Road Pavement Damage Detection using Computer Vision Techniques: Approaches, Challenges and Opportunities

The work presented in this paper is the result of a preliminary research aimed at using computer vision techniques for road pavement damage detection in the context of a smart city. It first introduces the related concepts. Then, it surveys the state of the art and existing solutions, presenting their main features, strengths and limitations. The most promising solutions are identified. Finally, it discusses open challenges and research directions in this area

2,4,5-Triaminopyrimidines as blue fluorescent probes for cell viability monitoring: synthesis, photophysical properties, and microscopy applications

Monitoring cell viability is critical in cell biology, pathology, and drug discovery. Most cell viability assays are cell-destructive, time-consuming, expensive, and/or hazardous. Herein, we present a series of newly synthesized 2,4,5-triaminopyrimidine derivatives able to discriminate between live and dead cells. To our knowledge, these compounds are the first fluorescent nucleobase analogues (FNAs) with cell viability monitoring potential. These new fluorescent molecules are synthesized using highly efficient and cost- effective methods and feature unprecedented photophysical properties (longer absorption and emission wavelengths, environment-sensitive emission, and unprecedented brightness within FNAs). Using a live– dead Saccharomyces cerevisiae cell and theoretical assays, the fluorescent 2,4,5-triaminopyrimidine derivatives were found to specifically accumulate inside dead cells by interacting with dsDNA grooves, thus paving the way for the emergence of novel and safe fluorescent cell viability markers emitting in the blue region. As the majority of commercially available viability dyes emit in the green to red region of the visible spectrum, these novel markers might be useful to meet the needs of blue markers for co-staining combinations

THE AMBIGUITY IN FOREST PROFILES AND XTINCTION ESTIMATED FROM MULTIBASELINE INTERFEROMETRIC SAR

This paper demonstrates by simulation that in the estimation of vegetation profiles from multibaseline interferometric synthetic aperture radar (InSAR), the peak extinction coefficient is poorly determined for typical interferometric coherence and phase accuracies. This coefficient determines overall density and affects the relative density profiles estimated from interferometry. This paper shows that a given radar power profile gives rise to a family of vegetation density profiles, depending on the peak extinction assumed. It is further  demonstrated that estimating the peak extinction requires coherence accuracies of better than 0.1% and phase accuracies of better than a few tenths of a degree, both of which exceed the performance of typical or envisioned SAR systems. Two recommended approaches to profile production with InSAR are 1) use the radar power profile instead of the vegetation density profile for biomass estimation and other ecosystem characterization (in analogy to LIDAR power which is most frequently used for lidar studies of biomass) or 2) apply external information to establish the extinction characteristics needed for vegetation density profiles.Esse artigo procura demonstrar, por simulação, que na estimativa de perfis de volume da vegetação por interferometria  com múltiplas linhas de base, o pico de extinção não é adequadamente determinado pela coerência interferométrica e fase, com acurácias típicas de InSAR. Esse pico determina a densidade global, afetando os perfis de densidade relativa da vegetação estimados por interferometria. Esse trabalho mostra que para um dado perfil de potência-radar há uma série de perfis de densidade da vegetação, dependendo do pico de extinção assumido. É ainda demonstrado que a estimativa do pico de  extinção requer exatidões de coerência melhores que 0,1%, bem como, de acurácias de fases que alguns décimos de graus, valores esses que atualmente excedem o desempenho de sistemas SAR em operação ou aqueles previstos. As duas abordagens recomendadas para a produção de perfis com InSAR são: (1) utilizar o perfil-radar, ao invés do perfil de densidade de vegetação, para estimação de biomassa e outras caracterizações de ecossistema (em nalogia à potência-lidar, a qual é mais  frequentemente utilizada nos estudos de biomassa baseados em LIDAR); ou (2) aplicar informação externa para estabelecer as características de extinção necessárias aos perfis de densidade de vegetação

CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function

Various kinases, including a cyclin-dependent kinase (CDK) family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL) proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs), including an unusual ?J helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1-4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and ?J helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy

