Enzyme-Responsive Hydrogels as Potential Drug Delivery Systems—State of Knowledge and Future Prospects

Fast advances in polymer science have provided new hydrogels for applications in drug delivery. Among modern drug formulations, polymeric type stimuli-responsive hydrogels (SRHs), also called smart hydrogels, deserve special attention as they revealed to be a promising tool useful for a variety of pharmaceutical and biomedical applications. In fact, the basic feature of these systems is the ability to change their mechanical properties, swelling ability, hydrophilicity, or bioactive molecules permeability, which are influenced by various stimuli, particularly enzymes. Indeed, among a great number of SHRs, enzyme-responsive hydrogels (ERHs) gain much interest as they possess several potential biomedical applications (e.g., in controlled release, drug delivery, etc.). Such a new type of SHRs directly respond to many different enzymes even under mild conditions. Therefore, they show either reversible or irreversible enzyme-induced changes both in chemical and physical properties. This article reviews the state-of-the art in ERHs designed for controlled drug delivery systems (DDSs). Principal enzymes used for biomedical hydrogel preparation were presented and different ERHs were further characterized focusing mainly on glucose oxidase-, β-galactosidase- and metalloproteinases-based catalyzed reactions. Additionally, strategies employed to produce ERHs were described. The current state of knowledge and the discussion were made on successful applications and prospects for further development of effective methods used to obtain ERH as DDSs.     

Experiences with large-scale operational trials of ALTO-enhanced P2P filesharing in an intra-ISP scenario

Application Layer Traffic Optimization (ALTO) has recently gained attention in the research and standardisation community as a way for a network operator to guide the peer selection process of distributed applications by providing network layer topology information. In particular P2P applications are expected to gain from ALTO, due to the many connections peers form among each other, often without taking network layer topology information into account. In this paper, we present results of an extensive intra-ISP trial with an ALTO-enhanced P2P filesharing software. In summary, our results show that—depending on the concrete setting and on the distribution of upload capacity in the network—ALTO enables an ISP to save operational costs significantly while not degrading application layer performance noticeably. In addition, based on our experience we are able to give advice to operators on how to save costs with ALTO while not sacrificing application layer performance at all.     

Fatigue performance of metastable β titanium alloys: Effects of microstructure and surface finish

This investigation examined the role of microstructure and surface finish on the high cycle fatigue (HCF) performance of TIMETAL LCB (Ti-6.8Mo-4.5Fe-1.5Al). The as-received microstructure of LCB consisted of elongated β grains with a semicontinuous grain boundary α layer. In contrast, a fine equiaxed β + spheroidized α LCB microstructure was achieved by hot swaging and solution (recrystallization) anneal. The latter modification of the prior β grain structure, together with the size, morphology, and distribution of the primary α phase, resulted in a significant enhancement in the tensile and HCF properties. Furthermore, prestraining (PS), as would be expected during the fabrication of an automotive coil spring, and prior to aging for 30 min at temperatures between 500 and 550 °C, led to additional increases in tensile strength. In contrast, the HCF performance was always reduced when PS prior to aging was included in the overall processing procedure. Finally, shot-peening and roller-burnishing both resulted in an increased fatigue life in the finite life regimen; however, significant reductions in the 10⁷ cycle fatigue strengths were observed when these procedures were used. These observations have been explained by including the effect of process-induced residual tensile stresses in the fatigue analysis, resulting in subsurface fatigue crack nucleation. This paper was presented at the Beta Titanium Alloys of the 00’s Symposium sponsored by the Titanium Committee of TMS, held during the 2005 TMS Annual Meeting & Exhibition, February 13–16, 2005 in San Francisco, CA.     

Recurrent unexplained syncope: the role of head-upright tilt table testing

Recurrent episodes of sudden unexplained syncope are a common complaint of patients referred to health care professionals for evaluation. Traditional evaluations are both time consuming and expensive and leave many patients without a diagnosis. Although vasovagally mediated episodes of hypotension and bradycardia have been thought to be a common cause of unexplained syncope, this was traditionally a diagnosis of exclusion. Head-upright tilt table testing has recently emerged as a valuable method for confirming the diagnosis of vasovagal syncope and has allowed a better understanding of this phenomena. This article reviews the pathophysiology of vasovagal syncope, the use of head-upright tilt table testing in its diagnosis, and potential therapies used to prevent recurrences.     

