Steel futures and company characteristics: which companies use steel futures?

My thesis examines the link between firm characteristics and the usage of steel futures working with annual data from 1,536 steel-related companies’ between 2003 and 2015. I use fixed effects regression with binary response to estimate a firm’s likelihood of using steel futures. The chance of using steel futures for firms with a high degree of steel exposure relative to less steel exposed ones, is significantly positively affected by firm size, leverage, debt structure, return on assets and investment grade

Stirb an einem anderen Tag : Virus versus Immunsystem

Jeder Mensch kämpft täglich erfolgreich mit Krankheitserregern, ohne dass er sich der komplexen molekularen Vorgänge dabei bewusst wäre. Wie in einem Hollywood-Streifen geht es rasant zur Sache. Ist das Immunsystem angeschlagen oder trifft es auf starke Gegner, kann eine Infektion binnen weniger Tage außer Kontrolle geraten und lebensbedrohliche Reaktionen hervorrufen. Der menschliche Organismus benötigt eine effiziente Verteidigungsstrategie gegen die Eindringlinge und muss, ebenso wie der britische Geheimdienst im Bond-Film, in die Ausbildung geübter Agenten investieren, Agenten mit Doppel-Null-Status. Agenten wie James Bond

African mahogany (Khaya senegalensis) plantations in Australia - status, needs and progress

The Australian African mahogany estate comprises over 12,000 ha of industrial plantations, farm-forestry plots and trials, virtually all derived from Africa-sourced wild seed. However, the better trees have given high-value products such as veneers, high-grade boards and award-winning furniture. Collaborative conservation and improvement by the Northern Territory (NT) and Queensland governments since 2000 realised seed orchards, hedge gardens and genetic tests revealing promising clones and families. Private sector R&D since the mid 2000s includes silvicultural-management and wood studies, participatory testing of government material and establishing over 90 African provenances and many single-tree seedlots in multisite provenance and family trials. Recent, mainly public sector research included a 5-agency project of 2009-12 resulting in advanced propagation technologies and greater knowledge of biology, wood properties and processing. Operational priority in the short term should focus on developing seed production areas and ‘rolling front’ clonal seed orchards. R&D priorities should include: developing and implementing a collaborative improvement strategy based on pooled resources; developing non-destructive evaluation of select-tree wood properties, micropropagation (including field testing of material from this source) to ‘industry ready’ and a select-tree index; optimising seed production in orchards; advancing controlled pollination techniques; and maximising benefits from the progeny, clone and provenance trials. Australia leads the world in improvement and ex situ conservation of African mahogany based on the governments’ 13-year program and more recent industry inputs such that accumulated genetic resources total over 120 provenances and many families from 15 of the 19 African countries of its range. Having built valuable genetic resources, expertise, technologies and knowledge, the species is almost ‘industry ready’. The industry will benefit if it exploits the comparative advantage these assets provide. However the status of much of the diverse germplasm introduced since the mid 2000s is uncertain due to changes in ownership. Further, recent reductions of government investment in forestry R&D will be detrimental unless the industry fills the funding gaps. Expansion and sustainability of the embryonic industry must capitalise on past and current R&D, while initiating and sustaining critical new work through all-stakeholder collaboration

Präsentation des Prion-Proteins auf virus-ähnlichen Partikeln : eine neue Vakzinierungsstrategie

