Insights into angiogenesis in non-small cell lung cancer : molecular mechanisms, polymorphic genes, and targeted therapies

We would like to thank Dr. Miguel Nunes from Department of Informatic of Faculty of Medicine of the University of Porto, Porto, Portugal, for his help in technical support, and Prof. Henrique Queiroga, Department of Pneumology of Faculty of Medicine of the University of Porto, Porto, Portugal, for his critical contribution in this manuscript reviewLung cancer is a highly prevalent disease worldwide. Currently, there are more than 150 million patients with lung cancer in the world, with more than 1 million new cases diagnosed per year. Tumoral angiogenesis is an important hallmark of this disease, but despite being extensively studied, the complete angiogenic mechanisms are not fully elucidated. Recent studies have reported a correlation between pharmacological inhibition of these angiogenic mechanisms and improvement of overall survival in lung cancer patients, mainly for those in advanced stages. The family of vascular endothelial growth factor (VEGF) proteins has critical roles in tumoral angiogenesis. An interaction between VEGF-A and VEGF receptor 2 (VEGFR-2) is the main pathway of activation and maintenance of angiogenesis. In tumors, this process is intimately correlative with progression and metastasis. Some studies suggested that serum levels of VEGF are higher in patients with lung cancer, especially in some types of non-small cell lung cancer (NSCLC). Other studies revealed that genetic polymorphisms of VEGF correlate with susceptibility, prognosis, and therapeutic response of some patients with NSCLC. This paper aims to review the impact of angiogenesis, especially on VEGF pathways, in NSCLC, and highlights the relevance of known and new patents disclosed of anti-angiogenic therapies in these patients

A Novel Multi-Criteria Local Latin Hypercube Refinement System for Commutation Angle Improvement in IPMSMs

The commutation angle, γ, of an interior permanent magnet synchronous motor's (IPMSM) vector diagram, plays an important role in compensating the back electromotive force (back-EMF); both under phase current variations and an extended speed range, is required by the application. This commutation angle is defined as the angle between the fundamental of the motor phase current and the fundamental of the back-EMF. It can be utilised to provide a compensating effect in IPMSMs. This is due to the reluctance torque component being dependent on the commutation angle of the phase current even before entering the extended speed range. A real-time maximum torque per current and voltage strategy is demonstrated to find the trajectory and optimum commutation angles, γ, where the level of accuracy depends on the application and available computational speed. A magnet volume reduction using a novel multi-criteria local Latin hypercube refinement (MLHR) sampling system is also presented to improve the optimisation process. The proposed new technique minimises the magnet mass to motor torque density whilst maintaining a similar phase current level. A mapping of γ allows the determination of the optimum angles, as shown in this paper. The 3rd generation Toyota Prius IPMSM is considered as the reference motor, where the rotor configuration is altered to allow for an individual assessment.</p

Do ativismo no STF ao ativismo do TCU: é possível falar em ativismo legislativo no Brasil? / From activism in the STF to activism in TCU: is it possible to speak in legislative activism in Brazil?

O presente estudo procurou observar o ativismo judicial por parte do poder legislativo, em especial, por meio de algumas decisões do TCU. A hipótese levantada seria de que ao se permitir o ativismo por parte do judiciário, abrir-se-ia um precedente para que o mesmo pudesse ser realizado pelos demais poderes. Para tanto, o estudo inicia com as origens do que seja ativismo judicial, sua relação com o neo-consitucionalismo e os principais estudos publicados. São apontados, ainda, os principais autores  e argumentos favoráveis e contra o ativismo, dentre os quais se destacam aqueles que, empiricamente, demostram que a administração pública está mais bem preparada para conferir concretude aos direitos programáticos em relação ao judiciário, colocando-se sob questionamento os fundamentos daqueles autores que visualizam no judiciário o papel de protagonista na garantia de direitos programáticos aos menos favorecidos. O Caso da súmula 222 do TCU e da decisão 663/TCU confirmaram a hipótese de que o ativismo deixou de ser, unilateralmente, realizado pelo judiciário e passou a permear os demais poderes, em prejuízo, contudo, do pacto federativo e da separação dos poderes, conforme já alertava a doutrina

Oral bacterial microbiota and traumatic injuries of free-ranging Phrynops geoffroanus (Testudines, Chelidae) in southeastern Brazil