Role of mitochondria in the switch mechanism of the cell death mode from apoptosis to necrosis--studies on rho0 cells

Detailed mechanisms of the switch of the cell death mode from apoptosis to necrosis remain to be solved, although the intracellular level of ATP and that of free radicals have been postulated to be the major factors involved in the mechanisms. In the present study menadione (MEN)-induced cell injury processes were studied using rho0 cells derived from human osteosarcoma 143B cells and parental rho+ cells co-treated with inhibitors of electron transfer chain of mitochondria or oligomycin, an inhibitor of ATP synthesis. Treatment of rho+ cells with 100 microM MEN induced apoptosis, which reached the maximum at 6 h, and was followed by an abrupt decrease thereafter, while necrotic cells (NC) increased continuously when they were judged by Annexin V and PI double staining. On the other hand, MEN induced apoptotic and necrotic changes much faster in rho0 cells compared to rho+ cells. The frequency to find apoptotic cells (AP) in the former cells was distinctly smaller than that to find NC judged by Annexin V and PI double staining. Electron microscopically, a major population of rho0 cells treated with MEN for 6 h consisted of intermediate cells, and a small number of AP co-existed. At 9 h of the treatment intermediate cells were exclusively seen, and AP were hardly detected. When parental rho+ cells were treated with MEN in the presence of oligomycin or oligomycin plus antimycin A both apoptotic and necrotic changes of the cells were distinctly accelerated. The intracellular level of superoxide in rho0 cells continuously increased after the MEN treatment, whereas that of ATP remained distinctly low before and after the MEN treatment compared to that in rho+ cells. These data suggest that the intracellular level of superoxide may be a key factor controlling the switch from apoptosis to necrosis.     

The factor structure of the SF-36 Health Survey in 10 countries: results from the IQOLA Project. International Quality of Life Assessment

Studies of the factor structure of the SF-36 Health Survey are an important step in its construct validation. Its structure is also the psychometric basis for scoring physical and mental health summary scales, which are proving useful in simplifying and interpreting statistical analyses. To test the generalizability of the SF-36 factor structure, product-moment correlations among the eight SF-36 Health Survey scales were estimated for representative samples of general populations in each of 10 countries. Matrices were independently factor analyzed using identical methods to test for hypothesized physical and mental health components, and results were compared with those published for the United States. Following simple orthogonal rotation of two principal components, they were easily interpreted as dimensions of physical and mental health in all countries. These components accounted for 76% to 85% of the reliable variance in scale scores across nine European countries, in comparison with 82% in the United States. Similar patterns of correlations between the eight scales and the components were observed across all countries and across age and gender subgroups within each country. Correlations with the physical component were highest (0.64 to 0.86) for the Physical Functioning, Role Physical, and Bodily Pain scales, whereas the Mental Health, Role Emotional, and Social Functioning scales correlated highest (0.62 to 0.91) with the mental component. Secondary correlations for both clusters of scales were much lower. Scales measuring General Health and Vitality correlated moderately with both physical and mental health components. These results support the construct validity of the SF-36 translations and the scoring of physical and mental health components in all countries studied.     

Generating Cloned Goats by Somatic Cell Nuclear Transfer—Molecular Determinants and Application to Transgenics and Biomedicine

The domestic goat (Capra aegagrus hircus), a mammalian species with high genetic merit for production of milk and meat, can be a tremendously valuable tool for transgenic research. This research is focused on the production and multiplication of genetically engineered or genome-edited cloned specimens by applying somatic cell nuclear transfer (SCNT), which is a dynamically developing assisted reproductive technology (ART). The efficiency of generating the SCNT-derived embryos, conceptuses, and progeny in goats was found to be determined by a variety of factors controlling the biological, molecular, and epigenetic events. On the one hand, the pivotal objective of our paper was to demonstrate the progress and the state-of-the-art achievements related to the innovative and highly efficient solutions used for the creation of transgenic cloned does and bucks. On the other hand, this review seeks to highlight not only current goals and obstacles but also future challenges to be faced by the approaches applied to propagate genetically modified SCNT-derived goats for the purposes of pharmacology, biomedicine, nutritional biotechnology, the agri-food industry, and modern livestock breeding.     

用户身份管理策略研究

In recent years there has been a fast grow of various electronic services.Each service requires specif-ic credentials for authenticating and authorizing user ac-cess or specific subset of user's personal information for transactions the service offers.Such a situation causes problems with remembering multiple,service-specific authentication data,with controlling user's personal data spread across different services-problems with managing user's identities.This paper is an overview on Identity Management(IdM...     

Unsupervised classification methods in food sciences: discussion and outlook

This paper reviews three unsupervised multivariate classification methods: principal component analysis, principal component similarity analysis and heuristic cluster analysis. The theoretical basis of each method is presented in brief, and assumptions inherent to the methods are highlighted. A literature review shows that these methods have sometimes been used inappropriately or without referencing all essential parameters. The paper also brings to the attention of the reader a relatively unknown method: probabilistic or model‐based cluster analysis. The goal of this method is to uncover the true classification of objects rather than a convenient classification provided by the other methods. For this reason it is felt that model‐based cluster analysis will have broad application in the future. Copyright © 2008 Society of Chemical Industry