gebhart/patrepeval huggingface dataset:
¿Es posible encontrar un fitoestrógeno para la terapia de reemplazo hormonal, que disminuya el riesgo de cáncer? – Tema de Proyecto Anillos de Investigación del Programa Bicentenario en Ciencia y Tecnología (2007)

Se describe una nueva linea de investigacion que tiene como objetivo investigar principios activos presentes en especies vegetales chilenas, para identificar alguna(s) que produzcan los efectos farmacologicos deseables para su uso como terapia de reemplazo hormonal en mujeres peri o postmenopausicas, pero que no aumenten, o incluso disminuyan, el riesgo de desarrollar cancer mamario o endometrial. Esta posibilidad se basa en el hallazgo previo de nuestro equipo de investigadores de un nuevo tipo de receptores estrogenicos responsables de respuestas estrogenicas no genomicas y de nuestro hallazgo de diferencias entre los receptores estrogenicos citosolico-nucleares clasicos de los diferentes tipos celulares uterinos. Si existiera, como anteriormente se creia, un solo tipo de receptor de estrogenos, no seria posible el desarrollo de este nuevo farmaco estrogenico selectivo que buscamos, pues todos los receptores tendrian la misma afinidad por este agente, el que en consecuencia, induciria todas las respuestas a la estimulacion estrogenica (incluyendo aquellas que deseamos prevenir, como las que presentan riesgo de desarrollo de cancer), o que actuaria como antiestrogeno, antagonizando todas las respuestas a los estrogenos en el utero. La existencia de multiples receptores estrogenicos, diferentes entre si, permite la posibilidad de disociar las diversas respuestas, es decir, inducir aquellas que se busca con fines terapeuticos, pero no aquellos efectos adversos o respuestas que presenten riesgo. Si se llega a descubrir un principio activo con estos requisitos, seria patentable
The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders (2021)

Despite the increasing impact of opioid use disorders on society, there is a disturbing lack of effective medications for their clinical management. An interesting innovative strategy to treat these disorders consists in the protection of endogenous opioid peptides to activate opioid receptors, avoiding the classical opioid-like side effects. Dual enkephalinase inhibitors (DENKIs) physiologically activate the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins and increasing their half-lives and physiological actions. The activation of opioid receptors by the increased enkephalin levels, and their well-demonstrated safety, suggests that DENKIs could represent a novel analgesic therapy and a possible effective treatment for acute opioid withdrawal, as well as a promising alternative to opioid substitution therapy minimizing side effects. This new pharmacological class of compounds could bring effective and safe medications avoiding the major limitations of exogenous opioids, representing a novel approach to overcome the problem of opioid use disorders. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.
IDO, une enzyme dangereuse pour l’obésité (2018)

International audience
Activation of the virus-induced IKK/NF-?B signalling axis is critical for the replication of human cytomegalovirus in quiescent cells (2007)

Activation of the IKK/NF-kappaB signalling pathway is a hallmark of human cytomegalovirus (HCMV) infection. However, its role in regulating major immediate-early promoter (MIEP)-dependent transcription and HCMV replication remains controversial. This study uses a combination of genetic approaches to investigate the effects of cell culture conditions on the importance of virus-induced NF-kappaB activation during the infection of endothelial cells or fibroblasts. Adenoviral-mediated expression of a dominant-negative mutant of IKK2 kinase (dnIKK2) in human umbilical vein endothelial cells resulted in a strong reduction of IkappaBalpha degradation and NF-kappaB activation following infection with an HCMV clinical isolate. Viral replication was impaired in dnIKK2-expressing cells that were growth-arrested before infection, but not in replicating cells. The inhibitory effect of dnIKK2 was independent from the virus strain and the cell type used, because replication of the laboratory AD169 strain was impaired as well in dnIKK2-expressing quiescent fibroblasts. Moreover, progressive disruption of NF-kappaB response elements within the MIEP in recombinant HCMV viruses derived from the clinical isolate prevented their replication in quiescent cells but not in actively growing cells. These results demonstrate an essential role of virus-induced IKK/NF-kappaB activity to trigger both viral IE gene expression and productive replication in quiescent cells.
NOX2 inhibition reduces oxidative stress and prolongs survival in murine KRAS-induced myeloproliferative disease (2018)

