Selection of optimal antisense accessible sites of survivin and its application in treatment of gastric cancer

AIM: To select the optimal antisense accessible sites of survivin, a highly expressed gene in tumor tissues, in order to explore a novel approach to improve biological therapy of gastric cancer. METHODS: The 20 mer random oligonucleotide library was synthesized, hybridized with in vitro transcribed total survivin cRNA, then digested by RNase H. After primer extension and autoradiography, the antisense accessible sites (AAS) of survivin were selected. Then RNADraw software was used to analyze and choose the AAS with obvious stem-loop structures, according to which the complementary antisense oligonucleotides (AS-ODNs) were synthesized and transferred into survivin highly- expressing gastric cancer cell line MKN-45. Survivin expression was detected by RT-PCR and Western Blotting. Cellular growth activities were assayed by tetrazolium bromide (MTT) colorimetry. Cellular ultrastructure was observed by electronic microscopy, while apoptosis was detected by annexin V-FITC and propidium iodide staining flow cytometry. RESULTS: Thirteen AAS of survivin were selected In vitro. Four AAS with stem-loop structures were chosen, locating at 207-226 bp, 187-206 bp, 126-145 bp and 44-63 bp of survivin cDNA respectively. When compared with non-tranfection controls, their corresponding AS-ODNs (AS-ODN1, AS-ODN2, AS-ODN3 and AS-ODN4) could reduce Survivin mRNA levels in MKN-45 cells by 54.3±±1.1% (t= 6.12, P<0.01), 86.1±±1.0% (t= 5.27, P<0.01), 32.2±±1.3% (t= 7.34, P<0.01) and 56.2±±0.9% (t = 6.45, P<0.01) respectively, while survivin protein levels were decreased by 42.2±±2.5% (t = 6.26, P<0.01), 75.4±±3.1% (t= 7.11, P<0.01), 28.3±±2.0% (t= 6.04, P<0.01) and 45.8±±1.2% (t = 6.38,P<0.01) respectively. After transfection with 600 nmol/L AS-ODN1-AS-ODN4for 24 h, cell growth was inhibited by 28.12±±1.54% (t= 7.62, P<0.01), 38.42±±3.12% (t= 7.75, P<0.01), 21.46±±2.63% (t= 5.94, P<0.01) and 32.12±1.77% (t = 6.17, P<0.01) respectively. Partial cancer cells presented the characteristic morphological changes of apoptosis, with apoptotic rates being 19.31±1.16% (t= 7.16,P<0.01), 29.24±1.94% (t = 8.15,P<0.01), 11.87±0.68% (t = 6.68, P<0.01) and 21.68±2.14% (t = 7.53, P<0.01) respectively. CONCLUSION: The MS of survivin could be effectively selected in vitro by random oligonucleotide library/RNase H cleavage method combined with computer software analysis, this has important reference values for further studying survivin-targeted therapy strategies for gastric cancer.

Predicting octanol/water partition coefficient using solvation free energy and solvent-accessible surface area

The regression model for octanol/water partition coefficients ( K ow ), is founded with only two molecular descriptors available through quantum chemical calculations: solvation free energy (Δ G S ), and solvent accessible surface area (SASA). For the properties of 47 organic compounds from 17 types, the model gives a correction coefficient (adjusted for degrees of freedom) of 0 959 and a standard error of 0 277 log unit. It is a suitable way to predict the partition properties that are related to solute solvent interactions in the water phase.

