gebhart/patrepeval huggingface dataset:
Fumagalone, a Reversible Inhibitor of Type 2 Methionine Aminopeptidase and Angiogenesis (2003)

Fumagillin and ovalicin constitute a family of structurally related natural products that possess antiangiogenic activity. We report the synthesis of a new fumagillin analogue, fumagalone, in which the spiroepoxide group is replaced with an aldehyde. Fumagalone inhibits type 2 methionine aminopeptidase (MetAP2) with IC(50) = 8 microM and endothelial cell proliferation with IC(50) = 52 nM. With dialysis and competition assays, it was unambiguously demonstrated that binding of fumagalone to MetAP2 is reversible.
The Bcl-2 Protein Family: Arbiters of Cell Survival (1998)

Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that dismantle the cell. More distant relatives instead promote apoptosis, apparently through mechanisms that include displacing the adapters from the pro-survival proteins. Thus, for many but not all apoptotic signals, the balance between these competing activities determines cell fate. Bcl-2 family members are essential for maintenance of major organ systems, and mutations affecting them are implicated in cancer.
A Three-Dimensional CFD Design Study of a Circulation Control Inlet Guide Vane for a Transonic Compressor (2009)

A three-dimensional computational investigation was conducted to evaluate the performance of a circulation control inlet guide vane (IGV) designed for a transonic compressor test rig. The general configuration of the IGV is an uncambered airfoil designed to exploit the Coanda effect for flow turning through the use of a jet that exhausts along a curved trailing edge. Computational fluid dynamics (CFD) was used in conjunction with an optimization approach to design an IGV that balances performance potential with manufacturing cost and complexity. Optimization parameters include geometry specifications such as jet height and trailing edge radius, as well as operational parameters such as jet supply pressure and inlet Mach number. The potential for positive flow turning was shown for all geometries examined. Operational goals such as increased turning at lower off-design inlet Mach numbers were demonstrated, and an optimum configuration was established.
XIAP Regulates Caspase Activity in Degenerating Axons (2013)

Our knowledge of the destructive events that regulate axonal degeneration is rudimentary. Here, we examine the role of caspases and their endogenous inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, caspase-6, and caspase-9 are present in axons and are cleaved upon nerve growth factor (NGF) withdrawal. We observed that caspase-3 activity is high in NGF-withdrawn axons and that CASP3(-/-) axons are protected from degeneration. XIAP(-/-) DRG sensory neurons degenerate more rapidly and contain more active caspase-3 than their wild-type counterparts, indicating that axonal caspases are normally regulated by XIAP. Importantly, axonal XIAP levels drop sharply after NGF withdrawal; if XIAP levels are maintained by overexpression, axonal caspase-3 activation and axonal degeneration are suppressed. Finally, we show that XIAP(-/-) embryos have stunted dermal innervation. We propose that XIAP-mediated caspase inhibition plays an important role in regulating morphogenic events that shape the nervous system during development.
Zinc-induced neuronal death in cortical neurons. (2000)

Although Zn2+ is normally stored and released in the brain, excessive exposure to extracellular Zn2+ can be neurotoxic. The purpose of the present study was to determine the type of neuronal cell death, necrosis versus apoptosis, induced by Zn2+ exposure. Addition of 10-50 microM ZnCl2 to the bathing medium of murine neuronal and glial cell cultures induced, over the next 24 hrs., Zn2+-concentration-dependent neuronal death; some glial death also occurred with Zn2+ concentrations above 30 microM. The neuronal death induced by 20 microM Zn2+ was characterized by coarse chromatin condensation, the formation of apoptotic bodies, and internucleosomal DNA fragmentation. It was attenuated in cortical cell cultures prepared from mice null for the bax gene, and by the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-CH2F (ZVAD, 100 microM), but not by the NMDA receptor antagonist, D-2-amino-5-phosphonovalerate (D-APV, 200 microM ). In contrast, the neuronal death induced by 50 microM Zn2+ was characterized by plasma membrane disruption and random DNA fragmentation; this death was attenuated by D-APV, but exhibited little sensitivity to ZVAD or deletion of bax. These results suggest that Zn2+ can induce cell death with characteristics of either apoptosis or necrosis, depending on the intensity of the Zn2+ exposure.
Characterization of glial subpopulations in cultures of the ovine central nervous system (1988)

