We are currently experiencing a climate crisis. The planet’s temperature is rising considerably due to the emission of greenhouse gases generated by human activities. This situation poses a challenge for everyone, including companies. Private sector actors are taking actions to mitigate the consequences of climate change, such as global warming. Some of these measures are imposed by national regulations, and others are motivated by the firms' own will. The latter include Science Based Target initiative (SBTi), a voluntary initiative that supports companies in setting climate targets to reduce emissions in line with climate science and the Paris Agreement. The number of companies taking action through participation in it is growing. However, SBTis a young initiative that should be further explored, as more research is needed on its effects. This master’s thesis responds to this gap by studying the impact of joining the SBTi on the financial performance of companies measured through stock returns, volatility and financial risk. For this purpose, the Difference-in-Differences (DiD) statistical technique has been applied through a linear regression model to a sample of 4869 companies. It includes both SBTi member and non-members. At the same time, this research also addresses a second objective, to estimate the determinants to join SBTi, since this is a voluntary action, through a Probit model. It has been found that there is a negative relationship when the financial variable is stock return. While when volatility and financial risk are measured, there is no statistically significant effect. These findings show that being a member of SBTi could reduce investor returns, but does not influence the other two financial indicators. This suggests that investors are not attracted to these companies and may indicate that they see the initiative as a costly distraction. Also, as investors manage their portfolios to reduce market downturns, investing in firms that are part of the initiative will not be something they will consider in terms of their votality. Although the initiative's objectives and commitments help to mitigate climate risks by encouraging the reduction of carbon dioxide emissions, they do not generate significant impacts on the level of financial risk, according to the observations. Regarding the results on the likelihood of joining SBTi, it was found that companies that produce lower returns to investors, have lower stock price fluctuations, have higher financial risk and pollute less, are more likely to be members. This suggests that the initiative should drive its efforts towards companies with these characteristics. This study is innovative in its field in that it addresses a topic of current interest but that has been little explored, the SBTi. It applies two methodologies, regression analysis through DiD and Probit model, but with global panel data, which makes it more challenging. This master’s thesis contributes to the research community in three ways. First, it fills a gap providing new insights into SBTi from a financial perspective. Second, it informs the initiative itself of the implications of its activity and makes it easier to identify potential members and attract them. Third, it can be useful for investors who want to be part of the fight against climate change and include these companies in their portfolios, but want to know the financial consequences of doing so. / Vi upplever för närvarande en klimatkris. Planetens temperatur stiger avsevärt på grund av utsläppen av växthusgaser som genereras av mänsklig verksamhet. Denna situation utgör en utmaning för alla, inklusive företag. Privata aktörer vidtar åtgärder för att mildra konsekvenserna av klimatförändringar, såsom global uppvärmning. Vissa av dessa åtgärder föreskrivs av nationella regleringar, medan andra motiveras av företagens egna vilja. Det senare inkluderar SBTi, en frivillig initiativ som stödjer företag i att fastställa klimatmål för att minska utsläppen i linje med klimatvetenskapen och Parisavtalet. Antalet företag som vidtar åtgärder genom deltagande i initiativet ökar. Dock är SBTi en ung initiativ som bör undersökas mer, eftersom merforskning behövs om dess effek. Denna avhandling fyller detta gap genom att studera effekten av att delta i SBTi på företagens finansiella prestationer, mätt genom aktieavkastning, volatilitet och finansiell risk. För detta ändamål har den statistiska tekniken DiD tillämpats genom en linjär regressionsmodell på ett urval av 4869 företag. Det omfattar både medlemmar och icke-medlemmar av SBTi. Samtidigt behandlar denna forskning även ett andra mål, att uppskatta faktorer som påverkar beslutet att delta i SBTi, eftersom detta är en frivillig åtgärd, genom en Probit-modell. Det har konstaterats att det finns ett negativt samband när den finansiella variabeln är aktieavkastning. När volatilitet och finansiell risk mäts finns det däremot ingen statistiskt signifikant effekt. Dessa resultat visar att att vara medlem i SBTi kan minska avkastningen för investerare, men påverkar inte de andra två finansiella indikatorerna. Detta tyder på att investerare inte lockas av dessa företag och kan indikera att de ser initiativet som en kostsam distraktion. Dessutom, eftersom investerare hanterar sina portföljer för att minska marknadsnedgångar, kommer investeringar i företag som är en del av initiativet inte vara något de överväger med avseende på volatilitet. Även om initiativets mål och åtaganden bidrar till att mildra klimatrisker genom att främja minskning av koldioxidutsläppen, genererar de inte signifikanta effekter på finansiell risknivå enligt observationerna. Vad gäller resultaten angående sannolikheten att delta i SBTi, visade det sig att företag som ger lägre avkastning till investerare, har lägre aktieprisfluktuationer, har högre finansiell risk och förorenar mindre, har större sannolikhet att vara medlemmar. Detta tyder på att initiativet bör rikta sina ansträngningar mot företag med dessa egenskaper. Denna studie är nyskapande inom sitt område genom att den behandlar ett ämne av aktuellt intresse men som är relativt outforskat, nämligen SBTi. Den tillämpar två metoder, regressionsanalys med DiD och en Probit-modell, men med globala paneldata, vilket gör det mer utmanande. Denna avhandling bidrar till forskarsamhället på tre sätt. För det första fyller den en lucka genom att ge nya insikter om SBTi ur ett finansiellt perspektiv. För det andra informerar den själva initiativet om konsekvenserna av dess verksamhet och underlättar identifieringen av potentiella medlemmar och att locka dem. För det tredje kan den vara användbar för investerare som vill vara en del av kampen mot klimatförändringar och inkludera dessa företag i sina portföljer, men som vill känna till de finansiella konsekvenserna av att göra det.

