565 research outputs found
Passion with Purpose A Case Study of St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is “leading the way the world understands, treats, and defeats childhood cancer and other life threatening diseases” (St. Jude Children’s Research Hospital). Fifty-five years ago when St. Jude opened its doors, the overall childhood cancer survival rate was 20 percent; today, the overall childhood cancer survival rate exceeds 80 percent. Through research and discovery, St. Jude has played a pivotal role in increasing this survival rate. St. Jude, a non-profit organization and hospital in Memphis, Tennessee, operates primarily through donations. St. Jude-American Lebanese Syrian Associated Charities (ALSAC) is the fundraising and awareness organization with the sole purpose of keeping St. Jude Children Research Hospital’s doors open. This senior Honors capstone project will explore the connection between passion paired with purpose and the success of St. Jude Children’s Research Hospital. This capstone develops a detailed case study gleaned from interviews with several St. Jude-ALSAC representatives who provide provocative insights into leadership structure at St. Jude and more importantly, the role that passion plays in an employee’s commitment to the organization’s values, vision, and mission
A simplified analytical approach for optimal planning of distributed generation in electrical distribution networks
DG-integrated distribution system planning is an imperative issue since the installing of distributed generations (DGs) has many effects on the network operation characteristics, which might cause significant impacts on the system performance. One of the most important characteristics that mostly varies because of the installation of DG units is the power losses. The parameters affecting the value of the power losses are number, location, capacity, and power factor of the DG units. In this paper, a new analytical approach is proposed for optimally installing DGs to minimize power loss in distribution networks. Different parameters of DG are considered and evaluated in order to achieve a high loss reduction in the electrical distribution networks. The algorithm of the proposed approach has been implemented using MATLAB software and has been tested and investigated on 12-bus, 33-bus, and 69-bus IEEE distribution test systems. The results show that the proposed approach can provide an accurate solution via simple algorithm without using exhaustive process of power flow computations
Descemet stripping automated endothelial keratoplasty in Fuchs' corneal endothelial dystrophy: Anterior segment optical coherence tomography and in vivo confocal microscopy analysis
Background: To evaluate the in vivo corneal changes using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) in patients with Fuchs' dystrophy who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) and the relationship between these changes and the postoperative visual recovery up to 1-year follow-up. Methods: Before DSAEK and 1 day, 3, 6 and 12 months after surgery 31 patients (39 pseudophakic eyes) underwent a complete ophthalmological evaluation including best corrected visual acuity (BCVA), IVCM (subepithelial haze, interface haze, graft thickness) and AS-OCT (graft thickness). Results: Graft thickness measurements by AS-OCT were strongly correlated to those obtained using IVCM at every follow-up stage (intraclass correlation coefficientâ\u88\u88=â\u88\u880.95 to 0.97 between 3 and 12 months, Pâ\u88\u88<â\u88\u880.001 for all coefficients). No correlation between BCVA and graft thickness measured by AS-OCT at any follow-up stage was found, while at 3 and 6 postoperative months the correlations between BCVA and preoperative subepithelial haze (râ\u88\u88=â\u88\u880.61, Pâ\u88\u88<â\u88\u880.001 and râ\u88\u88=â\u88\u880.46, Pâ\u88\u88=â\u88\u880.002), interface haze (râ\u88\u88=â\u88\u880.51, Pâ\u88\u88<â\u88\u880.001 and râ\u88\u88=â\u88\u880.46, Pâ\u88\u88=â\u88\u880.003), postoperative subepithelial haze (râ\u88\u88=â\u88\u880.43, Pâ\u88\u88=â\u88\u880.004 and râ\u88\u88=â\u88\u880.39, Pâ\u88\u88=â\u88\u880.001) were significant. Conclusions: The study confirmed corneal subepithelial haze and interface haze as important factors limiting visual acuity after DSAEK, while graft thickness was not related to BCVA
International human rights law in the EU Global Human Rights Sanctions Regime
Il presente contributo si propone di esaminare il regime globale di sanzioni dell’Unione europea in materia di diritti umani nella prospettiva del diritto internazionale e, in particolare, verificare quale sia il ruolo delle norme internazionali sui diritti umani. L’articolo, infatti, intende rispondere alla seguente domanda: con il regime sanzionatorio in esame, l’Unione mira ad assicurare il rispetto delle norme internazionali in materia di diritti umani reagendo a presunte violazioni di tali norme da parte di Stati terzi o attori non statali o, piuttosto, ha voluto creare un nuovo strumento di politica estera che potesse influenzare la condotta di tali Stati/attori indipendentemente dalla presunta violazione di queste norme? La rilevanza della questione è evidente laddove si consideri il noto dibattito sulla conformità delle sanzioni unilaterali al diritto internazionale e, in particolare, le tesi che ne condizionano la liceità all’eventualità che queste siano qualificabili come ritorsioni o come contromisure lecite. Così, esaminando tanto gli atti che istituiscono il regime sanzionatorio in parola quanto le misure restrittive adottate finora, l’articolo stabilirà se tali misure possano essere considerate come reazioni a violazioni delle norme internazionali dei diritti umani e dunque, purché alcune altre condizioni siano soddisfatte, contromisure lecite.his article aims to examine the EU Global Human Rights Sanctions Regime from the perspective of international law and, in particular, assess the place of international human rights law therein. Indeed, it seeks to answer the following question: Is this regime meant and has it been used in practice as an instrument to enforce international human rights rules by reacting to their alleged violation or rather as a foreign policy tool aiming at influencing other States/actors conducts? The relevance of this question is evident in light of the general debate on whether unilateral sanctions are only lawful under international law insofar as they qualify as either retorsions or lawful countermeasures. Thus, by a thorough examination of the acts establishing the sanctions regime at hand, as well as the restrictive measures taken so far in its context, the article will determine whether said measures can be considered as reactions to violations of international human rights rules – hence, provided that all other relevant conditions are met, lawful countermeasures
