Functionality of bioactive compounds in Brazilian strawberry (Fragaria x ananassa Duch.) cultivars: Evaluation of hyperglycemia and hypertension potential using in vitro models

Fruits of seven fully ripened strawberry cultivars grown in Brazil (Dover, Camp Dover, Camarosa, Sweet Charlie, Toyonoka, Oso Grande, and Piedade) were evaluated for total phenolics, antioxidant activity based on DPPH radical scavenging assay, and functionality such as inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potentially managing hyperglycemia and hypertension. The total phenolics content ranged from 966 to 1571 mu g of gallic acid/g of fruit fresh weight for Toyonoka and Dover, respectively. No correlation was found between total phenolics and antioxidant activity. The major phenolic compounds in aqueous extracts of strawberries were ellagic acid, quercetin, and chlorogenic acid. Strawberries had high alpha-glucosidase inhibitory activity. However, alpha-amylase inhibitory activity was very low in all cultivars. This suggested that strawberries could be considered as a potential dietary source with anti-hyperglycemic potential. The evaluated cultivars had no significant ACE inhibitory activity, reflecting low anti-hypertensive potential.

Modelos de simulação em MATSim aplicados à análise de sistemas de transporte

Dissertação para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização de Vias de Comunicação e Transportes

A gestão dos custos da qualidade: Modelo A.B.Q.C. aplicado à Mercauto

Mestrado em Controlo e Gestão dos Negócios

Quality indicators in the education of children with profound Intellectual and multiple disabilities

Todas as crianças, independentemente das suas necessidades, deveriam ter acesso a uma educação de qualidade e a serem incluídas nas suas famílias e comunidades. Esta afirmação inclui as crianças mais vulneráveis, em particular as crianças com dificuldades intelectuais e multideficiência. Os resultados da investigação sobre a educação de crianças com dificuldades intelectuais e multideficiência ainda não produziram até ao momento informação suficiente que possa ser usada para desenvolver indicadores de qualidade para a avaliação das práticas e dos serviços. A investigação nesta área é limitada por constrangimentos éticos, dificuldades na determinação de amostras e desafios metodológicos, sendo reduzido o número de estudos capaz de produzir a informação necessária. Este artigo tem como objetivo discutir fatores que contribuam para a qualidade do envolvimento de crianças com dificuldades intelectuais e multideficiência em atividades educativas, com base na experiência das autoras e na informação disponível que tem sido publicada sobre este assunto. Com base nesta discussão é sugerido um conjunto de indicadores que poderão ajudar os profissionais a dirigir as suas observações para a qualidade da oferta educativa e para aspetos significativos dos desempenhos das crianças quando envolvidas em atividades curriculares.

Otimização da atividade de picking num armazém de peças – um caso de estudo

Mestrado em Engenharia Mecânica – Gestão Industrial

Dispersão da Refractariedade Auricular como Substrato Electrofisiológico da Vulnerabilidade Auricular em Doentes com Fibrilhação Auricular Paroxística

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.

The role of ascorbate peroxidase, guaiacol peroxidase, and polysaccharides in cassava (Manihot esculenta Crantz) roots under postharvest physiological deterioration

Abstract This study aimed to investigate the role of ascorbate peroxidase (APX), guaiacol peroxidase (GPX), polysaccharides, and protein contents associated with the early events of postharvest physiological deterioration (PPD) in cassava roots. Increases in APX and GPX activity, as well as total protein contents occurred from 3 to 5 days of storage and were correlated with the delay of PPD. Cassava samples stained with periodic acid-Schiff (PAS) highlighted the presence of starch and cellulose. Degradation of starch granules during PPD was also detected. Slight metachromatic reaction with toluidine blue is indicative of increasing of acidic polysaccharides and may play an important role in PPD delay. Principal component analysis (PCA) classified samples according to their levels of enzymatic activity based on the decision tree model which showed GPX and total protein amounts to be correlated with PPD. The Oriental (ORI) cultivar was more susceptible to PPD.

All different or all the same? Exploring the diversity of professional practices in Portuguese school psychology

"Published online: 29 March 2016"

Combinatorial Synthesis and Biological Evaluation of Inhibitors of D-Ala-D-Ala-Ligase

