Functional antibody responses to the Plasmodium falciparum merozoite

Plasmodium falciparum is a leading cause of death among children under the age of five and pregnant women in sub-Saharan Africa. More than one third of the world’s population is at risk of contracting malaria, and 70 % of the cases are found in sub-Saharan Africa. Emerging drug resistance in parasites and limited effect of vector control calls for an effective vaccine. It is known that individuals living in malaria endemic countries develop naturally acquired immunity after repeated exposure. Antibodies are important components of acquired immunity, and it has been shown that passive transfer of antibodies from immune donors to individuals with P. falciparum infections reduced parasitemia and clinical symptoms. Antibodies against several P. falciparum merozoite antigens have been found to be associated with protective immunity. It is of great importance to understand the underlying functional role of antibodies in the development of protective immunity against severe malaria. In a cross-sectional study in Uganda, the quantitative and qualitative differences in antibody responses to a panel of merozoite antigens in children with uncomplicated or severe malaria were evaluated using a set of assays including ELISA, Invasion Inhibition Assays (IIA), NH4SCN-ELISA and Surface Plasmon Resonance (SPR). Children with uncomplicated malaria had higher antibody levels against PfEBA-181, MSP2-Fc27, MSP2-3D7 and PfAMA1 when compared to children with severe malaria. Acquired antibodies against PfRh2 and PfAMA1 in ELISA correlated with invasion inhibition of two clinical isolates in IIA, and anti-PfAMA1-antibodies in ELISA correlated with increased anti- PfAMA1-antibody affinity in SPR. Importantly, the only assay that correlated with initial parasitemia in the children was the IIA. Both MSP2-Fc27 and MSP2-3D7 allelic variants were present in both children groups, but there was a higher number of genotypes in uncomplicated malaria compared to in children with severe malaria. P. falciparum clinical isolates collected from Ugandan children with uncomplicated malaria or severe malaria were further investigated for rosetting, parasite multiplication and RBC invasion. Optimal in vitro growth conditions were established, which allowed for phenotypic studies of clinical P. falciparum isolates. Presence of serum in growth cultures was found to be essential for optimal surface presentation of PfEMP1 and maintenance of rosettes. Higher peripheral parasitemia, higher rosetting levels and higher multiplication rates were observed in children with severe malaria and these correlated positively with one another. Rosetting might enhance successful merozoite invasion in vivo, hence could be the reason it is found to be associated with severe disease. Furthermore, parasite invasion into trypsinand chymotrypsin-treated RBC differed between the uncomplicated and severe groups, and isolates from children with uncomplicated malaria showed higher sensitivity to enzyme treatment. The majority of clinical isolates used a sialic acid independent invasion pathway. Parasite invasion is central to parasite replication and virulence, and it is essential to know which invasion pathways are used for vaccine studies. Naturally acquired antibody responses to P. falciparum merozoite antigens was further studied in a longitudinal study over almost one year in children and adults from Nigeria. The malaria protective effects of the hemoglobin S (HbAS) allele were also investigated. In both children and adults, the antibody response against PfEBA175 was more prominent than that against PfRh2, and cytophilic IgG1 and IgG3 against PfEBA175 were the predominant antibodies even though we could also see some response for IgG2 and IgG4. Individuals with higher total IgG responses against both PfEBA175 and PfRh2 had lower parasitemia over the course of the study period. Furthermore, children with HbAS had higher antibody responses against merozoite antigens compared to adults, and this might have protective effects against malaria. In conclusion this thesis emphasizes the great importance of using a combination of functional assays, such as SPR and IIA, to study the functional role of acquired antibodies in the development of protective immunological responses against severe malaria. Furthermore, investigations of parasite invasion and rosetting in the context of pathogenesis of severe malaria are crucial as both are important for parasite replication and virulence. Taken together, future vaccine studies should include functional assays that would allow the investigation of differences in immunological responses against severe and uncomplicated malaria. Also, to consider the protective effects of red blood polymorphisms and their role in acquired immunity in the populations, would be of great value for future vaccine studies

Investigation of peripheral nerve sensitivity in two animal models of Autism Spectrum Disorder (ASD)