Climatic Aptitude Evaluation for Grapevine Cultivation in Pão de Açúcar, Alagoas

The grapes production in Brazil is comprised in southeastern and southern regions and also in the semi-arid Pernambuco. Environmental, climatic and even human factors influence on quality of grape production, which are sensitive to weather changes. In Alagoas State, a pilot project was carried out for Municipalities of Rio Largo, Pão de Açúcar and Delmiro Gouveia between 2013 to 2015 years; but the results were incipient. This work evaluated the climatic aptitude for grapevine cultivation for municipality of Pão de Açúcar. For climate characterization, three indices of the Geoviticure Multicriteria Climatic Classification System (MCC) were adopted: Heliothermic (HI), Cold Night (CI) and Dryness (DI), considering different cycles during the year. The Zuluaga Index (IZ) was also used to evaluate the risk of incidence of fungal diseases of the vine, especially in relation at mildew incidence (Plasmoparaviticola), a major disease in humid regions. According on CI, DI and ZI indices, the municipality of Pão de Açúcar presented climatic aptitude for vines production with highest quality potential between August to January months, classified as preferential for all indexes analyzed

Rabbit derived VL single-domains as promising scaffolds to generate antibody–drug conjugates

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.This work was supported by the Portuguese Funding Agency, Fundação para a Ciência e Tecnologia, FCT IP (SAICT/2017/32085, PTDC/QUI-OUT/3989/2021 and Ph.D. fellowship SFRH/BD/131468/2017 to ASA and SFRH/BD/90514/2012 to JD). CIISA has provided support through Project UIDB/00276/2020, funded by FCT and LA/P/0059/2020-AL4AnimalS. Research Institute for Medicines (iMed.ULisboa) acknowledges the financial support of Fundação para a Ciência e Tecnologia (Projects: PTDC/QUI-OUT/3989/2021; UIDB/04138/2020 and UIDP/04138/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).info:eu-repo/semantics/publishedVersio

Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination

<p>Abstract</p> <p>Background</p> <p>The need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td). This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster.</p> <p>Methods</p> <p>Following the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG) and antidiphtheria toxin IgG (ADT IgG) levels were measured (mIU/ml) in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants.</p> <p>Results</p> <p>Twenty-two women (Group A) began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022) and decreased with time since last vaccination (p = 0.016). Among the 66 women who began vaccination in adolescence and adulthood (Group B), with monovalent TT, ATT IgG levels decreased with age at first dose (p < 0.001) and with time since last vaccination (p = 0.041). In Group A, antidiphtheria toxin IgG kinetics was very similar to that observed for ATT IgG. Among women not vaccinated with diphtheria toxoid, ADT IgG levels decreased with age. Serological response to both components of Td was good but more pronounced for ATT IgG.</p> <p>Conclusion</p> <p>Our study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid). The adult booster intervals could be wider, probably of 20 years. This also seems to apply to protection against diphtheria, but issues on the herd immunity and on the circulation of toxigenic strains need to be better understood.</p

Estudo de seguimento por dois anos de idosos residentes em São Paulo, Brasil: metodologia e resultados preliminares

