A software modelling exercise using FCA

This paper describes an exercise in object-oriented modelling where Formal Concept Analysis is applied to a formal specification case study using Object-Z. In particular, the informal description from the case study is treated as a set of use-cases from which candidate classes and objects are derived. The resulting class structure is contrasted with the existing Object-Z design and the two approaches are discussed

Exploring model-based development for the verification of real-time Java code

Many safety- and security-critical systems are real-time systems and, as a result, tools and techniques for verifying real-time systems are extremely important. Simulation and testing such systems can be exceedingly time-consuming and these techniques provide only probabilistic measures of correctness. There are a number of model-checking tools for real-time systems. However, they provide formal verification for models, not programs. To increase the confidence in real-time programs written in real-time Java, this paper takes a modelling approach to the design of such programs. First, models can be mechanically verified, to check whether they satisfy particular properties, by using current real-time model-checking tools. Then, programs are derived from the model by following a systematic approach. To illustrate the approach we use a nontrivial example: a gear controller

Portfolio Vol. IV N 3

Benson, Virginia. Rejected. Prose. 3. Phillips, Alison. Lure in April. Poetry. 6. Shields, Margaret. Wedding Morning. Prose. 7. Willett, Thelma. Ex Libris: G.K.W. Poetry. 8. Benson, Virginia. High Note. Poetry. 8. Maxwell, Bob. Discovery. Poetry. 8. Eschman, Karl. The Case for Modern Music. Prose. 8-9. Wyman, John. Dissonance. Prose. 10-11. Hart, Dorothy. The Origin of Memorial Day. Prose. 12. Reed, Roger. Notes on the Drama. Prose. 13. Parker, Mab. Black Girl. Picture. 14. Mather, William. The Pasquin. Prose. 15. Hammer, John. Over the Green Grass. Prose. 16. Maxwell, Bob. Genesis... Poetry. 19. Maxwell, Bob. We Three. Poetry. 19. Stransky, Ed. Concerning The Well-Known \u27Butch.\u27 Prose. 20. Seagrave, Leslie. Memory. Prose. 21

CAPACIDADE AERÓBIA DE JOGADORES DE GOALBALL: ESTUDO DE CASO DE UMA EQUIPE DO SUL DO PAÍS

Goalball is a specific sport for people with visual impairments. The game requires high levels of tactile, auditory and spatial awareness and it demands intermittent high intensity efforts supported predominantly by aerobic metabolism. Thus, the aim of this research report was to analyze the aerobic capacity of the goalball athletes of south country team, after a period of stoppage (vacation). For this purpose, three goalball players, aged between 27 and 49 years old, and practice time of 9 ± 6 years participated in the study. The test used for the evaluation was the modified Beep that has been validated to measure the aerobic capacity of athletes with visual impairment. The data were treated using descriptive statistics. The VO2max estimate was calculated using the modified beep test validation regression equation. As a result, the players presented VO2max of 33.1 ± 9.5 ml/Kg.min. When analyzing individually, only one of the players has aerobic capacity similar to that of elite athletes from male teams in the country. It is concluded that the aerobic capacity of these players needs to be better developed to accord the demands required in the game that can assist in a better performance. Received on: 2021/06/30 Reformulated on: 2021/01/14 Accepted: 2021/01/15O goalball é uma modalidade específica para pessoas com deficiência visual. O jogo exige elevados níveis de consciência tátil, auditiva e espacial e demanda esforços intermitentes de alta intensidade suportado predominantemente pelo metabolismo– aeróbio. Assim, o objetivo deste relato de pesquisa foi analisar a capacidade aeróbia dos atletas de goalball de uma equipe do sul do país no inicio da temporada, após período de paralisação (férias). Para tanto, participaram do estudo três jogadores de goalball com idade entre 27 e 49 anos e tempo médio de prática de 9 ± 6 anos.  O teste utilizado para a avaliação foi o Beep modificado validado para mensurar a capacidade aeróbia de atletas com deficiência visual. Os dados foram tratados por meio de estatística descritiva, sendo o cálculo da estimativa do VO2máx realizado a partir da equação de regressão de validação do teste beep modificado. Como resultado, os jogadores apresentaram valores médios de VO2máx de 33,1 ± 9,5 ml/Kg.min. Ao analisar de maneira individual, apenas um dos jogadores apresenta capacidade aeróbia semelhante à de atletas de elite de equipes masculinas do país. Conclui-se que a capacidade aeróbia desses jogadores precisa ser melhor desenvolvida para que estes atendam às demandas exigidas no jogo auxiliando em um melhor desempenho. Recebido em: 30/06/2020 Reformulado em: 14/01/2021 Aceito em: 15/01/202

Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus

Onchocerciasis, commonly known as river blindness, is caused by the filarial nematode Onchocerca volvulus and is transmitted by a blackfly vector. Over 37 million people are thought to be infected, with over 90 million at risk. Infection predominantly occurs in sub-Saharan Africa. Foci also exist in the Arabian Peninsula and Central and South America. Ivermectin, the sole pharmaceutical available for mass chemotherapy, has been used on a community basis for annual or semi-annual treatment since 1987. Multiple treatments with ivermectin kill the microfilariae that are responsible for the pathology of onchocerciasis. More importantly, ivermectin suppresses the reproductive activity of the adult female worms, thus delaying or preventing the repopulation of the skin with new microfilariae and thereby reducing transmission. This study extends earlier reports of sub-optimal responses to ivermectin by examining repopulation levels of microfilaria one year after treatment, worm burdens per nodule, the age structure of adult female worms recovered from nodules, and the reproductive status of adult female worms 90 days after ivermectin treatment. In some communities which have shown a pattern of sub-optimal response to treatment, the data is consistent with an emergence of ivermectin non response or resistance manifested by a loss of the effect of ivermectin on the suppression of parasite reproduction

Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

Onchocerca volvulus is the causative agent of onchocerciasis, or “river blindness”. Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug and evidence of drug resistance. Drug resistance has a genetic basis. In this study, genetic changes in β-tubulin, a gene associated with ivermectin resistance in nematodes, were seen in parasites obtained from the patients exposed to repeated ivermectin treatment compared with parasites obtained from the same patients before any exposure to ivermectin. Furthermore, the extent of the genetic changes was dependent on the level of ivermectin treatment exposure. This genetic selection was associated with a lower reproductive rate in the female parasites. The data indicates that this genetic selection is for a population of O. volvulus that is more tolerant to ivermectin. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes. Monitoring for the possible development and spread of ivermectin resistance, as part of the control programmes, should be implemented so that any foci of resistant parasites can be treated by alternative control measures

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.publishedVersio

Two Multiâ Center Studies Evaluating Locally Delivered Doxycycline Hyclate, Placebo Control, Oral Hygiene, and Scaling and Root Planing in the Treatment of Periodontitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142011/1/jper0490.pd

Agricultural Research Service Weed Science Research: Past, Present, and Future

The U.S. Department of Agriculture-Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed-crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America\u27s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency\u27s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being