Dual Quorum Quenching Capsules: Disrupting two bacterial communication pathways that lead to virulence

Healthcare Associated Infections (HAIs) in the United States, are estimated to cost nearly $10 billion annually. And, while device-related infections have decreased, the 60% attributed to pneumonia, gastrointestinal pathogens and surgical site infections (SSIs) remain prevalent. Furthermore, these are often complicated by antibacterial resistance that ultimately cause 2 million illnesses and 23,000 deaths in the US annually. Antibacterial resistance is an issue increasing in severity as existing antibiotics are losing effectiveness, and fewer new antibiotics are being developed. As a result, new methods of combating bacterial virulence are required. Modulating communications of bacteria can alter phenotype, such as biofilm formation and toxin production. Disrupting these communications provides a means of controlling virulence without directly interacting with the bacteria of interest, a strategy contrary to traditional antibiotics. Inter- and intra-species bacterial communication is commonly called quorum sensing because the communication molecules have been linked to phenotypic changes based on bacterial population dynamics. By disrupting the communication, a method called ‘quorum quenching’, bacterial phenotype can be altered. Virulence of bacteria is both population and species dependent; each species will secrete different toxic molecules, and total population will affect bacterial phenotype9. Here, the kinase LsrK and lactonase SsoPox were combined to simultaneously disrupt two different communication pathways with direct ties to virulence leading to SSIs, gastrointestinal infection and pneumonia. To deliver these enzymes for site-specific virulence prevention, two naturally occurring polymers were used, chitosan and alginate. Chitosan, from crustacean shells, and alginate, from seaweed, are frequently studied due to their biocompatibility, availability, self-assembly and biodegrading properties and have already been verified in vivo for wound-dressing. In this work, a novel functionalized capsule of quorum quenching enzymes and biocompatible polymers was constructed and demonstrated to have dual-quenching capability. This combination of immobilized enzymes has the potential for preventing biofilm formation and reducing bacterial toxicity in a wide variety of medical and non-medical applications.

Nurses’ clinical communication skills

Abstract Background: Providing nursing care involves an interpersonal relationship between the nurse and the patient which is created through communication. The importance of clinical communication skills is a current priority when it comes to health care workers’ education and training and has been attracting more and more attention. As a consequence clinical communication skills are now present in more and more academic programmes. Objectives: To assess nurses’ clinical communication skills; to identify the variables that might inluence the clinical communication skills; to analyse nurses’ perspective regarding the training in the clinical communication ield. Material and methods: Quantitative, non-experimental, descriptive and correlational and crosssectional study. We used the questionnaire to collect socio-demographic and professional data, and the Clinical Communication Skills Scale based on the Kalamazoo Consensus Statement (KCS)1,2 and which had already been used in Portugal.3 The sample was formed by 275 practitioner nurses who have been working in health care institutions located in the center of Portugal. Results: The Scale we used presents 5 factors that explain 64.33% of the total variation: To in‑ volve the patient; To facilitate dialogue; To understand concerns; To communicate in an asser‑ tive way; To carry out the interview. The majority of the nurses consider that the training they had in the communication skills ield during their nursing course was good or very good, however we could see that 23.3% think it was mediocre. Almost all of them (98.9%) agree that there should be a better and more speciic training in the ield of clinical communication skills as far, as nurses as concerned. Nurses who had training in this area, older nurses, those who work directly with patients and those who have been working for a longer period of time show better communication skills. Conclusion: Although they think that the training they has was good, we could conirm that there was a deicit in nurses’ clinical communication skills and that nurses themselves refer they need more training in this area. Data point out to a more signiicant investment in clinical communication as far as nurses’ training is concerned and they suggest the promotion of lifelong learning opportunities in this area.

