Molecular characterisation of the thioredoxins in the parasitic nematode haemonchus contortus

University of Technology, Sydney. Faculty of Science.Thioredoxins are a family of small proteins conserved through evolution, essential for cellular homeostasis. The 'classic' thioredoxin, identified in most species, is a 12 kDa protein with a Cys-Gly-Pro-Cys (CGPC) active site. The thioredoxin system, composed of thioredoxin, thioredoxin reductase and peroxiredoxin, is essential to protect cells from metabolically produced reactive oxygen. This and the diversification of this system through evolution identified it as a target for the control of many diseases, including parasitic infections. This work characterises the thioredoxins of Haemonchus contortus, a parasite with increasing economic impact on sheep and wool production in Australia. Five thioredoxin proteins were identified, expressed and characterised (HcTrx1-5). H. contortus contained the classic thioredoxin (HcTrx1), but the major thioredoxin was a 16 kDa protein (HcTrx3) with a Cys-Pro-Pro-Cys (CPPC) active site, which is related to tryparedoxin, a unique protein in Trypanosomes. Both proteins were expressed through the lifecycle and both had a similar ability to reduce the disulphide bonds of insulin compared to the classic thioredoxins in Escherichia coli and sheep. Both proteins were regenerated by thioredoxin reductase, but unlike the ovine thioredoxin, both were also able to reduce oxidised glutathione, directly reduce hydrogen peroxide and indirectly reduce hydrogen peroxide coupled with H.contortus peroxiredoxin. Two thioredoxin-like proteins were identified with homology to thioredoxins reported in human cells, a 31 kDa protein with a CGPC classic active site (HcTrx2) and a 28 kDa protein with a Cys-Pro-Ala-Cys (CPAC) active site, a transmembrane domain and an endoplasmic reticulum localisation signal (HcTFx4). These had different activities to the classic HcTrx1 in that HcTrx2 could not directly reduce insulin, but could when coupled to thioredoxin reductase. In contrast, HcTrx4 could directly reduce insulin, but could not react with thioredoxin reductase. The results suggest that HcTrx4 is not a thioredoxin, but acts as a protein-disulphide isomerase (PDI). Other characterised PDis, contain at least two active sites, in contrast to the one active site in the H.contortus protein. HcTrx5 is a 20 kDa protein with a unique active site Cys-Arg-Ser-Cys (CRSC). Although this active site has a charge change, HcTrx5 was able to reduce insulin, be regenerated by thioredoxin reductase and react with H.contortus peroxiredoxin. However, HcTrx5 was also regenerated by glutathione reductase coupled with glutathione, showing it had the activity of a glutaredoxin as well as a thioredoxin, an activity not reported for any thioredoxin. This study characterised the thioredoxins of a parasitic nematode. The differences identified may provide new drug targets for the control of many tropical diseases for which drug resistance is emerging as a major problem. Preliminary investigations showed increased H.contortus thioredoxin expression in a drug resistant strain. HcTrxl was highly increased in ivermectin resistant parasites and may provide a marker of drug resistance

The cosine law at the atomic scale: Toward realistic simulations of Knudsen diffusion

We propose to revisit the diffusion of atoms in the Knudsen regime in terms of a complex dynamical reflection process. By means of molecular dynamics simulation we emphasize the asymptotic nature of the cosine law of reflection at the atomic scale, and carefully analyze the resulting strong correlations in the reflection events. A dynamical interpretation of the accomodation coefficient associated to the slip at the wall interface is also proposed. Finally, we show that the first two moments of the stochastic process of reflection non uniformly depend on the incident angle

Functionally Graded Alumina/Mullite Coatings for Protection of Silicon Carbide Ceramic Components from Corrosion

During the six months of this reporting period, we accomplished the following: Preparatory work was done on the development of the feed supply system (for mixtures of AlCl{sub 3}, SiCl{sub 4}, H{sub 2} and CO{sub 2}) and effluent treatment section for the CVD system we plan to employ for coating preparation. A comprehensive literature survey of past work done on the chemical vapor deposition of silica, alumina and aluminosilicates (mullite) was carried out, and work was initiated on the study of thermochemical equilibrium in the Al/Si/Cl/C/O/H system so as to identify the boundaries of the region of the space of operating parameters and conditions where preparation of functionally graded mullite/ alumina coatings through CVD from metal chloride, CO{sub 2}, and H{sub 2} is feasible. Since the alumina/mullite films that are proposed to be developed can also be applied to carbon matrix composites provided that a layer that bridges the gap that exists between the thermal expansion coefficient of carbon and that of mullite is employed, experiments were conducted on the preparation of compositionally graded carbon/silicon carbide coatings. Deposition from mixtures of ethylene and methyltrichlorosilane or tetrachlorosilane (silicon tetrachloride) in hydrogen was used for the preparation of SiC/C coatings, and our experiments focused on the study of the occurrence of multiple steady states in the deposition process and the effects of the type of chlorosilane on the deposition rate and the deposit composition and their variation along the length of the reactor. The results showed that when operation is carried out outside the multiplicity region, codeposition of SiC and C from ethylene and chlorosilanes is a feasible route for preparation of SiC/C graded coatings