Prionenerkrankungen sind neurodegenerative Erkrankungen, zu denen Scrapie beim Schaf, Bovine Spongiforme Enzephalopathien beim Rind und beispielsweise die Creutzfeld-Jakob-Erkrankung beim Menschen zählen. Bei dem Erreger der Erkrankung handelt es sich um ein infektiöses Protein, das sogenannte Prionen Protein PrPSc. Die primäre Sequenz des PrPSc ist identisch zur Sequenz eines weit verbreiteten zellulären Proteins PrPc. Es wird angenommen, dass die Vermehrung durch die Umfaltung des zellulären Gegenspielers PrPc stattfindet. Als möglicher therapeutischer Ansatz gegen diese Erkrankungen wird eine Vakzinierung diskutiert. Eine krankheitsverlangsamende Wirkung durch passive Immunisierung mit spezifischen Antikörpern, die die zelluläre Form des Proteins PrPc erkennen, wurde bereits im Tiermodell gezeigt. Die Erzeugung einer Immunantwort gegen PrPc erfordert die Umgehung der wirtsspezifischen Toleranz gegen das Selbstantigen PrPc. Ziel der vorliegenden Arbeit war die Entwicklung von Impfstoffkandidaten für eine aktive Immunisierung gegen Prionenerkrankungen. Es wurden Vakzine auf der Basis von Virus-ähnlichen Partikeln (Retropartikel) entwickelt, die vom murinen Leukämievirus (MLV) bzw. vom humanen Immundefizienzvirus (HIV) abgeleitet wurden. Sowohl die Präsentation der zellulären Form PrPc als auch der pathogenen Form PrPSc wurde adressiert. Zur Präsentation auf Retropartikeln wurde PrPc entweder an die Transmembrandomäne des Plättchen-abgeleiteten Wachstumsfaktor Rezeptors (PDGFR) oder an den N-terminus des retroviralen Hüllproteins (Env) von MLV fusioniert wurde. In beiden Fällen konnten die entsprechenden PrPD- bzw. PrPE-Retropartikel erfolgreich hergestellt werden, die des Weiteren mittels Immunfluoreszenzfärbung, Western Blot Analyse, Immunogold-Elektronen-mikroskopie sowie ELISA Methoden charakterisiert wurden. Sowohl für PrPD- als auch für PrPE-Retropartikel konnte gezeigt werden, dass PrPc inkorporiert und auf der Oberfläche der viralen Partikel präsentiert wurde, wenn N-terminal trunkierte Formen von PrPc verwendet wurden. Die für PrPc typischen Glykosylierungsmuster konnten durch spezifischen Glykosidase-Verdau nachgewiesen werden. Die präsentierten PrPc-Varianten wurden unter nativen Bedingungen von PrP-spezifischen Antikörpern erkannt. Im Gegensatz zu den N-terminal trunkierten Varianten wurde das komplette PrPc nicht in Retropartikel inkorporiert. Mittels Elektronen-Mikroskopie konnte bei der Inkorporation von PrPc-Varianten keine Veränderung der charakteristischen retroviralen Morphologie der Partikel festgestellt werden. MLV-abgeleitete PrPD-Retropartikel wurden anschließend erfolgreich zur Immunisierung von Mäusen eingesetzt. Dabei wurden, im Gegensatz zur Immunisierung mit Vakzinen, die auf bakteriell hergestelltem PrPc basierten, spezifische Antikörpertiter erhalten. Versuche zur Präsentation der pathogenen Form wurden zum einen durch Konvertieren der Proteinase K-sensitiven in die Proteinase K-resistente Form des PrP auf der Oberfläche der PrPD-Retropartikel durchgeführt. Der Nachweis mittels Proteinase K-Verdau wurde hier speziell für virale Partikel adaptiert, die Umwandlung der PrPD-Retropartikel in Proteinase K-resistent Formen konnte jedoch nicht beobachtet werden. Zum anderen wurde ein PrPc-codierendes replikationskompetentes MLV-abgeleitetes Retrovirus erzeugt. Dieses konnte über sechs Passagen genetisch stabil auf murinen Fibroblasten propagiert werden, zeigte allerdings nach Infektion einer Prionen-infizierten Zelllinie, die PrPSc stetig propagierte, keine Replikation. Neben virus-ähnlichen Partikeln standen damit MLV-abgeleitete replikationskompetente Viren zur Verfügung, die PrPc stabil im viralen Genom enthalten und auf ihrem Hüllprotein präsentieren. Basierend auf Hinweisen aus der Literatur war die Inkorporation von PrPc in Virus-ähnliche Partikel zu erwarten, da es sich um ein Zelloberflächenprotein handelt. Der fehlende Einbau des kompletten PrP in retrovirale Partikel war daher unerwartet. Anders als für die trunkierten PrPc-Varianten war sowohl die Fusion mit PDGFR als auch die N-terminale Env-Fusion für PrPc inhibiert. Das komplette PrPc unterliegt im Vergleich zu trunkierten Formen einem erhöhten Zelloberflächen-Umsatz und weist eine geringere Halbwertszeit auf. Diese beiden Faktoren können einen Beitrag zur verminderten Inkorporation in retrovirale Partikel leisten. Die in der vorliegenden Arbeit beschriebenen PrPD-Retropartikel stellen das erste erfolgreiche System zur Erzeugung PrP-spezifischer Immunantworten gegen die native Zelloberflächen-Form des PrPc dar. Ein möglicher Mechanismus