The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in-vitro endothelial cell model

BACKGROUND: During the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model. RESULTS: The results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area. CONCLUSIONS: These findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.Israel Cancer Research Fund (ICRF), Teva Pharmaceutical Industries Ltd

Threshold responses to morphogen gradients by zero-order ultrasensitivity

Translating a graded morphogen distribution into tight response borders is central to all developmental processes. Yet, the molecular mechanisms generating such behavior are poorly understood. During patterning of the Drosophila embryonic ventral ectoderm, a graded mitogen-activated protein kinase (MAPK) activation is converted into an all-or-none degradation switch of the Yan transcriptional repressor. Replacing the cardinal phosphorylated amino acid of Yan by a phosphomimetic residue allowed its degradation in a MAPK-independent manner, consistent with Yan phosphorylation being the critical event in generating the switch. Several alternative threshold mechanisms that could, in principle, be realized by this phosphorylation, including first order, cooperativity, positive feedback and zero-order ultrasensitivity, were analyzed. We found that they can be distinguished by their kinetics and steady-state responses to Yan overexpression. In agreement with the predictions for zero-order kinetics, an increase in Yan levels did not shift the degradation border, but significantly elevated the time required to reach steady state. We propose that a reversible loop of Yan phosphorylation implements a zero-order ultrasensitivity-like threshold mechanism, with the capacity to form sharp thresholds that are independent of the level of Yan

A thermionic energy converter with a molybdenum-alumina cermet emitter

A study is made of the properties of cermets as electrode materials for thermionic energy converters. For thermodynamic reasons it is expected that all cermets composed of pure Mo and refractory oxides have the same bare work function. From data on the work function of Mo in an oxygen atmosphere this bare work function is estimated to be F=4.9 eV (at T=1400¿°C). Experimentally, the bare work function of Al2O3-Mo cermets was found to be F=4.5 eV, independent of the relative amounts of Al2O3 and Mo. The cesiated work function of the Al2O3-Mo cermets was found to be 0.15 eV lower than the cesiated work function of pure Mo. The bare work function of Mo3Al was found to be F=4.0 eV. The cesiated work function of Mo3Al at collector temperature conditions was 0.3 eV lower than the cesiated work function of pure Mo. The electrical power density of a diode with an Al2O3-Mo cermet emitter was 0.4 W/cm2 at 1300¿°C. The barrier index at this temperature was 2.36 V. The high barrier index is attributed to a high plasma voltage drop Vd=0.91 V

The effect of nanoparticle size on the probability to cross the blood-brain barrier: an in-vitro endothelial cell model.

BACKGROUND: During the last decade nanoparticles have gained attention as promising drug delivery agents that can transport through the blood brain barrier. Recently, several studies have demonstrated that specifically targeted nanoparticles which carry a large payload of therapeutic agents can effectively enhance therapeutic agent delivery to the brain. However, it is difficult to draw definite design principles across these studies, owing to the differences in material, size, shape and targeting agents of the nanoparticles. Therefore, the main objective of this study is to develop general design principles that link the size of the nanoparticle with the probability to cross the blood brain barrier. Specifically, we investigate the effect of the nanoparticle size on the probability of barbiturate coated GNPs to cross the blood brain barrier by using bEnd.3 brain endothelial cells as an in vitro blood brain barrier model. RESULTS: The results show that GNPs of size 70 nm are optimal for the maximum amount of gold within the brain cells, and that 20 nm GNPs are the optimal size for maximum free surface area. CONCLUSIONS: These findings can help understand the effect of particle size on the ability to cross the blood brain barrier through the endothelial cell model, and design nanoparticles for brain imaging/therapy contrast agents.Israel Cancer Research Fund (ICRF), Teva Pharmaceutical Industries Ltd

