Targeted Delivery of siRNA

Therapeutic application of siRNA requires delivery to the correct intracellular location, to interact with the RNAi machinery within the target cell, within the target tissue responsible for the pathology. Each of these levels of targeting poses a significant barrier. To overcome these barriers several strategies have been developed, such as chemical modifications of siRNA, viral nucleic acid delivery systems, and nonviral nucleic acid delivery systems. Here, we discuss progress that has been made to improve targeted delivery of siRNA in vivo for each of these strategies

Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization

The use of nanotechnology in medicine has the potential to have a major impact on human health for the prevention, diagnosis, and treatment of diseases. One particular aspect of the nanomedicine field which has received a great deal of attention is the design and development of nanoparticulate nanomedicines (NNMs) for drug delivery (i.e., drug-containing nanoparticles). NNMs are intended to deliver drugs via various mechanisms: solubilization, passive targeting, active targeting, and triggered release. The NNM approach aims to increase therapeutic efficacy, decrease the therapeutically effective dose, and/or reduce the risk of systemic side effects. In order to move a NNM from the bench to the bedside, several experimental challenges need to be addressed. This review will discuss the current trends and challenges in the clinical translation of NNMs as well as the potential pathways for translational development and commercialization. Key issues related to the clinical development of NNMs will be covered, including biological challenges, large-scale manufacturing, biocompatibility and safety, intellectual property (IP), government regulations, and overall cost-effectiveness in comparison to current therapies. These factors can impose significant hurdles limiting the appearance of NNMs on the market, irrelevant of whether they are therapeutically beneficial or not

Does the expansion of a motorway network lead to economic agglomeration? Evidence from China:Evidence from China

In contrast to most existing studies examining the generative effects of transport infrastructure, this paper addresses the distributive effects of transport infrastructure in China. Using panel data from 274 Chinese municipalities in the 2000-2010 period, our study explores the role of motorway network in the evolution of spatial economic agglomerations. Our results confirm the existence of a distributive effect of road infrastructure in China, and show that an improvement in the motorway network leads to a higher degree of geographic concentration of economic activities. However, in our simulation new motorway construction appears to facilitate spatial dispersal when transport costs fall below a critical level. Moreover, the improved road network has led to a loss of industry in China's lagging areas. Accordingly, current transport investment policy, especially in lagging western areas, has not contributed to spatial equity in China, which contrasts with investment in education, for example. (C) 2015 Elsevier Ltd. All rights reserved

Швидько Ганна Кирилівна

У довіднику висвітлюються основні етапи життя, наукової, педагогічної та громадської роботи відомого українського історика, доктора історичних наук, професора, заслуженого діяча науки і техніки України, дійсного члена Української Академії історичних наук Ганни Кирилівни Швидько. В ньому вміщено перелік праць вченого з 1970 по 2003 р., названі аспіранти та здобувачі, які виконали кандидатські дисертації під її керівництвом. Покажчик опублікованих праць Г.К.Швидько, розкиданих по різних виданнях, є не тільки показником її внеску в українську історичну науку, але й допомогою тим, хто займається історією України XVI-XVIII ст., а також історією Придніпровського краю, якому присвячено більше ста опублікованих розвідок науковця і краєзнавця. Довідник розраховано на науковців та усіх, хто цікавиться історією української науки та історією місцевого краю

Enhanced localization of liposomes with prolonged blood circulation time in infected lung tissue

Abstract In an experimental model of unilateral pneumonia caused by Klebsiella pneumoniea in rats we investigated whether intravenous administration of liposomes with prolonged blood circulation time resulted in significant localization of liosomes in infected lung tissu. Liposomes (100 nm) composed of hydrogenated phosphatidylinositol:hydrogenated phosphatidylcholine:cholesterol (mola ratio, 1:10:5) radiolabeled with gallium-67-deferoxamine showed relatively long blood circulation time. The degree of localization of these long circulating liposomes in the infected lef lung was significantly higher compared to that of localization of 110 nm egg phosphatidylglycerol:egg phosphatidylcholine:cholesterol (molar ratio, 1:10:5) liposomes which exhibited relatively short blood circulation time. At 16 h after administration of the long circulating liposomes (when 10% of the injected dose was still present in the bloodstream) localization of liposomes in the infected left lung was increased up to 10-fold compared to the left lung of uninfected rats, and appeared to be highly correlated with the intensity of the infection. In the uninfected right lung the localization of long circulating liposomes was not increased. The degree of localization of liposomes in the infected tissue is dependent on the residence time of liposomes in the blood compartment. The extent of localization of long circulating liposomes in infected tissue appeared to be dependent on the liposomal dose administered

Ocular pharmacoscintigraphic and aqueous humoral drug availability of ganciclovir-loaded mucoadhesive nanoparticles in rabbits

The present report describes the improved ocular retention and aqueous humoral drug availability of ganciclovir (GCV) when administered via topical instillation of different kind of nanoparticles onto the rabbit eye. GCV was loaded into PLGA nanoparticles, chitosan-coated nanoparticles and chitosan-coated niosomal nanoparticles. All three formulations contained nanoparticles equally round in shape with a mean particle size in the range of 180–200 nm. The ocular corneal retention property was evaluated by gamma scintigraphy, revealing that the clearance was slowest in the case of the chitosan-containing formulations. GCV in chitosan-coated PLGA nanoparticles and chitosan-coated niosomal nanoparticles showed approx. 6-fold higher aqueous humor drug availability as compared to a GCV solution and nearly 2.5-fold higher as compared to the chitosan-lacking GCV-PLGA nanoparticles. The results indicate that the use of a mucoadhesive chitosan coating can improve the ocular residence time and aqueous humoral availability of GCV when administered topically in nanoparticle