Selection of Optimal Antisense Accessible Sites of Uroplakin Ⅱ mRNA for Bladder Urothelium

The optimal antisense accessible sites （AAS） of uroplakin Ⅱ （UP Ⅱ ） mRNA, a specific gene expressed in bladder urothelium, were selected in order to provide a novel method for targeted therapy of transitional cell carcinoma （TCC） of bladder. The 20 mer random oligonucleotide library was synthesized, hybridized with in vitro transcripted total UPⅡ cRNA, then digested by RNase H. After primer extension and autoradiography, the AAS of UPⅡ were selected. The RNADraw soft- ware was used to analyze and choose the AAS with obvious stem-loop structures, according to which the complementary antisense oligonucleotides （AS-ODN） were synthesized. With the AS-ODN0 designed only by RNADraw as a control, the AS-ODNs were transferred into UP Ⅱ highly-expressing cell line RT4. The cellular expression of UPⅡ mRNA was detected by RT-PCR and Western blot. Twelve AAS of UPⅡ mRNA were selected in vitro. Four AAS with stem-loop structures were chosen, locating at 558-577, 552-571, 217-236 and 97-116 bp of UP Ⅱ mRNA respectively. After transfection with the corresponding AS-ODN （AS-ODN1, AS-ODN2, AS-ODN3 and AS-ODN4） for 18 h, the UPⅡ mRNA levels in RT4cells were reduced by 29,3%, 82.7%, 71.3% and 70.9%, while UP Ⅱ protein levels were decreased by 20.2%, 78.5%, 65.2% and 64.4% respectively, which were significantly higher than those of AS-ODN0 （14.3%, 12.1% respectively） （P〈0.01）. The AAS of UPⅡ mRNA was effectively selected in vitro by random oligonucletide library/RNase H cleavage method in combination with computer software analysis, which had important reference values for further studying biological functions of UP Ⅱ gene and targeted therapeutic strategy for TCC of bladder.

Accessible Tourism in Rome

The topics of inclusion and disability are currently discussed in modern society.In particular,the concept of accessibility draws a wide range of attention legislation,architecture and tourism.Accessible tourism is a quality perspective of tourism,and it provides a panorama of change and evolution.The paper,which focuses on the city of Rome,analyzes the advantages and criticisms of these"forgotten"and underestimated market niches.Information,transports,space distribution,and safety are involved in the development of the accessible destination.The paper opens a reflection about the opportunity and the perspective of improving a quality and accessible tourism in the Eternal City.

Attitudes of Future Tourism Sector Employees Towards Organise Accessible Tourism

The aim of this paper is to show a theoretical approach to the evolution of concepts perceiving disability, taking into account the medical, social, and geographical models, as the basis for the development of principles concerning the organisation of accessible tourism for people with disabilities （PWD）. The main research objective was to identify the current attitudes of future, potential employees in the tourism （tourism and recreation students at the time of the study） towards accessible tourism. The study was based on surveys performed in May 2013 at the Adam Mickiewicz University in Poznafi （UAM, Poland） and the State University in Irkutsk （HFY, Russia）, a total sample of 216 people. The main section of the survey contained four questions regarding issues such as： optimal ways to organise tourism products for people with a disability; attitudes towards spending leisure time together with people with a disability; and specific requirements concerning the introduction of various types of improvements in tourism products aimed at people with a disability. In both cases, the results revealed that future tourism employees hold attitudes which are prevailingly open and positive towards the needs of tourists with disabilities. However, the hypothesis that the main factor influencing a reluctance to enter into contact with PwD is a lack of experience in this area, resulting in insufficient knowledge of what conditions the behaviour of PwD was also confirmed. This is a highly significant conclusion which should consider if mandatory educational programmes in the field of tourism and recreation studies are to be improved.

Construction of a transposase accessible chromatin landscape reveals chromatin state of repeat elements and potential causal variant for complex traits in pigs

Background:A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits.However,the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs.Results:Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq,and identified 557,273 merged peaks,which greatly expanded the pig regulatory ele-ment repository.We revealed tissue-specific regulatory elements which were associated with tissue-relevant biologi-cal functions.We identified both positive and negative significant correlations between the regulatory elements and gene transcripts,which showed distinct distributions in terms of their strength and distances from corresponding genes.We investigated the presence of transposable elements(TEs)in open chromatin regions across all tissues,these included identifications of porcine endogenous retroviruses(PERVs)exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements.Furthermore,we prior-itized a potential causal variant for polyunsaturated fatty acid in the muscle.Conclusions:Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions,as well as regula-tory variants of loci associated with complex traits in pigs.

