Health-related quality of life outcomes after kidney transplantation

With the improvements in short and long term graft and patient survival after renal transplantation over the last two decades Health-Related Quality of Life (HRQL) is becoming an important additional outcome parameter. Global and disease specific instruments are available to evaluate objective and subjective QOL. Among the most popular global tools is the SF-36, examples of disease specific instruments are the Kidney Transplant Questionnaire (KTQ), the Kidney Disease Questionnaire (KDQ) and the Kidney Disease-Quality of Life (KDQOL). It is generally accepted that HRQL improves dramatically after successful renal transplantation compared to patients maintained on dialysis treatment but listed for a transplant. It is less clear however which immunosuppressive regimen confers the best QOL. Only few studies compared the different regimens in terms of QOL outcomes. Although limited in number, these studies seem to favour non-cyclosporine based protocols. The main differences that could be observed between patients on cyclosporine versus tacrolimus or sirolimus therapy concern the domains of appearance and fatigue. This may be explained by two common adverse effects occurring under cyclosporine therapy, gingival hyperplasia and hair growth. Another more frequently occurring side effect under calcineurin inhibitor therapy is tremor, which may favour CNI free protocols. This hypothesis, however, has not been formally evaluated in a randomised trial using HRQL measurements. In summary HRQL is becoming more of an issue after renal transplantation. Whether a specific immunosuppressive protocol is superior to others in terms of HRQL remains to be determined

Antigen Cross-Presentation of Immune Complexes

The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α+ DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8+ T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8− DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets

Analýza vlivu ošetření formy mikropostřikem ve vztahu ke kvalitě odlitku bloku motoru 1.0. MPI EVO

Tato bakalářská práce se zabývá analýzou vlivu ošetření formy mikropostřikem ve vztahu ke kvalitě odlitku bloku motoru 1.0. MPI EVO. Teoretická část se věnuje obecnému popisu tlakového lití a jeho periferií, především pak termoregulačnímu systému formy a metodám ošetření líce formy, neboť tyto součásti jsou úzce spjaty s experimentální částí práce. Experimentální část probíhala ve spolupráci se společností Škoda Auto a.s. a zabývá se analýzou vlivu ošetření formy mikropostřikem na výslednou kvalitu odlitku. Cílem této práce je určení zmetkovitosti odlévaného bloku v závislosti na použité technologii ošetření líce formy.This bachelor thesis deals with the analysis of ifluence treating the die casting mold by micro-spraying in relation to the quality of the cast of engine block. Theoretical part devotes to general description of die casting and its parts, primarily to the thermoregulation system of casting mold and methods of treating the obverse casting mold, because these components are closely connected to experimental part of this thesis. Experimental part took place in cooperation at Škoda Auto a.s. and deals with the analysis of ifluence treating the decasting mold microspraying to final quality of the cast. The main goal of this thesis is to determine the wastage rate of the casted block depending on the technology which was used for treating the obverse casting mold

Manipulator of Tools used for vertical tool magazine

Cílem této práce je návrh variant, výběr optimální varianty a konstrukční řešení manipulátoru nástrojů pro svislý zásobník nástrojů ke svislému soustruhu řady SKG firmy TOS HULÍN a.s. Součástí je také technická zpráva a ekonomické zhodnocení. Je zde vyřešena základní koncepce, hlavní rozměry, funkční a pevnostní výpočty vybraných částí manipulátoru. Všechny výpočty a postupy jsou v souladu s platnými normami.The aim of this thesis is to design different variants, choose an optimal one and the constructional solution of a tool manipulator for vertical lathe from SKG line by TOS HULÍN a.s. This thesis also includes technical and economical report. There is a solution of a basic conception, main dimensions, functional calculations and calculations of rigidity of chosen parts of this manipulator. All computations and methods are in accord with valid standards.

Estudio de las propiedades características de las cónicas a partir de experiencias físicas mediante el uso del concepto de linealización

Resumen: Esta propuesta parte de la teoría de aprendizaje significativo planteada por Ausubel y es desarrollada posteriormente por otros autores, en la cual el acceder a un conocimiento determinado depende de los conceptos previos que se tienen; para estudiar las características que presentan diferentes curvas y como estas facilitan el estudio en otros campos. La implementación se hace con estudiantes del grado 10°1 de la Institución Educativa Federico Ozanam del municipio de Medellín, con los cuales se desarrollan varias guías donde estas sirven como medios para acercar al concepto y evaluar el proceso en forma simultánea. Como resultado se establece la viabilidad del trabajo transversal entre las áreas de física y matemáticas y el acercamiento de los estudiantes a la modelación de situaciones cotidianas.Abstract: This proposal begins from the theory of the meaningful learning presented by Ausubel and later developed for different authors, in which to access to a knowledge depends of the previous concepts that exist; to study the characteristics that present different curves and how these make easier the study in others fields. The implementation is carried out with tenth graders students in the Federico Ozanam High School, a public institution of Medellin city, in which are develop some guides that serve as a ways to close to the concept and to evaluate the process in simultaneously form. As result, establishes the viability of the transversal work between the Physics and Mathematics areas and the approach of the students to the modeling to daily situations

Lactobacillus johnsonii ameliorates intestinal, extra-intestinal and systemic pro-inflammatory immune responses following murine Campylobacter jejuni infection

Campylobacter jejuni infections are progressively increasing worldwide. Probiotic treatment might open novel therapeutic or even prophylactic approaches to combat campylobacteriosis. In the present study secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally reassociated with a commensal murine Lactobacillus johnsonii strain either 14 days before (i.e. prophylactic regimen) or 7 days after (i.e. therapeutic regimen) peroral C. jejuni strain 81–176 infection. Following peroral reassociation both C. jejuni and L. johnsonii were able to stably colonize the murine intestinal tract. Neither therapeutic nor prophylactic L. johnsonii application, however, could decrease intestinal C. jejuni burdens. Notably, C. jejuni induced colonic apoptosis could be ameliorated by prophylactic L. johnsonii treatment, whereas co-administration of L. johnsonii impacted adaptive (i.e. T and B lymphocytes, regulatory T cells), but not innate (i.e. macrophages and monocytes) immune cell responses in the intestinal tract. Strikingly, C. jejuni induced intestinal, extra-intestinal and systemic secretion of pro-inflammatory mediators (such as IL-6, MCP-1, TNF and nitric oxide) could be alleviated by peroral L. johnsonii challenge. In conclusion, immunomodulatory probiotic species might offer valuable strategies for prophylaxis and/or treatment of C. jejuni induced intestinal, extra- intestinal as well as systemic pro-inflammatory immune responses in vivo

Screen for ISG15-crossreactive Deubiquitinases

Background: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. Results: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. Conclusions: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice