194 research outputs found
A kinetic approach for the estimation of intracellular concentrations of nitrosative species in cells challenged by nitric oxide
No full textThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references.by Vasileios Theodoros Dendroulakis.Ph.D
The role of Smad signaling pathway in human glomerulonephritis
No full textGlomerulonephritides (GNs) comprise a group of glomerular diseases of immune origin leading in many instances in total renal parenchymal destruction and fibrosis thus resulting in the need for renal function replacement with dialysis methods. In the last years a significant progress in the detection of the molecular mechanisms that lead to renal fibrosis has been made TGF-β’s crucial role in these processes has been well documented. However, little is known on the implication of Smad signaling pathway (which mediates TGF-β signals) in mediating renal injury. The aim of the present study was to elucidate pSmad2/3, p300 Sp1, Smad7 and Ski (members of the Smad signaling pathway) expression in renal biopsies from patients with GN and to investigate their possible role in the pathogenesis and the progression of renal injury. 157 renal biopsies from patients with GN as well as 15 normal controls from nephrectomy specimens due to renal cancer were employed in the study. 91 patients had primary GN and 66 secondary while 86 GNs were proliferative and 71 nonproliferative. The immunohistochemical expression of pSmad2/3, p300, Sp1, Smad7 and Ski was evaluated. Correlations with patients clinical data (serum creatinine and 24 hour urinary protein collection) as well as with indices of histologic injury (glomerulosclerosis, interstitial fibrosis, tubular atrophy and interstitial inflammation) were also performed. There was a dramatic increase in the expression of pSmad2/3 Sp1 and p300 in all glomerular cells of GNs compared to control. Moreover nuclear Smad7 expression was increased mostly in proliferative GNs while a concomitant elimination of its cytoplasmic expression in glomeruli of all GNs and a decrease of Ski expression were denoted. Regarding the tubules there was an increase in pSmad2/3, Sp1 and p300 proximal tubular expression in all GNs and an increase in nuclear Smad7 expression in proliferative GNs while in distal and collecting tubules there was an increased pSmad2/3 and nuclear Smad7 expression with a concomitant decrease in cytoplasmic Smad7, Ski expression was equally reduced in all tubular types. Glomerular pSmad2/3, p300 and nuclear Smad7 expression was increased in proliferative GNs compared to nonproliferative particularly m the secondary group. Tubular pSmad2/3 and nuclear Smad7 as well as proximal tubular p300 Sp1 and cytoplasmic Smad7 expression were also increased in proliferative GNs. On the contrary no difference was detected in Sk1 expression between proliferative and nonproliferative GNs. Positive correlations between the expression of pSmad2/3, p300, Sp1 and Smad7 in glomeruli and proximal tubules were detected. Glomerular and proximal tubular pSmad2/3 and Sp1 as well as glomerular nuclear Smad7 expression exhibited a positive correlation with serum creatinine levels while pSmad2/3, Sp1 and p300 expression in different tubular types showed a positive correlation with indices of histologic injury. All molecules (except for Ski) were very often detected in glomerular lesions. In conclusion Smad signaling pathway seems to be activated in human GN and this activation is probably implicated in the pathogenesis and the progression of renal disease. Future treatment strategies that will target this signaling cascade will probably provide a major contribution to the abolishment of the progression and the treatment of human GN.Οι σπειραματονεφρίτιδες (ΣΝ) αποτελούν μια ομάδα νοσημάτων του σπειράματος ανοσολογικής αιτιολογίας που σε πολλές περιπτώσεις οδηγούν στην πλήρη καταστροφή του νεφρικού παρεγχύματος με αποτέλεσμα τη νεφρική ίνωση και την ανάγκη υποκατάστασης της νεφρικής λειτουργίας με μεθόδους εξωνεφρικής κάθαρσης. Τα τελευταία χρόνια έχει σημειωθεί σημαντική πρόοδος στην ανίχνευση των μοριακών μηχανισμών που οδηγούν στη νεφρική ίνωση. Κεντρικό ρόλο στη διαδικασία αυτή φαίνεται να διαδραματίζει το Smad σηματοδοτικό μονοπάτι που διαμεσολαβεί τα σήματα του TGF-β στα νεφρικά κύτταρα. Ο ρόλος του TGF-β στη νεφρική βλάβη είναι πλέον καλά τεκμηριωμένος. Αντίθετα ελάχιστα είναι γνωστά για την έκφραση και τη λειτουργία του Smad σηματοδοτικού μονοπατιού στις ανθρώπινες ΣΝ. Ο σκοπός της παρούσας μελέτης ήταν η διερεύνηση της έκφρασης των παραγόντων