The cellular composition and in vitro development of glial cultures derived from the rat CNS has been well studied. However, less information is available on similar cultures from other species, particularly higher mammals. To study ovine glial development in vitro, cultures from 50-day fetal to adult animals were characterized with various immunocytochemical markers, which are frequently used to define neural cell subsets in rat cultures. As in rats, both A2B5+ and A2B5- astrocytes can be identified in ovine cultures. However, ovine A2B5+ and A2B5- could not be reliably differentiated by their morphology, which was more influenced by whether the cells were in serum-free or serum-containing media than by their A2B5-positive or -negative status. In addition, ovine A2B5+ astrocytes were present in cultures from early fetal brain before the development of identifiable oligodendrocytes, unlike rat type II astrocytes, which develop only after the appearance of oligodendrocytes. An A2B5+ cell, morphologically similar to the rat 02-A cell, can be found in cultures from fetal ovine cerebrum or cerebellum. A2B5+/glial fibrillary acidic protein (GFAP)- cells in cultures from 100- to 115-day ovine cerebellum appeared to differentiate into A2B5+ astrocytes in serum-containing media. However, in serum-free media, although the A2B5+ cells assumed a more "oligodendroglial-like" morphology, they did not express galactocerebroside or myelin basic protein, suggesting that these cells may not be bipotential as is the rat 02-A cell. Oligodendroglial differentiation was not induced by treatment with dibutyryl cyclic AMP or insulin-like growth factor I. Many cells in cultures from a variety of fetal ages did not label with any of the immunocytochemical markers used, suggesting the need for more cell-type-specific markers to identify neural cell subsets in higher mammals.
Omeprazole Compared with Misoprostol for Ulcers Associated with Nonsteroidal Antiinflammatory Drugs (1998)

The overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol.
25C-NBOMe short characterisation (2020)

Abstract Purpose N -Methoxybenzyls, a group of toxic phenylethylamine derivatives of the 2C family compounds, are a new class of potent serotonin 5-HT 2A receptor agonist hallucinogens with potential harmful effects. This study summarizes current state of knowledge of one of the most dangerous representative of this group— N -(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe). Due to hallucinogenic properties similar to those observe after lysergic acid diethylamide (LSD) usage (altered thoughts, feelings, and awareness of one’s surroundings), this compound is very attractive to hallucinogenic substances users. Methods An exhaustive literature search was carried out in PubMed, Google Scholar and other biomedical data bases without limiting period, to identify relevant articles. Results Despite frequent recreational use, knowledge about the 25C-NBOMe action and toxic and fatal consequences is still very limited. Most data on this drug come from clinical reports, from cases of acute fatal and non-fatal intoxications. Some animal and in vitro studies indicated a route of metabolism of the drug in the body. The drug and its metabolites were also detected in human blood and urine using combinations of chromatographic separation and mass spectrometry detection. Conclusions Overall, findings show that 25C-NBOMe is a powerful hallucinogen. Easy online availability, low prize and the lack of knowledge of 25C-NBOMe makes this substance potentially very dangerous to its users. Thus, further investigation on the mechanism of action, chemical, pharmacological and toxicological properties is needed to evaluate 25C-NBOMe potential harmful effects.
Biofunctionalization of electrowetting-on-dielectric digital microfluidic chips for miniaturized cell-based applications (2011)

In this paper we report on the controlled biofunctionalization of the hydrophobic layer of electrowetting-on-dielectric (EWOD) based microfluidic chips with the aim to execute (adherent) cell-based assays. The biofunctionalization technique involves a dry lift-off method with an easy to remove Parylene-C mask and allows the creation of spatially controlled micropatches of biomolecules in the Teflon-AF(®) layer of the chip. Compared to conventional methods, this method (i) is fully biocompatible; and (ii) leaves the hydrophobicity of the chip surface unaffected by the fabrication process, which is a crucial feature for digital microfluidic chips. In addition, full control of the geometry and the dimensions of the micropatches is achieved, allowing cells to be arrayed as cell clusters or as single cells on the digital microfluidic chip surface. The dry Parylene-C lift-off technique proves to have great potential for precise biofunctionalization of digital microfluidic chips, and can enhance their use for heterogeneous bio-assays that are of interest in various biomedical applications.
Hormones and sexual function. (1999)

