SpaciMS: spatial and temporal operando resolution of reactions within catalytic monoliths

Monolithic catalysts are widely used as structured catalysts, especially in the abatement of pollutants. Probing what happens inside these monoliths during operation is, therefore, vital for modelling and prediction of the catalyst behavior. SpaciMS is a spatially resolved capillary-inlet mass spectroscopy system allowing for the generation of spatially resolved maps of the reactions within monoliths. In this study SpaciMS results combined with 3D CFD modelling demonstrate that SpaciMS is a highly sensitive and minimally invasive technique that can provide reaction maps as well as catalytic temporal behavior. Herein we illustrate this by examining kinetic oscillations during a CO oxidation reaction over a Pt/Rh on alumina catalyst supported on a cordierite monolith. These oscillations were only observed within the monolith by SpaciMS between 30 and 90% CO conversion. Equivalent experiments performed in a plug-flow reactor using this catalyst in a crushed form over a similar range of reaction conditions did not display any oscillations demonstrating the importance of intra monolith analysis. This work demonstrates that the SpaciMS offers an accurate and comprehensive picture of structured catalysts under operation.

A phase I study of the Heat Shock Protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced, solid tumours.

PURPOSE: A phase I study to define toxicity and recommend a phase II dose of the HSP90 inhibitor alvespimycin (17-DMAG; 17-dimethylaminoethylamino-17-demethoxygeldanamycin). Secondary endpoints included evaluation of pharmacokinetic profile, tumor response, and definition of a biologically effective dose (BED). PATIENTS AND METHODS: Patients with advanced solid cancers were treated with weekly, intravenous (i.v.) 17-DMAG. An accelerated titration dose escalation design was used. The maximum tolerated dose (MTD) was the highest dose at which = 1/6 patients experienced dose limiting toxicity (DLT). Dose de-escalation from the MTD was planned with mandatory, sequential tumor biopsies to determine a BED. Pharmacokinetic and pharmacodynamic assays were validated prior to patient accrual. RESULTS: Twenty-five patients received 17-DMAG (range 2.5-106 mg/m(2)). At 106 mg/m(2) of 17-DMAG 2/4 patients experienced DLT, including one treatment-related death. No DLT occurred at 80 mg/m(2). Common adverse events were gastrointestinal, liver function changes, and ocular. Area under the curve and mean peak concentration increased proportionally with 17-DMAG doses 80 mg/m(2) or less. In peripheral blood mononuclear cells significant (P

Phase I study of GSK461364, a specific and competitive Polo-like Kinase 1 (PLK1) inhibitor in patients with advanced solid malignancies.

Purpose: GSK461364 is an ATP-competitive inhibitor of polo-like kinase 1 (Plk1). A phase I study of two schedules of intravenous GSK461364 was conducted. Experimental Design: GSK461364 was administered in escalating doses to patients with solid malignancies by two schedules, either on days 1, 8, and 15 of 28-day cycles (schedule A) or on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (schedule B). Assessments included pharmacokinetic and pharmacodynamic profiles, as well as marker expression studies in pretreatment tumor biopsies. Results: Forty patients received GSK461364: 23 patients in schedule A and 17 in schedule B. Dose-limiting toxicities (DLT) in schedule A at 300 mg (2 of 7 patients) and 225 mg (1 of 8 patients) cohorts included grade 4 neutropenia and/or grade 3–4 thrombocytopenia. In schedule B, DLTs of grade 4 pulmonary emboli and grade 4 neutropenia occurred at 7 or more days at 100 mg dose level. Venous thrombotic emboli (VTE) and myelosuppression were the most common grade 3–4, drug-related events. Pharmacokinetic data indicated that AUC (area under the curve) and C max (maximum concentration) were proportional across doses, with a half-life of 9 to 13 hours. Pharmacodynamic studies in circulating tumor cells revealed an increase in phosphorylated histone H3 (pHH3) following drug administration. A best response of prolonged stable disease of more than 16 weeks occurred in 6 (15%) patients, including 4 esophageal cancer patients. Those with prolonged stable disease had greater expression of Ki-67, pHH3, and Plk1 in archived tumor biopsies. Conclusions: The final recommended phase II dose for GSK461364 was 225 mg administered intravenously in schedule A. Because of the high incidence (20%) of VTE, for further clinical evaluation, GSK461364 should involve coadministration of prophylactic anticoagulation.