pSmad2/3, p300, Sp1, Smad7 και Ski (μορίων που συμμετέχουν στο Smad σηματοδοτικό μονοπάτι) σε νεφρικές βιοψίες ασθενών με ΣΝ και η ανίχνευση της δράσης τους όσον αφορά την παθογένεση και την εξέλιξη της νεφρικής βλάβης. Χρησιμοποιήθηκαν 157 βιοψίες ασθενών με ΣΝ και 15 φυσιολογικά νεφρικά δείγματα από ασθενείς που είχαν υποβληθεί σε νεφρεκτομή για καρκίνο του νεφρού. Οι σπειραματονεφρίτιδες κατηγοριοποιήθηκαν σε πρωτοπαθείς (n=91) και δευτεροπαθείς (n=66) ή υπερπλαστικές (n=86) και μη υπερπλαστικές (n=71). Η μελέτη της έκφρασης των pSmad2/3, p300, Sp1, Smad7 και Ski έγινε με τη χρήση ανοσοϊστοχημικής μεθόδου. Έγιναν συσχετίσεις με κλινικά δεδομένα των ασθενών (κρεατινίνη ορού και λεύκωμα ούρων 24ώρου), καθώς και δείκτες ιστολογικής βλάβης (σπειραματοσκλήρυνση, διάμεση ίνωση, σωληναριακή ατροφία και διάμεση φλεγμονή). Παρατηρήθηκε πολύ μεγάλη αύξηση της έκφρασης των pSmad2/3, Sp1 και p300 σε όλα τα σπειραματικά κύτταρα των ΣΝ σε σχέση με την ομάδα ελέγχου. Επίσης, αυξήθηκε η έκφραση του πυρηνικού Smad7 στις υπερπλαστικές κυρίως ΣΝ με ταυτόχρονη εξάλειψη της κυτταροπλασματικής έκφρασής του σε όλες τις ΣΝ και παράλληλη μείωση της έκφρασης του Ski. Όσον αφορά τα σωληνάρια, στα εγγύς παρατηρήθηκε αύξηση της έκφρασης των pSmad2/3, Sp1 και p300 σε όλες τις ΣΝ και αύξηση του πυρηνικού Smad7 στις υπερπλαστικές, ενώ στα άπω και τα αθροιστικά παρατηρήθηκε αύξηση της έκφρασης του pSmad2/3 και του πυρηνικού Smad7 με ταυτόχρονη μείωση του κυτταροπλασματικού Smad7. Το Ski παρουσίασε σημαντική μείωση της έκφρασής του στις ΣΝ σε όλους τους τύπους σωληναρίων. Η σπειραματική έκφραση των pSmad2/3, p300 και του πυρηνικού Smad7 ήταν αυξημένη στις υπερπλαστικές ΣΝ και κυρίως τις δευτεροπαθείς. Η σωληναριακή έκφραση των pSmad2/3 και Smad7 και η εγγύς σωληναριακή των p300, Sp1 και του κυτταροπλασματικού Smad7 ήταν επίσης αυξημένες στις υπερπλαστικές ΣΝ. Αντίθετα, το Ski δεν παρουσίασε διαφορές στην έκφραση μεταξύ των υπερπλαστικών και μη υπερπλαστικών ΣΝ. Ακόμη, ανιχνεύθηκαν σημαντικές συσχετίσεις μεταξύ της έκφρασης των pSmad2/3, p300, Sp1 και Smad7 στο σπείραμα και τα εγγύς σωληνάρια. Η σπειραματική και εγγύς σωληναριακή έκφραση των pSmad2/3, Sp1 και η σπειραματική του πυρηνικού Smad7 έδειξαν να συσχετίζονται θετικά με τα επίπεδα της κρεατινίνης του ορού, ενώ η έκφραση αυτών και του p300 σε διαφόρους τύπους σωληναρίων εμφάνισαν θετική συσχέτιση με δείκτες ιστολογικής βλάβης. Τέλος η έκφραση όλων των μορίων (εκτός του Ski) ήταν συχνότατη στις στοιχειώδεις σπειραματικές βλάβες. Συμπερασματικά, το Smad σηματοδοτικό μονοπάτι φαίνεται να ενεργοποιείται στις ανθρώπινες ΣΝ. Μάλιστα, η ενεργοποίησή του αυτή πιθανώς συμβάλλει στην παθογένεση αλλά και την εξέλιξη της νεφρικής βλάβης. Μελλοντικές θεραπευτικές στρατηγικές που θα στοχεύουν στην αναστολή του μονοπατιού αυτού ίσως συμβάλλουν στην παρεμπόδιση της εξέλιξης και τη θεραπεία των ανθρωπίνων ΣΝ
The EU’s 2030 Climate and Energy Policy Framework: How net metering slips through its net
No full textNet metering is a support scheme for the promotion of renewable energy sources (RES) that is linked with state-of-the-art trends, especially in the field of electricity, such as distributed generation, self-consumption and energy communities. Whilst the European Union (EU) Clean Energy Package has established a more coherent and comprehensive regime for RES support schemes in general, it makes no explicit reference to net metering schemes. This raises questions as to how and under which terms net metering schemes are compatible with EU law. Against this background, this article aims to analyse the relevant EU law provisions and conduct a comparative analysis of net metering regimes in four Member States to demonstrate that the national schemes enacted and applied have significantly different design features. The article argues that a more coordinated and specific approach on net metering at the EU level should emerge.Iliopoulos, TG (corresponding author), Hasselt Univ, Rergy & Environm Law, Hasselt, Belgium
[email protected]
A Modular Logic Approach for Expressing Web Services in XML Applying Dynamic Rules in XML
