86 research outputs found
ROUND-ROBIN TOURNAMENTS WITH EFFORT CONSTRAINTS
We study a round-robin tournament with n symmetric players where in each of the n-1 stages each of the players competes against a different player in the Tullock contest. Each player has a limited budget of effort that decreases within the stages proportionally to the effort he exerted in the previous stages. We show that when the prize for winning (value of winning) is equal between the stages, a player's effort is weakly decreasing over the stages. We also show how the contest designer can influence the players' allocation of effort by changing the distribution of prizes between the stages. In particular, we analyze the distribution of prizes over the stages that balance the effort allocation such that a player exerts the same effort over the different stages. In addition, we analyze the distribution of prizes over the stages that maximizes the players' expected total effort.
Laughlin-like states in bosonic and fermionic atomic synthetic ladders
The combination of interactions and static gauge fields plays a pivotal role
in our understanding of strongly-correlated quantum matter. Cold atomic gases
endowed with a synthetic dimension are emerging as an ideal platform to
experimentally address this interplay in quasi-one-dimensional systems. A
fundamental question is whether these setups can give access to pristine
two-dimensional phenomena, such as the fractional quantum Hall effect, and how.
We show that unambiguous signatures of bosonic and fermionic Laughlin-like
states can be observed and characterized in synthetic ladders. We theoretically
diagnose these Laughlin-like states focusing on the chiral current flowing in
the ladder, on the central charge of the low-energy theory, and on the
properties of the entanglement entropy. Remarkably, Laughlin-like states are
separated from conventional liquids by Lifschitz-type transitions,
characterized by sharp discontinuities in the current profiles, which we
address using extensive simulations based on matrix-product states. Our work
provides a qualitative and quantitative guideline towards the observability and
understanding of strongly-correlated states of matter in synthetic ladders. In
particular, we unveil how state-of-the-art experimental settings constitute an
ideal starting point to progressively tackle two-dimensional strongly
interacting systems from a ladder viewpoint, opening a new perspective for the
observation of non-Abelian states of matter.Comment: 19 pages, 17 figures. Updated version after publication in Phys. Rev.
Horizontal transfer of RNAi between honeybees and Varroa destructor
Dissertação de mestrado em Biotecnologia Farmacêutica, apresentada à Faculdade de Farmácia da Universidade de CoimbraEste trabalho abrange uma revisão do estado de arte do processo de liofilização e da sua aplicação na área da Nanotecnologia. O foco principal desta revisão é a caracterização dos produtos liofilizados inovadores existentes no mercado e em fase de desenvolvimento clÃnico, com aplicação em Oncologia.
Na área farmacêutica, a exploração das propriedades únicas das nanopartÃculas tornou-se diferenciadora pela demonstração de efeitos na biodisponibilidade de moléculas ativas e também na proteção contra a degradação enzimática. Mais recentemente, as nanopartÃculas têm sido usadas para proporcionar um aumento da especificidade e efetividade no direcionamento dos fármacos aos locais alvo, permitindo a diminuição da dose eficaz e da toxicidade geral. Com tudo isto, o desenvolvimento de nanoestruturas para transporte de fármacos tem sido objeto de um interesse crescente, tendo em vista colmatar alguns pontos negativos existentes nos sistemas de dosagem tradicionais.
No entanto, a estabilidade das nanopartÃculas pode constituir um problema, pelo que a sua concepção não é propriamente linear. No caso especÃfico das nanodispersões coloidais, fatores fÃsicos e quÃmicos contribuem para uma baixa estabilidade a longo termo, provocando a destabilização do sistema que limita a sua aplicação clÃnica.
A liofilização surge neste cenário como um processo tecnológico que pode minimizar os problemas de estabilidade das suspensões aquosas de nanopartÃculas. Trata-se de uma técnica de desidratação muito eficiente quando comparada com as demais, que tem vindo a apresentar melhorias na estabilidade destas suspensões coloidais, e por esta razão merece destaque. Cada produto possui um ciclo de liofilização único em função das suas particularidades, o que faz com que este processo seja uma operação unitária. Para ser percetÃvel a forma como o processo de liofilização é executado cumprindo as boas práticas laboratoriais (BPL/GLP) e de fabrico (BPF/GMP) são explÃcitos, neste estudo, os requisitos normativos a ter em conta.
A liofilização, além de ser útil ao nÃvel da estabilidade, é ainda utilizada para outras finalidades que estão descritas no estudo. De forma a elucidar toda a operação envolvida neste processo é feita uma breve abordagem das etapas envolvidas, dos métodos utilizados, das
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aplicações farmacêuticas e dos principais pros e contras, com o intuito de entender a importância da formulação de nanopartÃculas liofilizadas.
Será ainda dedicado um capÃtulo ao estudo dos componentes e das condições do processo para conseguir obter resistência à s tensões a que as suspensões de nanopartÃculas são submetidas durante a fase de congelamento na liofilização. Nesta fase, o efeito crioprotetor ou lioprotetor é determinante, dado que na reidratação do produto é mandatório que as propriedades originais das nanopartÃculas sejam mantidas.
A respeito dos avanços recentes com aplicação deste processo, são ainda apresentadas as formulações liofilizadas que estão inseridas no mercado e os ensaios clÃnicos e pré-clÃnicos existentes para o tratamento de doenças do foro oncológico, com referência aos produtos protegidos por patente.
