Interleaver design for trellis-coded differential 8-PSK modulation with non-coherent detection

The effect of finite interleaver size on bit error rate (BER) performance of coded 8-DPSK is determined by means of computer simulations. The losses evaluated in this way include the SNR degradation due to the timing and frequency errors of the symbol synchronizer and the automatic frequency control (AFC) of the receiver. BER measurements are presented using a conventional 2/3 rate convolutional 8-state trellis-code for typical Rayleigh and Rician fading channels. It is shown that for a Rician channel with a Rician parameter of 7 dB, a Doppler spread of 100 Hz and a data rate of 2400 bps, an interleaver with size 16 x 16 symbols performs nearly as well as a very large interleaver. It is also shown that for very fast Rayleigh channels, the BER-curves flatten out at large SNR

Clinical Guidelines in Practice: How Well are Primary Care Providers Following National Chronic Kidney Disease Recommendations?

Chronic kidney disease (CKD), prevalent in more the 10% of the United States population is a progressive, degenerative disease affecting the renal function of afflicted individuals. In recent decades CKD has gained awareness among clinicians and medical professional due to growing concern for the many complications that arise in patients with CKD. For providers, CKD patient populations pose a significant challenge in terms of quality treatment because of the many associated risk factors and co-morbidities associated with a CKD diagnosis. The KDIGO (Kidney Disease; Improving Global Outcomes) 2012 clinical guidelines for the treatment of CKD were published under the sponsorship of the National Kidney Foundation in order to create uniform measures aimed to improve quality care and effective treatment of the CKD population. The purpose of this study is to investigate the extent to which these measures are being implemented and adhered to among providers at the practice level. Analysis of adherence to six specific measures of the KDIGO guidelines offers insight into the areas of implementation strengths and weaknesses. Results of this study indicate a widespread variation in the level of adherence to each measure on the practice level as well as variation among individual providers to each measure. While adherence levels were high among providers for certain measures, high adherence was not uniform across all six measures. Results of this study indicate the potential for improvement in CKD treatment through the use of centralized implementation structures such as practice based research networks (PBRN) or practice facilitation in order to generate higher adherence to all six KDIGO measures

Everyday intensities: rhetorical theory, composition studies, and the affective field of culture

textCulture is not only constructed by articulated discourses and social forms, but also through lived experience, embodied processes, and public feelings that are best described as what Raymond Williams calls the “practical consciousness” and “structures of feeling” of everyday life. Rhetorical theory has yet to account adequately for this operation of rhetoric through circulating affective channels. This dissertation addresses three key concepts of rhetorical theory, and recontextualizes them within an affective field: rhetorical situation, rhetorical analysis, and epistemic rhetoric. Drawing from Spinozan theory to delineate the connections between affect and culture, I begin from the premise that rhetoric is a means of production within culture, as well as a hermeneutic tool for reading culture. Yet our theories and pedagogies have tended to privilege the latter over the former. By locating three specific instances of this tendency (in theories of rhetorical situation, textual analysis, and epistemic rhetoric), and reconsidering them in light of contemporary scholarship on affect and culture, this project seeks to broaden our pedagogical and theoretical vocabularies, making them more suitable for describing the full range of rhetorical practice in culture.Englis

Good guy or bad guy: the opposing roles of microRNA 125b in cancer

MicroRNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally silence target mRNAs. Dysregulation of miRNAs is a frequent event in several diseases, including cancer. One miRNA that has gained special interest in the field of cancer research is miRNA-125b (miR-125b). MiR-125b is a ubiquitously expressed miRNA that is aberrantly expressed in a great variety of tumors. In some tumor types, e. g. colon cancer and hematopoietic tumors, miR-125b is upregulated and displays oncogenic potential, as it induces cell growth and proliferation, while blocking the apoptotic machinery. In contrast, in other tumor entities, e. g. mammary tumors and hepatocellular carcinoma, miR-125b is heavily downregulated. This downregulation is accompanied by de-repression of cellular proliferation and anti-apoptotic programs, contributing to malignant transformation. The reasons for these opposing roles are poorly understood. We summarize the current knowledge of miR-125b and its relevant targets in different tumor types and offer several hypotheses for the opposing roles of miR-125b: miR-125b targets multiple mRNAs, which have diverse functions in individual tissues. These target mRNAs are tissue and tumor specifically expressed, suggesting that misregulation by miR-125b depends on the levels of target gene expression. Moreover, we provide several examples that miR-125b upregulation dictates oncogenic characteristics, while downregulation of miR-125b corresponds to the loss of tumor suppressive functions. Thus, in different tumor entities increased or decreased miR-125b expression may contribute to carcinogenesis

DNA-Vakzinierung mit Idiotyp Zytokin Fusionskonstrukten gegen Lymphome im Mausmodell