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social communication and restricted behaviours, and associated with sensory alterations, gastrointestinal dysfunction and disruptions in the circadian rhythm. This study utilised two animal models of ASD, the BTBR T+tf/J and the prenatal exposure to VPA mouse models of ASD, compared to the control C57 BL/6J strain. The aim of this study was to investigate changes in circadian rhythm and peripheral sensation in the two mouse models of ASD, and identify potential pathways involved. Methods: Home-cage testing was conducted using LABORAS platforms, to record the animals’ behaviour over 24 hours (C57 n = 8; BTBR = 9, VPA = 4). Cutaneous sensory thresholds were determined using the dynamic hot (DHP) and cold plate (DCP) tests (C57 n = 6; BTBR n = 6; VPA n = 4), and sensory function of the gastrointestinal tract was outlined using ex-vivo jejunum preparations, by recording the afferent nerve responses to mechanical and chemical stimuli. Values are mean +/- SEM analysed with two-way ANOVA using GraphPad Prism. Results: the VPA mice exhibited altered circadian rhythm in the dark (active) phase compared to the BTBR and C57 mice (P=<0.05). In the DHP, the BTBR mice (n = 6) responded at a higher temperature (C57 - 38C; BTBR - 40C), responded significantly less to heat (P<0.0005), while VPA mice (n = 4) showed similarresponses to the C57 mice. In the DCP, VPA mice start to respond at a lower temperature (C57 - 16C; VPA - 2C), responded slightly less to cold (P=0.055), while the BTBR mice showed similar responses to C57 mice. In the afferent nerve recordings of the jejunum, the BTBR tissue exhibited significantly decreased responses to mechanical distension at a filling rate of 600 µl/min (P<0.0006; BTBR n = 9; C57 n = 10). Peak firing rate at 50 mmHg was 92.68 (+/- 12.80) imp/s-1 in recordings from C57 (n = 10) tissue and 76.49 (+/- 15.44) imp/s-1 in BTBR tissue (n = 9). BTBR afferents also showed an altered response profile to TRPV1 activation (P=<0.0001, BTBR n = 5; C57 n = 5), whereby nerve firing took significantly longer to desensitize compared to control afferents, suggesting altered function of TRPV1. Preparations from BTBR mice also exhibited significantly increased response to intraluminal application of an inflammatory soup (P<0.05), BTBR n = 5; C57 n = 5). Conclusion: the VPA model of ASD showed marked alterations in circadian rhythm and reduced response to cold stimuli, and the BTBR mouse model of ASD exhibited significantly decreased response to heat and significantly altered afferent nerve activity from the jejunum in response to various stimuli. Future studies should investigate whether these changes correlate with CNS dysfunction or whether altered peripheral sensation could drive some of the central deficits observed in ASD

Valmistumassa olevien sairaanhoitajaopiskelijoiden näkemykset vetovoimaisesta hoitotyön johtamisesta

Opinnäytetyön tarkoituksena oli kuvata valmistumassa olevien sairaanhoitajaopiskelijoiden näkemyksiä vetovoimaisesta hoitotyön johtamisesta. Teimme kyselyn oppimistehtävän muodossa opiskelijoille, jotka kävivät Johtaminen, yhteiskunta ja yrittäjyys kurssia. Osallistujat olivat sairaanhoitajaopiskelijoita, joita oli yhteensä 28. Opinnäytetyö toteutettiin kvalitatiivisella eli laadullisella tutkimusmenetelmällä. Teoreettinen lähdeaineisto kerättiin tutkimuksista ja magneettisairaalaan sekä hoitotyön johtamiseen liittyvästä kirjallisuudesta. Tuloksia analysoitaessa deduktiivis-induktiivisen sisällön analyysin periaatteita soveltaen, haettiin kolmeen kysymykseen vastausta: Mitä on hyvä vetovoimainen johtaminen? Mitkä tekijät edistävät vetovoimaista johtamista? Mitkä tekijät ehkäisevät vetovoimaista johtamista? Opinnäytetyön tulosten perusteella valmistumassa olevien sairaanhoitajaopiskelijoiden näkemysten mukaan hyvään vetovoimaiseen johtajuuteen kuuluvat: tuki kehittymisessä, ammatillinen toiminta sekä työhyvinvoinnin huomioiminen johtamisessa. Magneettisairaalamalliin kuuluvia hyvää vetovoimaista johtajuutta edistäviä tekijöitä olivat: imago, kollegiaalisuus, muutosjohtajuus, voimavarojen vahvistaminen, työvuoroihin vaikuttaminen, johdon kommunikointi, palautteiden kulku, koulutusmahdollisuudet, haastavien tilanteiden selvittäminen, hoitotyön mallien käyttäminen ja hoitotyön laatu. Hyvää vetovoimaista johtajuutta ehkäiseviä tekijöitä olivat: huono työhyvinvointi, epäammattimaisuus, epäsuvaitsevaisuus, välinpitämättömyys johdon suunnalta, yhteistyökyvyttömyys ja kehityksen pysähtyminen. Opinnäytetyön tavoitteena oli tuoda tietoa työpaikkojen vetovoimaisuudesta ja niihin vaikuttavista tekijöistä sekä hyvästä hoitotyön johtamisesta. Työ auttaa kehittämään hoitotyön johtamista sekä ymmärtämään, mitkä asiat ovat työhön sitoutumisen ja ammattikiinnostuksen ylläpitämisen kannalta tärkeitä sairaalassa.The purpose of the final study was to examine graduating nursing student’s vision of the attractive management of nursing. The task of the final project was to determine what is good management according to the graduating student’s vision. The final project’s assignment was sent via email to the teacher of management, society and entrepreneurship. The amount of student who responded was 28. The final project was conducted by a qualitive research method. The theoretical body of the final project was gathered from researches and literature about the Magnet Hospital and leadership. The data from the questions about attractive management as well as promoting and preventive factors of management were analyzed using the principles of deductive-inductive analysis. The questions measured factors which graduating student’s considered as contributing components that define good and attractive management and that affect job-hunting together with commitment to work and the results were mostly in line with the factors of the Magnet Hospital model. Those are for example support in personal development, professionalism, consideration of workers wellbeing, imago, collegiality, transformational management, resource allocation, influencing shifts, the communication between leaders and workers, feedback, training possibilities, determination of challenging situations, appreciation of nursing, the usage of nursing models and the quality of nursing. Factors that prevent good and attractive management were lack of wellbeing, unprofessionalism, lack of tolerance, manager’s indifference towards nurse staff, inability to co-operate and stagnation of development. The intention of the final study was to bring new information about management, magnetism and factors that affect magnetism. The final study helps to develop the quality of nursing and to understand which factors are important in a hospital interested in improving commitment to work and professional interest