Orotate complexes of rhodium(I) and iridium(I): effect of coligand, counter ion, and solvent of crystallisation on association via complementary hydrogen bonding

The new complexes [NEt3H][M(HL)(cod)] (M = Rh 1 or Ir 2; H3L = 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid, erotic acid; cod = cycloocta-1,5-diene) have been prepared by the reaction between [M2Cl2(cod)(2)] and erotic acid in dichloromethane in the presence of Ag2O and NEt3. They crystallise as dichloromethane adducts 1 . CH2Cl2 and 2 . CH2Cl2 from dichloromethane-hexane solutions. These isomorphous structures contain doubly hydrogen-bonded dimers, with additional hydrogen bonding to NEt3H+ cations and bridging CH2Cl2 molecules to form tapes. The use of (NBu4OH)-O-n instead of NEt3 gave the related complex [NBu4n][Rh(HL)(cod)] 1' which has an innocent cation not capable of forming strong hydrogen bonds and in contrast to 1 exists as discrete doubly hydrogen-bonded dimers. Complex 1' cocrystallises with 2,6-diaminopyridine (dap) via complementary triple hydrogen bonds to give [NBu4n][Rh(HL)(cod)]. dap . CH2Cl2 3. Complex 3 exhibits an extended sheet structure of associated [2 + 2] units, with layers of NBu4n, cations separating the sheets. These structural data together with those reported previously for platinum orotate complexes suggest that the steric requirements of the other ligands co-ordinated to the metal are important in influencing their hydrogen-bonding abilities. The solvent of crystallisation, the hydrogen-bonding propensity of the coligand and the nature of the counter ion also determine the type of association in the solid state.

A phase I study of combined docetaxel and repeated high activity Re-186-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

Purpose Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and Re-186-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity.

A Phase I Trial of Bortezomib in Combination with Epirubicin, Carboplatin and Capecitabine (VECarboX) in Advanced Gastric and Gastro-oesophageal Junction Adenocarcinoma

PURPOSE:
The protease inhibitor bortezomib attenuates the action of NF-κB and has shown preclinical activity alone and in combination with chemotherapy.

DESIGN:
A Phase I dose-escalation study was performed administering bortezomib (0.7, 1.0, 1.3 and 1.6 mg m(-2) on days 1 and 8 from cycle 2 onwards) in combination with Epirubicin 50 mg m(-2) intravenously on day 1, Carboplatin AUC 5 day 1 and Capecitabine 625 mg m(-2) BD days 1-21 every 21 days (VECarboX regimen), in patients with advanced oesophagogastric adenocarcinoma. The primary objective was to define the maximum tolerated dose (MTD) of Bortezomib when combined with ECarboX.

RESULTS:
18 patients received bortezomib 0.7 (n = 6), 1.0 (n = 3), 1.3 (n = 6) and 1.6 mg m(-2) (n = 3) and a protocol amendment reducing the capecitabine dose to 500 mg m(-2) BD was enacted due to myelotoxicity. Common treatment-related non-haematological adverse events of any grade were fatigue (83.3 %), anorexia (55.6 %), constipation (55.6 %) and nausea (55.6 %). Common Grade 3/4 haematological toxicities were neutropenia (77.8 %) and thrombocytopenia (44.4 %). Objective responses were achieved in 6 patients (33.3 %) and a further 5 patients (27.8 %) had stable disease for >8 weeks.

CONCLUSIONS:
The addition of Bortezomib to ECarboX is well tolerated and response rates are comparable with standard chemotherapy.