Managing pressure: patterns of appraisals and coping strategies of non-elite and elite athletes during competition

The purpose of this study was to compare moment-to-moment appraisals and coping strategies of 4 non-elite and 2 elite male trap shooters during competitions and in particular during periods of competition perceived as critical to performance. Appraisals and coping patterns of trap shooters were captured via verbal reports of thinking provided between sets of shots during major competitions. Verbal reports were coded according to an appraisal and coping typology. Coded data as well as shooting performance data were subjected to a sequential analysis of probabilities of pairs of events. Fewer reports of negative appraisals (NEGAs) and more frequent reports of problem-focused coping (PFC) were observed among both elite athletes compared to non-elite athletes. After making a NEGA, non-elite shooters often progressed to the next target without attempting to cope, whereas elite shooters used both PFC and emotion-focused coping (EFC) before proceeding to the next target. After missing a target, the non-elite athletes used more EFC than expected. These results indicate that elite athletes are more likely to cope with NEGAs than non-elite athletes using a wider variety of coping strategies. Athletes might benefit from increased awareness of the potentially detrimental impact of NEGAs on performance and by integrating coping strategies within preparatory routines.

L’interaction comme méthode d’apprentissage du Français langue étrangère (FLE) en Suède

Mon travail s’inspire de l’idée de la Direction nationale de l’enseignement scolaire suédoise (Skolverket, 2011) qui suggère que « les élèves doivent avoir la possibilité de développer une capacité de communication et de compréhension de la langue ». Mon mémoire commence par une introduction générale, continue avec une analyse des manuels utilisés dans l’apprentissage du FLE et des activités favorisant l’interaction - échange réciproque verbale ou non verbale, pour terminer par une conclusion générale. Comme il n’existe pas d’enseignement sans méthodes appropriées, il existe des manuels qu’on peut utiliser afin de faciliter l’apprentissage par l’interaction de la langue cible. Les activités de communication orale et écrite d’ordre pédagogique sont indispensables. Tout comme l’écrit Revue française de pédagogie (1994 :133) « La classe est un système social complexe dont les parties sont en interaction dynamique, acteurs (enseignant et élève[s]), situation, matière selon des statuts sociaux. ». Pour effectuer mes recherches, j’ai porté mon attention sur l’analyse des manuels scolaires qu’il m’a été permis de consulter. Il s’agit des manuels d’entraide comme : Mais oui 3 et Escalade littéraire. Concernant l’analyse du matériel didactique favorisant l’interaction, ces deux manuels proposent des exercices de réflexion selon le niveau de l’apprenant. Dans mon travail, je m’intéresse à l’aspect didactique et linguistique de ces deux manuels scolaires.

Pedagogical interventions to overcome communication apprehension in employment interviews among career students.