Associations of sNfL with clinico-radiological measures in a large MS population

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice. METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay. RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable. INTERPRETATION: Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking

Εκτίμηση δεικτών ηλιακής ακτινοβολίας σε αστικό περιβάλλον

73 σ.Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) "Περιβάλλον και Ανάπτυξη"Οι πρώτες δορυφορικές εικόνες και οι ανθρώπινες αποστολές στο διάστημα, μας έκαναν να συνειδητοποιήσουμε ότι ο πλανήτης μας, ως σύστημα, έχει μοναδική εισροή ενέργειας τον ήλιο. Αναμφισβήτητα, η ηλιακή ακτινοβολία που φθάνει στην επιφάνεια του πλανήτη μας κινεί άμεσα ή έμμεσα πολλές φυσικές και βιολογικές δραστηριότητες. Μπορούν να αναφερθούν χαρακτηριστικά η κίνηση του ανέμου, οι κύκλοι του νερού και άλλων στοιχείων της ζωής (π.χ. ο κύκλος του άνθρακα), τα ορυκτά καύσιμα, η παραγωγή της τροφής των ζωντανών οργανισμών με τη διαδικασία της φωτοσύνθεσης κ.ά. Η γνώση της εισερχόμενης ηλιακής ακτινοβολίας αποτελεί για τον άνθρωπο μια πολύ χρήσιμη πληροφορία για τον προγραμματισμό και την εκτέλεση μιας σειράς δραστηριοτήτων. Ως τέτοιες μπορούν να αναφερθούν εφαρμογές στη γεωργία, στις αγοραπωλησίες (real estate), στις κατασκευές (π.χ. βιοκλιματικά κτήρια, ταμιευτήρες), σε αθλητικές δραστηριότητες (χιονοδρομικά κέντρα κ.ά.) και σε επενδύσεις στην παραγωγή ενέργειας (φωτοβολταϊκά συστήματα, θερμοσίφωνες κ.ά.). Τα φυτά, μέσω της θεμελιώδους διαδικασίας της φωτοσύνθεσης, έχουν επιφορτιστεί με τη μετατροπή της ηλιακής ενέργειας σε οργανικά υλικά. Ακραίες όμως συνθήκες φωτισμού, καταπονούν τα φυτά τα οποία υιοθετούν διάφορες στρατηγικές (π.χ. της ανθεκτικότητας), που τους εξασφαλίζουν την επιβίωσή τους. Ο φωτισμός που δέχεται μια περιοχή, δεν μπορεί να αποτελέσει από μόνος του παράγοντα καθορισμού βιοποικιλότητας των φυτών, καθώς τα ελάχιστα επίπεδα φωτισμού εξασφαλίζονται σχεδόν σε κάθε σημείο του πλανήτη. Η δυνητικά εισερχόμενη ηλιακή ακτινοβολία που εξαρτάται από το γεωγραφικό πλάτος την ημέρα του έτους και την ώρα της ημέρας, διαφέρει σημαντικά από αυτή που πραγματικά φθάνει στην επιφάνεια, αφού υπεισέρχονται τοπογραφικοί και κλιματικοί παράγοντες που την υποβαθμίζουν. Με τη βοήθεια των Γεωγραφικών Συστημάτων Πληροφοριών (GIS), έχουν κατασκευαστεί χάρτες που μας δίνουν πληροφορίες για την εισερχόμενη ηλιακή ακτινοβολία σε μεγάλες όμως περιοχές. Η πληροφορία αυτή δεν μπορεί να είναι αξιόπιστη σε περιοχές όπου η τοπογραφία του χώρου παρουσιάζει μεγάλη παραλλακτικότητα, όπως στο αστικό περιβάλλον. Αναμφίβολα, οι πολυκατοικίες και άλλα ψηλά κτήρια, δημιουργούν έντονη σκίαση σε γειτνιάζοντα σημεία. Το ποσό της ακτινοβολίας που δέχονται τα σημεία αυτά αποτελούν κλάσμα της εισερχόμενης ακτινοβολίας. Πράγματι, οι μετρήσεις που έγιναν στο σημείο που πραγματεύεται η παρούσα μελέτη και οι περαιτέρω υπολογισμοί, έδειξαν πως αυτό δέχεται σε ετήσια βάση μόλις το 77% της εισερχόμενης ακτινοβολίας. Συμπερασματικά λοιπόν θα λέγαμε, πως σε αστικό περιβάλλον, η πραγματική εισερχόμενη ακτινοβολία που δέχεται σημείο του ενδιαφέροντός μας, μπορεί να προκύψει μόνο από σημειακές μετρήσεις, οι οποίες θα λαμβάνουν υπ` όψιν τους το ύψος και το αζιμούθιο των εμποδίων.The first satellite images and space missions have made us realize that our planet, as a system, receives its exclusive inflow of energy from the sun. Undeniably, the solar radiation that reaches our planet’s surface prompts, either directly or indirectly, many natural and biological activities. We can characteristically mention wind movement, the water circle and the circles of other elements (e.g. the carbon circle), fossil fuels, food production for the living organisms through the photosynthesis process, etc. The knowledge of incoming solar radiation is a very useful piece of information to man, both for planning and accomplishing a number of activities. The following could be mentioned as such: applications in agriculture, in real estate, in building (for example, bioclimatic buildings, reservoirs), in sports activities (ski resorts etc) and in investments on the generation of energy (PV systems, boilers, etc). The plants, through the fundamental process of photosynthesis, are responsible for the conversion of solar energy into organic matter. However, intensive light conditions harm the plants, which adopt various strategies (e.g. resistivity) to ensure their survival. The lighting of a certain area can not, in itself, become a factor that defines plant biodiversity, as the minimum lighting levels are found in almost every part of the planet. The potential incoming solar radiation, which depends on the latitude, the day of year and the time of day, differs significantly from that which, in reality, reaches the surface, as location and climatic factors intervene and diminish it. With the help of Geographic Information Systems (GIS), we have created maps that provide information about the incoming solar radiation, with reference, however, to extended areas. This information can not be reliable in regions where the area topography presents great variations, as in urban environments. Undoubtedly, apartment buildings and other tall buildings cause intense shading in neighboring spots. The amount of radiation that these spots are submitted to is a fraction of the incoming radiation. Indeed, the measurements that were conducted on the spot that the present study discusses, as well as further calculations, showed that this spot is submitted to merely a 77% of the incoming radiation in a yearly basis.Νικόλαος Χ. Σωτήρχο

