Improving Adenovirus Based Gene Transfer: Strategies to Accomplish Immune Evasion

Adenovirus (Ad) based gene transfer vectors continue to be the platform of choice for an increasing number of clinical trials worldwide. In fact, within the last five years, the number of clinical trials that utilize Ad based vectors has doubled, indicating growing enthusiasm for the numerous positive characteristics of this gene transfer platform. For example, Ad vectors can be easily and relatively inexpensively produced to high titers in a cGMP compliant manner, can be stably stored and transported, and have a broad applicability for a wide range of clinical conditions, including both gene therapy and vaccine applications. Ad vector based gene transfer will become more useful as strategies to counteract innate and/or pre-existing adaptive immune responses to Ads are developed and confirmed to be efficacious. The approaches attempting to overcome these limitations can be divided into two broad categories: pre-emptive immune modulation of the host, and selective modification of the Ad vector itself. The first category of methods includes the use of immunosuppressive drugs or specific compounds to block important immune pathways, which are known to be induced by Ads. The second category comprises several innovative strategies inclusive of: (1) Ad-capsid-display of specific inhibitors or ligands; (2) covalent modifications of the entire Ad vector capsid moiety; (3) the use of tissue specific promoters and local administration routes; (4) the use of genome modified Ads; and (5) the development of chimeric or alternative serotype Ads. This review article will focus on both the promise and the limitations of each of these immune evasion strategies, and in the process delineate future directions in developing safer and more efficacious Ad-based gene transfer strategies

On regularity properties of a surface growth model

We show local higher integrability of derivative of a suitable weak solution to the surface growth model, provided a scale-invariant quantity is locally bounded. If additionally our scale-invariant quantity is small, we prove local smoothness of solutions.Comment: 18 page

Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm

Recombinant Adenovirus (Ad) based vectors have been utilized extensively as a gene transfer platform in multiple pre-clinical and clinical applications. These applications are numerous, and inclusive of both gene therapy and vaccine based approaches to human or animal diseases. The widespread utilization of these vectors in both animal models, as well as numerous human clinical trials (Ad-based vectors surpass all other gene transfer vectors relative to numbers of patients treated, as well as number of clinical trials overall), has shed light on how this virus vector interacts with both the innate and adaptive immune systems. The ability to generate and administer large amounts of this vector likely contributes not only to their ability to allow for highly efficient gene transfer, but also their elicitation of host immune responses to the vector and/or the transgene the vector expresses in vivo. These facts, coupled with utilization of several models that allow for full detection of these responses has predicted several observations made in human trials, an important point as lack of similar capabilities by other vector systems may prevent detection of such responses until only after human trials are initiated. Finally, induction of innate or adaptive immune responses by Ad vectors may be detrimental in one setting (i.e., gene therapy) and be entirely beneficial in another (i.e., prophylactic or therapeutic vaccine based applications). Herein, we review the current understanding of innate and adaptive immune responses to Ad vectors, as well some recent advances that attempt to capitalize on this understanding so as to further broaden the safe and efficient use of Ad-based gene transfer therapies in general

Interior regularity criteria for suitable weak solutions of the Navier-Stokes equations

We present new interior regularity criteria for suitable weak solutions of the 3-D Navier-Stokes equations: a suitable weak solution is regular near an interior point $z$ if either the scaled $L^{p,q}_{x,t}$-norm of the velocity with $3/p+2/q\leq 2$, $1\leq q\leq \infty$, or the $L^{p,q}_{x,t}$-norm of the vorticity with $3/p+2/q\leq 3$, $1 \leq q < \infty$, or the $L^{p,q}_{x,t}$-norm of the gradient of the vorticity with $3/p+2/q\leq 4$, $1 \leq q$, $1 \leq p$, is sufficiently small near $z$

Development of context training ideas for the organization of industrial training in college

Обоснована целесообразность применения технологии контекстного обучения для производственного обучения студентов колледжа с целью оптимизации формирования их компетенцийThe authors substantiate the advisability of using contextual learning technology for industrial training of college students in order to optimize the formation of their professional competence

Wireless power transfer in magnetic resonance imaging at a higher-order mode of a birdcage coil