Die vorliegende Arbeit beschäftigt sich mit neuen Ansätzen zur Immuntherapie von B-Zell-Lymphomen. Als Mausmodell wurden das Lymphom A20 und der eher leukämisch wachsende BCL1-Tumor verwendet. Alle Zellen eines B-Zell-Lymphoms produzieren einen identischen Antikörper, den sogenannten Idiotyp, der als tumorspezifisches Antigen benutzt werden kann: Die antigenbindenden variablen Regionen von schwerer und leichter Kette sind für die Tumorzellen jedes Patienten spezifisch. Die variablen Regionen lassen sich mit einem flexiblen Linker-Peptid zu single-chain Fragmenten (scFv) fusionieren. Die Antigenbindung und die Struktur als Tumorantigen bleiben dabei erhalten. Die BCL1-Sequenz war bereits bekannt, sie ließ sich mit Hilfe familienspezischer Primer mit PCR amplifizieren und klonieren. Bei der stark hypermutierten Sequenz des A20-Idiotyps versagte das Standardverfahren der Konsensus-Primer, erst eine 5'-RACE-PCR war erfolgreich. Der optimale Effektormechanismus (humoral, CD4 oder CD8 vermittelt) zur Immuntherapie von Lymphomen ist nicht bekannt. Bei DNA-Vakzinen lässt sich die Immunantwort besonders effektiv modulieren. Hier wurde ein System entwickelt, um rasch die Wirksamkeit verschiedener Kombinationen in vivo untersuchen zu können: Der scFv-Idiotyp wurde mit einem Zytokin (IL1beta, IL4, IL12, GM-CSF oder Flt3 ligand) und/oder einem Adjuvans (Tetanus Toxin Fragment C oder HBsAg) gekoppelt. In vitro wurde die Expression, die Faltung des scFv und die biologische Aktivität bestätigt. Neben der spezifischen Zytokinwirkung stabilisieren die Fusionspartner die scFv-Proteine deutlich. Zunächst wurde mit dem Modellantigen HBsAg die Immunisierungstechnik optimiert: Intradermale Plasmid-Injektion in die Ohr Pinna ergab konsistent hohe Antikörper-Titer. Bereits ohne in vitro-Restimulation konnte eine starke zelluläre Antwort nachgewiesen werden. Weiterhin wurde für die beiden Tumormodelle A20 und BCL1 die Wachstumskinetik invivo bestimmt und ein Pilotversuch (32 Tiere) mit drei ausgewählten Konstrukten durchgeführt: Von sechs splenektomierten Mäusen zeigte nur eine nach zwei Immunisierungen eine spezifische zelluläre Antwort gegen A20. In keiner Versuchsgruppe zeigte sich eine signifikante Lebensverlängerung nach Lymphomchallenge. Zusammenfassend ist erstmalig ein System entwickelt worden, das es auf einfache Weise ermöglicht, die Wirksamkeit von verschiedenen Zytokinen und Adjuvantien zur Idiotyp-Vakzinierung zu untersuchen. Dieses System bietet viel Raum für Optimierungen

Assembly, trafficking and function of gamma-secretase

gamma-Secretase catalyzes the final cleavage of the beta-amyloid precursor protein to generate amyloid-beta peptide, the principal component of amyloid plaques in the brains of patients suffering from Alzheimer's disease. Here, we review the identification of gamma-secretase as a protease complex and its assembly and trafficking to its site(s) of cellular function. In reconstitution experiments, gamma-secretase was found to be composed of four integral membrane proteins, presenilin (PS), nicastrin (NCT), PEN-2 and APH-1 that are essential and sufficient for gamma-secretase activity. PS, which serves as a catalytic subunit of gamma-secretase, was identified as a prototypic member of novel aspartyl proteases of the GxGD type. In human cells, gamma-secretase could be further defined as a heterogeneous activity consisting of distinct complexes that are composed of PS1 or PS2 and APH-1a or APH-1b homologues together with NCT and PEN-2. Using green fluorescent protein as a reporter we localized PS and gamma-secretase activity at the plasma membrane and endosomes. Investigation of gamma-secretase complex assembly in knockdown and knockout cells of the individual subunits allowed us to develop a model of complex assembly in which NCT and APH-1 first stabilize PS before PEN-2 assembles as the last component. Furthermore, we could map domains in PS and PEN-2 that govern assembly and trafficking of the complex. Finally, Rer1 was identified as a PEN-2-binding protein that serves a role as an auxiliary factor for gamma-secretase complex assembly. Copyright (c) 2006 S. Karger AG, Basel

Editors' Introduction to Issue 2 of Artifacts

The second issue of Artifacts features articles on a range of topics, from an historical narrative of Mizzou's medical school to a critical analysis of engineering failure during Hurricane Katrina. These texts reflect sophisticated research skills, including archival and discipline-specific research. Every piece in Issue 2 developed from assignments in undergraduate writing classes at The University of Missouri

Editor's Introduction to Issue 3 of Artifacts

All Mizzou students have one important thing in common: they are writers. Thanks to the writing intensive courses across the University, students have the opportunity to experience different writing situations in every discipline. Mizzou students learn that different writing contexts demand different sets of strategies. Not only does the content change, but the way research and arguments are presented also change. The essays featured in Artifacts Issue 3 reflect the variety of writing that Mizzou students create every day. From technical reports to historical research to literary analysis, these essays are all snapshots of the Mizzou writer at work

Presenilin-1 affects trafficking and processing of βAPP and is targeted in a complex with nicastrin to the plasma membrane

Amyloid β-peptide (Aβ) is generated by the consecutive cleavages of β- and γ-secretase. The intramembraneous γ-secretase cleavage critically depends on the activity of presenilins (PS1 and PS2). Although there is evidence that PSs are aspartyl proteases with γ-secretase activity, it remains controversial whether their subcellular localization overlaps with the cellular sites of Aβ production. We now demonstrate that biologically active GFP-tagged PS1 as well as endogenous PS1 are targeted to the plasma membrane (PM) of living cells. On the way to the PM, PS1 binds to nicastrin (Nct), an essential component of the γ-secretase complex. This complex is targeted through the secretory pathway where PS1-bound Nct becomes endoglycosidase H resistant. Moreover, surface-biotinylated Nct can be coimmunoprecipitated with PS1 antibodies, demonstrating that this complex is located to cellular sites with γ-secretase activity. Inactivating PS1 or PS2 function by mutagenesis of one of the critical aspartate residues or by γ-secretase inhibitors results in delayed reinternalization of the β-amyloid precursor protein and its accumulation at the cell surface. Our data suggest that PS is targeted as a biologically active complex with Nct through the secretory pathway to the cell surface and suggest a dual function of PS in γ-secretase processing and in trafficking