Female sexual function, as well as sexual dysfunction often seen during menopause, is assumed to be closedly related to the hormonal milieu of the body, particularly that of the target organs of the sex steroids. Estrogen as the hormone associated with female reproductive functioning is given first consideration in treating complaints of dysfunction, especially dyspareunia. However, simply restoring some, or all, of the estrogenization of the premenopausal years does not always lead to improvement in overall sexual functioning. Decreased libido is often still present in situations that appear to be anatomically satisfactory. Thus, exogenous testosterone, in a number of dosage forms, is often used adjunctively. Although the results are often gratifying, side effects may be a problem for some women. Treated women should be monitored for increased facial oiliness, acne, hirsutism, and alopecia.
Nucleoside Monophosphate Complex Structures of the Endonuclease Domain from the Influenza Virus Polymerase PA Subunit Reveal the Substrate Binding Site inside the Catalytic Center (2009)

Highly pathogenic influenza virus strains currently in circulation pose a significant risk of a global pandemic. Following the reported crystal structure of the endonuclease domain from the avian influenza virus polymerase PA subunit, here we report the results of a systematic X-ray crystallographic analysis of its complex with adenosine, uridine, and thymidine nucleoside monophosphates (NMPs). Electron density corresponding to the monophosphate moiety of each nucleotide was apparent in each NMP complex and bound to the catalytic metal. A hydrophobic site was found to contribute to nucleoside binding. The NMP complex structures should represent the conformation of the bound product after nuclease cleavage. Moreover, one solvent molecule was found to occupy an equivalent position to the second reported Mn(2+) ion, where it mediates the interaction between bound NMPs and the N-terminal PA domain in the presence of the Mg(2+) ion. The results presented here indicate a possible cleavage mechanism and identify a distinct nucleotide binding pocket. The identification of this binding pocket opens a new avenue for anti-influenza drug discovery, targeting the cap-dependent endonuclease, in response to the worldwide threat of influenza.
The Structure of a Transcribing T7 RNA Polymerase in Transition from Initiation to Elongation (2008)

Structural studies of the T7 bacteriophage DNA-dependent RNA polymerase (T7 RNAP) have shown that the conformation of the amino-terminal domain changes substantially between the initiation and elongation phases of transcription, but how this transition is achieved remains unclear. We report crystal structures of T7 RNAP bound to promoter DNA containing either a 7- or an 8-nucleotide (nt) RNA transcript that illuminate intermediate states along the transition pathway. The amino-terminal domain comprises the C-helix subdomain and the promoter binding domain (PBD), which consists of two segments separated by subdomain H. The structures of the intermediate complex reveal that the PBD and the bound promoter rotate by approximately 45 degrees upon synthesis of an 8-nt RNA transcript. This allows the promoter contacts to be maintained while the active site is expanded to accommodate a growing heteroduplex. The C-helix subdomain moves modestly toward its elongation conformation, whereas subdomain H remains in its initiation- rather than its elongation-phase location, more than 70 angstroms away.
Lymphoid Hyperplasia Resulting in Immune Dysregulation Is Caused by Porcine Reproductive and Respiratory Syndrome Virus Infection in Neonatal Pigs (2004)