A Mobile Accessible Closed Multi-Part Group Communication Scheme in IPv6 Network

To solve the problems of current IP multicast which includes poor inter-domain many-to-many group support, security vulnerabilities and dependency to specific multicast infrastructure, a mobile accessible closed multi-part group （MACMPG） communication protocol in IPv6 network is proposed. By extending the single source multicast protocol, the communication channel for multi-part group communication across domains is established. Based on lPv6 CGA, the secure closed group communication scheme is designed. The access to the multicast traffic only confined to the authorized senders and receivers and only trusted routers are allowed to be the branch points of MACMPG tree. By tunneling mechanism, the MACMPG traffic can be transmitted across non-MACMPG routing area, and the mobile nodes can join the group remotely and roam freely between domains, which eliminates the dependency on specific IP multicast routing.

Accessible KnowledgemKnowledge on Accessibility

Although serious efforts are made internationally and nationally, it is a slow process to make our physical environment accessible. In the actual design process, architects play a major role. But what kinds of knowledge, including research-based knowledge, do practicing architects make use of when designing accessible environments？ The answer to the question is crucially important since it affects how knowledge is distributed and how accessibility can be ensured. In order to get first-hand knowledge about the design process and the sources from which they gain knowledge, 11 qualitative interviews were conducted with architects with experience of designing for accessibility. The analysis draws on two theoretical distinctions. The first is research-based knowledge versus knowledge used by architects. The second is context-independent knowledge versus context-dependent knowledge. The practitioners found their primary support in context-dependent knowledge, whereas context-independent knowledge was criticized as being too prescriptive. Further, they tended to ask for assistance from the researcher in person rather than reading research publications. The findings challenge research in two ways--first, to produce context-dependent knowledge to structure the first step of the design process, second, to develop new ways to ensure a knowledge flow between research and practice.

Rich Cultural Experiences Accessible at Home

AS the raging novel coronavirus disease(COVID-19)enveloped all of China,a myriad of cultural institutions across the country have been temporarily closed to reduce the flow of people,including museums,public libraries,cultural centers,extra-curricular training courses,and even cinemas.However,a diverse range of dynamic cultural activities,enabled and powered by technological advancements and Internet-based technological platforms,are vying to provide the public with rich online cultural experiences and content.

Study on Accessible Long-Term Care Mobile Application for Visually Impaired Users

A result revealed by the Department of Statistics, 29,000 elderly people have registered for Visually Impaired Card in 2014, which was 51.2% of all visually impaired people. With annual growth rate of 1.56%, this number increased yearly by 1,100 people. According to WHO, 285 million people worldwide were estimated to be visually impaired, which is 4.24% of overall population in 2012. From age distribution point of view, most visually impaired people, accounted for 2.76% of overall population, were above age 50. In average, there are 7 visually impaired people in every 100 people above 50 years old. In Taiwan, 549,000 people over age 50 are estimated to be visually impaired. Therefore we expect there is a large amount of visually impaired people. The main purpose of this research is to collect adaptability information on the cognitive model of senior visually impaired people on their work status, social participation status, and leisure activities via questionnaire survey. Furthermore, descriptive video service is used to as an accessible long-term care application for visually impaired senior users. To solve disability circumstances and improve home care quality through visually impaired APP POe （proof-of-concept）. The result of this research will serve as an important basis for other researches in related study field, a reference for practice application. As a result in encouraging profit-seeking enterprises design a user oriented products. And even be an opening for mobile accessibility services benchmark on technology social care for disability and senior users.