Identification of a collagen type I adhesin of Bacteroides fragilis

Bacteroides fragilis is an opportunistic pathogen which can cause life threatening infections in humans and animals. The ability to adhere to components of the extracellular matrix, including collagen, is related to bacterial host colonisation. Collagen Far Western analysis of the B. fragilis outer membrane protein (OMP) fraction revealed the presence two collagen adhesin bands of ∼31 and ∼34 kDa. The collagen adhesins in the OMP fraction were separated and isolated by two-dimensional SDS-PAGE and also purified by collagen affinity chromatography. The collagen binding proteins isolated by both these independent methods were subjected to tandem mass spectroscopy for peptide identification and matched to a single hypothetical protein encoded by B. fragilis NCTC 9343 (BF0586), conserved in YCH46 (BF0662) and 638R (BF0633) and which is designated in this study as cbp1 (collagen binding protein). Functionality of the protein was confirmed by targeted insertional mutagenesis of the cbp1 gene in B. fragilis GSH18 which resulted in the specific loss of both the ∼31 kDa and the ∼34 kDa adhesin bands. Purified his-tagged Cbp1, expressed in a B. fragilis wild-type and a glycosylation deficient mutant, confirmed that the cbp1 gene encoded the observed collagen adhesin, and showed that the 34 kDa band represents a glycosylated version of the ∼31 kDa protein. Glycosylation did not appear to be required for binding collagen. This study is the first to report the presence of collagen type I adhesin proteins in B. fragilis and to functionally identify a gene encoding a collagen binding protein. © 2014 Galvão et al.

Revenue diversification in higher education: the case of Portugal

Socio-economic changes, alterations in societal expectations and new public policies have put pressures on higher education public funding, bringing the issue of funding diversification to the forefront. Income diversification, namely, generation of funds from private, as well as from competitive public sources, has become increasingly important in European higher education due to a complex financial environment and perceived deficit of innovation transfer. Although there are numerous studies about changes in national funding systems and allocation mechanisms, few have focused on diversification of funding sources, especially in the European context, making Portugal no exception. Thus, this study aims at exploring income diversification at the institutional level and its influence on the internal organisational structures. For this purpose two Portuguese public universities were chosen as case studies. The empirical material was collected through semi-structured interviews with top management and middle management of each university and through documentary analysis. Data analysis demonstrated that both universities are in the process of institutionalizing and formalising practices of income diversification, notably by getting more professional in how they are dealing with external stakeholders, such as businesses, local community, and students. However, the study also revealed that there is no formal, organised strategy to deal with income diversification. In general, the universities are reacting to external demands rather than pro-actively exploring opportunities. In this respect, the analysis determined several factors that promote or inhibit income diversification activities. Quality and favourable organizational culture were named by the interviewees as the most relevant factors for successful income diversification. External factors such as legal arrangements and funding conditions were cited as major constraints. This research has also revealed that revenue diversification activities tend to develop along the continuum towards higher sophistication and systematisation of activities that are supported by a powerful infrastructure. Together with efforts at the institutional level, the role of government policies proves to be crucial in providing tools and incentives to higher education institutions and creating a harmonious higher education system.

DNA damage in two bivalve species: Mytilus galloprovincialis and Ruditapes decussatus from the South coast of Portugal

Dissertação de mest., Estudos Marinhos e Costeiros, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2009

Estimation of unemployment rates in small areas of Portugal: a best linear unbiased prediction approach versus a hierarchical Bayes approach

The high level of unemployment is one of the major problems in most European countries nowadays. Hence, the demand for small area labor market statistics has rapidly increased over the past few years. The Labour Force Survey (LFS) conducted by the Portuguese Statistical Office is the main source of official statistics on the labour market at the macro level (e.g. NUTS2 and national level). However, the LFS was not designed to produce reliable statistics at the micro level (e.g. NUTS3, municipalities or further disaggregate level) due to small sample sizes. Consequently, traditional design-based estimators are not appropriate. A solution to this problem is to consider model-based estimators that "borrow information" from related areas or past samples by using auxiliary information. This paper reviews, under the model-based approach, Best Linear Unbiased Predictors and an estimator based on the posterior predictive distribution of a Hierarchical Bayesian model. The goal of this paper is to analyze the possibility to produce accurate unemployment rate statistics at micro level from the Portuguese LFS using these kinds of stimators. This paper discusses the advantages of using each approach and the viability of its implementation.