Amid growing evidence that numerous viral infections can produce immunopathology, including nonspecific polyclonal lymphocyte activation, the need to test the direct impact of an infecting virus on the immune system of the host is crucial. This can best be tested in the isolator piglet model in which maternal and other extrinsic influences can be excluded. Therefore, neonatal isolator piglets were colonized with a benign Escherichia coli, or kept germfree, and then inoculated with wild-type porcine reproductive and respiratory syndrome virus (PRRSV) or sham medium. Two weeks after inoculation, serum IgM, IgG, and IgA levels were 30- to 50-, 20- to 80-, and 10- to 20-fold higher, respectively, in animals receiving virus vs sham controls, although <1% was virus specific. PRRSV-infected piglets also had bronchial tree-associated lymph nodes and submandibular lymph nodes that were 5-10 times larger than colonized, sham-inoculated animals. Size-exclusion fast performance liquid chromatography revealed that PRRSV-infected sera contained high-molecular-mass fractions that contained IgG, suggesting the presence of immune complexes. Lesions, inflammatory cell infiltration, glomerular deposits of IgG, IgM, and IgA, and Abs of all three isotypes to basement membrane and vascular endothelium were observed in the kidneys of PRRSV-infected piglets. Furthermore, autoantibodies specific for Golgi Ags and dsDNA could be detected 3-4 wk after viral inoculation. These data demonstrate that PRRSV induces B cell hyperplasia in isolator piglets that leads to immunologic injury and suggests that the isolator piglet model could serve as a useful model to determine the mechanisms of virus-induced immunopathology in this species.
Design of compliance chamber and after-load in apparatus for cultured endothelial cells subjected to stresses (2006)

In order to create a hemodynamic environment that can simulate the physiological condition of arteries, an in vitro experiment apparatus was designed whose key modules were compliance chamber and after-load. These two modules were developed based on the theories of hemodynamics. Both the normal and shear stress to which endothelial cells are exposed can be controlled with these modules, thus facilitating the research of endothelial cells subjected to stresses.
Metastatic breast cancer subtypes and central nervous system metastases (2014)

After CNS-M, the Lum/HER2+ subtype appears associated with the longest OS. Prospective clinical trials would be required for evaluating the potential role of screening for asymptomatic CNS lesions and of more aggressive CNS-M treatment in Lum/HER2+ subtype.
The Presence of Substituents on the Aryl Moiety of the Aryl Phosphoramidate Derivative of d4T Enhances Anti-HIV Efficacy in Cell Culture:  A Structure−Activity Relationship (1999)

New substituted-aryl phosphoramidate derivatives of the anti-HIV drug d4T were synthesized as membrane-soluble intracellular prodrugs for the free bioactive phosphate to establish relationship(s) between compound structure and in vitro antiviral activity. The majority of compounds demonstrated an elevation of in vitro potency relative to that of the parent nucleoside, and unlike d4T, all retained full activity in thymidine kinase-deficient cells. The compound bearing a p-chloro aryl group (8e) expressed nanomolar activity in vitro, a 14-fold increase in activity relative to that of the unsubstituted phosphoramidate (100-fold compared to d4T). An assay using pig liver esterase was used to establish the stability of the compounds to enzymatic degradation. While there was no apparent correlation between in vitro activity and half-life of enzymatic degradation, there was a close correlation between compound lipophilicity, determined by octanol/water partition coefficient, and in vitro potency. We suggest that substitutions made to the aryl moiety of the aryl phosphoramidate of d4T that result in enhancing lipophilicity may serve to increase the cellular uptake of the prodrug by passive diffusion, leading to the expression of antiviral potency at reduced prodrug concentrations.
Integrated plasmonic semi-circular launcher for dielectric-loaded surface plasmon-polariton waveguide (2011)

A semi-circular plasmonic launcher integrated with dielectric-loaded surface plasmon-polaritons waveguide (DLSPPW) is proposed and analyzed theoretically, which can focus and efficiently couple the excited surface plasmon polaritons (SPPs) into the DLSPPW via the highly matched spatial field distribution with the waveguide mode in the focal plane. By tuning the incident angle or polarization of the illuminating beam, it is shown that the launcher may be conveniently used as a switch or a multiplexer that have potential applications in plasmonic circuitry. Furthermore, from an applicational point of view, it is analyzed how the coupling performance of the launcher can be further improved by employing multiple semi-circular slits.
Whose Sweet Angel Child? Blues Women, Langston Hughes, and Writing during the Harlem Renaissance (1996)

Reckless Blues When I was young, nothing but a child,When I was young, nothing but a child,All you men tried to drive me wild. Now I'm growing old,Now I'm growing old,And I got what it takes to get all you men's soul. My mama says I'm reckless, my daddy says I'm wild,My mama says I'm reckless, my daddy says I'm wild,I ain't good lookin', but I'm somebody's angel child. Daddy, Mama wants some loving; Daddy, mama wants some huggingHoney, Pretty Poppa, Mama wants some loving, I vow.Honey, Pretty...
RNA and DNA isolation from recalcitrant plant tissues. (1990)