During 2006 and 2007, we collected free-ranging Phrynops geoffroanus, from two anthropogenically altered rivers in southeastern Brazil. Oral microbiological samples were taken for isolation of aerobic and facultative anaerobic bacteria; a physical examination was performed;and we evaluated possible effects on the turtles’ health. Twenty-nine species of bacteria were isolated in Piracicaba River turtles (n=10), and twenty-four species in Piracicamirim stream turtles (n=8), most of them gram-negative. In both sites, potential pathogens for reptiles were: Escherichia coli, Klebsiella pneumoniae, Enterobacter agglomerans, Citrobacter freundii, and Bacillus sp. Although boatpropeller lesions were common on the carapace of the turtles, we have not found turtles with signs of clinical diseases. The oral bacterial microbiota of P. geoffroanus inhabiting the Piracicaba River basin are composed of a diverse microbe spectrum, and long-term studies of the effects of pollution and traumatic injuries on this population and its microbial flora are warranted

A semiautomated microfluidic platform for real-time investigation of nanoparticles' cellular uptake and cancer cells' tracking

Aims: develop a platform composed of labeled dendrimer nanoparticles and a microfluidic device for real-time monitoring of cancer cells fate. Materials and Methods: The physicochemical and biological characterization of the developed Carboxymethyl-chitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles were performed using TEM, AFM, Zeta Sizer, DSC and cytotoxicity screening. Cancer cell lines derived from different tumor types, including HeLa (Cervical Carcinoma), HCT-116 (Colon Carcinoma) and U87MG (Glioblastoma), were exposed to different concentrations of CMCht/PAMAM dendrimer nanoparticles over a period of 3 days (MTS/DNA). Results: Nanoparticles were successfully modified with an average size of 50 nm. Internalization levels go from 87% to 100% in static and from 95% to 100% in dynamic conditions. Viability levels range from 95% to 100% in static and from 90% to 100% in dynamic conditions, being HCT the most sensitive to the presence of the NP. Conclusions: the results show different responses to the presence of 0.5 mg.mL-1 dendrimer nanoparticles when comparing static to dynamic conditions, with a tendency towards higher sensitivity when subjected to confinement. This work demonstrated that the proposed microfluidic-based platform allows real-time cell monitoring, which, upon more studies, namely the assessment of the drug release effect, could be used for cancer theranostics.FR Maia acknowledges ERC-2012-ADG 20120216–321266 (ComplexiTE) for her Postdoc scholarship. JM Oliveira thanks Portuguese Foundation for Science and Technology (FCT) for his distinction attributed under the FCT Investigator program (IF/00423/2012). BM Costa also thanks Portuguese Foundation for Science and Technology (PTDC/SAU-GMG/113795/2009 and IF/00601/2012 to BM Costa), Fundação Calouste Gulbenkian (BM Costa) and Liga Portuguesa Contra o Cancro (BM Costa). MR Carvalho also thanks the funding through the LA ICVS/3Bs project (UID/Multi/50026/2013). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.info:eu-repo/semantics/publishedVersio

Microbiota bacteriana oral e lesões traumáticas no cágado Phrynops geoffroanus (Testudines, Chelidae) no sudeste do Brasil

Entre 2006 e 2007, coletamos amostras microbiológicas da cavidade oral de cágados Phrynops geoffroanus de vida livre, em dois rios antropizados da região sudeste do Brasil, para o isolamento de bactérias aeróbicas e anaeróbicas facultativas, e realizamos um exame físico e avaliamos possíveis efeitos sobre o estado de saúde dos animais. Vinte e nove espécies de bactérias foram isoladas em cágados do rio Piracicaba (n=10), e vinte e quatro espécies em animais do ribeirão Piracicamirim (n=8), a maioria delas gram-negativas. Em ambos os sítios estudados foram isolados patógenos potenciais para répteis, como Escherichia coli, Klebsiella pneumoniae, Enterobacter agglomerans, Citrobacter freundii e Bacillus sp. Embora lesões na carapaça dos cágados, causadas por hélices de barcos, foram um achado comum no exame físico, não encontramos animais com sinais clínicos de doenças. A microbiota bacteriana oral dos cágados que habitam a bacia do rio Piracicaba é composta por um amplo espectro de bactérias, e estudos de longa duração sobre os efeitos da poluição e de lesões traumáticas nesta população e de sua microbiota oral são recomendados.During 2006 and 2007, we collected free-ranging Phrynops geoffroanus, from two anthropogenically altered rivers in southeastern Brazil. Oral microbiological samples were taken for isolation of aerobic and facultative anaerobic bacteria; a physical examination was performed; and we evaluated possible effects on the turtles' health. Twenty-nine species of bacteria were isolated in Piracicaba River turtles (n=10), and twenty-four species in Piracicamirim stream turtles (n=8), most of them gram-negative. In both sites, potential pathogens for reptiles were: Escherichia coli, Klebsiella pneumoniae, Enterobacter agglomerans, Citrobacter freundii, and Bacillus sp. Although boat propeller lesions were common on the carapace of the turtles, we have not found turtles with signs of clinical diseases. The oral bacterial microbiota of P. geoffroanus inhabiting the Piracicaba River basin are composed of a diverse microbe spectrum, and long-term studies of the effects of pollution and traumatic injuries on this population and its microbial flora are warranted

