Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer

Oncolytic virotherapy - the use of viruses that specifically kill tumor cells - is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In the present work, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD$8^+$ T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.Comment: 14 pages, 4 figure

Expression of the human carboxylesterase 2 enzyme (CES2) in mammalian cells

Dissertation to obtain a Master Degree in BiotechnologyThe carboxylesterase 2 enzyme (CES2), the main carboxylesterase (CES) expressed in human intestine, has a key role in the metabolism of ester containing xenobiotics including the activation of several prodrugs and therefore, it can influence significantly the bioavailability of these compounds. CES2 is receiving an increasing attention due to its potential application in anti-cancer combined therapies, for the treatment of different pathologies like colon adenocarcinoma and malignant glioma. Unlike carboxylesterase 1 (CES1), the structure of this enzyme is not yet known. Since the knowledge of the structure of this protein will be crucial for the understanding of its properties, it becomes relevant the establishment of a process for the production and purification at the milligram level. The development and optimization of human recombinant CES2 production process, using human embryonic kidney cells (HEK-293T cells), is described in this thesis. First, the C-terminal 10xHistidine tag CES2 (CES2-10xHis) was produced using adherent cultures, and then the process was transferred to suspension cultures with serum-free media and finally scaled up to a five-litre stirred tank bioreactor. An affinity chromatography purification process was applied to obtain the CES2-10xHis protein, with a high purity grade. Despite being an Endoplasmic Reticulum (ER) anchored protein, secretion of CES2 to serum free media was achieved due to the presence of the in frame C-terminal 10xHistidine tag. With this elegant procedure we avoided the addition of extra N-terminal signaling sequences or the mutation or deletion of the C-terminal Histidine - Threonine - Glutamic acid - Leucine (HTEL) motif responsible for anchoring the protein in the lumen of the ER. Secretion contributed to a good production yield; however, the global process yield was quite low, due to difficulties in the purification step, which we attributed to protein aggregation

Infliximab in Recalcitrant Generalized Pustular Arthropatic Psoriasis

Generalized pustular psoriasis is an unstable inflammatory type of psoriasis, with widespread areas of erythema and sterile pustules, associated with fever and systemic symptoms. Infliximab is a monoclonal antibody with anti-TNFalpha activity, approved for use in psoriasis. We describe a male patient with a long history of stable arthropathic psoriasis, hospitalized with a generalized pustular psoriasis and acute exacerbation of articular complaints. The disease was resistant to multiple therapies (acitretin, methotrexate and corticosteroids), so the patient was started on infliximab, with a very rapid response of both cutaneous and articular symptoms. He had complete clearing of lesions at week 12, and marked improvement of the articular symptoms. No recurrence occurred at 8 months of follow-up with infliximab every 8 weeks. Infliximab had an extremely rapid therapeutic action response on a recalcitrant generalized pustular psoriasis. The articular response was also excellent, with significant improvement of quality of life