A relevância deste trabalho traduz-se no facto de o resultado da pesquisa ser orientado em ambiente empresarial e académico, com vista à inserção no processo de valorização da propriedade intelectual de uma spin-off da Universidade de CoimbraThis work aims at conducting a review of the state of art of the lyophilization process and its application in the field of Nanotechnology. The main focus is the characterization of existing innovative freeze-dried products on the market and in clinical evaluation, with applications in Oncology.
In the pharmaceutical area, the unique properties of nanoparticles began to demonstrate positive effects on the bioavailability of active molecules and also in protecting against enzymatic degradation. More recently, nanoparticles have been used to provide increased specificity and effectiveness in the targeting of drugs to specific locations, thereby reducing the effective dose and toxicity. With all this, the development of nanostructures for drug delivery has provided the solution for existing weaknesses in traditional dosing systems.
However, the stability of the nanoparticles is not exactly a linear topic. In the case of colloidal nanodispersions, physical and chemical factors contribute to a low long term stability, leading to destabilization of the system and thus creating an obstacle to its clinical application.
Lyophilization in this scenario appears as a technological process that can minimize stability problems of aqueous suspensions of nanoparticles. It is a very efficient dewatering technique, which has been presenting improvements in the stability of these colloidal suspensions, and therefore noteworthy. Each product has a single lyophilization cycle on the basis of their features, which makes this process a unitary operation. To be noticeable how the freeze-drying process is performed in compliance with the good laboratory practice (BPL/GLP) and manufacturing practice (BPF/GMP), the regulatory requirements to be considered are explicit in this study.
This technique, besides being useful for stability issues, it is still used for other purposes which are described in the study. In order to elucidate the entire operation involved in this process, it is made a brief approach of the steps involved, the methods used, the pharmaceutical applications and the main pros and cons of the formulation of lyophilized nanoparticles.
The study also comprises a chapter on the components and process conditions to achieve resistance to the stresses to which the nanoparticulate suspensions are subjected during the
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freezing stage of the lyophilization. At this stage, the cryoprotectant or lioprotetor effect is decisive for the rehydration, in order to preserve that the original properties of the nanoparticles.
Regarding the recent advances in the application of this process, this study presents the most recent lyophilized formulations on the market and in clinical and preclinical trials for the treatment of oncological diseases, with reference to the proprietary products.
The main conclusions of this work will be included in the valuing process of the intellectual property of a spin-off from the University of Coimbra, combining an academic and business perspective on a pharmaceutical process of industrial application
Frozen section analysis and sentinel lymph node biopsy in well differentiated thyroid cancer
BACKGROUND: The aim of this study is to prospectively review the role of sentinel lymph node (SLN) biopsy in the management of well differentiated thyroid carcinoma (WDTC), and to determine the efficacy of intraoperative frozen section analysis at detecting SLN metastasis and central compartment involvement. METHODS: The SLN biopsy protocol using 1% methylene blue was performed in 300 patients undergoing thyroidectomy for WDTC. A limited pretracheal central compartment neck dissection (CCND) was performed on all patients. Lymph nodes staining blue were considered as SLN’s. Both frozen and permanent section analyses were performed. RESULTS: SLN’s with metastasis were found in 14.3% (43/300) of cases. Of this, 11% (33/300) were positive on intraoperative frozen section analysis. Frozen section results failed in predicting central compartment involvement in 15 cases (5%) whereas central neck compartment involvement was missed in 5 cases (1.7%) when based on permanent section results. On frozen section analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% CI) of our SLN biopsy technique aiming to remove all disease from the central compartment was 68.8% (53.6-80.9), 100% (98.1-100), 100% (87.0-100) and 94.4% (90.7-96.7) respectively with P < 0.0001. On permanent section analysis, the values were 89.6% (76.6-96.1), 100% (98.1-100), 100% (89.8-100), and 98.1% (95.3-99.3) with P < 0.0001. CONCLUSION: This data series demonstrates that patients with WDTC have positive SLN’s in 14.3% of cases. Moreover, when the SLN’s are negative for metastasis on frozen section, the central compartment was disease-free in 94.4% of cases. Finally, this study shows that 23.3% of positive SLN’s were false negatives on intraoperative frozen section. According to this data, SLN involvement is an accurate predictor of central compartment metastasis, however surgeons should use caution when relying on intraoperative frozen section to determine whether to perform a CCND
Large-scale field application of RNAi technology reducing Israeli acute paralysis virus disease in honey bees (Apis mellifera, Hymenoptera: Apidae).
The importance of honey bees to the world economy far surpasses their contribution in terms of honey production; they are responsible for up to 30% of the world's food production through pollination of crops. Since fall 2006, honey bees in the U.S. have faced a serious population decline, due in part to a phenomenon called Colony Collapse Disorder (CCD), which is a disease syndrome that is likely caused by several factors. Data from an initial study in which investigators compared pathogens in honey bees affected by CCD suggested a putative role for Israeli Acute Paralysis Virus, IAPV. This is a single stranded RNA virus with no DNA stage placed taxonomically within the family Dicistroviridae. Although subsequent studies have failed to find IAPV in all CCD diagnosed colonies, IAPV has been shown to cause honey bee mortality. RNA interference technology (RNAi) has been used successfully to silence endogenous insect (including honey bee) genes both by injection and feeding. Moreover, RNAi was shown to prevent bees from succumbing to infection from IAPV under laboratory conditions. In the current study IAPV specific homologous dsRNA was used in the field, under natural beekeeping conditions in order to prevent mortality and improve the overall health of bees infected with IAPV. This controlled study included a total of 160 honey bee hives in two discrete climates, seasons and geographical locations (Florida and Pennsylvania). To our knowledge, this is the first successful large-scale real world use of RNAi for disease control
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