Towards Smart, Sustainable, Accessible and Inclusive City for Persons with Disability by Taking into Account Checklists Tools

The main characteristics of potential smart cities in the future, smart citizens, smart energy, smart buildings, smart mobility, smart technology, smart healthcare, smart infrastructure, smart governance and education, and finally smart security are the aspects of smart cities. In the smart city, smart accessible infrastructure creates an inclusive environment for people with disabilities, in which they can integrate into the community and enjoy their civil, cultural, political, social and economic rights and entitlements. The aim of this study is to integrate disabled people into society so that they can actively participate in society and lead to a normal life. An integrated approach is needed to ensure that people with disabilities are not left alone. A combination of mainstreaming and targeted action is required for all interventions. People with disabilities have the same basic needs as everyone else: health protection and treatment, basic services, housing and income. Targeted intervention measures need to complement disability mainstreaming by addressing specific needs identified by general responses, including such interventions need not add materially to the overall cost, especially if the requirements of the maximum number of users are considered in the initial planning. This paper recommends how we can use an appropriate design checklist as a guide for our initial architectural concept and smart city planning to facilities reasonably accessible for people with disabilities in private and public buildings, making our cities smarter and more inclusive and helping to improve the quality of life for all people, especially people with disabilities.

Qualitative System Dynamics as a Tool in Accessible Design

A description of the Systems Dynamics paradigm is given and the reduced Qualitative System Dynamics (QSD) form explained. A simple example is given to illustrate the diagram construction. The principles of states (levels), rates and feedback loops are outlined. The QSD method is used to address the problem of accessibility by using human control of automation as an example, and applying the QSD method to evaluate the effects of the researcher and user in the de- sign of an accessible artefact. This simple automation model illustrates what can be found out from such a picture, in this indicating how the feedback from users has an influence on the time to deliver such designs.

NCHA:More Than 90%Museums Accessible to the Public Nationwide for Free

Recently,Li Qun,Vice Minister of the Ministry of Culture and Tourism and Director of National Cultural Heritage Administration(NCHA),said that China has a total of 6,565 museums with more than 90%museums accessible to the public for free.

Assistive robots for Beijing Winter Paralympic torch relay: Accessible technologies to restore human functionality

The success of the Beijing Winter Olympics and Paralympics epitomized the vision of a community with a shared future for humankind.Various robots and artificial intelligence technologies were used in various games and events,such as assisting in parades,logistics,and security inspections.The integration of unmanned robotic systems into torch relays was one of the highlights of the Winter Olympics.

Accessible chromatin regions and their functional interrelations with gene transcription and epigenetic modifications in sorghum genome

Accessible chromatin regions(ACRs)provide physical scaffolds to recruit transcriptional co-regulators and displace their nearby nucleosomes in multiple plant species.Characterization of ACRs and investigation of their biological effects in Sorghum bicolor has lagged behind.Regulation of gene expression relies on the transcriptional co-regulators that are recruited to ACRs to affect epigenomic modifications of surrounding nucleosomes.In this study,we employed transposase-accessible chromatin sequencing to identify ACRs and decipher how the presence of ACRs affects gene expression and epigenetic signatures in the Sorghum genome.As a result,21077 ACRs,which are mapped to 22.9%of genes and 2.7%of repeats,were identified.The profiling of ACRs on gene structures reveals a narrow and sharp peak around the transcription start site,with relatively weak and broad signals covering the entire gene body and an explicit but wide peak from the transcription termination site to its downstream regions.We discovered that the correlations between gene expression levels and profiled ACR densities are dependent on the positions of ACRs.The occurrence of genic ACRs cumulatively enhances the transcriptional activity of intergenic ACR-associated genes.In addition,an intricate crosstalk among ACRs,gene expression,and epigenetic marks has been unveiled by integrating multiple-omics analyses of whole-genome bisulfite sequencing,6mA immunoprecipitation followed by sequencing,RNA sequencing,chromatin immunoprecipitation sequencing,and DNase I hypersensitive sites sequencing datasets.Our study provides a genome-wide landscape of ACRs in sorghum,decrypts their interrelations with various epigenetic marks,and sheds new light on their roles in transcriptional regulation.