INTRODUCTION: Previous cross-sectional studies have shown a high prevalence of chronic disease and disability among the elderly. Given Brazil s rapid aging process and the obvious consequences of the growing number of old people with chronic diseases and associated disabilities for the provision of health services, a need was felt for a study that would overcome the limitations of cross-sectional data and shed some light on the main factors determining whether a person will live longer and free of disabling diseases, the so-called successful aging. The methodology of the first follow-up study of elderly residents in Brazil is presented. METHOD: The profile of the initial cohort is compared with previous cross-sectional data and an in-depth analysis of nonresponse is carried out in order to assess the validity of future longitudinal analysis. The EPIDOSO ( Epidemiologia do Idoso ) Study conducted a two-year follow-up of 1,667 elderly people (65+), living in S. Paulo. The study consisted of two waves, each consisting of household, clinical, and biochemical surveys. RESULTS AND CONCLUSIONS: In general, the initial cohort showed a similar profile to previous cross-sectional samples in S. Paulo. There was a majority of women, mostly widows, living in multigenerational households, and a high prevalence of chronic illnesses, psychiatric disturbances, and physical disabilities. Despite all the difficulties inherent in follow-up studies, there was a fairly low rate of nonresponse to the household survey after two years, which did not actually affect the representation of the cohort at the final household assessment, making unbiased longitudinal analysis possible. Concerning the clinical and blood sampling surveys, the respondents tended to be younger and less disabled than the nonrespondents, limiting the use of the clinical and laboratory data to longitudinal analysis aimed at a healthier cohort. It is worth mentioning that gender, education, family support, and socioeconomic status were not important determinants of nonresponse, as is often the case.INTRODUÇÃO: Estudos transversais recentes mostraram alta prevalência de doenças crônicas e incapacidades físicas entre idosos. Considerando o rápido processo de envelhecimento do Brasil e as conseqüências que esse aumento de idosos com doenças crônicas e incapacidades associadas acarretará para o sistema de saúde, fazia-se necessário estudo que pudesse superar as limitações dos dados transversais, permitindo determinar quais os fatores determinantes de uma vida longa e livre de doenças incapacitantes, o chamado envelhecimento bem sucedido. É apresentada a metodologia do primeiro estudo epidemiológico longitudinal com idosos residentes na comunidade, no Brasil. MÉTODO: O perfil do cohorte inicial é comparado com dados de estudos anteriores a com o perfil dos não respondentes para avaliar a validade de análises longitudinais futuras.O projeto EPIDOSO (Epidemiologia do Idoso) seguiu por dois anos 1.667 idosos (65+), residentes em São Paulo. Consistiu de duas ondas, cada qual com três inquéritos: domiciliar, clínico e laboratorial. RESULTADOS E CONCLUSÕES: O perfil da população não diferiu de estudos anteriores, mostrando maioria de mulheres, viúvas, vivendo em domicílios multigeracionais, com uma alta prevalência de doenças crônicas, distúrbios psiquiátricos e incapacidades físicas. A despeito de todas as dificuldades inerentes a um estudo longitudinal, o grupo de não-respondentes ao segundo inquérito domiciliar não diferiu significativamente dos respondentes, assegurando análises longitudinais livres desse tipo de viés. Em relação aos inquéritos clínico e laboratorial, os não-respondentes mostraram-se mais velhos e mais incapacitados que os respondentes, limitando o uso dos dados clínicos e laboratoriais a análises pertinentes a uma cohorte mais jovem e saudável. Sexo, educação, apoio familiar e nível socioeconômico não influenciaram de forma significativa a taxa de não - resposta, ao contrário do que se costuma verificar.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Effect of the carbon nanotube surface characteristics on the conductivity and dielectric constant of carbon nanotube/poly(vinylidene fluoride) composites

Commercial multi-walled carbon nanotubes (CNT) were functionalized by oxidation with HNO3, to introduce oxygen-containing surface groups, and by thermal treatments at different temperatures for their selective removal. The obtained samples were characterized by adsorption of N2 at -196°C, temperature-programmed desorption and determination of pH at the point of zero charge. CNT/poly(vinylidene fluoride) composites were prepared using the above CNT samples, with different filler fractions up to 1 wt%. It was found that oxidation reduced composite conductivity for a given concentration, shifted the percolation threshold to higher concentrations, and had no significant effect in the dielectric response

The Enhanced Efficacy of Intracellular Delivery of Doxorubicin/C6-Ceramide Combination Mediated by the F3 Peptide/Nucleolin System Is Supported by the Downregulation of the PI3K/Akt Pathway

Targeting multiple cellular populations is of high therapeutic relevance for the tackling of solid tumors heterogeneity. Herein, the ability of pegylated and pH-sensitive liposomes, functionalized with the nucleolin-binding F3 peptide and containing doxorubicin (DXR)/C6-ceramide synergistic combination, to target, in vitro, ovarian cancer, including ovarian cancer stem cells (CSC), was assessed. The underlying molecular mechanism of action of the nucleolin-mediated intracellular delivery of C6-ceramide to cancer cells was also explored. The assessment of overexpression of surface nucleolin expression by flow cytometry was critical to dissipate differences identified by Western blot in membrane/cytoplasm of SKOV-3, OVCAR-3 and TOV-112D ovarian cancer cell lines. The former was in line with the significant extent of uptake into (bulk) ovarian cancer cells, relative to non-targeted and non-specific counterparts. This pattern of uptake was recapitulated with putative CSC-enriched ovarian SKOV-3 and OVCAR-3 sub-population (EpCAMhigh/CD44high). Co-encapsulation of DXR:C6-ceramide into F3 peptide-targeted liposomes improved cytotoxic activity relative to liposomes containing DXR alone, in an extent that depended on the intrinsic resistance to DXR and on the incubation time. The enhanced cytotoxicity of the targeted combination was mechanistically supported by the downregulation of PI3K/Akt pathway by C6-ceramide, only among the nucleolin-overexpressing cancer cells presenting a basal p-Akt/total Akt ratio lower than 1