing adjuvant in the context of the Ag85B DNA-based vaccination, and could also prove to be a promising candidate for DNA vaccine development against TB.
Promoter activity of the proliferating-cell nuclear antigen gene is associated with inducible CRE-binding proteins in interleukin 2-stimulated T lymphocytes. (1994)

The proliferating-cell nuclear antigen (PCNA) gene encodes an auxiliary factor of DNA polymerase delta and functions in DNA replication during S phase. It is expressed at much higher levels in proliferating cells than in quiescent cells. We have studied the regulatory role of the 5'-flanking sequence of the murine PCNA gene in interleukin 2 (IL-2)-responsive cloned T cells (L2). Analysis of a set of deletion constructs in transient transfection assays measuring heterologous reporter gene (luciferase) activity demonstrated that the 182-bp 5'-flanking region provides full promoter activity in IL-2-stimulated L2 cells. While many elements contribute to PCNA promoter strength in IL-2-stimulated cells, the largest decrease in activity occurred with deletion of the tandem CRE (cyclic AMP response element) binding sites located at nucleotides -37 to -52. With a gel mobility shift assay, several IL-2-inducible DNA-protein complexes were detected, including CREB (CRE-binding) and ATF1 (activating transcription factor) proteins that are specific for the PCNA-CRE sequence. Methylation interference analysis confirmed specific binding of these proteins to the CRE sites. Mutation at the PCNA-CRE motif abolishes IL-2-inducible binding and reduces substantially PCNA promoter activity. These results indicate that IL-2-stimulated PCNA transcription may be partially mediated by these CRE-binding proteins.
Oxygen in Human Tumors: Correlations between Methods of Measurement and Response to Therapy: Summary of a Workshop Held November 19-20, 1992, at the National Cancer Institute, Bethesda, Maryland (1993)

Knowledge about the oxygenation of human tumors and its importance in the response to radiotherapy is crucial to the effort to develop improved treatment methods for radiotherapy. The measurement of oxygenation of human tumors and correlations with response to radiotherapy were the subjects of a recent workshop sponsored by the National Cancer Institute. The following methods for measuring oxygen or hypoxia, or a parameter related to either, were presented: polarographic oxygen electrodes, the comet and alkaline elution assays for radiation-induced DNA damage, nitroimidazole binding assays, hemoglobin saturation assays, magnetic resonance spectroscopy, electron spin resonance spectroscopy, phosphorescence imaging, and an assay for tumor interstitial pressure. The electron spin resonance, alkaline elution, and phosphorescence imaging methods have not been used in human tumors. The comet assay, nitroimidazole binding assays, magnetic resonance spectroscopy, cryospectroscopy, and near-infrared spectroscopy have been employed in human tumors, but correlations to treatment response have not been made. Polarographic measurements have indicated that the presence of hypoxia correlates with a poor response to radiotherapy in cervical cancers, but additional data are needed on early-stage disease, and with long-term follow-up on local control and survival. If these confirm the correlation between hypoxia and poor response to radiotherapy, additional tumor sites should be studied. Future clinical trials of treatments that sensitize, exploit, or kill hypoxic cells should identify and include the individual patients with hypoxic tumors. Fundamental unanswered questions regarding the assessment of tumor oxygenation concern the need for invasive procedures, the spatial resolution needed for prediction of response to radiotherapy, the importance of reoxygenation, differences between tumors in rates and degrees of reoxygenation, whether measurements made during a course of therapy are of value, and correlations among methods and with other predictive assays such as intrinsic radiosensitivity and potential doubling time.
Vaccination with Vesicular Stomatitis Virus-Vectored Chimeric Hemagglutinins Protects Mice against Divergent Influenza Virus Challenge Strains (2015)

Universal influenza vaccination strategies should be capable of protecting against a wide array of influenza viruses, and we have developed such an approach utilizing a single viral vector system. The potent antibody responses that these vaccines generate are shown to protect mice against lethal influenza challenges with highly divergent viruses. Notably, intranasal vaccination offers significantly better protection than intramuscular vaccination in a lethal virus challenge model. The results described in this study offer insights into the mechanisms by which chimeric hemagglutinin (HA)-based vaccines confer immunity, namely, that the invariant stalk of cHA antigens is superior to full-length HA antigens at inducing cross-reactive humoral immune responses and that VSV-cHA vaccine-induced protection varies by site of inoculation, and contribute to the further development of universal influenza virus vaccines.
Generation dependent reduction of tTA expression in double transgenic NZL‐2/tTACMV mice (2001)

Despite the overall successful application of the tet-system to regulate gene expression in vitro and in vivo, nothing is known so far about the long-term stability of this system in transgenic mice. In this study, mice of generation F2, F3, F4, or F10 of two independent tTA(CMV) transgenic lines were bred with NZL-2 mice containing a tTA-responsive bidirectional promoter that allows the simultaneous expression of two reporter genes encoding luciferase and beta-galactosidase. Analysis of the expression of transgenes in double transgenic mice revealed a dramatic reduction of tTA transactivator mRNA over time. As a consequence, the expression of both reporter genes was gradually reduced from generation to generation in tissues of embryonic and adult NZL-2/tTA(CMV) mice. Luciferase activity in NZL-2/tTA(CMV)(F10) mice was reduced 8-10-fold compared to NZL-2/ tTA(CMV)(F2) mice, and beta-galactosidase expression was no longer detectable. In summary, we describe the long-term instability of the tet-system in our NZL-2/tTA(CMV) double transgenic mice. The molecular basis of this observation and experimental tools to overcome this limitation need to be addressed in future.
Electrically conductive bacterial nanowires produced by Shewanella oneidensis strain MR-1 and other microorganisms (2006)

Shewanella oneidensis MR-1 produced electrically conductive pilus-like appendages called bacterial nanowires in direct response to electron-acceptor limitation. Mutants deficient in genes for c-type decaheme cytochromes MtrC and OmcA, and those that lacked a functional Type II secretion pathway displayed nanowires that were poorly conductive. These mutants were also deficient in their ability to reduce hydrous ferric oxide and in their ability to generate current in a microbial fuel cell. Nanowires produced by the oxygenic phototrophic cyanobacterium Synechocystis PCC6803 and the thermophilic, fermentative bacterium Pelotomaculum thermopropionicum reveal that electrically conductive appendages are not exclusive to dissimilatory metal-reducing bacteria and may, in fact, represent a common bacterial strategy for efficient electron transfer and energy distribution.
Angiotensinogen Is Related to the Antitrypsin-Antithrombin-Ovalbumin Family (1983)

The recently reported amino acid sequence of rat angiotensinogen was subjected to a computer-assisted search for homology with known sequences stored in a data bank and found to be significantly related to that of plasma alpha 1-antitrypsin, itself a member of a family that includes antithrombin III and ovalbumin. An alignment of the four sequences shows indisputably the common ancestry of all four proteins.