Report for the scientific sojourn carried out at the Max Planck Institut of Molecular Phisiology, Germany, from 2006 to 2008.The work carried out during this postdoctoral stage was focused on two different projects. Firstly, identification of D-Ala D-Ala Inhibitors and the development of new synthethic approaches to obtain lipidated peptides and proteins and the use of these lipidated proteins in biological and biophysical studies. In the first project, new D-Ala D-Ala inhibitors were identified by using structural alignments of the ATP binding sites of the bacterial ligase DDl and protein and lipid kinases in complex with ATP analogs. We tested a series of commercially available kinase inhibitors and found LFM-A13 and Tyrphostine derivatives to inhibit DDl enzyme activity. Based on the initial screening results we synthesized a series of malononitrilamide and salicylamide derivatives and were able to confirm the validity of these scaffolds as inhibitors of DDl. From this investigation we gained a better understanding of the structural requirements and limitations necessary for the preparation of ATP competitive DDl inhibitors. The compounds in this study may serve as starting points for the development of bi-substrate inhibitors that incorporate both, an ATP competitive and a substrate competitive moiety. Bisubstrate inhibitors that block the ATP and D-Ala binding sites should exhibit enhanced selectivity and potency profiles by preferentially inhibiting DDl over kinases. In the second project, an optimized synthesis for tha alkylation of cysteins using the thiol ene reaction was establisehd. This new protocol allowed us to obtain large amounts of hexadecylated cysteine that was required for the synthesis of differently lipidated peptides. Afterwards the synthesis of various N-ras peptides bearing different lipid anchors was performed and the peptides were ligated to a truncated N-ras protein. The influence of this differently lipidated N-ras proteins on the partioning and association of N-Ras in model membrane subdomains was studied using Atomic Force Microscopy.

WALK Community Garden

WALK operate a Community Garden in Dublin 12 which promotes the growing of fresh fruit, vegetable, salad leaves and flowers which change seasonally. The garden helps create a sense of community and advocates the benefits of growing healthy food, environmental awareness and sustainability. It offers an opportunities for people to take part in hand-on, activity based learning with some formal training offered to local groups and individuals with varying levels of skill and ability. This outdoor space fosters an interest in growing and guides people in learning new skills which can be transferred to their own gardens or allotments. Dublin City Council Initiative Type Community Food Growing Projects Location Dublin 12 Funding Dublin City Council Partner Agencies Dublin City Council Dublin Mainstream Access Project Scoil Colm

Combination of bevacizumab and 2-weekly pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer. A multicenter, single-arm phase II trial (SAKK 24/06).

BACKGROUND: Pegylated liposomal doxorubicin (PLD) and bevacizumab are active agents in the treatment of metastatic breast cancer (MBC). We carried out a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of PLD and bevacizumab as first-line treatment in MBC patients. METHODS: Bevacizumab (10 mg/kg) and PLD (20 mg/m(2)) were infused on days 1 and 15 of a 4-week cycle for a maximum of six cycles. Thereafter, bevacizumab monotherapy was continued at the same dose until progression or toxicity. The primary objective was safety and tolerability, and the secondary objective was to evaluate efficacy of the combination. RESULTS: Thirty-nine of 43 patients were assessable for the primary end point. Eighteen of 39 patients (46%, 95% confidence interval 30% to 63%) had a grade 3 toxicity. Sixteen (41%) had grade 3 palmar-plantar erythrodysesthesia, one had grade 3 mucositis, and one severe cardiotoxicity. Secondary end point of overall response rate among 43 assessable patients was 21%. CONCLUSIONS: In this nonrandomized single-arm trial, the combination of bimonthly PLD and bevacizumab in locally recurrent and MBC patients demonstrated higher than anticipated toxicity while exhibiting only modest activity. Based on these results, we would not consider this combination for further investigation in this setting.

Identification and characterization of novel classes of macrophage migration inhibitory factor (MIF) inhibitors with distinct mechanisms of action.

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is considered an attractive therapeutic target in multiple inflammatory and autoimmune disorders. In addition to its known biologic activities, MIF can also function as a tautomerase. Several small molecules have been reported to be effective inhibitors of MIF tautomerase activity in vitro. Herein we employed a robust activity-based assay to identify different classes of novel inhibitors of the catalytic and biological activities of MIF. Several novel chemical classes of inhibitors of the catalytic activity of MIF with IC(50) values in the range of 0.2-15.5 microm were identified and validated. The interaction site and mechanism of action of these inhibitors were defined using structure-activity studies and a battery of biochemical and biophysical methods. MIF inhibitors emerging from these studies could be divided into three categories based on their mechanism of action: 1) molecules that covalently modify the catalytic site at the N-terminal proline residue, Pro(1); 2) a novel class of catalytic site inhibitors; and finally 3) molecules that disrupt the trimeric structure of MIF. Importantly, all inhibitors demonstrated total inhibition of MIF-mediated glucocorticoid overriding and AKT phosphorylation, whereas ebselen, a trimer-disrupting inhibitor, additionally acted as a potent hyperagonist in MIF-mediated chemotactic migration. The identification of biologically active compounds with known toxicity, pharmacokinetic properties, and biological activities in vivo should accelerate the development of clinically relevant MIF inhibitors. Furthermore, the diversity of chemical structures and mechanisms of action of our inhibitors makes them ideal mechanistic probes for elucidating the structure-function relationships of MIF and to further determine the role of the oligomerization state and catalytic activity of MIF in regulating the function(s) of MIF in health and disease.