<p>Sepsis and septic shock are life-threating conditions, which resulted from a continuum of the body’s response to overwhelming infection. Elimination of bacteria through antibiotics is not sufficient, because the host is still left with a large amount of lipopolysaccharide (LPS) that prevents the host immune system from returning to normal homeostasis. Synthetic LPS antagonists that can bind to LPS via electrostatic and/or hydrophobic interactions cause systemic toxicities. Moreover, LPS elimination alone may not address already established complications of sepsis. To address these challenges, we propose to develop nanoparticle formulations of LPS antagonists (D-TZP) that can be delivered systemically. Specifically, cholecalciferol (vitamin D) was encapsulated in a self-assembly of tannic acid/Fe³⁺ coordination complex (pTA) capsule, forming a core that could be surface-modified with LPS adsorbents, such as low molecular weight succinylated chitosan (LMZWC) and polymyxin B (PMB). D-TZP suppressed pro-inflammatory effects of LPS on the engineered human monocytes with significantly less cytotoxicity than free PMB at the equivalent dose. D-TZP increased the maximum tolerated dose of PMB by both intraperitoneal and intravenous administration. In the LPS-induced mouse model of sepsis, systemic administration of D-TZP immediately after LPS challenge neutralized the lethal effect of LPS. D-TZP also reduced the mortality of mice when given 2 h after the LPS challenge. D-TZP inhibited the mortality in the cecal ligation and puncture (CLP)-induced bacteremia mouse model when given IV 2 h after the insult. In the CLP model, the D-TZP-treated animals also showed lower levels of both TNF-α and IL-10 cytokines as well as D-dimer levels, reflecting the attenuation of disseminated intravascular coagulation, compared to the vehicle-treated control group. Collectively, these results support that the D-TZP is a safe and effective systemic intervention of sepsis.<br></p>

Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: The facilities for radionuclide production at iThemba LABS have undergone a number of significant upgrades over the last decade in order to increase the production capacity and to diversify the product portfolio. Central to this effort is a new vertical beam target station (VBTS) and its associated targetry, designed and built to operate at higher proton beam intensities for the large-scale production of relatively long-lived, high-value radionuclides such as 22Na, 68Ge and 82Sr. Along with the VBTS, an existing smaller horizontal beam target station was adapted to accommodate targetry for 18F production, mainly to supply 18F-FDG for use in positron emission tomography (PET). The production capacity was further enhanced by means of a beam splitter to enable bombardments in two target stations simultaneously. This required new developments on several systems, e.g. beam diagnostics, control, interlocking and cooling. This project brings together a number of different aspects of the upgraded facilities as well as the associated research and development that enable the production of radionuclides in the medium energy region, up to approximately 70 MeV. Investigations were performed on the cooling of the interfacial windows between the cyclotron vacuum and the targets as well as the direct cooling of the targets themselves during intense proton bombardments. For this purpose, empirical as well as computational fluid dynamics (CFD) calculations were performed. In