Mutations leading to constitutive RAS activation contribute in myeloid leukemogenesis. RAS mutations in myeloid cells are accompanied by excessive formation of reactive oxygen species (ROS), but the source of ROS and their role for the initiation and progression of leukemia have not been clearly defined. To determine the role of NOX2-derived ROS in RAS-driven leukemia, double transgenic LSL-Kras<sup>G12D</sup> × Mx1-Cre mice expressing oncogenic KRAS in hematopoietic cells (M-Kras<sup>G12D</sup>) were treated with N<sup>α</sup>-methyl-histamine (NMH) that targeted the production of NOX2-derived ROS in leukemic cells by agonist activity at histamine H<sub>2</sub> receptors. M-Kras<sup>G12D</sup> mice developed myeloid leukemia comprising mature CD11b<sup>+</sup>Gr1<sup>+</sup> myeloid cells that produced NOX2-derived ROS. Treatment of M-Kras<sup>G12D</sup> mice with NMH delayed the development of myeloproliferative disease and prolonged survival. In addition, NMH-treated M-Kras<sup>G12D</sup> mice showed reduction of intracellular ROS along with reduced DNA oxidation and reduced occurence of double-stranded DNA breaks in myeloid cells. The in vivo expansion of leukemia was markedly reduced in triple transgenic mice where KRAS was expressed in hematopoietic cells of animals with genetic NOX2 deficiency (Nox2<sup>-/-</sup> × LSL-Kras<sup>G12D</sup> × Mx1-Cre). Treatment with NMH did not alter in vivo expansion of leukemia in these NOX2-deficient transgenic mice. We propose that NOX2-derived ROS may contribute to the progression of KRAS-induced leukemia and that strategies to target NOX2 merit further evaluation in RAS-mutated hematopoietic cancer.
Limits on the performance of near field phase aberration correction (2002)

Speed of sound inhomogeneities cause significant degradation of ultrasonic images. In some parts of the body inhomogeneities can be modeled as a thin time delay screen at the surface of the skin. Such aberrators may be compensated for by adjusting time delays used for transmit and receive focusing. This compensation is subject to error because of imperfect estimation of the required compensating time delays (time delay estimation error or TDEE) and because of integration of the aberrator across relatively large array elements (aberrator integration error or AIE). The authors present analytical expressions which predict the magnitude of AIE and TDEE. They also present expressions which describe the accumulation of errors for a number of array geometries. The derived expressions are utilized in examples which illustrate the tradeoffs inherent to the design of phase aberration correction algorithms and transducers. These examples indicate that two-dimensional arrays with as many as one thousand elements may be needed for accurate phase aberration correction.
Characterization of the platelet agglutinating activity of thrombospondin (1985)

Thrombospondin (TSP) is a glycoprotein secreted from the alpha-granules of platelets upon activation. In the presence of divalent cations, the secreted protein binds to the surface of the activated platelets and is responsible for the endogenous lectin-like activity associated with activated platelets. Platelets fixed with formaldehyde following activation by thrombin are agglutinated by exogenously added TSP. Fixed, nonactivated platelets are not agglutinated. The platelet agglutinating activity of TSP is optimally expressed in the presence of 2 mM each of Mg2+ and Ca2+. Reduction of the disulfide bonds within the TSP molecule inhibits its platelet agglutinating activity. TSP bound to the surface of fixed, activated platelets can be eluted by the addition of disodium ethylenediaminetetraacetate. This approach was exploited to identify the region of the TSP molecule containing the platelet binding site. The binding site resides within a thermolytic fragment of TSP with Mr 140 000 but is not present in the Mr 120 000 fragment derived from the polypeptide of Mr 140 000. Since both the Mr 140 000 and 120 000 fragments contain fibrinogen binding sites, this finding suggests that the binding of TSP to the platelet surface requires interaction with other platelet surface components in addition to fibrinogen. The observation that fibrinogen only partially inhibits the TSP-mediated agglutination of fixed, activated platelets is consistent with this interpretation.
N-Methylation dissociates methamphetamine's neurotoxic and behavioral pharmacologic effects (1997)