Новый сортообразец льна многолетнего (Línum perénne L.) Блюз селекции ФГБНУ ФНЦО

Relevance and research material. Flax is a perennial herbaceous plant with a high decorative value, with a long flowering, blooms in the first year of vegetation. The plant is undemanding to the growing conditions. As a result of multiple selection selections from a foreign variety, the long-term flax variety No. L-22 "Blues" recommended for use for decorative purposes was derived. The leaves and the bright color of the flowers provide a contrast to the perennial borders and flower beds. It looks good both in single and group plantings, as well as in cutting.Results. The study was carried out in the open ground of the Moscow Region (2015-2022) on experimental plots of the flower crops sector of the Federal Scientific Vegetable Center. The most aligned form according to decorative features is L–22 with high seed productivity of inflorescences, decorative and winter hardiness. Variety testing and preliminary propagation of a promising long-term flax variety was carried out. Signs such as "plant height"Актуальность и материал исследований. Лен – многолетнее травянистое растение, обладающее высокой декоративностью, с продолжительным цветением, зацветает в первый год вегетации. Растение нетребовательное к условиям произрастания. В результате многократных селекционных отборов из иностранного сорта, выведен сортообразец льна многолетнего №Л22 Блюз, рекомендованный к использованию в декоративных целях. Листья и яркая окраска цветков обеспечивают контраст многолетним бордюрам и клумбам. Хорошо смотрится как в одиночных так и групповых посадках, а так же в срезке.Результаты. Изучение льна многолетнего проводилось в открытом грунте Московской области (2015-2022 годы) на опытных участках сектора цветочных культур ФГБНУ ФНЦО. Выделена наиболее выровненная по декоративным признакам форма – Л-22 с высокой семенной продуктивностью соцветий, декоративностью и зимостойкостью. Проведено сортоиспытание и предварительное размножение перспективного сортообразца льна многолетнего. Такие признаки как «высота растения», «диаметр куста», «число декоративных побегов», «диаметр цветка», имели низкое или среднее значение варьирования, что характеризует данный образец как наиболее выровненный. Таким образом, сортообразец лена многолетнего, рекомендован к выращиванию и использованию в декоративных целях. Голубая окраска цветков обеспечивают контраст многолетним бордюрам и клумбам, поэтому он пользуется большой популярностью у садоводов. Используется в самых разных групповых композициях: в миксбордерах, альпинариях, цветниках и бордюрах, хорошо смотрится в срезке. Отличается стойкостью окраски цветков при выгорании на солнце; устойчивостью к болезням и вредителям; большим количеством цветков на растении; высокой семенной продуктивностью

ИТОГИ РАБОТЫ ЛАБОРАТОРИИ СТАНДАРТИЗАЦИИ, НОРМИРОВАНИЯ И МЕТРОЛОГИИ ВНИИССОК

The results of the laboratory of standardization, regulation and metrology in recent years are shown. Based on research, two intergovernmental standards, one national standard, and 24 standards of the organization were developed, agreed, approved, and put into effect.Приведены результаты работы лаборатории стандартизации, нормирования и метрологии за последние годы. В институте на основании исследований разработаны, согласованы, утверждены и введены в действие: два межгосударственных стандарта, один национальный стандарт и 24 стандарта организации

Information Needs and Requirements for Decision Support in Primary Care: An Analysis of Chronic Pain Care

Decision support system designs often do not align with the information environments in which clinicians work. These work environments may increase Clinicians’ cognitive workload and harm their decision making. The objective of this study was to identify information needs and decision support requirements for assessing, diagnosing, and treating chronic noncancer pain in primary care. We conducted a qualitative study involving 30 interviews with 10 primary care clinicians and a subsequent multidisciplinary systems design workshop. Our analysis identified four key decision requirements, eight clinical information needs, and four decision support design seeds. Our findings indicate that clinicians caring for chronic pain need decision support that aggregates many disparate information elements and helps them navigate and contextualize that information. By attending to the needs identified in this study, decision support designers may improve Clinicians’ efficiency, reduce mental workload, and positively affect patient care quality and outcomes

MicroRNA-26a Is Strongly Downregulated in Melanoma and Induces Cell Death through Repression of Silencer of Death Domains (SODD)

Melanoma is an aggressive cancer that metastasizes rapidly and is refractory to conventional chemotherapies. Identifying microRNAs (miRNAs) that are responsible for this pathogenesis is therefore a promising means of developing new therapies. We identified miR-26a through microarray and quantitative reverse-transcription–PCR (qRT-PCR) experiments as an miRNA that is strongly downregulated in melanoma cell lines as compared with primary melanocytes. Treatment of cell lines with miR-26a mimic caused significant and rapid cell death compared with a negative control in most melanoma cell lines tested. In surveying targets of miR-26a, we found that protein levels of SMAD1 (mothers against decapentaplegic homolog 1) and BAG-4/SODD were strongly decreased in sensitive cells treated with miR-26a mimic as compared with the control. The luciferase reporter assays further demonstrated that miR-26a can repress gene expression through the binding site in the 3′ untranslated region (3′UTR) of SODD (silencer of death domains). Knockdown of these proteins with small interfering RNA (siRNA) showed that SODD has an important role in protecting melanoma cells from apoptosis in most cell lines sensitive to miR-26a, whereas SMAD1 may have a minor role. Furthermore, transfecting cells with a miR-26a inhibitor increased SODD expression. Our findings indicate that miR-26a replacement is a potential therapeutic strategy for metastatic melanoma, and that SODD, in particular, is a potentially useful therapeutic target