addition, the local radiation shield of the VBTS as well as the beam transport in some of the targetry was investigated by means of Monte Carlo radiation transport calculations. Excitation functions for the production of various radionuclides in the 66 MeV proton bombardment of 192Os, 159Tb, natGd, 155Gd, 152Gd, 93Nb, natZr and 89Y were measured and compared with theoretical predictions by means of statistical nuclear model calculations as well as the TENDL-2012 library. In particular, the production of 186Re, selected radioterbiums (149;152;155Tb) and radiozirconiums (88;89Zr) is of interest in existing and emerging diagnostic and therapeutic applications in nuclear medicine. A study on 28Mg production in the proton bombardment of natCl using stacked chloride targets was also performed at 200 MeV. This radionuclide is of interest as 28Mg is the only practical radiotracer of Mg. Finally, new targetry for the production of 18F was developed, modelled and optimized for the non-standard degraded beam employed in this particular case. / AFRIKAANSE OPSOMMING: Die fasiliteite vir die produksie van radionukliede by iThemba LABS is gedurende die afgelope dekade aansienlik opgegradeer om die produksiekapasiteit te verhoog en om die portfolio van produkte te diversifiseer. Sentraal tot hierdie poging is ’n vertikale-bundel skyfstasie (VBTS) wat gebou is om skywe met hoër intensiteit protonbundels te bombardeer ten einde relatief langlewende, hoë-waarde radionukliede op grootmaat te produseer, insluitende 22Na, 68Ge en 82Sr. Terselfdetyd is ’n bestaande, kleiner horisontale-bundel skyfstasie aangepas om skywe vir die produksie van 18F te huisves, meestal om 18FFDG vir positronemissietomografie (PET) te lewer. Die produksiekapasiteit is verder verhoog d.m.v. ’n bundeldeler sodat bundel gelyktyding aan twee skyfstasies gelewer kan word. Dit het ontwikkelingswerk vereis aan verskeie stelsels, insluitende diagnostiek, beheer, vergrendeling en verkoeling. Hierdie projek bring verskeie aspekte bymekaar t.o.v. die opgegradeerde produksiefasiliteite sowel as die geassosieerde navorsing en ontwikkeling benodig vir radionukliedproduksie in die middelenergiegebied tot ongeveer 70 MeV. Die verkoeling van die foelievensters tussen die vakuum van die siklotron en die skyfgerei is ondersoek sowel as die direkte verkoeling van skywe onder intense protonbombardement. Hierdie studie sluit beide empiriese sowel as numeriese vloeidinamika berekeninge in. Verder is die afskerming van die VBTS asook die bundeltransport in verskeie skywe ondersoek m.b.v. Monte Carlo stralingstransport berekeninge. Opwekkrommes vir die produksie van verskeie radionukliede met protongeïnduseerde reaksies tot en met 66 MeV op 192Os, 159Tb, natGd, 155Gd, 152Gd, 93Nb, natZr en 89Y is gemeet en vergelyk met statistiese kernmodel berekeninge sowel as die TENDL-2012 biblioteek. Die produksie van 186Re, verskeie radioterbiums (149;152;155Tb) en radiozirkoniums (88;89Zr) is van spesifieke belang vir bestaande en toekomstige diagnostiese en terapeutiese toepassings in die kerngeneeskunde. ’n Studie op die produksie van 28Mg in die bombardement van natCl met 200 MeV protone is ook onderneem. In hierdie ondersoek is ’n stapel chloriedskywe gebruik. Die 28Mg is van belang omdat dit die enigste Mg radioisotoop is wat geskik is as ’n radiospoorder van dié element. Laastens is nuwe skyfgerei vir die produksie van 18F ontwikkel, gemodelleer en geoptimiseer vir die nie-standaard afgeremde bundel wat benut word in hierdie geval.