The present studies further examined the effect of N-methylation on the behavioral and neurotoxic effects of methamphetamine. Drug discrimination studies employing a training dose of 1 mg/kg of methamphetamine were used to confirm and extend previous behavioral studies indicating that N-methylation reduced the behavioral activity of methamphetamine 5- to 10-fold. In subsequent neurotoxicity studies, rats received doses of methamphetamine (10 mg/kg, s.c., every 6 h x 5) or its N-methylated derivative, N,N-dimethylamphetamine (100 mg/kg, s.c., every 6 h x 5) that, based on the results of the behavioral studies, would be expected to produce behaviorally equivalent effects. Saline-treated rats served as controls. Two weeks after treatment, the status of brain dopamine (DA) and serotonin (5-HT) neurons was assessed by measuring DA and 5-HT axon terminal markers. As anticipated, methamphetamine produced neurochemical deficits indicative of DA and 5-HT axon terminal damage. By contrast, despite the fact that it was given at a dose behaviorally equivalent to methamphetamine, N-N-dimethylamphetamine failed to produce signs of DA or 5-HT neurotoxicity. These results indicate that N-methylation dissociates methamphetamine's neurotoxic and behavioral pharmacologic effects, and suggest that it may be possible to separate the neurotoxic and pharmacologic effects of other substituted amphetamine derivatives with potentially useful clinical activity (e.g. fenfluramine and methylenedioxymethamphetamine).
Differential Transmission Spectroscopy (DTS) in Cu2O in the Presence of Cold Excitons (2000)

A high density of cold 1s orthoexcitons was created in Cu2O using two counterpropagating high-power femtosecond infrared (IR) laser beams tuned to half the 1s exciton resonance energy. The initial 1s exciton gas density was estimated to reach up to 1020 cm—3. The resulting differential absorption spectrum revealed a pronounced screening of the yellow np absorption lines, up to complete disappearance of the 2p exciton for the highest pump intensity. On the other hand, no change in the n = 1 phonon-assisted absorption continuum was detected, showing that the Mott condition for dissociation into a two-component plasma was not reached for the n = 1 excitons.
The Representation of Interaural Time Differences in High-Frequency Auditory Cortex (2014)

Early representations of auditory features often involve neuronal populations whose tuning is substantially wider than behavioral discrimination thresholds. Although behavioral discrimination performance can be sometimes achieved by single neurons when using the appropriate part of their (wide) tuning curves, neurons that encode the resulting high-acuity representations have rarely been described. Here we demonstrate the existence of neurons with extremely narrow tuning for interaural time differences (ITDs), a major physical cue for the azimuth of sound sources. The tuning width of ITD-tuned brainstem neurons is mostly determined by the properties of their acoustic input, and may be 10-100 times wider than behavioral thresholds. In contrast, we show that tuning widths of some neurons in the primary auditory cortex in the cat high-frequency auditory cortex (measured using transposed stimulus) can be very sharp and approach behavioral thresholds. Furthermore, while best ITDs of brainstem neurons often lie outside the range of naturally encountered ITDs (the ethological range), the range of best ITDs of the narrowly tuned cortical neurons corresponds well to the ethological range. Thus, our results suggest that the auditory cortex contains a high-resolution representation of ITDs that explicitly decodes the widely tuned brainstem representations.
Synthesis and characterization of side‐chain liquid crystalline polysiloxanes containing oligooxyethylene spacers and benzyl ether based mesogenic groups (1990)