Холотропное дыхание как метод реализации потенциала личности сотрудника

На сегодняшний день в организациях существует множество проблем, из-за которых возникают сложности как в управлении предприятием, так и в эффективной работе сотрудников. Для любого управляющего компанией важно, чтобы сотрудник был уверенным, умеющим нестандартно мыслить, инициативным, целеустремленным, но в большинстве случаев на предприятии такие сотрудники отсутствуют или их количество ограниченно. В любом сотруднике кроется творческая личность, которая не всегда может быть реализована на практике или же просто подавлена. Для того чтобы предприятие могло эффективно функционировать, важно, чтобы каждый сотрудник мог разобраться в своих проблемах и обрести внутреннюю гармонию, которая позволит ему настроиться на работу и выполнять ее эффективно. Методика холотропного дыхания может помочь личности реализовать свой скрытый потенциал. Цель работы: определить значимость методики холотропного дыхания в организации и выявить, какое влияние она оказывает как на сотрудников, так и на предприятие в целом. Методы исследования: анализ литера- туры по данной проблематике, аналитический метод. Результаты: выводы, полученные в данном исследовании, способствуют определению действенности методики холотропного дыхания и значимости ее применения в организации. Today there are many problems in organizations which lead to difficulties in the management of an enterpriseand in the effective work of the staff. For any company manager it is important that the employee wasconfident, able to think outside the box, initiative, committed, but in most cases such employees are absent ortheir number is limited. There is creative personality in any employee which can’t always be revealed or issimply suppressed. In order for a company to operate effectively, it is important that every employee couldunderstand their problems and find inner harmony, which will allow them to tune into work and perform itefficiently. The technique of holotropic breathwork can help the person to realize their hidden potential. Objective:to determine the significance of the technique of holotropic breathwork in the organization and itsimpact on the employees and the enterprise as a whole. Methods: review of the literature on this subject,data analysis. Results. The findings of this study help to identify the effective methods of holotropic breathworkand the importance of its application in the organization

Sterically stabilized amphotericin B-liposomes: Toxicity and biodistribution in mice

In this study it was investigated whether long-circulating amphotericin B (AMB) containing liposomes could be prepared by incorporation of polyethylene glycol (1900) derivatized distearoylphosphatidylethanolamine (PEG-DSPE), and whether the incorporation of PEG-DSPE affected toxicity and biodistribution of the preparation in mice. Toxicity of two formulations of liposomes containing both PEG-DSPE and AMB (PEG-AMB-LIP, types 1 and 2) was compared with that of AMB-liposomes without PEG-DSPE (AMB-LIP) as well as that of MB-deoxycholate (AMB-DOC). The maximum tolerated dosage (MTD) of AMB-DOC, expressed in terms of death during treatment for 5 consecutive days or significant increases in the parameters used to monitor renal and hepatic functions, was 0.8 mg/kg per day. AMB-LIP were the least toxic, the MTD being 11 mg/kg per day. The formulation with AMB complexed to DSPG (PEG-AMB-LIP type 1) was as toxic as AMB-DOC. This PEG-AMB-LIP formulation was omitted from further studies on biodistribution. With AMB complexed to PEG-DSPE (PEG-AMB-LIP type 2) toxicity was substantially reduced, resulting in a MTD of 9 mg/kg per day. Biodistribution of radiolabeled PEG-AMB-LIP type 2 was compared with that of AMB-LIP. Blood residence time of PEG-AMB-LIP type 2 was prolonged as compared to AMB-LIP; For PEG-AMB-LIP type 2 at 24 h after administration 30% of the injected dosage of AMB in intact liposomes was circulating versus 6% for AMB-LIP

Pembuatan Aplikasi Sistem Informasi Persebaran Toko Batik Di Kota Pekalongan Berbasis Android

Pekalongan is located in the lowlands along the north coast of Java Island, at a height of approximately one meter above sea level. The geographical position of Pekalongan is between 6° 50\u27 42" to 6° 55\u27 44\u27\u27 North Latitude and 109° 37\u27 55\u27\u27to 109° 42\u27 19\u27\u27 East Longitude.Pekalongan area of about 42.25 km2 or approximately 0.14% from the area of Central Java Province.Pekalongan is known by the nickname city of Batik, because batik Pekalongan has distinctive and varied livery. Therefore, Pekalongan is espected to provide a practical and informative information for tourists, so it can be an attraction and increase the number of tourists coming to Pekalongan. This research uses of spatial and non spasial data in the form of batik store name, the owner\u27s name, phone number, address, and products sold with using the popularity of android smartphone as a platform system information.This application was developed using an SDK Andoidframework, java and PHP programming languages, and MySQL as base data, and Google Maps. The final result of this research is the Android application of the distribution of batik store in Pekalongan is accompanied by information (as has been mentioned above) from each store for easier searching the location of the batik stores in Pekalonga