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Systemic Administration of CpG Oligodeoxynucleotide and Levamisole as Adjuvants for Gene-Gun-Delivered Antitumor DNA Vaccines
Michal mahel,Ingrid Poláková,Eva Sobotková,Eva Vajdová
Clinical and Developmental Immunology , 2011, DOI: 10.1155/2011/176759
Abstract: DNA vaccines showed great promise in preclinical models of infectious and malignant diseases, but their potency was insufficient in clinical trials and is needed to be improved. In this study, we tested systemic administration of two conventional adjuvants, synthetic oligodeoxynucleotide carrying immunostimulatory CpG motifs (CpG-ODN) and levamisole (LMS), and evaluated their effect on immune reactions induced by DNA vaccines delivered by a gene gun. DNA vaccination was directed either against the E7 oncoprotein of human papillomavirus type 16 or against the BCR-ABL1 oncoprotein characteristic for chronic myeloid leukemia. High doses of both adjuvants reduced activation of mouse splenic CD8
Systemic Administration of CpG Oligodeoxynucleotide and Levamisole as Adjuvants for Gene-Gun-Delivered Antitumor DNA Vaccines
Michalmahel,Ingrid Poláková,Eva Sobotková,Eva Vajdová
Journal of Immunology Research , 2011, DOI: 10.1155/2011/176759
Abstract: DNA vaccines showed great promise in preclinical models of infectious and malignant diseases, but their potency was insufficient in clinical trials and is needed to be improved. In this study, we tested systemic administration of two conventional adjuvants, synthetic oligodeoxynucleotide carrying immunostimulatory CpG motifs (CpG-ODN) and levamisole (LMS), and evaluated their effect on immune reactions induced by DNA vaccines delivered by a gene gun. DNA vaccination was directed either against the E7 oncoprotein of human papillomavirus type 16 or against the BCR-ABL1 oncoprotein characteristic for chronic myeloid leukemia. High doses of both adjuvants reduced activation of mouse splenic CD8+ T lymphocytes, but the overall antitumor effect was enhanced in both tumor models. High-dose CpG-ODN exhibited a superior adjuvant effect in comparison with any combination of CpG-ODN with LMS. In summary, our results demonstrate the benefit of combined therapy with gene-gun-delivered antitumor DNA vaccines and systemic administration of CpG-ODN or LMS. 1. Introduction After pioneering studies showing the expression of protein antigens from plasmid DNA and the ability of these antigens to induce both humoral and cell-mediated immunity in the early 1990s [1–3], DNA vaccines against some infectious diseases and also malignant tumors were quickly developed and successfully tested in animal models. However, the efficacy of DNA immunization in initial clinical trials was disappointing [4]. Immune reactions induced by DNA vaccines can be enhanced by adjuvants that are classified into two groups by Sasaki et al. [5]—genetic and conventional. While genetic adjuvants are plasmids producing cytokines, chemokines or other immunomodulatory molecules, conventional adjuvants are chemical compounds increasing or modulating immune responses. As genetic adjuvants are of the same nature as DNA vaccines, they can be easily codelivered in any method of DNA vaccine administration. However, conventional adjuvants can be mixed and codelivered with DNA vaccines injected as a solution, but their codelivery with DNA vaccines administered via a gene gun is limited by the mode of application. Only local application of the conventional adjuvant imiquimod was more widely tested in combination with gene-gun delivery of plasmid DNA [6, 7]. Of five conventional (chemical) adjuvants tested after addition to an intramuscular DNA vaccine, levamisole (LMS), a synthetic phenylimidazolthiazole, induced the strongest Th1 immune reactions [8]. The high immunostimulatory activity of LMS in DNA vaccination
Activation of Community Television and its Influence on Students’ Creative Thinking Level  [PDF]
Michal Aflalo, Baruch Offir
Psychology (PSYCH) , 2010, DOI: 10.4236/psych.2010.12010
Abstract: The goal of the research was to examine whether a relation exists between students’ experience in community television and changes in their creative thinking ability. Community television is a tool that enables the expression of wishes, opinions, ideas, thoughts, experiences and skills via community television broadcasts. Learning in community television affords experience with different types of activities. Each role requires different skills and characteristics. In the present research we used job analysis to characterize the different experiences within the framework of community television. Job analysis is a technique for presenting detailed information on activities carried out within the framework of the job. The job analysis used in this research is based on a list of abilities, traits, skills and fields of knowledge from which the person suitable for the role should be chosen. The influence of students’ experience in community television on their creative thinking level was examined, as well as whether different experiences in community television have a different effect on the students’ creative thinking. The research population included 157 subjects who underwent a set of tests for evaluating their creative tendency (curiosity, originality, and general creativity score). All subjects experienced the production of a movie, while learning the secrets of television production and experiencing production roles according to their personal choice (director, editor, photographer, actor). The choice of experience was made according to each student’s personal choice, with the aim of enabling the expression via multiple intelligences. The tendency to creativity was measured using a tendency to creativity questionnaire [1]. After the learning and the process of producing the movie, the subjects took the same set of tests in order to examine the change that took place following this process. They were also interviewed in order to discover their opinions and feelings regarding the process they underwent. Analysis of the tests and the interviews indicates that students who experienced community television production roles improved their creative tendency level in all experience roles: director, editor, photographer and actor. An open experience system that integrates different levels of experience and active learning, autonomous learning and affords expression for multiple experiences with the aim of creating a common project in which all contribute their share towards the final product can develop the tendency for creativity among students.