Chemistry and relevant thermophysical properties of Pb84.3Li15.7 liquid solutions: Updated view and identification of new and coherent values
The liquid breeding blanket concept of a fusion reactor is based on the employment of the eutectic Lead-Lithium solution (LLE), where Lithium, enriched in 6Li, has the purpose of regenerating Tritium by reacting with neutrons, while Lead enhances the process acting as neutrons multiplier. Anyway, despite the huge interest on this binary system, LLE is not characterized yet by a fully consolidated description of its basic thermophysical properties and, in many cases, the spread of values reported so far in literature remains still significant. The purpose of this paper is hence to check again the many data available in literature, with a special attention to the ones more recently published, trying to explain and solve their inhomogeneity. Taking into account the general features of the Pb-Li interaction and particularly the not ideal behaviour of the Pb-Li liquid solutions, the following thermophysical properties of the LLE are dealt in detail: specific heat; density and volumetric thermal expansion coefficient; thermal conductivity and diffusivity; electrical resistivity; Sieverts' constant of Hydrogen. Based on the deep analysis of all the reported experimentation and through the adoption of several comparison criteria, the most trustable correlation is sought for each of the above properties; additionally, when a robust correlation couldn't be retrieved, a new, optimized, one has been proposed, capable also to foresee correctly the effect of small composition variations and to assure the internal coherence among linked properties. Specific heat and density values resulted at the end accurately described and not needing for additional experimentation; thermal properties and electrical resistivity can be evaluated with decent confidence, even if their uncertainty could be somehow reduced by future investigations; for Sieverts' constant it has not possible yet to identify a unique, trustable correlation, anyway the range of values correctly assumed up to 900K has been significantly restricted
Generation of monoclonal antibodies against native viral proteins using antigen-expressing mammalian cells for mouse immunization
Due to their rising incidence and progressive geographical spread, infections with mosquito-borne viruses, such as dengue (DENV), chikungunya and zika virus, have developed into major public health challenges. Since all of these viruses may cause similar symptoms and can occur in concurrent epidemics, tools for their differential diagnosis and epidemiological monitoring are of urgent need.; Here we report the application of a novel strategy to rapidly generate monoclonal antibodies (mAbs) against native viral antigens, exemplified for the DENV nonstructural glycoprotein 1 (NS1). The described system is based on the immunization of mice with transfected mammalian cells expressing the target antigens in multiple displays on their cell surface and thereby presenting them efficiently to the host immune system in their native conformation. By applying this cell-based approach to the DENV NS1 protein of serotypes 1 (D1NS1) and 4 (D4NS1), we were able to rapidly generate panels of DENV NS1 serotype cross-reactive, as well as D1NS1- and D4NS1 serotype-specific mAbs. Our data show that the generated mAbs were capable of recognizing the endogenous NS1 protein in DENV-containing biological samples.; The use of this novel immunization strategy, allows for a fast and efficient generation of hybridoma cell lines, producing mAbs against native viral antigens. Envisaged applications of the mAbs include the development of test platforms enabling a differentiation of the DENV serotypes and high resolution immunotyping for epidemiological studies
Grid-Listening and Grid-Ringing: Alternative Concepts for Grid-Following and Grid-Forming within Power Systems Frequency Transients
The paper introduces the concepts of grid-listening and grid-ringing as alternative ways to interpret the classes of converter control commonly known as grid-following and grid-forming. The intrinsic nature of these two controls define their interaction within the frequency transients in power systems, and in particular with the disturbance propagation and the synchronization process. The grid-following interacts with the oscillations in the system just detecting them: for that, it can be regarded as grid-listening. The grid-forming interacts with the power-frequency oscillations contributing to them: for that, it can be regarded as grid-ringing. This conceptual revisiting is illustrated with a representative system, and further discussed with some examples on a benchmark power syste
From reverse to structural vaccinology : profiling of CyRPA as new Plasmodium falciparum malaria vaccine candidate antigen
Malaria is one of the most important and life-threatening infectious diseases worldwide. In 2015 malaria claimed about 429 000 lives, mostly among children below five year of age in sub‐Saharan Africa, and caused 212 million clinical episodes in a population of approximately 3.3 billion people living in regions at risk of infection. The development of an effective malaria vaccine is recognized as one of the most promising approaches for preventing infections and reducing transmission. To date, there is no vaccine on the market for prevention of malaria and only a few candidate vaccines were able to induce some protective efficacy. Thus, there is an urgent need to accelerate the pace of design and development of new malaria vaccine candidates that induce broad and long-lasting protective immunity. Reverse vaccinology and structural vaccinology are two complementary techniques that hold much promise in this regard.