Cet article rapporte un procede d'isolement et de purification de DNA et de RNA a partir de tissus de plantes (exemple: Pinus)
Learning modular policies for robotics (2014)

A promising idea for scaling robot learning to more complex tasks is to use elemental behaviors as building blocks to compose more complex behaviour. Ideally, such building blocks are used in combination with a learning algorithmthat is able to learn to select, adapt, sequence and co-activate the building blocks. While there has been a lot of work on approaches that support one of theserequirements, no learning algorithm exists that unifies all these properties in one framework.%Adaptation of the parameter vector is needed to reuse the elemental behaviours for more than one situation. %Second, the learning architecture needs to learn to select between and to sequence such parametrized building blocks. Finally,%the expressibility of a modular control architecture can be drastically increased if the architecture supports co-activate the single building blocks.%In this paper we give an overview of our work on learning such a modular control architecture. In this paper we present our work on a unified approach for learning such a modular control architecture. We introduce new policy search algorithmsthat are based on information-theoretic principles and are able to learn to select, adapt and sequence the building blocks. Furthermore, we developed a new representation for the individual building block that support co-activation and principled ways for adapting the movement. Finally, we summarize our experiments for learning modular control architectures in simulation and with real robots.
Breast cancer patient's cell-mediated immune response to thomsen-friedenreich (T) antigen (1980)

Thomsen-Friedenreich (T) antigenic specificity as determined with human serum anti-T was found in reactive form in breast adenocarcinomata but not in healthy and generally not in benign breast tissues. T-antigenic specificity was demonstrable in all metastatic breast carcinoma lesions. T specificity was also present in adeno- and squamous cell carcinomata from other organs; it was not found in the four melanomata, one glioblastoma, and seven benign non-breast tumors. Breast carcinoma patients but not healthy people showed cellular immunity to T antigen in vivo and in vitro. Most striking was the delayed-type cutaneous hypersensitivity reaction that was positive in over 85% of the ductal breast carcinoma patients tested, negative in over 94% benign breast disease patients, and in all presumably healthy individuals investigated. T antigen is readily available from healthy red blood cells in uncontaminated form, and free of HL-A and Australia antigens.
Identification of Tyr-185 as the site of tyrosine autophosphorylation of recombinant mitogen-activated protein kinase p42mapk. (1992)

Tyrosine phosphorylation of 42-kDa mitogen-activated protein kinase (p42mapk) occurs during expression of the recombinant protein in Escherichia coli, as well as during in vitro phosphorylation of the protein purified from this source. Structural analyses were performed to identify the site(s) of tyrosine phosphorylation of recombinant p42mapk, both during expression of the protein in E. coli and during in vitro incubations with ATP/Mg2+/Mn2+. Mass spectrometry and phosphopeptide mapping showed that tyrosine phosphorylation of recombinant p42mapk occurs on Tyr-185, the site of regulatory tyrosine phosphorylation that occurs in mitogen-stimulated mammalian cells.
CD94/NKG2 is the predominant inhibitory receptor involved in recognition of HLA-G by decidual and peripheral blood NK cells (1997)

Prior studies demonstrated that NK cells isolated from adult peripheral blood kill the HLA-A-, HLA-B-, and HLA-C-deficient B lymphoblastoid cell line 721.221, but many are unable to kill 721.221 cells transfected with HLA-G, a molecule expressed preferentially on fetal cytotrophoblasts. To determine the biologic relevance of this recognition, we established NK cell clones from the placenta and demonstrate that these NK cells also were unable to kill 721.221 cells expressing HLA-G. Recognition of HLA-G by NK cells was prevented in the presence of anti-CD94 mAb, implicating CD94/NKG2 as the predominant inhibitory NK cell receptor for HLA-G used by decidual NK cells. In contrast, mAbs against the killer cell inhibitory receptors recognizing HLA-Cw3-related, HLA-Cw4-related, or HLA-Bw4 ligands did not affect NK cell killing of the HLA-G transfectants.