zur Erklärung basiert auf der Induktion der T-Zellhilfe sowie eines Beitrags des angeborenen Immunsystems. Eine weitere Verbesserung der Immunantwort sollte sich mit den in dieser Arbeit hergestellten MLV- und HIV-abgeleiteten Partikeln, die zusätzlich mit PrP-codierenden Sequenzen ausgestattet wurden sowie mit den replikationskompetenten MLV-Varianten verwirklichen lassen.Prion diseases, also called transmissible spongiform encephalopathies, are a group of fatal neurodegenerative conditions that affect humans and a wide variety of animals. To date there is no therapeutic or prophylactic approach against prion diseases available. The causative infectious agent is the prion, also termed PrPSc, which is a pathological conformer of a cellular protein named prion protein PrPc. Prions are thought to multiply upon conversion of PrPc to PrPSc in a self-propagating manner. Immunotherapeutic strategies directed against PrPc represent a possible approach in preventing or curing prion diseases. Accordingly, it was already shown in animal models, that passive immunization delays the onset of prion diseases. The present thesis aimed at the development of a candidate vaccine towards the active immunization against prion diseases, an immune response, which has to be accompanied by the circumvention of host tolerance to the self-antigen PrPc. The vaccine development was approached using virus-like particles (retroparticles) derived from either the murine leukemia (MLV) or the human immunodeficiency virus (HIV). The display of PrP on the surface of such particles was addressed for both the cellular and the pathogenic form of PrP. The display of PrPc was achieved by either fusion to the transmembrane domain of the platelet derived growth factor receptor (PDGFR) or to the N-terminal part of the viral envelope protein (Env). In both cases, the corresponding PrPD- and PrPE-retroparticles were successfully produced and analyzed via immune fluorescence, Western Blot analysis, immunogold electron microscopy as well as by ELISA methods. Both, PrPD- and PrPE-retroparticles showed effective incorporation of N-terminally truncated forms of PrPc but not for the complete protein. PrPc at this revealed the typical glycosylation pattern, which was specifically removed by a glycosidase enzyme. Upon display of PrPc on retroparticles the protein remained detectable by PrP-specific antibodies under native conditions. Electron microscopy analysis of PrPc-variants revealed no alteration of the characteristic retroviral morphology of the generated particles. MLV-derived PrPD-retroparticles were successfully used in immunization studies. Contrary to approaches using bacterially expressed PrPc, the immunization of mice resulted in a specific antibody response. The display of the pathogenic isoform was aimed by two different strategies. The first one was directed at the conversion of the proteinase K (PK) sensitive from of PrP on the surface of PrPD-retroparticles into the PK resistant form. Albeit specific adaption of the PK digestion assay detecting resistant PrP, no PrP conversion was observed for PrPD-retroparticles. The second approach utilized a replication competent variant of the ecotropic MLV displaying PrPc on the viral Env protein. This MLV variant was stable in cell culture for six passages but did not replicate on scrapie-infected, PrPSc-propagating neuroblastoma cells. Thus, besides PrPc-displaying virus-like particles a replication competent MLV variant was obtained, which stably incorporated PrPc at the N-terminus of the viral Env protein. The incorporation of the cell-surface located PrPc into particles was expected from previously obtained data on protein display in the context of retrovirus-derived particles. Thus, the lack of incorporation observed for the complete PrPc sequence was rather unexpected and was found to be inhibited at both, fusion to PDGFR and the viral Env. In contrast to N-terminally truncated PrPc, the complete PrPc was shown to exhibit increased cell surface internalization rates and half-life times eventually contributing to the observed results. The PrP-vaccination approach described in this work represents the first successful system inducing PrP-specific antibody responses against the prion protein in wt mice. Explanations at this are based on the induction of specific T cell help or effects of the innate immunity, respectively. MLV-and HIV-derived particles bearing the PrP-coding sequence or being replication competent variants generated during this thesis might help to further improve the PrP-specific immune response