Abstract The synthesis of side‐chain liquid crystalline polysiloxanes containing oligooxyethylene spacers and 4‐methoxyphenyl benzyl ether and 6‐cyano‐2‐naphthyl benzyl ether based mesogenic groups is presented. The phase behavior of both monomeric and polymeric liquid crystals was characterized by differential scanning calorimetry and optical polarized microscopy. All synthesized polysiloxanes present smectic mesomorphism. The insertion of oxygen atoms into the flexible aliphatic spacers leads to decrease in both glass transition and isotropization temperatures of the resulting side‐chain liquid crystalline polymers.
ORBIT: A Real-World Few-Shot Dataset for Teachable Object Recognition (2021)

Object recognition has made great advances in the last decade, but predominately still relies on many high-quality training examples per object category. In contrast, learning new objects from only a few examples could enable many impactful applications from robotics to user personalization. Most few-shot learning research, however, has been driven by benchmark datasets that lack the high variation that these applications will face when deployed in the real-world. To close this gap, we present the ORBIT dataset and benchmark, grounded in the real-world application of teachable object recognizers for people who are blind/low-vision. The dataset contains 3,822 videos of 486 objects recorded by people who are blind/low-vision on their mobile phones. The benchmark reflects a realistic, highly challenging recognition problem, providing a rich playground to drive research in robustness to few-shot, high-variation conditions. We set the benchmark's first state-of-the-art and show there is massive scope for further innovation, holding the potential to impact a broad range of real-world vision applications including tools for the blind/low-vision community. We release the dataset at https://doi.org/10.25383/city.14294597 and benchmark code at https://github.com/microsoft/ORBIT-Dataset.
Development of a Practical Synthesis of a Pyrazolopyridinone-Based p38 MAP Kinase Inhibitor (2010)

A practical synthesis of the pyrazolopyridinone-based p38 MAP kinase inhibitor (4) was required for an ongoing program. The synthesis of a key pyrazolopyridinone building block was refined and optimized to provide kilogram quantities of 10 without chromatography or extractive workups. An efficient building-block strategy was employed to give optimal control of the key quality attributes, and in situ Raman spectroscopy was used to monitor and understand the complex solid-state properties of 4.
MAP-1B/TAU functional redundancy during laminin-enhanced axonal growth (1996)

When cultured cerebellar macroneurons develop attached to a laminin-containing substrate or after the acute addition of laminin to the tissue culture medium, there is an acceleration in the rate and extent of axonal elongation. Furthermore, laminin is capable of inducing axonal formation and microtubule stabilization in neurons arrested at stage II of neuritic development by tau suppression (Caceres and Kosik, 1990; Caceres et al., 1991). Laminin-enhanced or induced axonal extension is paralleled by a selective and dramatic incorporation of phosphorylated MAP-1b into axonal microtubules. Axonal formation in neurons growing in the presence of laminin is prevented by treatment of the cultures with a mixture of MAP-1b and tau antisense oligonucleotides, but not by the single suppression of any one of these MAPs. However, suppression of MAP-1b, but not of tau, greatly reduces the increase in the rate and extent of axonal elongation induced by laminin. No such effects are elicited by MAP-1b antisense oligonucleotides in neurons growing in the absence of laminin, e.g. polylysine alone, where most of the MAP-1b present in the cells is dephosphorylated and not associated with the cytoskeleton. Taken collectively, these data suggest that, with regard to axonal elongation, MAP-1b and tau can be functionally substituted, and that extracellular matrix molecules, such as laminin, affect axonal extension by promoting the in vivo utilization of MAP-1b.
A Voltage Drop-Based Approach to Include Cold Load Pickup in Design of Distribution Systems (2004)

In distribution systems with large residential load, thermostatically controlled devices contribute major portion of total load. Restoration of such systems after prolonged interruption may create a load significantly higher than the normal load. This condition is called cold load pickup (CLPU). The enduring component of CLPU may cause severe voltage drops along the feeders and transformer heating, thus making the system restoration difficult. This paper discusses an approach to include restoration under CPLU conditions in distribution system planning and expansion. The approach can be applied to determine the most optimal transformer size and feeder sizes while ensuring the minimal restoration time and acceptable voltages and transformer heating during CLPU conditions. The aim is to develop a tool that can be used in conjunction with the overall distribution system design to ensure quality power even in emergency conditions while minimizing the cost.
Evaluation of Neutrophil Gelatinase-Associated Lipocalin as a Marker of Kidney Injury in Dogs (2013)