Supermarket Loss Estimates for Fresh Fruit, Vegetables, Meat, Poultry, and Seafood and Their Use in the ERS Loss-Adjusted Food Availability Data

A certain amount of food in supermarkets is deemed unusable (“food loss”) because of moisture loss, spoilage, and other causes. This study analyzed updated food loss estimates for fresh fruit, vegetables, meat, poultry, and seafood obtained through a competitive grant with the Perishables Group, Inc. This independent consulting firm compared supplier shipment data with point-of-sale data from six large national and regional supermarket retailers to identify loss in 2005 and 2006. The new estimates, when incorporated into the ERS Loss-Adjusted Food Availability data, had little impact on aggregate per capita food loss estimates in 2006 because the new estimates were, on average, close to the previous loss assumptions. The new estimates increased annual per capita estimates of fresh fruit available at the retail level by 0.7 pounds (0.6 percent), 4.2 pounds (2.7 percent) for fresh vegetables, and 4.8 pounds (2.7 percent) for fresh meat, poultry, and seafood. The commodity-specific food loss estimates are more accurate than in previous years.Conversion factor, food loss, fruit, meat, poultry, seafood, supermarket, vegetables, Agribusiness, Agricultural Finance, Financial Economics,

T-LESS: An RGB-D Dataset for 6D Pose Estimation of Texture-less Objects

We introduce T-LESS, a new public dataset for estimating the 6D pose, i.e. translation and rotation, of texture-less rigid objects. The dataset features thirty industry-relevant objects with no significant texture and no discriminative color or reflectance properties. The objects exhibit symmetries and mutual similarities in shape and/or size. Compared to other datasets, a unique property is that some of the objects are parts of others. The dataset includes training and test images that were captured with three synchronized sensors, specifically a structured-light and a time-of-flight RGB-D sensor and a high-resolution RGB camera. There are approximately 39K training and 10K test images from each sensor. Additionally, two types of 3D models are provided for each object, i.e. a manually created CAD model and a semi-automatically reconstructed one. Training images depict individual objects against a black background. Test images originate from twenty test scenes having varying complexity, which increases from simple scenes with several isolated objects to very challenging ones with multiple instances of several objects and with a high amount of clutter and occlusion. The images were captured from a systematically sampled view sphere around the object/scene, and are annotated with accurate ground truth 6D poses of all modeled objects. Initial evaluation results indicate that the state of the art in 6D object pose estimation has ample room for improvement, especially in difficult cases with significant occlusion. The T-LESS dataset is available online at cmp.felk.cvut.cz/t-less.Comment: WACV 201