A imagem do enfermeiro em cuidados paliativos

Curso de mestrado em enfermagem médico cirúrgicaNa sociedade, a imagem de qualquer categoria profissional pode ser associada a poder, reconhecimento ou mesmo estatuto social. Partindo deste pressuposto o estudo realizado pretende explorar e descrever a imagem que os cuidadores dos doentes paliativos têm dos enfermeiros. Para dar cumprimento a este objectivo desenvolvemos um estudo de carácter exploratório e descritivo, à luz de uma abordagem qualitativa. Participaram no estudo 13 cuidadores (n=13) que cuidavam dos doentes no seu domicílio a serem seguidos na consulta da dor da Unidade Local de Saúde de Castelo Branco (ULSCB), seleccionados por conveniência e inquiridos por entrevista semiestruturada. Os dados foram tratados através de análise de conteúdo de forma manual, de modo a sentir e compreender todas as emoções que se escondem para além do conteúdo verbal. Os resultados apontam que os cuidadores têm uma imagem muito positiva, aumentando progressivamente o valor dessa imagem de acordo com o número e tipo de necessidades dos doentes que cuidam, independentemente da idade, formação, profissão ou meio onde residem os cuidadores. Salientamos, no entanto, que ainda persiste a ideia da vocação. Assim como a persistência das actividades históricas dos enfermeiros, administrar terapêutica, e fazer pensos. Começa no entanto a emergir outras funções independentes, observadas pelos cuidadores, designadamente a relação com doente. A comunicação, para além de ser um instrumento da enfermagem é muito valorizada pelos cuidadores, assim como a vertente relacional, em detrimento das técnicas, possivelmente pela filosofia de cuidados já implementados, onde concluímos, que o enfermeiro ocupa um lugar de grande destaque, revelado por este estudo. Palavras chave: Imagem; Enfermeiros; Paliativos; Cuidador; Comunicação.Abstract In society, the image of any professional category may be associated with power, recognition or even social status. Under this assumption the study aims to explore and describe the image that caregivers of palliative patients have of nurses. To fulfill this objective we developed a study with an exploratory and descriptive character, based on qualitative research. Thirteen caregivers participated in the study (n = 13) that cared for the sick at home to be followed in an outpatient pain consultation from the Local Health Unit of Castelo Branco (ULSCB), respondents were selected by convenience and interviewed by a semi-structured interview. The data was processed through content analysis manually in order to feel and understand all the emotions that lurk beyond the verbal content. The results indicate that caregivers have a very positive image, progressively increasing the value of that image according to the number and type of care needs of the patients, regardless of age, education, profession or environment where caregivers reside. We emphasize, however, that the idea of vocation still remains. Just as the persistence of historical activities of nurses, like - administering medications and making bandages. However other independent functions begin to emerge, observed by caregivers, particularly the relationship with the patient. Communication, in addition to being an instrument of nursing, is highly valued by caregivers, as well as the relational aspect, in detriment to nursing techniques, possibly by the philosophy of care already in implemented, where we concluded that nurses occupy a place of great prominence, revealed by this study. Keywords: Image; Nurses; Palliative; Caregiver; Comunication

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The Potential of Visible Spectroscopy as a Tool for the In-Line Monitoring of Lignin Methylolation

Out of the 50 to 70 million tons of lignin that are produced annually, only 1 to 2% are used for value-added products. Currently, 90% of the total market of this compound corresponds to lignosulphonates (LS). The most successful industrial attempts to use lignin for wood adhesives rely on using it as a partial substitute in phenolformaldehyde or ureaformaldehyde resins. However, lignins aromatic ring presents a low number of reactive sites. Several methods have been proposed to improve its reactivity, such as prior methylolation with formaldehyde. Off-line methods are commonly applied to monitor this reactions progress, but this introduces a significant delay in the analysis. This study proposes a new method for in-line monitoring of the methylolation reaction using visible spectroscopy. In order to monitor the reaction progress, principal component analysis was applied to the spectra, and the obtained scores were analyzed. When these results were plotted against those obtained by the off-line methods, a satisfactory regression was obtained at 50 °C (R2 = 0.97) and 60 °C (R2 = 0.98) for two different LS samples. Therefore, it was concluded that visible spectroscopy is a promising technique for studying lignin methylolation.</jats:p

Returns and Betas: status of the airline industry

In this report an analysis will be conducted concerning the historical betas, in order to conclude the inherent past volatility of the securities with the market, comparing themwith the current status of the industry. A further analysis is also conducted with regards to past returns byassessing which airline security was able to bring higher gains to its shareholders. Lastly, by applying the previous results, a sensitivity analysis is conducted to understand the impact in Delta’s valuation if the 1st Quartile, Median and 3rd Quartile historical past betas were used to assess the share’s fair value

Lesão alveolar difusa (Fase proliferativa - fibrótica)

ABSTRACTDiffuse Alveolar Damage (DAD) is the usual manifestation of the Adult Respiratory Distress Syndrome (ARDS). From a pathology point of view it presents on three different stages: acute or exsudative, subacute or proliferative and chronic or fibrotic. We describe a clinical case of a 67 year old male who was taken as an inpatient at Hospital Geral de Santo António. The respiratory symptoms have begun a week before. A lung biopsy showed DAD lesion (proliferative /fibrotic stage). He was submitted to mechanical ventilation until death ocurred, 25 days after admission.REV PORT PNEUMOL 2000; VI (6): 691-69