Analysis of a Firm's Optimal Size Based on Accessible Market Capacity

E-commerce has dramatically reduced the limitation of space and time on economic activities,resulting in individuals having access to a huge number of consumers.In this paper,we propose a company's optimal size decision model containing management costs as a means of investigating the evolution of the company size in e-commerce.Given that production decisions are made based on accessible market capacity,we explain how a company enters the market,and we draw an evolutionary path of the optimal company size.The results show that in the early expansion stage of accessible market capacity,a firm's optimal size keeps increasing;after reaching a peak,the change in a firm's optimal size depends on its cost management.When the accessible market capacity reaches a threshold,the firm will no longer be in the market,and may no longer exist.Finally,we construct a simulation framework based on complex adaptive systems to validate our proposed model.A simulation experiment confirms our model and reveals the dynamic co-evolution process of individual producers and firms.

The Internet accessible mathematical computation framework

The Internet Accessible Mathematical Computation (IAMC) framework aims to make it easy to supply mathematical computing powers over the Internet/Web. The protocol-based IAMC framework enables developers to create interoperable clients and servers easily and independently. Presented are conceptual and experimental work on the IAMC framework architecture and major components: the Mathematical Computation Protocol (MCP), a client prototype (Dragonfly), a server prototype (Starfish), a mathematical encoding converter (XMEC), and an open mathematical compute engine interface (OMEI).

Ordered mesoporous carbon fiber bundles with high-density and accessible Fe-NX active sites as efficient ORR catalysts for Zn-air batteries

Fe-NX/C electrocatalysts have aroused extensive interest in accelerating sluggish oxygen reduction reaction (ORR) kinetics as potential alternatives to platinum catalysts in rechargeable Zn-air batteries (ZABs).However,the low density and poor accessibility of Fe-NXsites have severely restricted the electrocatalytic performance of Fe-NX/C.Herein,Fe,N co-doped ordered mesoporous carbon fiber bundles are prepared through a ligand-assisted strategy with nitrogen-rich 1,10-phenanthroline as space isolation agent.1,10-Phenanthroline reveals a six-membered heterocyclic structure containing abundant nitrogen species to tightly coordinate with Fe ions,which is conducive to achieving high-density Fe-NXsites.Meanwhile,the adoption of SBA-15 as hard-templates enables the catalysts with highly ordered channels and large specific surface areas,improving the accessibility of Fe-NXsites.The optimal catalyst (PDA-Fe-900) demonstrates a positive half-wave potential of 0.84 V (vs.RHE) in alkaline solution,outperforming the commercial Pt/C (0.83 V).In addition,PDA-Fe-900 delivers comparable ORR performance to commercial Pt/C in acidic electrolyte.Impressively,when PDA-Fe-900 is employed as an air cathode,it achieves large power densities of 163.0 m W/cm^(2) in liquid-state ZAB and 116.6 m W/cm^(2) in the flexible solid-state ZAB.This work provides an efficient ligand-assisted pathway for fabricating catalysts with dense and accessible FeNXsites as high-performance ORR electrocatalysts for ZABs.

Research on Construction of an Accessible Environment in the Context of Building a Country with a Strong Transportation Network

Transportation is a basic service industry concerned with people’s livelihood and well-being. China has unveiled guidelines on improving China’s strength in transportation. By 2035, an accessible travel service system should basically be built, according to the guidelines jointly released by the Communist Party of China Central Committee and the State Council. It is of great practical significance to accelerate the construction of an accessible transportation environment in the new era, which can improve the equalization of public services and promote the safe, convenient, and comfortable travel of the disabled and the elderly. In line with the development status of transportation in China, and through an analysis on the requirements for building a country with a strong transportation network, this paper proposes the framework and content for the establishment of an accessible transportation system in China.

SHARED BY ALL,ACCESSIBLE TO ALL

Four nucleic acid tests,14 days of quarantine with daily reports on body temperature,and another 14 days of isolation in future.This is part of what Roy van den Hurk had to go through to attend the Third China International Import Expo(CIIE) in Shanghai this month.