Career programs in the Cegep system base their training on various learning activities, which are followed by a practicum. The objective is to achieve a certain number of competencies, deemed necessary by the Ministry of Education, for entry-level occupations in to the workforce. The Graphic Communications program offered at Champlain College Saint-Lambert is a three-year career program that leads to employment in the field of graphics. Many students have part-time jobs during their schooling period but most of those jobs do not relate to their field of study. Several graduates stated they were unable to persuade employers to hire them for an externship or stage at the end of their program. While jobs are important for their general skills, since they are not directly related to the field, these jobs may not have given the students a suitable model for the conduct of an employment interview. Practice interviews may be one of many successful training methods to lower communication apprehension (CA) levels. CA is defined as "an individual's level of fear or anxiety associated with either real or anticipated communication with another person or persons." This paper examines the literature on CA and employment interviews and evaluates whether pedagogical interventions, including monitored phone calls to employers and practice-videotaped interviews, allow students to feel more confident about interviewing for a future job. A qualitative tool was used to gather scientific measurements of the participants' levels of CA both at the beginning and at the end of the Career Planning course. Open-ended reflective journals gathered quantitative data on the impact specific instructional strategies had on the participants. The pedagogical interventions that were examined and tested were as follows: preparation of scripts, monitored phone calls, videotaped practice interviews, and inclass access to professional assistance. Results indicate that all interventions had a positive impact on lowering levels of CA. It is clear that positive conclusions were drawn by the students as to usefulness of these activities. Overall, participants who responded to the reflective journal questions felt positive about the contribution of this preparatory career course to their CA levels. The results of the quantitative tool were consistent with previous research and the analysis of the reflective journals gave additional support to the usefulness of the interventions on students' confidence levels. Recommandations for improvements to the curriculum include the need for students to be taugh formally about metacognition and how to monitor it. Students need to be exposed to videotaped interviews more often. They should be better prepared for unexpected interview questions, and they should experience formal rehearsals with one of their instructors before the actual practice interview. Some of these recommendations have already been successfully implemented in the program's curriculum.||Résumé:Le but de ce travail était de vérifier si certaines activités pédagogiques sont efficaces pour faire baisser le niveau d'anxiété lié à la communication orale lors de leurs entrevues d'embauche. L'objectif des programmes techniques au Québec est de fournir aux étudiants un certain nombre de compétences définies par le ministèe de l'Éducation, des Loisirs et du Sport afin que ces derniers puissent fournir des services de techniciens spécialisés aux entreprises. Le programme nommé Office Systems Technology (412) du collège Champlain de Saint-Lambert, a choisi la voie de la spécialisation en microédition et hypermédia en 1999 et a changé son nom pour Graphic Communications en 2005. Les programmes techniques au Cégep incluent un stage en milieu de travail à la fin d'un programme de trois ans et par le fait même, une entrevue pour obtenir un stage en entreprise. La compétence visée par cette étude est l'intégration au marché du travail et le cheminement professionnel des étudiants. Lors d'enquêtes informelles, plusieurs étudiants du programme ont fait part de leurs difficultés à trouver un stage en fin d'études. Certains auteurs suggèrent que ces étudiants n'ont pas de modèles appropriés lors de la tenue d'une entrevue d'emploi. Ils proposent de diminuer le niveau d'anxiété lié à la communication orale lors d'entrevues d'embauche en offrant des pratiques d'entrevue aux étudiants. Cette recherche a examiné la littérature au sujet de l'anxiété de communication, plus précisément lors d'entrevues. Elle avait pour mandat d'évaluer si les activités pédagogiques d'un cours de préparation à la