Adolescents’ Subtypes of Attachment Security with Fathers and Mothers and Self-Perceptions of Socioemotional Adjustment  [PDF]
Michal Al-Yagon
Psychology (PSYCH) , 2011, DOI: 10.4236/psych.2011.24046
Abstract: The study examined adolescents’ secure attachment with both versus one parent, for deeper understanding of adolescents’ perceptions of their socioemotional adjustment. Specifically, the current study aimed to identify different attachment profiles with father and mother among 203 adolescents aged 15 - 17 years and to examine whether these profiles associated differently with their self-rated peer-network loneliness and peer-dyadic loneliness, positive and negative affect, and internalizing behavior problems. Descriptive statistics demonstrated that more adolescents were classified as securely attached to mothers than to fathers. No significant associations emerged between adolescents’ sex and attachment classification distributions with mothers or fathers. Using k-means clustering methods, four distinct clusters emerged: secure attachment to both parents/to neither/to only father/to only mother. Tukey HSD and Scheffe procedures validated the attachment clusters, revealing significant inter-cluster differences on all of the adolescents’ socioemotional measures. The current results also highlighted that the group of adolescents who felt securely attached to both parents was least vulnerable to experiencing socioemotional difficulties. In addition, secure attachment only to one's mother and not to one's father did not seem to act as a protective factor for these adolescents, with the exception of protection from peer-dyadic loneliness. Discussion focused on understanding the possible contribution of parent-adolescent secure attachment among these subgroups of typically developing adolescents.
Alternative UV Sensors Based on Color-Changeable Pigments  [PDF]
Martina Vikova, Michal Vik
Advances in Chemical Engineering and Science (ACES) , 2011, DOI: 10.4236/aces.2011.14032
Abstract: Photochromism is a chemical process in which a compound undergoes a reversible change between two states having separate absorption spectra, i.e. different color [1]. In our previous work we have published some solutions of problems of measuring photochromic textile sample by standard commercial spectrophotometric systems [2]. Main problem with measurement of kinetic behavior of photochromic pigments by standard spectrophotometer is relatively long time period between individual measurements (5 s) and impossibility of measuring whole color change during exposure without interruption of illumination of sample during measurement. It means, standard commercial spectrophotometers enable off-line measurement of kinetic behavior during exposure period and quasi on-line measurement during reversion period. Based on this problem, it is only possible to obtain precise data during reversion—decay process and growth process (exposure) is affected by high variability of data. Following this knowledge, we developed original experimenttal system with short time scanning of color change of photochromic samples during growth and decay period of color change. In this study it is presented new view on the relationship between intensity of UV-A radiation and color change half-life t1/2. Via this relation, it is demonstrated the possibility of the flexible textile-based sensors construction in the area of the radiation intensity identification.
The Relationship between Self-Esteem, Sense of Mastery and Humor as Personal Resources and Crisis-Coping Strategies in Three Generations  [PDF]
Pnina Ron, Michal Rovner
Advances in Aging Research (AAR) , 2014, DOI: 10.4236/aar.2014.32024

Aim: The study’s aim is to examine the coping strategies from a perspective of intergenerational transmission. Methods: A self-report questionnaire was completed by 504 students, their parents, and their grandparents. Tools on the questionnaire assessed crisis perception as well as levels of sense of humor, sense of mastery, and self-esteem, as independent variables, and crisis-coping strategies, as the dependent variable. Results: Findings indicated that there was intergenerational transmission of the problem-focused coping strategy in general, and of the intra-personal resources of self-esteem, and sense of mastery, in particular. The major theoretical contribution of the study is in extending the concept of intergenerational transmission to include an additional realm; findings also substantiated and reinforced previous knowledge regarding the strategies for coping with stress and crises among various age groups. Conclusions: In terms of applicability, recognizing the phenomenon of intergenerational transmission provides a clinical tool that increases the possibility of coping with complex problems. In addition, it suggests the need to increase clients’ awareness of the significant effects of intergenerational transmission.