Enhancement of stimulated Brillouin scattering of higher-order acoustic modes in single-mode optical fiber

This paper was published in Optics Letters and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/abstract.cfm?URI=ol-30-20-2685. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.Solving the elastic wave equation exactly for a GeO2-doped silica fiber with a steplike distribution of the longitudinal and shear velocities and density, we have obtained the dispersion, attenuation, and fields of the leaky acoustic modes supported by the fiber. We have developed a model for stimulated Brillouin scattering of these modes in a pump-probe configuration and provided their Brillouin gains and frequencies for an extended range of core sizes and GeO2 doping. Parameter ranges close to cutoff of the acoustic modes and pump depletion enhance the ratio of higher-order peaks to the main peak in the Brillouin spectrum and are suitable for simultaneous strain-temperature sensing.Shahraam Afshar V., V. P. Kalosha, Xiaoyi Bao, Liang Che

TGF-beta i nastanak karcinoma prostate

All transforming growth factors beta (TGFß) are cytokines that regulate several cellular functions such as cell growth, differentiation and motility. They may also have a role in immunosuppression. Their role is important for normal prostate development. TGFß is active in the regulation of balance between epithelial cell proliferation and apoptosis through stromal epithelia via the androgen receptor action. TGFß protects and maintains prostate stem cells, an important population necessary for prostate tissue regeneration. However, TGFß is shown to have a contrasting role in prostate tumor genesis. In the early stages of tumor development, TGFß acts as a tumor suppressor, whereas in the later stages, TGFß becomes a tumor promoter by inducing proliferation, invasion and metastasis. In this review, we outline complex interactions that TGFß-mediated signaling has on prostate tumor genesis, focusing on the role of these interactions during the course of prostate cancer and, in particular, during disease progression.Svi transformacijski faktori rasta beta (TGFß) su citokini koji reguliraju nekoliko staničnih funkcija kao što su rast, diferencijacija i pokretljivost stanice. Oni također imaju značajnu ulogu u imunosupresiji. Njihova je uloga osobito značajna za normalan razvoj prostate. TGFß je aktivan u regulaciji ravnoteže između proliferacije epitelnih stanica i apoptoze kroz stromalni epitel preko djelovanja androgenog receptora. TGFß štiti i održava matične stanice prostate, značajan čimbenik za regeneraciju tkiva prostate. Do danas publicirani rezultati iznalaze da TGFß ima suprotnu ulogu u nastanku tumora prostate. U ranim fazama razvoja tumora TGFß djeluje kao supresor tumora, dok u kasnijim fazama TGFß postaje tumorski promotor inducirajući proliferaciju, invazivni rast i razvoj metastaza. U ovom preglednom članku opisuju se složene interakcije koje TGFß-posredovani mehanizmi imaju na nastanak tumora prostate, s osobitim naglaskom na mehanizme djelovanja tijekom nastanka karcinoma prostate i naročito tijekom progresije osnovne bolesti