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此篇論文研究當無通膨目標、存在固定通膨目標及央行宣示通膨目標之三種不同情況下，央行之最適貨幣政策。我們建立數個顯示不同通膨和產出比重之模型，並探討當央行偏離中位數投票者偏好時，對貨幣政策有何影響。 若社會福利函數中之產出的比重較重，在無通膨目標、存在固定通膨目標下，通膨偏誤皆較大。但央行宣示通膨目標時，無論通膨或產出比重較重，視其不同條件而定，通膨偏誤可能較大或較小。另外，央行偏離通膨目標的懲罰，罰責越重使央行宣告之通膨率對民眾預期通膨之影響可能越大，亦可能越小。 將央行偏離中位數投票者偏好之因素納入考量時，在無通膨目標、存在固定通膨目標下，社會福利函數中之通膨比重較重時，通膨偏誤仍較低，而央行宣示通膨目標時，通膨偏誤仍可能較大或較小。但引入央行偏離中位數投票者偏好時，在某些條件下，通膨偏誤可能進一步下降。 / The paper studies the central bank’s monetary policy under pure discretionary, noncontingent targeting and targeting with announcement. We construct models with different weight on inflation and output in the social welfare function. Furthermore, we introduce the central bank’s deviations from the preference of the medium voters into the models to show the effects on monetary policy. The inflation bias is larger when there is more weight on output in the social welfare function in the case of pure discretionary policy and noncontingent targeting. In the case of targeting with announcement, regardless of more weight on inflation or on output, the inflation bias is either larger or smaller under different conditions. Besides, a greater penalty on the central bank’s deviations from the inflation target may increase or decrease the effect of announcements on the public’s inflation expectations. With consideration of the central bank’s deviations from the preference of the medium voters, the inflation bias is still smaller when there’s more weight on inflation in the social welfare function in the case of pure discretionary policy and noncontingent targeting. In targeting with announcement, the inflation bias may still be larger or smaller. However, with the central bank’s deviations from the preference of the medium voters, the inflation bias can be reduced further under some conditions.

Advances in airpower and bombing capabilities have brought airpower to the forefront of military strategy. Four cases are examined to explain the historical uses and goals of strategic and morale bombing of enemy civilian populations: Germany, Japan, Vietnam and Iraq. This historical data is complemented by psychological theory that helps to predict the effectiveness of these bombing campaigns on the civilian will to resist. This paper argues that strategic and morale bombing on civilian populations does not decrease the enemy will to resist.

Keičiantis visuomenei buvo pradėta švietimo reforma, kuriamos naujos Bendrosios programos ir išsilavinimo standartai. Bendrosios programos grindžiamos mokytojo bei mokyklos darbo savarankiškumu ir atsakingumu, orientuoja mokyklas savarankiškai spręsti mokinių darbo krūvio klausimus individualiomis programomis, atsižvelgiant į mokinių amžiaus tarpsnius, poreikius, gebėjimus, mokymosi stilius, suteikiama galimybė mokiniams susikurti vertybių sistemą ir pasiekti asmeninę brandą. Tyrimo tikslas - Ištirti technologinio ugdymo tikslų įgyvendinimą pagrindinėje mokykloje. Tyrimo uždaviniai: 1. Išanalizuoti mokslinę, dalykinę, metodinę literatūrą tiriamuoju klausimu. 2. Palyginti 1994,1997,1999,2003,2008, 2009 metų Technologinio ugdymo Bendrąsias programas 3. Išsiaiškinti technologinio ugdymo tikslų kaitos priežastis 4. Išsiaiškinti svarbiausius technologinio ugdymo tikslus, jų įgyvendinimą Tyrimo organizavimas: viso buvo apklausta 116 technologijų mokytojų iš Rytų Lietuvos mokyklų. Tyrimo metodai: teorinis, statistinis. Apibendrinant atliktą mokslinės, dalykinės, metodinės literatūros analizę, paaiškėjo, kad technologinio ugdymo tikslai priklauso nuo ugdymo paradigmų, spartaus mokslo ir technikos vystymosi, žinių tobulėjimo ir integracijos gausos. Palyginus Technologinio ugdymo bendrąsias programas paaiškėjo, kad iki 1999 metų mokiniai buvo skatinami ugdyti darbinius įgūdžius ir darbo kultūros supratimą. Nuo 2003 metų ugdomi technologinio raštingumo pagrindai. Tyrimas... [toliau žr. visą tekstą] / The exchange was opened to the public education reform, new programs and general education standards. General program based on teacher and school autonomy and accountability of the work, guiding the school to address students self-employment pressures on individual programs, taking into account students ages, needs, abilities, learning styles, given the opportunity for students to create a system of values and the achievement of personal maturity. Purpose of the survey - Investigate the technological goals of education in schools. The tasks were: 1. To analyze the scientific, subject and methodological literature on the subject. 2. Compare 1994,1997,1999,2003,2008, 2009, Broad Technology education programs 3. Clarifying the objectives of technological change, the reasons for building 4. Figure out the most important technological goals of education, their implementation Organization of the research: There were interviewed 116 technology teachers from schools in eastern Lithuania. Methods of research: theoretical, statistical. Summary analysis of scientific, formal, methodical analysis of the literature shows that technological education are dependent on the educational paradigm, rapid scientific and technological development, knowledge development and integration of abundance. The comparison of the general technology education programs show that by 1999, students were encouraged to develop working skills and cultural understanding. Since 2003, educated in technological... [to full text]

Emergency surgeries are serviced by three main forms of capacity: dedicated operating room time reserved for emergency surgeries, alternative (on call) capacity, and lastly, canceling of elective surgeries. The objective of this research is to model capacity implications of meeting wait time targets for multiple priority levels in the context of emergency surgeries. Initial attempts to solve the capacity evaluation problem were made using a non-linear optimisation model, however, this model was intractable. A simulation model was then used to examine the trade-off between additional dedicated operating room capacity (and consequent idle capacity) versus increased re-scheduling of elective surgeries while keeping reserved time for emergency surgeries low. Considered performance measures include utilization of operating room time, elective re-scheduling, and wait times by priority class. Finally, the instantaneous utilization of different types of downstream beds is determined to aid in capacity planning. The greatest number of patients seen within their respective wait time targets is achieved by a combination of additional on call capacity and a variation of the rule allowing low priority patients to utilize on call capacity. This also maintains lower cancelations of elective surgeries than the current situation. Although simulation does not provide an optimum solution it enables a comparison of different scenarios. This simulation model can determine appropriate capacity levels for servicing emergency patients of different priorities with different wait time targets.