Com ha de ser una activitat científica efectiva basada en l'experimentació i l'estudi de l'entorn proper? Estudi de casos i proposta de criteris a tenir en compte en el disseny d’activitats científiques escolars en l’entorn

Actualment moltes fonts d'informació ens descriuen i argumenten com han de ser les activitats científiques a l'escola per garantir l'aprenentatge significatiu de l'alumnat, i d'altres estudis ens mostren com han de ser les activitats escolars en l'entorn; però no hi ha estudis que ens descriguin i argumentin com han de ser les activitats científiques escolars basades en l'experimentació i l'estudi de l'entorn proper. Així doncs, aquesta investigació s'endinsa per solucionar un problema actual que és: com ha de ser una bona activitat científica escolar basada en l'experimentació i l'estudi de l'entorn proper? En resposta a això, aquest treball es basa en una investigació avaluativa que analitza diversos projectes de ciències basats en l'entorn a partir de l'observació d'uns criteris específics elaborats, per una banda a partir de les idees d'experts sobre com ha de ser una bona activitat científica i com ha de ser una activitat escolar d'entorn efectiva; i per altra banda a partir de les idees extretes de les entrevistes fetes a mestres promotores de projectes científics escolars innovadors centrats i duts a terme en l'entorn proper.

A treatment planning method for sequentially combining radiopharmaceutical therapy and external radiation therapy.

PURPOSE: Effective cancer treatment generally requires combination therapy. The combination of external beam therapy (XRT) with radiopharmaceutical therapy (RPT) requires accurate three-dimensional dose calculations to avoid toxicity and evaluate efficacy. We have developed and tested a treatment planning method, using the patient-specific three-dimensional dosimetry package 3D-RD, for sequentially combined RPT/XRT therapy designed to limit toxicity to organs at risk. METHODS AND MATERIALS: The biologic effective dose (BED) was used to translate voxelized RPT absorbed dose (D(RPT)) values into a normalized total dose (or equivalent 2-Gy-fraction XRT absorbed dose), NTD(RPT) map. The BED was calculated numerically using an algorithmic approach, which enabled a more accurate calculation of BED and NTD(RPT). A treatment plan from the combined Samarium-153 and external beam was designed that would deliver a tumoricidal dose while delivering no more than 50 Gy of NTD(sum) to the spinal cord of a patient with a paraspinal tumor. RESULTS: The average voxel NTD(RPT) to tumor from RPT was 22.6 Gy (range, 1-85 Gy); the maximum spinal cord voxel NTD(RPT) from RPT was 6.8 Gy. The combined therapy NTD(sum) to tumor was 71.5 Gy (range, 40-135 Gy) for a maximum voxel spinal cord NTD(sum) equal to the maximum tolerated dose of 50 Gy. CONCLUSIONS: A method that enables real-time treatment planning of combined RPT-XRT has been developed. By implementing a more generalized conversion between the dose values from the two modalities and an activity-based treatment of partial volume effects, the reliability of combination therapy treatment planning has been expanded.

Standardizing Customized Features of a Configurable Product

Työn päätavoitteena on arvioida hissien automaattiovien usein toistuvien asiakaskohtaisesti räätälöityjen tuoteominaisuuksien vakioimisen kannattavuutta KONEen Hyvinkään tehtaalla. Työssä arvioidaan myös massaräätälöinnin periaatteiden soveltuvuutta erikoisovien toimitusprosessiin sekä toimintoperusteisen kustannustiedon tarpeellisuutta tuoteominaisuuksia koskevien päätösten teossa. Asiakaskohtaisesti räätälöity ovituotanto jaettiin kategorioihin, joiden volyymeja ja tuotemuutosten tekoon käytettyjä suunnittelutuntimääriä analysoimalla selvitettiin, muodostaako jokin räätälöitävä tuoteominaisuus riittävän suuren kappalemääräisen kysynnän tai suunnittelutuntien kulutuskohteen, jotta ominaisuuden vakiointi olisi kannattavaa. Ovien kustannusrakenne-esimerkkien avulla selvitettiin myös suunnittelun osuus kokonaiskustannuksista. Analyysien perusteella todettiin asiakaskohtaisten muutosten olevan hajanaisia ja vain muutaman ominaisuuden osalta muodostuvan tarpeeksi suuri ja yhtenäinen kokonaisuus, joka olisi taloudellisesti kannattavaavakioida. Monimutkaisen tuoterakenteen vuoksi massaräätälöinnin opit eivät ole suoraan kopioitavissa hissien erikoisovien toimitusprosessiin, mutta sisältävät hyödyllisiä toimintamalleja prosessin kehittämiseen.