Get PDFRuleML is considered to be a markup language for the semantic web. It allows the enrichment of web ontologies by adding definitions of derived concepts and it enhances interoperability among different systems and tools by publishing rules in an XML format. Moreover the in-creasing demand for interfaces that enhance information sharing has given rise to XML doc-uments that include embedded calls to web services. In this paper we propose a variation of RuleML that is based on modular logic programming. Our approach is based in a two level architecture. In the first level a modular logic language, called M-log, is presented. This lan-guage encompasses several mechanisms for invoking web services. In the second level we ex-ploit the semantics of M-log to present a variation of RuleML with rich modeling capabilities. Formal foundations for this variation are given through direct translation to M-log semantics.Knowledge Management, XML, Modular Logic Programming, E-Services
Impaired desensitization of a human polymorphic α<sub>2B</sub>-adrenergic receptor variant enhances its sympatho-inhibitory activity in chromaffin cells
Get PDFAbstract Background α2-adrenergic receptors (ARs) mediate many cellular actions of epinephrine and norepinephrine and inhibit their secretion from adrenal chromaffin cells. Like many other G-protein coupled receptors (GPCRs), they undergo agonist-dependent phopshorylation and desensitization by GPCR Kinases (GRKs), a phenomenon recently shown to play a major role in the sympathetic overdrive that accompanies and aggravates chronic heart failure. A deletion polymorphism in the human α2B-AR gene (Glu301-303) causes impaired agonist-promoted receptor phosphorylation and desensitization in heterologous cell lines. Given the importance of α2-ARs in regulation of catecholamine secretion from chromaffin cells, we sought to investigate, in the present study, the desensitization properties and the sympatho-inhibitory activity of this variant in a chromaffin cell line. For this purpose, we expressed this variant and its wild type counterpart in the well-established chromaffin cell line PC12, and performed receptor phosphorylation and desensitization studies, as well as in vitro catecholamine secretion assays. Results Both the agonist-induced phosphorylation and agonist-dependent desensitization of the human Glu301-303 deletion polymorphic α2B-AR are significantly impaired in PC12 cells, resulting in enhanced signaling to inhibition of cholinergic-induced catecholamine secretion in vitro. Conclusion This α2B-AR gene polymorphism (Glu301-303 deletion) might confer better protection against conditions characterized and aggravated by sympathetic/catecholaminergic overstimulation in vivo.</p
Electrification of transportation sharing economy business models: the ride- and carsharing cases
Get PDFElectrification of urban transportation is on the rise. In April 2016, ridesharing company Teo Taxi launched a plug-in electric vehicle (PEV) fleet followed four months later by Uber. In 2020 Volkswagen will start a fully-electric carsharing platform, whereas other companies such as BMW already provide such a service. When driven, an electric vehicle garners profit for the platform through transportation. When parked, it can act as a controllable storage device either consuming surplus or injecting energy to the grid. Hence, managed PEV fleets provide unique grid-support opportunities, and added profits to the platform through vehicle-to-grid services. This thesis looks into two types of sharing economy business models with electric vehicles, namely the ride- and carsharing models. The former type of platform has transactional control over the vehicles, that is, private drivers respond to monetary incentives. The latter directly controls its fleet. This thesis develops a mathematical framework to analyze the aforementioned models through queuing theory. It characterizes viable control strategies for the platforms to co-optimize their revenues from both transportation and grid services. It develops profit maximization algorithms of the PEV fleet managers providing such services. Finally, variables of interest are plotted as a function of various platform parameters.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-05-01The student, Theodoros Mamalis, accepted the attached license on 2019-04-05 at 13:53.The student, Theodoros Mamalis, submitted this Thesis for approval on 2019-04-05 at 14:09.This Thesis was approved for publication on 2019-04-05 at 16:34.DSpace SAF Submission Ingestion Package generated from Vireo submission #13496 on 2019-08-22 at 15:05:24Made available in DSpace on 2019-08-23T20:35:45Z (GMT). No. of bitstreams: 2
MAMALIS-THESIS-2019.pdf: 2332090 bytes, checksum: a2df675a94167b12291ed9bda0a2837c (MD5)
LICENSE.txt: 4214 bytes, checksum: 665df018a4a9135b6c3dd9707efe87cb (MD5)
Previous issue date: 2019-04-05Embargo set by: Seth Robbins for item 112110
Lift date: 2021-08-23T20:36:18Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 112110 on 2021-08-24T09:15:31Z
- …