Mycobacterium tuberculosis (Mtb), a pathogenic bacterium, is the causative agent in the vast majority of human tuberculosis (TB) cases. Nearly one-third of the world’s population has been affected by TB and annually two million deaths result from the disease. Because of the high cost of medication for a long term treatment with multiple drugs and the increase of multidrug-resistant Mtb strains, faster-acting drugs and more effective vaccines are urgently demanded. Several metabolic pathways of Mtb are attractive for identifying novel drug targets against TB. Hence, a high quality genome-scale metabolic network of Mtb (HQMtb) was reconstructed to investigate its whole metabolism and explore for new drug targets. The HQMtb metabolic network was constructed using an unbiased approach by extracting gene annotation information from various databases and consolidating the data with information from literature. The HQMtb consists of 686 genes, 607 intracellular reactions, 734 metabolites and 471 E.C. numbers, 27 of which are incomplete. The HQMtb was compared with two recently published Mtb metabolic models, GSMN-TB by Beste et al. and iNJ661 model by Jamshidi and Palsson. Due to the different reconstruction methods used, the three models have different characteristics. The 68 new genes and 80 new E.C. numbers were found only in the HQMtb and resulting in approximately 52 new metabolic reactions located in various metabolic pathways, for example biosynthesis of steroid, fatty acid metabolism, and TCA cycle. Through a comparison of HQMtb with a previously published human metabolic network (EHMN) in terms of protein signatures, 42 Mtb metabolic genes were proposed as new drug targets based on two criteria: (a) their protein functional sites do not match with any human protein functional sites; (b) they are essential genes. Interestingly, 13 of them are found in a list of current validated drug targets. Among all proposed drug targets, Rv0189c, Rv3001c and Rv3607c are of interest to be tested in the laboratory because they were also proposed as drug target candidates from two research groups using different methods.

Background: Small nucleolar RNAs (snoRNAs) are one of the most ancient families amongst non-protein-coding RNAs. They are ubiquitous in Archaea and Eukarya but absent in bacteria. Their main function is to target chemical modifications of ribosomal RNAs. They fall into two classes, box C/D snoRNAs and box H/ACA snoRNAs, which are clearly distinguished by conserved sequence motifs and the type of chemical modification that they govern. Similarly to microRNAs, snoRNAs appear in distinct families of homologs that affect homologous targets. In animals, snoRNAs and their evolution have been studied in much detail. In plants, however, their evolution has attracted comparably little attention. Results: In order to chart the phylogenetic distribution of individual snoRNA families in plants, we applied a sophisticated approach for identifying homologs of known plant snoRNAs across the plant kingdom. In response to the relatively fast evolution of snoRNAs, information on conserved sequence boxes, target sequences, and secondary structure is combined to identify additional snoRNAs. We identified 296 families of snoRNAs in 24 species and traced their evolution throughout the plant kingdom. Many of the plant snoRNA families comprise paralogs. We also found that targets are well-conserved for most snoRNA families. Conclusions: The sequence conservation of snoRNAs is sufficient to establish homologies between phyla. The degree of this conservation tapers off, however, between land plants and algae. Plant snoRNAs are frequently organized in highly conserved spatial clusters. As a resource for further investigations we provide carefully curated and annotated alignments for each snoRNA family under investigation.