carrière ont été efficaces pour faire baisser les taux d'anxiété en communication orale lors d'entrevues. En plus, une conseillère à l'emploi fut invitée à plusieurs reprises afin de fournir un support professionnel en classe, étant donné que les étudiants ne prennent pas nécessairement le temps de consulter des professionnels en raison de leurs activités personnelles trop nombreuses. Le type d'enseignement évalué est considéré comme stratégique, étant donné qu'il agit au niveau cognitif et métacognitif de l'étudiant. Le cours de préparation à l'emploi débute par la vérification des acquis antérieurs des étudiants et il tient compte de leur motivation scolaire et professionnelle. De plus, il est axé sur la construction du savoir en proposant des activités de plus en plus complexes, débutant par la rédaction de textes à utiliser lors d'appels aux employeurs, en passant par la préparation et la pratique d'appels et se terminant par des entrevues d'emploi qui serviront de modèle à perfectionner par chaque étudiant. Ces entrevues se font avec des employeurs qui ont déjà embauché des étudiants du programme de Graphic Communications au collège Champlain de Saint-Lambert et sont enregistrées sur bande vidéo afin de permettre une visualisation ultérieure et cohérente avec les objectifs visés. La méthodologie de cette recherche inclut deux outils, un quantitatif et un qualitatif. L'outil quantitatif permet de mesurer scientifiquement les taux d'appréhension en communication des étudiants au début et à la fin du cours de préparation à l'emploi. Cet outil est la fusion de deux outils, le Personal Report of Communication Apprehension ou PRCA-24, qui fut développé par McCroskey (1984), en tandem avec celui de Wongprasert & Ayres (2000), qui lui met l'accent sur les entrevues d'emploi. Les réponses à cet outil combiné sont évaluées sur une échelle Likert de cinq points. L'outil qualitatif est une série de questions auxquelles les étudiants ont répondu quatre fois lors de la session. Les réponses à ces questions ont été analysées et les commentaires des étudiants évalués. Il découle de cette analyse que les niveaux d'anxiété des étudiants qui ont participé (14) étaient définitivement à la baisse en fin de cours. La pratique téléphonique structurée, dans un laboratoire avec les téléphones, a été très révélatrice pour les étudiants. Ils ont appris comment utiliser un script comme piste de départ pour un appel et qu'il était possible de contourner certains obstacles de façon professionnelle. Ensuite, lors d'une visite d'une compagnie de graphisme, ils ont pu observer divers modèles d'emploi. Ils ont eu la possibilité de poser des questions sur le fonctionnement et les besoins de l'entreprise. Ceci facilita la rédaction de leur curriculum vitae en leur permettant de mieux décrire leurs acquis en fonction d'emplois recherchés. Par la suite, ils se sont préparés pour une pratique d'entrevue, filmée. Les interviewers avaient déjà travaillé avec le collège et avaient déjà embauché certains étudiants de ce programme, donc ils connaissaient leur potentiel. Une liste de questions possibles fut suggérée mais il n'en restait pas moins que les interviewers pouvaient les modifier, ceci étant représentatif du marché de l'emploi. Même si le collège fournit un enseignement en anglais, un des intervieweurs donna ses entrevues en français. Trois étudiants se sont portés volontaires, mais deux ont constaté qu'ils auraient dû pratiquer leur script en français avant l'entrevue pour mieux diminuer leur niveau d'anxiété. Finalement, les étudiants durent visionner leur segment d'entrevue : ceci leur a permis de voir si leur attitude non-verbale concordait avec ce qu'ils ressentaient en entrevue et d'emmener les correctifs appropriés. Les taux d'anxiété furent vérifiés une deuxième fois en fin de session et les résultats ont démontré une baisse des taux d'appréhension. Les résultats de cette étude concordent donc avec ceux trouvés dans la littérature et donnent de bonnes pistes pour l'amélioration de ce cours de préparation à la carrière. L'auteur recommande d'enseigner la métacognition de façon formelle et ainsi de faciliter la prise de conscience des apprentissages que les étudiants effectuent. De plus, les étudiants devraient être filmés en studio au moins une fois par année pour diminuer le facteur de stress causé par les caméras et finalement ils pourraient certainement bénéficier de pratiques formelles d'entrevue avec un instructeur avant l'entrevue filmée. L'augmentation des pratiques a déjà été mise en oeuvre dans le programme et des résultats positifs se sont ensuivis.