NGAL/creatinine ratio is a sensitive and specific marker of AKI. It can be used to screen patients at risk for AKI and can be utilized to diagnose milder forms of AKI potentially earlier in the course of the disease.
Visual QC Protocol for FreeSurfer Cortical Parcellations from Anatomical MRI (2022)

Quality control of morphometric neuroimaging data is essential to improve reproducibility. Owing to the complexity of neuroimaging data and subsequently the interpretation of their results, visual inspection by trained raters is the most reliable way to perform quality control. Here, we present a protocol for visual quality control of the anatomical accuracy of FreeSurfer parcellations, based on an easy-to-use open-source tool called VisualQC. We comprehensively evaluate its utility in terms of error detection rate and inter-rater reliability on two large multi-site datasets and discuss site differences in error patterns. This evaluation shows that VisualQC is a practically viable protocol for community adoption.
Metabolic engineering of Escherichia coli BL21 (DE3) for de novo production of l-DOPA from d-glucose (2019)

Deletion of key enzymes to channel flux towards the shikimate pathway coupled with the overexpression of pathway enzymes enhanced the availability of L-tyrosine for L-DOPA production. Enhancing the activity of HpaB increased L-DOPA production from glucose and glycerol. This work demonstrates that increasing the availability of L-tyrosine and enhancing enzyme activity ensures maximum L-DOPA productivity.
Suppression of attenuation of leaky surface acoustic waves by loading dielectric thin-film (2002)

The attenuation characteristics of leaky surface acoustic waves (LSAWs) on rotated Y-cut X-propagating LiNbO/sub 3/ loaded with dielectric thin-films such as Ta/sub 2/O/sub 5/ and SiO/sub 2/ were investigated theoretically and experimentally. The calculated attenuation as a function of the rotation angle from the Y-axis showed that the rotation angle giving the zero-attenuation shifts as the film-thickness is increased. This means that, within a certain range of the rotation angle, the attenuation can be suppressed by choosing the kind of film and its thickness. In fact, for the two cases of the free surface of 64/spl deg/ Y-X LiNbO/sub 3/ with RF-sputtered Ta/sub 2/O/sub 5/ film and the metallized surface of 41/spl deg/ Y-X LiNbO/sub 3/ with RF-sputtered SiO/sub 2/ film, the measured propagation losses decreased to 1/4/spl sim/1/2 in comparison to the sample without a film.
Establishing Appropriate Trust via Critical States (2018)

In order to effectively interact with or supervise a robot, humans need to have an accurate mental model of its capabilities and how it acts. Learned neural network policies make that particularly challenging. We propose an approach for helping end-users build a mental model of such policies. Our key observation is that for most tasks, the essence of the policy is captured in a few critical states: states in which it is very important to take a certain action. Our user studies show that if the robot shows a human what its understanding of the task's critical states is, then the human can make a more informed decision about whether to deploy the policy, and if she does deploy it, when she needs to take control from it at execution time.
The role of pit-1 in the regulation of the rat growth hormone-releasing hormone receptor gene transcription by glucocorticoids (2005)

Glucocorticoids are involved in the regulation of the rat growth hormone-releasing hormone (GHRH) receptor gene expression, but they act only in the presence of the pituitary specific transcription factor, pit-1. In this study, the role of pit-1 in the glucocorticoid stimulation of the GHRH-receptor gene transcription was examined. The results suggest the presence of a silencer element in the promoter and it is postulated that pit-1 permits glucocorticoid action through suppressing the inhibitory effect of an as yet unknown factor that binds to this element. The present results also suggest that the synergistic activation of the rat GHRH-receptor gene transcription depends on the proper distance between the proximal glucocorticoid response element and the pit-1 binding site.