111 research outputs found
Актуальные проблемы современного общества глазами начинающих социологов
Article is dedicated to the analysis of “Sociology” session held as a part of the International conference for students, post-graduate students and young scientists “Lomonosov-2015”. Authors, professors of the MSU Faculty of Sociology, argue that such events are crucial in terms recruitment and retaining of the young talents. Article also presents analysis of the papers presented at the conference which helps to have a deeper understanding of the young scholars’ scientific interests.Статья посвящена итогам проведения секции “Социология” Международной конференции студентов, аспирантов и молодых ученых “Ломоносов-2015”. Авторы обосновывают эффективность и необходимость подобных мероприятий как способа поиска и удержания талантливой молодежи. В статье также проводится анализ тематики докладов участников конференции, что позволяет составить представление об области научных интересов современных молодых исследователей
Investigating knowledge management factors affecting Chinese ICT firms performance: An integrated KM framework
This is an Author's Accepted Manuscript of an article published in the Journal of Information Systems Management, 28(1), 19 - 29, 2011, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/10580530.2011.536107.This article sets out to investigate the critical factors of Knowledge Management (KM) which are considered to have an impact on the performance of Chinese information and communication technology (ICT) firms. This study confirms that the cultural environment of an enterprise is central to its success in the context of China. It shows that a collaborated, trusted, and learning environment within ICT firms will have a positive impact on their KM performance
Cognitive function in a randomized trial of evolocumab
Inga Stuķēna as well as a complete list of investigators is provided in the Supplementary Appendix, available at NEJM.org. https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701131/suppl_file/nejmoa1701131_appendix.pdf Funding Information: (Funded by Amgen; EBBINGHAUS ClinicalTrials.gov number, NCT02207634.) Supported by Amgen. We thank Sarah T. Farias, Ph.D., at UC Davis Health for providing the English-language and translated versions of the Everyday Cognition (ECog) tool. Publisher Copyright: Copyright © 2017 Massachusetts Medical Society.BACKGROUND: Findings from clinical trials of proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. METHODS: In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group. RESULTS: A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was −0.21±2.62 in the evolocumab group and −0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, −0.52 in the evolocumab group and −0.93 in the placebo group), episodic memory (change in raw score, −1.53 and −1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). In an exploratory analysis, there were no associations between LDL cholesterol levels and cognitive changes. CONCLUSIONS: In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months.publishersversionPeer reviewe
Space-VLBI observations of OH maser OH34.26+0.15: low interstellar scattering
We report on the first space-VLBI observations of the OH34.26+0.15 maser in
two main line OH transitions at 1665 and 1667 MHz. The observations involved
the space radiotelescope on board the Japanese satellite HALCA and an array of
ground radio telescopes. The map of the maser region and images of individual
maser spots were produced with an angular resolution of 1 milliarcsec which is
several times higher than the angular resolution available on the ground. The
maser spots were only partly resolved and a lower limit to the brightness
temperature 6x10^{12} K was obtained. The maser seems to be located in the
direction of low interstellar scattering, an order of magnitude lower than the
scattering of a nearby extragalactic source and pulsar.Comment: 8 pages, 2 tables, 9 figures, accepted for publication in MNRA
СПОСОБ РАЗДЕЛЬНОГО ОПРЕДЕЛЕНИЯ СОПРОТИВЛЕНИЙ ОБРАЗЦА ВЫСОКООМНОГО ПОЛУПРОВОДНИКА И КОНТАКТОВ К ОБРАЗЦУ