The role of non-coding RNA in the development of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease of the small pulmonary arteries, characterised by pulmonary vascular remodelling due to excessive proliferation and resistance to apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). The increased pulmonary vascular resistance and elevated pulmonary artery pressures result in right heart failure and premature death. Germline mutations of the bone morphogenetic protein receptor-2 (bmpr2) gene, a receptor of the transforming growth factor beta (TGF-β) superfamily, account for approximately 75%-80% of the cases of heritable form of PAH (HPAH) and 20% of sporadic cases or idiopathic PAH (IPAH). IPAH patients without known bmpr2 mutations show reduced expression of BMPR2. However only ~ 20% of bmpr2-mutation carriers will develop the disease, due to an incomplete penetrance, thus the need for a ‘second hit’ including other genetic and/or environmental factors is accepted. Diagnosis of PAH occurs most frequently when patients have reached an advanced stage of disease. Although modern PAH therapies can markedly improve a patient’s symptoms and slow the rate of clinical deterioration, the mortality rate from PAH remains unacceptably high. Therefore, the development of novel therapeutic approaches is required for the treatment of this multifaceted disease. Noncoding RNAs (ncRNAs) include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs are ~ 22 nucleotide long and act as negative regulators of gene ex-pression via degradation or translational inhibition of their target mRNAs. Previous studies showed extensive evidence for the role of miRNAs in the development of PAH. LncRNAs are transcribed RNA molecules greater than 200 nucleotides in length. Similar to classical mRNA, lncRNAs are translated by RNA polymerase II and are generally alternatively spliced and polyadenylated. LncRNAs are highly versatile and function to regulate gene expression by diverse mechanisms. Unlike miRNAs, which exhibit well-defined actions in negatively regulating gene expression via the 3’-UTR of mRNAs, lncRNAs play more diverse and unpredictable regulatory roles. Although a number of lncRNAs have been intensively investigated in the cancer field, studies of the role of lncRNAs in vascular diseases such as PAH are still at a very early stage. The aim of this study was to investigate the involvement of specific ncRNAs in the development of PAH using experimental animal models and cell culture. The first ncRNA we focused on was miR-143, which is up-regulated in the lung and right ventricle tissues of various animal models of PH, as well as in the lungs and PASMCs of PAH patients. We show that genetic ablation of miR-143 is protective against the development of chronic hypoxia induced PH in mice, assessed via measurement of right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodelling. We further report that knockdown of miR-143-3p in WT mice via anti-miR-143-3p administration prior to exposure of mice to chronic hypoxia significantly decreases certain indices of PH (RVSP) although no significant changes in RVH and pulmo-nary vascular remodelling were observed. However, a reversal study using antimiR-143-3p treatment to modulate miR-143-3p demonstrated a protective effect on RVSP, RVH, and muscularisation of pulmonary arteries in the mouse chronic hypoxia induced PH model. In vitro experiments showed that miR-143-3p overexpression promotes PASMC migration and inhibits PASMC apoptosis, while knockdown miR-143-3p elicits the opposite effect, with no effects observed on cellular proliferation. Interestingly, miR-143-3p-enriched exosomes derived from PASMCs mediated cell-to-cell communication between PASMCs and PAECs, contributing to the pro-migratory and pro-angiogenic phenotype of PAECs that underlies the pathogenesis of PAH. Previous work has shown that miR-145-5p expression is upregulated in the chronic hypoxia induced mouse model of PH, as well as in PAH patients. Genetic ablation and pharmacological inhibition (subcutaneous injection) of miR-145-5p exert a protective against the de-velopment of PAH. In order to explore the potential for alternative, more lung targeted delivery strategies, miR-145-5p expression was inhibited in WT mice using intranasal-delivered antimiR-145-5p both prior to and post exposure to chronic hypoxia. The decreased expression of miR-145-5p in lung showed no beneficial effect on the development of PH compared with control antimiRNA treated mice exposed to chronic hypoxia. Thus, miR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while the inhibition of miR-143-3p prevented the development of experimental pulmonary hypertension. We focused on two lncRNAs in this project: Myocardin-induced Smooth Muscle Long noncoding RNA, Inducer of Differentiation (MYOSLID) and non-annotated Myolnc16, which were identified from RNA sequencing studies in human coronary artery smooth muscle cells (HCASMCs) that overexpress myocardin. MYOSLID was significantly in-creased in PASMCs from patients with IPAH compared to healthy controls and increased in circulating endothelial progenitor cells (EPCs) from bmpr2 mutant PAH patients. Exposure of PASMCs to hypoxia in vitro led to a significant upregulation in MYOSLID expres-sion. MYOSLID expression was also induced by treatment of PASMC with BMP4, TGF-β and PDGF, which are known to be triggers of PAH in vitro. Small interfering RNA (siR-NA)-mediated knockdown MYOSLID inhibited migration and induced cell apoptosis without affecting cell proliferation and upregulated several genes in the BMP pathway in-cluding bmpr1α, bmpr2, id1, and id3. Modulation of MYOSLID also affected expression of BMPR2 at the protein level. In addition, MYOSLID knockdown affected the BMP-Smad and BMP-non-Smad signalling pathways in PASMCs assessed by phosphorylation of Smad1/5/9 and ERK1/2, respectively. In PAECs, MYOSLID expression was also induced by hypoxia exposure, VEGF and FGF2 treatment. In addition, MYOSLID knockdown sig-nificantly decreased the proliferation of PAECs. Thus, MYOSLID may be a novel modulator in pulmonary vascular cell functions, likely through the BMP-Smad and –non-Smad pathways. Treatment of PASMCs with inflammatory cytokines (IL-1 and TNF-α) significantly in-duced the expression of Myolnc16 at a very early time point. Knockdown of Myolnc16 in vitro decreased the expression of il-6, and upregulated the expression of il-1 and il-8 in PASMCs. Moreover, the expression levels of chemokines (cxcl1, cxcl6 and cxcl8) were sig-nificantly decreased with Myolnc16 knockdown. In addition, Myolnc16 knockdown decreased the MAP kinase signalling pathway assessed by phosphorylation of ERK1/2 and p38 MAPK and inhibited cell migration and proliferation in PASMCs. Thus, Myolnc16 may a novel modulator of PASMCs functions through anti-inflammatory signalling pathways. In summary, in this thesis we have demonstrated how miR-143-3p plays a protective role in the development of PH both in vivo animal models and patients, as well as in vitro cell cul-ture. Moreover, we have showed the role of two novel lncRNAs in pulmonary vascular cells. These ncRNAs represent potential novel therapeutic targets for the treatment of PAH with further work addressing to investigate the target genes, and the pathways modulated by these ncRNAs during the development of PAH.