Magnetic resonance imaging (MRI) is a crucial tool for medical visualization. In many cases, performing a scanning procedure requires the use of additional equipment, which can be powered by wires as well as via wireless power transfer (WPT) or wireless energy harvesting. In this Letter, we propose a novel scheme for WPT that uses a higher-order mode of the MRI scanner's birdcage coil for energy transmission. In contrast to the existing WPT solutions, our approach does not require additional transmitting coils. Compared to the energy harvesting, the proposed method allows supplying significantly more power. We perform numerical simulations demonstrating that one can use the fundamental mode of the birdcage coil to perform a scanning procedure while transmitting the energy to the receiver at a higher-order mode without any interference with the scanning signal or violation of safety constraints, as guaranteed by the mode structure of the birdcage. Also, we evaluate the specific absorption rate along with the energy transfer efficiency and verify our numerical model by a direct comparison with an experimental setup featuring a birdcage coil of a 1.5T MRI scanner.Comment: 6 pages, 5 figures + Supplementary Material 10 pages, 7 figure

Обилие, видовое разнообразие и структура сообщества метазойного микрозоопланктона в градиенте бухта — взморье (на примере Севастопольской бухты, Чёрное море)

Цель исследования — выявить закономерные изменения в обилии, видовом разнообразии и структуре сообществ метазойного микрозоопланктона (ММ) в градиентных условиях морского прибрежья на относительно небольших пространственных масштабах. Актуальность работы определяется малочисленностью подобных исследований, позволяющих опосредованно оценить степень антропогенного воздействия на морскую биоту и установить трофический статус локальных акваторий с помощью индексов видового разнообразия. Проанализированы три акватории прибрежья города Севастополя: открытое взморье, устье Севастопольской бухты и внутренняя её часть. Локализация станций отбора проб отражает градиент условий среды, характеризующийся разной степенью воздействия на биоту природных и антропогенных факторов. Исследования проведены в летний и осенний периоды года. Пробы ММ отбирали из трёх горизонтов водного столба — поверхностного, 0–5-метрового и 0–10-метрового слоёв. В открытом взморье и устье бухты численность ММ по вертикали была более выравненной, тогда как в глубине бухты различия между слоями могли достигать 5–700 раз. Максимальная численность ММ (1837,1 тыс. экз.·м−3) отмечена в начале августа в поверхностном слое во внутренней части бухты. С конца лета происходило снижение обилия во всех исследованных акваториях. Видовое разнообразие сообщества ММ, оценённое с помощью индексов Шеннона, Симпсона, Пиелу и др., уменьшалось в направлении от открытого взморья вглубь бухты. Эта закономерность сохранялась в оба сезона. Наиболее информативными оказались индекс Шеннона, индекс полидоминантности Симпсона и индекс выравненности Пиелу. Они хорошо отражали как сезонные изменения видового разнообразия, так и направленность изменений в градиенте трофности локальных акваторий бухты. С помощью многомерного анализа выявлены случаи существенной трансформации в структуре сообщества ММ придонного слоя вод в глубине бухты. Основной вероятной причиной этих локальных изменений является возникновение в загрязнённых участках бухты гипоксийных условий в нижних горизонтах вод, приводящее к деградации численности и видового состава исследуемого зоопланктонного сообщества

Synthis and Phisical And Chemical; Properties of SiO[2]-B[2]O[3] and SiO[2]-P[2]O[5] Thin Film Systems and Powders

The SiO[2]-B[2]O[3] and SiO[2]-P[2]O[5] films were synthesized by using film forming solutions having a P[2]O[5] content of up to 30% and B[2]O[3] up to 40%. Properties of the filmforming solutions and binary oxides were examined. The physical and chemical processes occurring in the solution during the heat treatment of films were examined. The conditions for producing films of different thicknesses were determined. The kinetic parameters were calculated

Prognosis of recurrent myocardial infarction based on shortliffe fuzzy models using the electrical characteristics of biologically active points

This report discusses the employment of the electrical characteristics of biologically active points (BAP) in the meridian of the heart to solve the task of prognosticating recurrence of myocardial infarctions during the rehabilitation period using fuzzy decision rule