The pathogenesis of malaria is primarily associated with blood-stage infection and there is strong evidence that antibodies specific for parasite blood-stage antigens can control parasitemia. This provides a strong rationale for incorporation of asexual blood-stage antigen components into an effective multivalent malaria subunit vaccine.
In this thesis, we exploited the great potential of the ‘omics’ sciences for the selection of hypothetical surface-exposed protein and the evaluation of their potential as vaccine candidate antigens. For the characterization of selected antigens we have exploited an entirely cell-based, rapid and reliable approach for the generation of antigen-specific and parasite cross-reactive monoclonal antibodies (mAbs): (I) generation of mammalian cell lines expressing high levels of the selected predicted malaria antigens as transmembrane proteins; (II) living-cell immunization of mice; (III) generation of hybridoma cell lines producing mAbs capable of recognizing the endogenous antigen in its native context.
This strategy has led us to the identification of the Plasmodium falciparum Cysteine-Rich Protective Antigen (PfCyRPA) as promising blood-stage malaria vaccine candidate: (I) PfCyRPA has limited natural immunogenicity, (II) is highly conserved among P. falciparum isolates and (III) forms together with the Reticulocyte-binding Homolog 5 (PfRH5) and the PfRH5-interacting Protein (PfRipr) a multiprotein complex crucial for P. falciparum erythrocyte invasion; (IV) PfCyRPA-specific mAbs showed parasite in vitro growth-inhibitory activity due to inhibition of merozoite invasion; (V) passive immunization experiments in P. falciparum infected NODscid IL2Rγnull mice engrafted with human erythrocytes demonstrated in vivo growth-inhibitory activity of PfCyRPA specific mAbs.
To investigate whether growth inhibitory antiPfCyRPA and antiPfRH5 Abs can be induced by active immunization with the adjuvanted recombinant proteins, PfCyRPA and PfRH5 were recombinantly expressed as soluble protein in mammalian and insect cells respectively, purified from culture supernatant and employed for immunization of mice. mAbs raised against recombinant PfCyRPA and PfRH5 proteins showed potent parasite growth-inhibitory activity both in vitro and in vivo. Furthermore, both in vitro and in vivo anti-PfCyRPA and anti-PfRH5 antibodies showed more potent parasite growth inhibitory activity in combination than on their own, supporting a combined delivery of PfCyRPA and PfRH5 in a vaccine.
To examine the 3D structure of PfCyRPA and to explore the dynamics of its surface loops, we generated co-crystals of it in complex with an inhibitory mAb and elucidated the 3D structure of PfCyRPA and of the epitope–paratope interface by X-ray crystallography. Elucidation of the structure of the epitope recognized by the protective mAb will strongly facilitate design of peptidomimetics in a structural vaccinology approach. The overall structure of PfCyRPA is a six-bladed β-propeller with each blade of the propeller being a four-stranded anti-parallel β-sheet. The five disulfide bonds of the protein are located within blades 1-5, stabilizing each individual blade. Since the 6th blade is composed of β-strands both from the N- and the C-terminus and has no disulfide bond, PfCyRPA has the potential to undergo large conformational changes by disassembly of blade 6.
Among additional hypothetical antigens investigated in the framework of this thesis, PF14_0044 showed interesting features: while none of the generated PF14_0044-specific mAbs significantly inhibited parasite growth, a synergistic in vitro inhibitory activity was observed when anti-PF14_0044 mAbs were combined with anti-PfCyRPA mAbs. Applying the principle of reverse vaccinology, we thus identified PfCyRPA and PF14_0044 as targets of merozoite invasion‐inhibitory antibodies.
Taken together results show how a combination of reverse and structural vaccinology approaches can enable the identification of new target antigens for incorporation into subunit vaccines
LA PROTEZIONE DELLA POPOLAZIONE CIVILE NEI TERRITORI OCCUPATI TRA DIRITTO INTERNAZIONALE UMANITARIO E DIRITTI UMANI
This PhD thesis deals with the protection of the civilian population in occupied territories. After defining the notion of 'military occupation\u2019 in the light of recent practice of both States and international organizations, as well as analysing the relevant provisions of International Humanitarian Law (IHL), the research focuses on the extraterritorial application of International Human Rights Law (IHRL) and the interplay between IHL and IHRL in occupied territories. The aim is to ascertain how to reconcile these two legal regimes whenever a conflict of norms arises, as in the case of the tension between internment of civilians in time of occupation (Art. 78 IVGC) and the right to personal liberty enshrined in human rights treaties (Art. 9 ICCPR and Art. 5 ECHR)
- …