Caracterización de la función cognitiva de niños con síndrome de down de 5 a 12 años en la ciudad de Bogotá

Los niños que padecen trisomía 21 poseen una serie de características físicas, neurológicas y neuropsicológicas específicas, las cuales han sido investigadas a profundidad en diferentes países, de lo cual se han desarrollado protocolos de evaluación para estos niños acorde a su nacionalidad (García, 2010). A pesar de que Colombia es uno de los países en los cuales el síndrome de Down se presenta con mayor frecuencia, hasta la fecha, no se encuentran estudios que enfaticen en las habilidades neuropsicológicas de esta población específica, por lo cual no se han desarrollado protocolos de evaluación adecuados para los niños con síndrome este síndrome. Esta investigación se llevó acabo con una población de 88 niños a los cuales se les aplicó el inventario de desarrollo BATTELLE, y se identificó que los niños con síndrome Down de 5 a 12 años obtienen un puntaje que se encuentra en 4 desviaciones estándar por debajo de la media típica. Lo anterior demuestra una característica específica de esta población en cuanto a patrones de desarrollo en las cuales, se evidencia dificultad más importante en las área cognición y de la comunicación expresiva. Con respecto a los intervalos de edad se identificó que a lo largo de estos el desempeño en las áreas evaluadas decrece. esto puede estar relacionado con la mayor complejidad de los hitos del desarrollo para una edad esperada. Debido a que los hitos del desarrollo esperados varían a lo largo de los periodos del ciclo vital del ser humano, estos tienden a aumentar su complejidad en etapas del desarrollo más avanzados; como estos niños poseen una serie de dificultades en las funciones ejecutivas y cognición, no lograrán alcanzar dichos hitos del desarrollo.

User scheduling for low earth orbit multi-user multiple-input-multiple-output non-terrestrial network systems

In rural and isolated areas without cellular coverage, Satellite Communication (SatCom) is the best candidate to complement terrestrial coverage. However, the main challenge for future generations of wireless networks will be to meet the growing demand for new services while dealing with the scarcity of frequency spectrum. As a result, it is critical to investigate more efficient methods of utilizing the limited bandwidth; and resource sharing is likely the only choice. The research community’s focus has recently shifted towards the interference management and exploitation paradigm to meet the increasing data traffic demands. In the Downlink (DL) and Feedspace (FS), LEO satellites with an on-board antenna array can offer service to numerous User Terminals (UTs) (VSAT or Handhelds) on-ground in FFR schemes by using cutting-edge digital beamforming techniques. Considering this setup, the adoption of an effective user scheduling approach is a critical aspect given the unusually high density of User terminals on the ground as compared to the on-board available satellite antennas. In this context, one possibility is that of exploiting clustering algorithms for scheduling in LEO MU-MIMO systems in which several users within the same group are simultaneously served by the satellite via Space Division Multiplexing (SDM), and then these different user groups are served in different time slots via Time Division Multiplexing (TDM). This thesis addresses this problem by defining a user scheduling problem as an optimization problem and discusses several algorithms to solve it. In particular, focusing on the FS and user service link (i.e., DL) of a single MB-LEO satellite operating below 6 GHz, the user scheduling problem in the Frequency Division Duplex (FDD) mode is addressed. The proposed State-of-the-Art scheduling approaches are based on graph theory. The proposed solution offers high performance in terms of per-user capacity, Sum-rate capacity, SINR, and Spectral Efficiency.