The method of separate determination of two−pole sample volume resistance and contact resistance is suggested. The method described is applicable to high−ohmic semiconductor samples: semiinsulating gallium arsenide, detector cadmium−zinc tel- luride (CZT), etc. The method is based on near−contact region illumination by monochromatic radiation of variable intensity from light emitting diodes with quantum energy exceeding band gap width of investigated material. It is necessary to obtain sample photo−current dependence upon light emitting diode current and to find the straight−line part of this dependence. The extrapola- tion of this linear part to ordinate axis gives cut−off current value. As bias voltage is known, it is easy to calculate sample volume resistance value. Afterwards, using dark current value, it is pos- sible to determine total contact resistance. The method was approbated on n−type semiinsulating GaAs sample. Contact resistance value was shown to be approximately equal to sample volume resistance. It means that influence of contacts must be taken into account when electrophysical data is analyzed.Предложен метод раздельного определения сопротивлений образца−двухполюсника и контактов к нему, который применим к образцам высокоомных полупроводниковых материалов: полуизолирующего арсенида галлия, детекторного теллурида кадмия−цинка (КЦТ) и др. Метод основан на засветке приконтакных областей образца моно- хроматическим излучением регулируемой интенсивности от светодиодов с энергией кванта, превышающей ширину запрещенной зоны исследуемого материала. Экстраполяция прямолинейного участка зависимости фототока через образец от тока через светодиоды к оси ординат позволяет найти ток отсечки, после чего по из- вестным значениям тока отсечки и напряжения смещения вычисляют значение сопротивления объема об- разца. Далее, зная темновое значение тока через образец, можно вычислить суммарное сопротивление контактов образца−двухполюсника. Метод опробован на образце полуизолирующего арсенида галлия n−типа электропроводности. Линейность контактов проверена по вольт−амперным характеристикам. Показано, что сопротивление контактов близко к сопротивлению объема образца, что подтверждает необходимость учета влияния контактов при анализе данных электрофизических измерений
Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life
<p>Abstract</p> <p>Background</p> <p>The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas.</p> <p>Methods</p> <p>Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA), a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1<sup>st </sup>bolus of Gd-DTPA over the first hour, and then re-imaged with a 2<sup>nd </sup>bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods.</p> <p>Results</p> <p>The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve.</p> <p>Conclusion</p> <p>Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature.</p
Selective Interaction of Syntaxin 1A with KCNQ2: Possible Implications for Specific Modulation of Presynaptic Activity
KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability. Notably, they differ from homomeric KCNQ2 channels in their distribution pattern within neurons, with unique expression of KCNQ2 in axons and nerve terminals. Here, combined reciprocal coimmunoprecipitation and two-electrode voltage clamp analyses in Xenopus oocytes revealed a strong association of syntaxin 1A, a major component of the exocytotic SNARE complex, with KCNQ2 homomeric channels resulting in a ∼2-fold reduction in macroscopic conductance and ∼2-fold slower activation kinetics. Remarkably, the interaction of KCNQ2/Q3 heteromeric channels with syntaxin 1A was significantly weaker and KCNQ3 homomeric channels were practically resistant to syntaxin 1A. Analysis of different KCNQ2 and KCNQ3 chimeras and deletion mutants combined with in-vitro binding analysis pinpointed a crucial C-terminal syntaxin 1A-association domain in KCNQ2. Pull-down and coimmunoprecipitation analyses in hippocampal and cortical synaptosomes demonstrated a physical interaction of brain KCNQ2 with syntaxin 1A, and confocal immunofluorescence microscopy showed high colocalization of KCNQ2 and syntaxin 1A at presynaptic varicosities. The selective interaction of syntaxin 1A with KCNQ2, combined with a numerical simulation of syntaxin 1A's impact in a firing-neuron model, suggest that syntaxin 1A's interaction is targeted at regulating KCNQ2 channels to fine-tune presynaptic transmitter release, without interfering with the function of KCNQ2/3 channels in neuronal firing frequency adaptation
Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells
<p>Abstract</p> <p>Background</p> <p>Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells.</p> <p>Methods</p> <p>Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured <it>in vivo </it>with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed <it>ex vivo </it>with fluorescence imaging.</p> <p>Results</p> <p>We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells.</p> <p>Conclusion</p> <p>The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.</p
Spontaneous motion of localized structures and localized patterns induced by delayed feedback
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