Profiles of ageing in the South of Portugal: education and cognitive functioning in elderly persons living in institutionalized and community contexts

The region of the Algarve shows huge differences between the coastline where population in the urban areas grows, and the inland rural areas, in some cases very isolated, which frequently have high ageing indexes. This general scenario, with an elderly population with very different economic and social conditions, frames the ongoing PhD research designed as a cross-sectional study of an intentional sample of elderly persons. The basic theoretical framework departs from the perspective of developmental psychology of life-span and the model of selection, optimisation and compensation for optimal ageing (Baltes & Baltes, 1990; Freund & Baltes, 2002). The present study is a first step in the analysis of empirical data collected in the PhD sample (N=156; age range 65 to 97 years; M = 80.4 years; SD = 7.2 years). Its purpose is to assess the cognitive functioning of participants, screening for cognitive impairment and examine the relations between the cognitive status of the subjects and a number of selected variables including educational level, age, physical activity and living contexts of the subjects. We accessed the cognitive status of the participants with the Portuguese version of Mini Mental State Examination (MMSE) finding a 10.3% prevalence of positive cases with cognitive impairment. The results also show significant relationships between the cognitive status accessed by the MMSE and educational level, professional qualification, age, living arrangement and activity level of the participants. The relationship verified between educational level and cognitive status of the participants was the largest correlation found in the study with the variability in educational level accounting for 44.8% of the variability in MMSE score. This results points in the same direction of several lines of research that corroborate the strong intercorrelation between education and cognitive functioning in old age.

Water framework directive implementation: intercalibration exercise for biological quality elements: a case study for the south coast of Portugal

This work summarises the Intercalibration Exercise (IE) required for the Common Implementation Strategy of the Water Framework Directive (WFD; 2000/60/EC) that was carried out in Portugal, and applied to a coastal region. The WFD aims to achieve good ec ological status for all waters in the European Community by 2015. The Ecological Status of a water body is determined us ing a range of Hydromorphological and Physico-Chemical Quality Elements as well Biological Quality Elements (BQE ). In coastal waters, the Biological Elements include Phytoplankton, Other Aquatic Flora and Benthic Inverteb rate Fauna. Good cooperation with the other Member States allowed the IE to proceed without a complete da ta set, and Portugal was ab le to intercalibrate and harmonise methods within the North Ea st Atlantic Geographica l Intercalibration Group for most of the BQE. The appropriate metrics and corre sponding methods were agreed under the framework of the RECITAL (Reference Conditions and Intercalibra tion) project, funded by the Port uguese Water Institu te, INAG. Some preliminary sampling was undertaken, but not su fficient to establish the Reference Conditions. The study area was a coastal lagoon in the southern part of Portugal. The focus was on the Phytoplankton Quality Element, but other BQE were also taken into account. Two sampli ng stations in Ria Formosa coastal lagoon were considered in this exercise: Ramalhete a nd Ponte. The metrics adopted by the Intercalibration Exercise groups were applied enabli ng the classification for the two sta tions of Good/High Status for the majority of the BQE parameters.

Identification of descendants of an extinct bovine population from the Algarve region of Portugal using numerical taxonomy analysis of morphological traits

The morphology of a sample of four bulls and 43 cows, presumed to be descendants of the extinct cattle breed ‘Algarvia’ (AG), was used to assign their relationship with animals from other Portuguese autochthonous breeds – Arouquesa (AR), Barrosa˜ (BA), Cachena (CA), Marinhoa (MA), Maronesa (MO), Minhota (MN), Mirandesa (MI), (only bulls), Alentejana (AL), Garvonesa (GA), Mertolenga (ME) and Preta (PR). Standard numerical taxonomic methods were applied to a set of 183 (cows) and 170 (bulls) traits, to derive average pairwise taxonomic distances among the sample of 257 cows and 76 bulls. Distance coefficients (morphological index of distance) ranged from 0.22 to 2.62 (cows) and from 0.49 to 2.13 (bulls). Unweighted pair group method using arithmetic averages (UPGMA)-based phenograms and a principal coordinate analysis showed that bulls were highly clustered and cows showed a tendency to cluster according to their geographical and breed origin. The AG population grouped together with GA, AL, ME and MN breeds in the Red Convex group. The average taxonomic distance among breeds was 1.02, the highest being 1.39 (ME versus BA) and the lowest being 0.64 (MA versus AR). The approach allowed for the identification of a phenotypically differentiated set of animals, comprising 19 cows and four bulls representative of the AG breed, and which can be targeted in further studies aiming at the recovery of this extinct breed.

Decapod crustacean larvae dynamics in the west continental coast of Portugal: the region adjacent to Aveiro coastal lagoon as model

Tese de dout., Ciências do Mar, Faculdade de Ciências do Mar e do Ambiente, Univ. do Algarve, 2010