NB-IoT via non terrestrial networks

Massive Internet of Things is expected to play a crucial role in Beyond 5G (B5G) wireless communication systems, offering seamless connectivity among heterogeneous devices without human intervention. However, the exponential proliferation of smart devices and IoT networks, relying solely on terrestrial networks, may not fully meet the demanding IoT requirements in terms of bandwidth and connectivity, especially in areas where terrestrial infrastructures are not economically viable. To unleash the full potential of 5G and B5G networks and enable seamless connectivity everywhere, the 3GPP envisions the integration of Non-Terrestrial Networks (NTNs) into the terrestrial ones starting from Release 17. However, this integration process requires modifications to the 5G standard to ensure reliable communications despite typical satellite channel impairments. In this framework, this thesis aims at proposing techniques at the Physical and Medium Access Control layers that require minimal adaptations in the current NB-IoT standard via NTN. Thus, firstly the satellite impairments are evaluated and, then, a detailed link budget analysis is provided. Following, analyses at the link and the system levels are conducted. In the former case, a novel algorithm leveraging time-frequency analysis is proposed to detect orthogonal preambles and estimate the signals’ arrival time. Besides, the effects of collisions on the detection probability and Bit Error Rate are investigated and Non-Orthogonal Multiple Access approaches are proposed in the random access and data phases. The system analysis evaluates the performance of random access in case of congestion. Various access parameters are tested in different satellite scenarios, and the performance is measured in terms of access probability and time required to complete the procedure. Finally, a heuristic algorithm is proposed to jointly design the access and data phases, determining the number of satellite passages, the Random Access Periodicity, and the number of uplink repetitions that maximize the system's spectral efficiency.

Fashion communication strategy: il caso Jacquemus

Il presente elaborato intende studiare la comunicazione di moda, nello specifico la comunicazione aziendale della casa di moda di lusso francese Jacquemus. Per fare ciò, si inizia approfondendo l’argomento della storia della moda e riflettendo su come essa possa essere uno strumento di comunicazione non verbale. Successivamente, si prendono in esame i concetti aziendali di Brand Identity, Brand Positioning e analisi SWOT per analizzare come l’azienda di moda francese ha costruito la sua identità di marca, come si posiziona nella mente dei consumatori e per individuare i suoi punti di forza, di debolezza, le sue opportunità di crescita e le minacce che possono, potenzialmente, ostacolarla. Infine, si prendono in considerazione le strategie di marketing attuate da Jacquemus al fine di rendere efficace la sua comunicazione d’impresa, tenendo conto dei nuovi media digitali a disposizione e concentrandosi anche sul modo in cui l’azienda è riuscita a contrastare la crisi dovuta al lockdown in piena pandemia da Covid-19.

Graph-based User Scheduling for MIMO LEO-based Satellite Communication Systems

The study of the user scheduling problem in a Low Earth Orbit (LEO) Multi-User MIMO system is the objective of this thesis. With the application of cutting-edge digital beamforming algorithms, a LEO satellite with an antenna array and a large number of antenna elements can provide service to many user terminals (UTs) in full frequency reuse (FFR) schemes. Since the number of UTs on-ground are many more than the transmit antennas on the satellite, user scheduling is necessary. Scheduling can be accomplished by grouping users into different clusters: users within the same cluster are multiplexed and served together via Space Division Multiple Access (SDMA), i.e., digital beamforming or Multi-User MIMO techniques; the different clusters of users are then served on different time slots via Time Division Multiple Access (TDMA). The design of an optimal user grouping strategy is known to be an NP-complete problem which can be solved only through exhaustive search. In this thesis, we provide a graph-based user scheduling and feed space beamforming architecture for the downlink with the aim of reducing user inter-beam interference. The main idea is based on clustering users whose pairwise great-circle distance is as large as possible. First, we create a graph where the users represent the vertices, whereas an edge in the graph between 2 users exists if their great-circle distance is above a certain threshold. In the second step, we develop a low complex greedy user clustering technique and we iteratively search for the maximum clique in the graph, i.e., the largest fully connected subgraph in the graph. Finally, by using the 3 aforementioned power normalization techniques, a Minimum Mean Square Error (MMSE) beamforming matrix is deployed on a cluster basis. The suggested scheduling system is compared with a position-based scheduler, which generates a beam lattice on the ground and randomly selects one user per beam to form a cluster.