Emotional responses to motion sickness in autonomous driving

In future autonomous cars, users, free from the primary task of driving, will have time and space to engage in other activities while traveling, such as reading a book, working on a laptop or watching a movie. Although the option for these activities are one of the great advantages of autonomous cars, this will also likely increase motion sickness (MS) inside the car. MS affects numerous individuals, and it occurs when the information received through the eyes differs from what is perceived by the body and the inner ear. Plus, MS can have an impact on the emotional component of the individuals experiencing it, making the experience of traveling in autonomous cars uncomfortable and difficult. Emotional design studies focus on the emotional response of individuals to a product or service. These studies typically employ self-report scales as assessment tools, such as SAM (Self-Assessment Manikin) and PrEmo (Product Emotion Measurement instrument). We present the first study measuring emotional responses to MS using both SAM and PrEmo scales. In our study, we induced MS by asking participants to watch a highly dynamic video of a first-person car trip. We also asked subjects to answer to SAM and PrEmo before and after the visualization of the video. Our results showed a change in the answers in time, that is, before vs. after the experience of MS. MS significantly altered individuals' emotional responses, worsening their condition. These results support the need for studies that reduce MS to improve the experience and well-being of individuals in autonomous cars.Landscape, Heritage and Territory Laboratory (Lab2PT), Ref. UID/04509/2020, financed by national funds (PIDDAC) through the FCT/MCTES and the European Structural and Investment Funds in the FEDER component, through the Operational Competitiveness and Internationalization Programme (COMPETE 2020) [Project n° 039334; Funding Reference: POCI- 01-0247-FEDER-039334]

Integrated Vitrinite Reflectance and Apatite Fission Track Thermocronology of the Lower Karoo rocks in the Moatize Basin, Tete Province, Mozambique

The Karoo in Mozambique is represented by Late Carboniferous to Late Triassic sediments that were deposited in rift basins that fringe or developed between Proterozoic cratons

Cell division protein FtsK coordinates bacterial chromosome segregation and daughter cell separation in Staphylococcus aureus

Funding Information: We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); FCT through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com . Funding Information: We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC-2017-CoG-771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA-MIC/6982/2020 (to HV); PTDC/BIA-PLA/3432/2012 (to SRF); FCT through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673-2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com. Publisher Copyright: © 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.Unregulated cell cycle progression may have lethal consequences and therefore, bacteria have various mechanisms in place for the precise spatiotemporal control of cell cycle events. We have uncovered a new link between chromosome replication/segregation and splitting of the division septum. We show that the DNA translocase domain-containing divisome protein FtsK regulates cellular levels of a peptidoglycan hydrolase Sle1, which is involved in cell separation in the bacterial pathogen Staphylococcus aureus. FtsK interacts with a chaperone (trigger factor, TF) and establishes a FtsK-dependent TF concentration gradient that is higher in the septal region. Trigger factor binds Sle1 and promotes its preferential export at the septal region, while also preventing Sle1 degradation by the ClpXP proteolytic machinery. Upon conditions that lead to paused septum synthesis, such as DNA damage or impaired DNA replication/segregation, TF gradient is dissipated and Sle1 levels are reduced, thus halting premature septum splitting.publishersversionpublishe

Impact of cardiology referral: clinical outcomes and factors associated with physicians' adherence to recommendations

OBJECTIVES: Cardiology referral is common for patients admitted for non-cardiac diseases. Recommendations from cardiologists may involve complex and aggressive treatments that could be ignored or denied by other physicians. The purpose of this study was to compare the outcomes of patients who were given recommendations during cardiology referrals and to examine the clinical outcomes of patients who did not follow the recommendations. METHODS: We enrolled 589 consecutive patients who received in-hospital cardiology consultations. Data on recommendations, implementation of suggestions and outcomes were collected. RESULTS: Regarding adherence of the referring service to the recommendations, 77% of patients were classified in the adherence group and 23% were classified in the non-adherence group. Membership in the non-adherence group (