IMECE2002/HTD-33632 BIFURCATION ANALYSIS FOR HORIZONTAL LONGITUDINAL FINS UNDER MULTI- BOILING CONDITIONS

ABSTRACT A numerical bifurcation analysis is carried out in order to determine the solution structure of a fin subject to multi-boiling heat transfer mode. The thermal analysis can no longer performed independently of the working fluid since the heat transfer coefficient is temperature dependent and includes the nucleate, the transition and the film boiling regime where the boiling curve is obtained experimentally for a specific fluid. The heat transfer process is modeled using one-dimensional heat conduction with or without heat transfer from the fin tip. Furthermore, five fin profiles are considered: the constant thickness, the trapezoidal, the triangular, the convex parabolic and the parabolic. The multiplicity structure is obtained in order to determine the different types of bifurcation diagrams, which describe the dependence of a state variable of the system (for instance the fin temperature or the heat dissipation) on a design (CCP) or operation parameter (base TD). Specifically the effects of the base TD, of CCP and of the Biot number are analyzed and presented in several diagrams since it is important to know the behavioral features of the heat rejection mechanism such as the number of the possible steady states and the influence of a change in one or more operating variables to these states. Stability analysis is carried out using the "resonance integral" technique and the Sturm-liouville eigensystem analysis

Associations of sNfL with clinico-radiological measures in a large MS population

Esclerosi múltiple; Cadena lleugera de neurofilaments sèricsEsclerosis múltiple; Cadena ligera de neurofilamentos séricosMultiple sclerosis; Serum neurofilament light chainObjective Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice. Methods Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay. Results Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable. Interpretation Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.Study funding was provided from the National Institutes of Health (K23NS117883 to E.S.S.; K01MH121582 to K.C.F.; U01NS111678 to P.A.C.), National Multiple Sclerosis Society (RG-1904-33834 to E.S.S.; RG-1904-33800 to P.A.C.), and Biogen