Egfr Activating Mutations And Their Association With Response To Platinum-doublet Chemotherapy In Brazilian Non-small Cell Lung Cancer Patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

Fatty Acid Synthase Inhibitors Induce Apoptosis In Non-tumorigenic Melan-a Cells Associated With Inhibition Of Mitochondrial Respiration.

The metabolic enzyme fatty acid synthase (FASN) is responsible for the endogenous synthesis of palmitate, a saturated long-chain fatty acid. In contrast to most normal tissues, a variety of human cancers overexpress FASN. One such cancer is cutaneous melanoma, in which the level of FASN expression is associated with tumor invasion and poor prognosis. We previously reported that two FASN inhibitors, cerulenin and orlistat, induce apoptosis in B16-F10 mouse melanoma cells via the intrinsic apoptosis pathway. Here, we investigated the effects of these inhibitors on non-tumorigenic melan-a cells. Cerulenin and orlistat treatments were found to induce apoptosis and decrease cell proliferation, in addition to inducing the release of mitochondrial cytochrome c and activating caspases-9 and -3. Transfection with FASN siRNA did not result in apoptosis. Mass spectrometry analysis demonstrated that treatment with the FASN inhibitors did not alter either the mitochondrial free fatty acid content or composition. This result suggests that cerulenin- and orlistat-induced apoptosis events are independent of FASN inhibition. Analysis of the energy-linked functions of melan-a mitochondria demonstrated the inhibition of respiration, followed by a significant decrease in mitochondrial membrane potential (ΔΨm) and the stimulation of superoxide anion generation. The inhibition of NADH-linked substrate oxidation was approximately 40% and 61% for cerulenin and orlistat treatments, respectively, and the inhibition of succinate oxidation was approximately 46% and 52%, respectively. In contrast, no significant inhibition occurred when respiration was supported by the complex IV substrate N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD). The protection conferred by the free radical scavenger N-acetyl-cysteine indicates that the FASN inhibitors induced apoptosis through an oxidative stress-associated mechanism. In combination, the present results demonstrate that cerulenin and orlistat induce apoptosis in non-tumorigenic cells via mitochondrial dysfunction, independent of FASN inhibition.

Imported Malaria In A Non-endemic Area: The Experience Of The University Of Campinas Hospital In The Brazilian Southeast.

Although malaria in Brazil almost exclusively occurs within the boundaries of the Amazon Region, some concerns are raised regarding imported malaria to non-endemic areas of the country, notably increased incidence of complications due to delayed diagnoses. However, although imported malaria in Brazil represents a major health problem, only a few studies have addressed this subject. A retrospective case series is presented in which 263 medical charts were analysed to investigate the clinical and epidemiological characterization of malaria cases that were diagnosed and treated at Hospital & Clinics, State University of Campinas between 1998 and 2011. Amongst all medical charts analysed, 224 patients had a parasitological confirmed diagnosis of malaria. Plasmodium vivax and Plasmodium falciparum were responsible for 67% and 30% of the infections, respectively. The majority of patients were male (83%) of a productive age (median, 37 years old). Importantly, severe complications did not differ significantly between P. vivax (14 cases, 9%) and P. falciparum (7 cases, 10%) infections. Severe malaria cases were frequent among imported cases in Brazil outside of the Amazon area. The findings reinforce the idea that P. vivax infections in Brazil are not benign, regardless the endemicity of the area studied. Moreover, as the hospital is located in a privileged site, it could be used for future studies of malaria relapses and primaquine resistance mechanisms. Finally, based on the volume of cases treated and the secondary complications, referral malaria services are needed in the non-endemic areas of Brazil for a rapid and efficient and treatment.