Klinička praksa hrvatskih urologa i usklađenost sa smjernicama u liječenju simptoma donjeg mokraćnog trakta u muškaraca

The aim of this study was to assess the Croatian urologists’ management of non-neurogenic male lower urinary tract symptoms (LUTS) and their compliance with the European Association of Urology (EAU) guidelines. A cross-sectional survey included 51/179 Croatian urologists. We developed a questionnaire with questions addressing compliance with EAU guidelines. The rate of performing recommended evaluations on the initial assessment of patients with benign prostate hyperplasia (BPH)/LUTS varied from 8.0% (serum creatinine and voiding diary) to 100.0% (physical examination, prostate specific antigen and ultrasound). The international prostate symptom score was performed by 31%, analysis of urine sediment by 83%, urine culture by 53%, and serum creatinine by 8% of surveyed urologists. Only 8% of urologists regularly used bladder diary in patients with symptoms of nocturia. Our results indicated that 97% of urologists preferred alpha blockers as the first choice of treatment; 5-alpha reductase inhibitors (5ARI) were mostly prescribed (84%) in combination with an alpha-blocker, preferably as a continuous treatment, whilst 29% of urologists used to discontinue 5ARI after 1-2 years. Half of the Croatian urologists used antimuscarinics in the treatment of BPH/LUTS and recommended phytotherapeutic drugs in their practice. In conclusion, Croatian urologists do not completely comply with the guidelines available.Cilj ovoga istraživanja bio je uvrditi kliničku praksu hrvatskih urologa u pristupu bolesnicima sa simptomima donjeg mokraćnog trakta (LUTS) i njihovo pridržavanje Smjernica Europskoga urološkog društva (EAU). Provedeno je presječno istraživanje među 51/179 (28%) hrvatskih urologa. Izradili smo upitnik koji sadrži pitanja glede poštivanja smjernica EAU. Primjena preporučenih pretraga u početnoj procjeni bolesnika s benignom hiperplazijom prostate (BPH)/LUTS varirala je od 8,0% (kreatinin i dnevnik mokrenja) do 100,0% (fizikalni pregled, antigen specifičan za prostatu (PSA) i ultrazvuk). U početnoj procjeni bolesnika s BPH/LUTS uz anamnezu i digitorektalni pregled hrvatski urolozi primjenjuju još PSA i ultrazvuk (100%). Međunarodni zbroj prostatičnih simptoma (IPSS) primjenjuje 31%, analizu sedimenta mokraće 83%, kulturu mokraće 53%, a serumski kreatinin 8% ispitanih urologa. Samo 8% urologa redovito koristi dnevnik mokrenja kod bolesnika sa simptomima nokturije. Rezultati su pokazali kako 62% hrvatskih urologa smatra da provodi dijagnostičku obradu koja je u skladu sa smjernicama EAU. U terapijskom pogledu rezultati pokazuju da 97% urologa smatra alfa blokatore lijekom prvog izbora. Inhibitori 5-alfa reduktaze (5ARI) uglavnom (84%) su propisani u kombinaciji s alfa-blokatorima, ponajprije kao kontinuirano liječenje, dok 29% prekida 5ARI nakon 1-2 godine. Polovica hrvatskih urologa rabi antimuskarinike u liječenju BPH/LUTS i preporučuje fitoterapiju u svojoj praksi. Praksa hrvatskih urologa nije u potpunosti usklađena sa smjernicama

An Enterprise Architecture Framework to organize Model Repositories

Abstract. Models are a valuable knowledge asset for an enterprise. An enterprise model repository can improve sharing of enterprise knowledge and thus can exploit the use of the knowledge for various applications. In this work we present a framework for the organisation of enterprise models. The framework was derived from enterprise architecture frameworks. It distinguishes three dimensions: aspect, perspective, and modelling language family. For each of these dimensions we derive possible values. The framework can be used for enterprise repositories but also for knowledge exchange in a community as proposed by the Open Model Initiative