Legal regulation of weaponis and ammunitio--

Právní úprava zbraní a střeliva Abstrakt Tématem předkládané práce je právní úprava zbraní a střeliva analyzovaná v kontextu dvou právních systémů, a to právní úpravy České republiky, obsažené především v ustanoveních zákona o zbraních, kterým se věnuje první kapitola této práce, a právní úpravy Spojených státu amerických, a to zejména na úrovni federálních předpisů včetně Druhého dodatku Ústavy, avšak s nezbytným přesahem do úpravy jednotlivých států federace, které jsou obsaženy v kapitole druhé. Strukturálně jsou kapitoly dále děleny na podkapitoly a čtenář je v rámci nich zasvěcen nejen do právních ustanovení příslušných předpisů, která autor práce připravil, a v případě těch cizojazyčných i přeložil, ale i do související judikatury a kontextu této komplexní problematiky, která je dále zprostředkována díky cizojazyčné i tuzemské literatuře, ze které práce rovněž vychází. Po provedení důkladné deskripce a rozboru všech příslušných ustanovení pak dochází ke komparaci nabytých znalostí v kapitole třetí a poslední, jež je syntézou i srovnáním vybraných aspektů, které byly vybrány tak, aby vhodně odrážely specifika úpravy fenoménu palných zbraní napříč odlišnými právními systémy, a to vždy v příslušném kontextu. V rámci tohoto akademickém exkurzu lze v práci vyzdvihnout důkladný rozbor rozhodnutí Nejvyššího...2 Legal regulation of weapons and ammunition Abstract The topic of the presented thesis is the legal regulation of weapons and ammunition analyzed in the context of two legal systems, namely the legislation of the Czech Republic, contained mainly in the provisions of the Weapons Act, which is the subject of the first chapter of this thesis, and the legislation of the United States of America, especially on at the level of federal regulations, including the Second Amendment to the Constitution, but with the necessary overlap into the regulation of the individual states of the federation, which are contained in Chapter Two. Structurally, the chapters are further divided into sub-chapters, and within them the reader is introduced not only to the legal provisions of the relevant regulations, which the author of the work prepared, and in the case of those in foreign languages, also translated, but also to the related jurisprudence and the context of this complex issue, which is further mediated thanks to foreign language and domestic literature, from which the work is also based. After a thorough description and analysis of all relevant provisions, a comparison of the acquired knowledge occurs in the third and last chapter, which is a synthesis and comparison of selected aspects that were chosen to appropriately...Katedra správního práva a správní vědyDepartment of Administrative Law and Administrative SciencePrávnická fakultaFaculty of La

Gaining Insights into Signed Music Through Performers

Signed music is best described as an inter-performative art form that combines lyrical and non-lyrical musical performances and is deeply rooted in the culture of deaf people who communicate through signed language (J. H. Cripps & Lyonblum, 2017; J. H. Cripps et al., in press [a]). The key investigative component for this article includes outlining the experiences that three Canadian performers had about their signed music creativity during a plenary at the Partition/Ensemble 2020 Conference held by the Canadian Association for Theatre Research in Montreal, Quebec. The panelists responded to two questions that they developed for themselves: What inspired us to become musicians? How did the creative process of composing the signed music piece occur from the beginning to the end? The paper also covers an open discussion that the three performers had among themselves. Some signed music work examples are provided for viewing to support the premise that deaf people have full capacity for the creation and enjoyment of music. The paper represents a departure from the long-held view that music can only prevail in the audible form. The insights gained from the three deaf performers are the first of their kind and will contribute to the musical world

Magnetronová depozice tenkovrstvých slitin ze systému W-Zr-Cu

Tato diplomová práce se zabývá přípravou a zkoumáním magnetronově naprašovaných tenkovrstvých materiálů ze systému W-Zr-Cu. Jedná se o zcela nové materiály, o kterých zatím nebyla publikována žádná studie. Cílem práce bylo připravit tyto materiály s širokém rozsahu složení a charakterizovat je pomocí různých analytických metod. Vrstvy byly zkoumány z hlediska struktury, mikrostruktury a povrchové morfologie pomocí rentgenové difrakce, skenovací elektronové mikroskopie a mikroskopie atomárních sil. Dále pak byly indetačními metodami měřeny mechanické vlastnosti, přičemž byl brán ohled na přítomnost pile-up efektů. V neposlední řadě byla také měřena elektrická rezistivita pomocí čtyřbodové metody. Naměřená data byla zpracovávána a diskutována v kontextu současného poznání dílčích systémů Zr-Cu, W-Zr a W-Cu.ObhájenoThis thesis deals with the preparation and investigation of magnetron sputtered thin film materials from the W-Zr-Cu system. These are completely new materials about which no study has been published so far. The aim of the thesis was to prepare these materials in a wide range of compositions and to characterize them using various analytical methods. The films were investigated in terms of structure, microstructure and surface morphology using X-ray diffraction, scanning electron microscopy and atomic force microscopy. Furthermore, mechanical properties were measured by indentation methods taking into account the presence of pile-up effects. Finally, the electrical resistivity was also measured using the four-point probe. The measured data were processed and discussed in the context of the current understanding of the Zr-Cu, W-Zr and W-Cu sub-systems