Antigravity—Its Manifestations and Origin  [PDF]
Michal K?í?ek, Lawrence Somer
International Journal of Astronomy and Astrophysics (IJAA) , 2013, DOI: 10.4236/ijaa.2013.33027

Dark energy has been introduced in order to explain the observed acceleration of the expansion of our Universe. It seems to be distributed almost uniformly and it has an essential influence on the present value of the Hubble constant which characterizes the rate of this expansion. The Newtonian theory of gravitation is formulated so that the laws of conservation of energy and momentum hold. However, the Universe is designed so that the total amount of energy is slowly, but continually increasing, since its expansion is accelerating. Our examples show that even the Solar System and also our Galaxy imperceptibly expand thanks to dark energy whose origins are tiny antigravity forces. We claim that these forces appear due to the finite speed of gravitational interaction, which causes gravitational aberration effects. We show that effects of dark energy are observable; they are not only globally, but also in local systems. These effects can be measured and are comparable with the present value of the Hubble constant.

The Prevalence and Risk Factors for Dry Eye Disease among Older Adults in the City of Lodz, Poland  [PDF]
Michal S. Nowak, Janusz Smigielski
Open Journal of Ophthalmology (OJOph) , 2016, DOI: 10.4236/ojoph.2016.61001
Abstract: Purpose: To estimate the prevalence and risk factors for dry eye disease (DED) in a sample population of Polish older adults. Material and methods: Cross-sectional and observational study of 1107 men and women of European Caucasian origin aged 35 - 97 years, who were interviewed and underwent detailed ophthalmic examinations. DED was defined as presence of a previous clinical diagnosis of dry eye with concomitant dry eye treatment. Results: The overall prevalence of DED in the researched population was 6.7% (95% CI 5.2 - 8.2). The prevalence of DED increased with age from 4.8% in age group 35 - 59 years to 8.3% in group aged ≥60 years. The prevalence of DED was also higher in women 8.1% than in men 4.7%. In multiple logistic regression modelling with age, gender, presence of cataract surgery and glaucoma or ocular hypertension (OHT) treatment, DED was significantly associated with older age (OR 1.99, 95% CI 1.21 - 3.30) and with female gender (OR 1.76, 95% CI 1.05 - 2.96). Conclusions: The prevalence of DED in our study population was comparable with the findings of other studies from Europe and the United States, with significantly higher rates among women and elderly subjects.
Integrated Conformational and Lipid-Sensing Regulation of Endosomal ArfGEF BRAG2
Kaheina Aizel,Valérie Biou,Jorge Navaza,Lionel V. Duarte,Valérie Campanacci,Jacqueline Cherfils ,Mahel Zeghouf
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001652
Abstract: The mechanisms whereby guanine nucleotide exchange factors (GEFs) coordinate their subcellular targeting to their activation of small GTPases remain poorly understood. Here we analyzed how membranes control the efficiency of human BRAG2, an ArfGEF involved in receptor endocytosis, Wnt signaling, and tumor invasion. The crystal structure of an Arf1–BRAG2 complex that mimics a membrane-bound intermediate revealed an atypical PH domain that is constitutively anchored to the catalytic Sec7 domain and interacts with Arf. Combined with the quantitative analysis of BRAG2 exchange activity reconstituted on membranes, we find that this PH domain potentiates nucleotide exchange by about 2,000-fold by cumulative conformational and membrane-targeting contributions. Furthermore, it restricts BRAG2 activity to negatively charged membranes without phosphoinositide specificity, using a positively charged surface peripheral to but excluding the canonical lipid-binding pocket. This suggests a model of BRAG2 regulation along the early endosomal pathway that expands the repertoire of GEF regulatory mechanisms. Notably, it departs from the auto-inhibitory and feedback loop paradigm emerging from studies of SOS and cytohesins. It also uncovers a novel mechanism of unspecific lipid-sensing by PH domains that may allow sustained binding to maturating membranes.
Fishing With (Proto)Net—A Principled Approach to Protein Target Selection
Michal Linial
Comparative and Functional Genomics , 2003, DOI: 10.1002/cfg.328
Abstract: Structural genomics strives to represent the entire protein space. The first step towards achieving this goal is by rationally selecting proteins whose structures have not been determined, but that represent an as yet unknown structural superfamily or fold. Once such a structure is solved, it can be used as a template for modelling homologous proteins. This will aid in unveiling the structural diversity of the protein space. Currently, no reliable method for accurate 3D structural prediction is available when a sequence or a structure homologue is not available. Here we present a systematic methodology for selecting target proteins whose structure is likely to adopt a new, as yet unknown superfamily or fold. Our method takes advantage of a global classification of the sequence space as presented by ProtoNet-3D, which is a hierarchical agglomerative clustering of the proteins of interest (the proteins in Swiss-Prot) along with all solved structures (taken from the PDB). By navigating in the scaffold of ProtoNet-3D, we yield a prioritized list of proteins that are not yet structurally solved, along with the probability of each of the proteins belonging to a new superfamily or fold. The sorted list has been self-validated against real structural data that was not available when the predictions were made. The practical application of using our computational–statistical method to determine novel superfamilies for structural genomics projects is also discussed.
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