Fertirrigação e regulador de crescimento na produção de mudas de café em tubete

The use of quality seedlings is important in establishing a productive coffee crop. However, the most widely used method to produce coffee seedlings is time consuming (6-12 months) and lacks new production technologies. This study aimed to assess the use of fertigation and a growth regulator in the production of coffee seedlings, in order to develop a system faster than the conventional method. For that, Topázio coffee cultivar seeds were pre-germinated and planted in tubes flled with substrate (composted pine bark), in a protected nursery. A randomized block design was used, in a 4 x 2 (fertigation levels x the use or not of growth regulator) factorial scheme, with four replications. Daily fertigation positively influenced all the growth variables evaluated. The foliar spraying of the growth regulator had little effect on seedling growth. When compared to the conventional system described in the literature, the coffee seedling production system described here reduced, by around 60 days, the production time and enables a largescale productionA utilização de mudas de boa qualidade é importante para a formação de uma lavoura produtiva de café. Entretanto, o método mais utilizado atualmente para a produção de mudas de cafeeiro é demorado (6-12 meses) e carece de novas tecnologias de produção. Objetivou-se avaliar a utilização de fertirrigação e regulador de crescimento na produção de mudas de cafeeiro, com vistas ao desenvolvimento de um sistema mais rápido que o sistema convencional de produção. Para isso, sementes da cultivar Topázio foram pré-germinadas e plantadas em tubetes com substrato (casca de pinus compostada), em viveiro coberto. Adotou-se o delineamento de blocos ao acaso, em esquema fatorial 4 x 2 (níveis de fertirrigação x utilização ou não de regulador de crescimento), com quatro repetições. A fertirrigação diária influenciou positivamente em todas as variáveis de crescimento analisadas. A pulverização foliar do regulador de crescimento apresentou pouco efeito sobre o crescimento das mudas. Quando comparado ao sistema convencional descrito na literatura, o sistema de produção de mudas de cafeeiro descrito neste trabalho reduziu, em cerca de 60 dias, o tempo de produção e permite a produção em larga escala.info:eu-repo/semantics/publishedVersio

Desburocratização e silêncio administrativo na liberação de atividade econômica

The Economic Freedom Act suppresses or reduces the state intervention in economic activity, what is convenient to study the desbureaucracy measures provided for in it. Beyond criticism on the way of regulation on low-risk activies (which dispenses governmental release), the utilization of eloquente silente on liberation acts of economic activies, althought might be advantageous to the development, and due to the existence of impediments to its application, is an exception to the duties of deciding and motivation that guide the public administration. Administrative silence could be limited to situations of recognition of subjetive law, denying it to the discretionary assessment acts of the Administration, and, based on a distinction between primary and secondary public interest, reserved for the Administration's financial or patrimonial interest. It should also impose the duty of supervision as an adjunct to the positive effect of silence, not only when the act of release is waived, additionally to obliging the individual to declare the beginning of activity. As a general rule, it doesn’t change special laws that do not establish positive effect of administrative silence or deny it on issues related to liberation of economic activity, notably for matters marked by principles such as precaution and prevention.A Lei da Liberdade Econômica suprime ou reduz a intervenção estatal na atividade econômica, sendo conveniente o estudo das medidas de desburocratização nela previstas. Além de ser criticável o modo da disciplina da atividade de baixo risco (que dispensa ato governamental de liberação), a adoção do silêncio eloquente nos atos de liberação de atividade econômica, conquanto possa ser vantajosa ao desenvolvimento, e mercê da existência de impedimentos à sua aplicação, é exceção aos deveres de decisão e de motivação que guiam a administração pública. O silêncio administrativo poderia ser limitado às situações de reconhecimento a direito subjetivo, negando-o aos atos de apreciação discricionária da Administração, e, a partir de uma distinção entre interesse público primário e secundário, reservado aos atos de interesse fazendário ou patrimonial da Administração. Deveria, ainda, impor adjunto ao efeito positivo do silêncio o dever de fiscalização, e não apenas quando houver dispensa do ato de liberação, além de obrigar o particular à declaração de início de atividade. Sendo norma geral, ela não altera leis especiais que não prevejam o efeito positivo do silêncio administrativo ou que o neguem em temas ligados à liberação de atividade econômica, notadamente para assuntos timbrados por princípios como precaução e prevenção