The Hedgehog (Hh) signaling pathway is essential for normal embryonic development, while its hyperactivation in the adult organism is associated with the development of various cancers. The role of the Hh signaling pathway in ovarian cancer has not been sufficiently investigated. Therefore, the present study investigated the role of protein patched homolog 1 (PTCH1), a component of the Hh signaling pathway, and changes in the promoter methylation status of the corresponding gene in a cohort of low-(LGSC) and high-grade serous ovarian carcinomas (HGSC) and HGSC cell lines (OVCAR8 and OVSAHO). PTCH1 protein expression level was analyzed using immunohistochemistry in tissue samples and immunofluorescence and western blotting in cell lines. DNA methylation patterns of the PTCH1 gene were analyzed using methylation-specific PCR. PTCH1 protein expression was significantly higher in HGSCs and LGSCs compared with controls (healthy ovaries and fallopian tubes). Similarly, ovarian cancer cell lines exhibited significantly higher PTCH1 protein expression compared with a normal fallopian tube non-ciliated epithelial cell line (FNE1). PTCH1 protein fragments of different molecular weights were detected in all cell lines, indicating possible proteolytic cleavage of this protein, resulting in the generation of soluble N-terminal fragments that are translocated to the nucleus. DNA methylation of the PTCH1 gene promoter was exclusively detected in a proportion of HGSC (13.5%) but did not correlate with protein expression. PTCH1 protein was highly expressed in serous ovarian carcinoma tissues and cell lines, while PTCH1 promoter methylation was only detected in HGSC. Further investigation is required to elucidate the possible mechanisms of PTCH1 activation in serous ovarian carcinomas.

Background The pandemic of Coronavirus infectious disease 2019 (COVID-19) poses a major public health challenge, and an effective vaccine is the potential mechanism to resolve this specific situation. The present study aimed to evaluate acceptance of COVID-19 vaccination among patients attending the Oncology Clinic of University Clinical Hospital Mostar. Material/Methods This cross-sectional observational study enrolled 364 patients with cancer from the Oncology Clinic of University Clinical Hospital Mostar during February 2021. Data were collected using a questionnaire that captured general information about the participants and their attitudes toward COVID-19 vaccination. Results Of the participants, 41.8% answered “Yes” when asked if they would take the vaccine once it becomes available, 37.6% answered “Not sure”, and 20.6% answered “No”. For patients in favor of vaccination, the main reasons reported were fear of getting sick (77.6%), the desire to contribute to herd immunity (57.8%), and trusting the recommendations of health professionals (57.2%). The main reasons for the patients’ vaccination refusal/indecision were doubts about the results from clinical trials of COVID-19 vaccines (49.1%), concerns about adverse effects (24.5%), and confusion about the various vaccine options (19.8%). The majority of participants (82.4%) stated that recommendation by their oncologist could influence their decision about vaccination. Of the participants who indicated unwillingness (refusal or indecision) to be vaccinated against COVID-19, 65.3% stated that recommendation by their oncologist could influence their decision about vaccination. Conclusions The findings from the present study showed most patients had refused or were indecisive regarding immunization with COVID-19 vaccine. Increasing physician awareness of this situation may result in higher rates of vaccination.

Summary This protocol describes a synthetic genomics pipeline to clone and engineer the entire 190-kbp genome of the African swine fever virus (ASFV) genotype II in yeast using transformation-associated recombination cloning. The viral genome was cloned using DNA directly extracted from a clinical sample. In addition, the precise deletion of a non-essential gene and its replacement by a synthetic reporter gene cassette are presented. This protocol is applicable to other ASFV genotypes and other large DNA viruses.

Azoheteroarenes are relatively new photoswitchable compounds, where one of the phenyl rings of an azobenzene molecule is replaced by a heteroaromatic five-membered ring. Recent findings on methylated azoheteroarenes show that these photoswitches have potential in various optically addressable applications. The thermal stability of molecular switches is one of the primary factors considered in the design process. For molecular memory or energy storage devices, long thermal relaxation times are required. However, inducing a short thermal isomerization lifetime is required to release stored energy or as an alternative to photoswitching to avoid overlapping absorption spectra that reduce switching fidelity. In this study, we investigate how oriented external electric fields can be used to tune the thermal isomerization properties of three unsubstituted heteroaryl azo compounds-azoimidazole, azopyrazole, and azopyrrole. We show that favorable electric field orientations can increase the thermal half-life of studied molecules by as much as 60 times or reduce it from tens of days to seconds, compared to their half-life values in the field-free environment. A deeper understanding of the relationship between structure and kinetic properties provides insight as to how molecular switches can be designed for their electric field response in switching applications.

Industrial systems have traditionally been kept isolated from external networks. However, business benefits are pushing for a convergence between the industrial systems and new information technology environments such as cloud computing, as well as higher level of connectivity between different systems. This makes cybersecurity a growing concern for industrial systems. In strengthening security, access control is a fundamental mechanisms for providing security in these systems. However, access control is relatively immature in traditional industrial systems, as compared to modern IT systems, and organizations' adherence to an established cybersecurity standard or guideline can be a deciding factor for choices of access control techniques used. This paper presents the results of a questionnaire study on the usage of access control within industrial system that are being developed, serviced or operated by Swedish organizations, contrasted to their usage of cybersecurity standards and guidelines. To be precise, the article focuses on two fundamental requirements of cybersecurity: identification and authentication control, and presents related findings based on a survey of the Swedish industry. The goal of the study is breaching the gap between the current state and the requirements of emerging systems with regards to access control.

DevOps represent the tight connection between development and operations. To address challenges that arise on the borderline between development and operations, we conducted a study in collaboration with a Swedish company responsible for ticket management and sales in public transportation. The aim of our study was to explore and describe the existing DevOps environment, as well as to identify how the feedback from operations can be improved, specifically with respect to the alerts sent from system operations. Our study complies with the basic principles of the design science paradigm, such as understanding and improving design solutions in the specific areas of practice. Our diagnosis, based on qualitative data collected through interviews and observations, shows that alert flooding is a challenge in the feedback loop, i.e. too much signals from operations create noise in the feedback loop. Therefore, we design a solution to improve the alert management by optimizing when to raise alerts and accordingly introducing a new element in the feedback loop, a smart filter. Moreover, we implemented a prototype of the proposed solution design and showed that a tighter relation between operations and development can be achieved, using a hybrid method which combines rule-based and unsupervised machine learning for operations data analysis.

The fourth industrial revolution (Industry 4.0) anticipates unplanned changes of production processes. Production changes may trigger synthesis, and preferably optimization, of architecture-level decisions, such as service deployment and composition. Performing such architecture-level decisions manually is difficult due to the ever-rising complexity of Industry 4.0 systems. In order to (semi-)automate the architecture synthesis and optimization, we propose an approach of service deployment and composition by using existing domain models. Our contribution is threefold: (1) We suggest a workflow with domain models for architecture synthesis in the industrial automation. (2) We display the formalization on a part of the workflow and provide an initial prototype of service deployment synthesis using a satisfiability modulo theories (SMT) solver. (3) We envision a way of service composition and code generation, and prototypically implemented it as conclusion of the suggested workflow. We demonstrate the practical use of the proposed approach in the Industry 4.0 scenario, i.e., flexible production of new products.

An asset administration shell (AAS), as a key concept of Industry 4.0 (I4.0), provides a machine-accessible interface to any kind of asset. To enable interoperability and smooth integration of the devices into the I4.0 middleware, an application implementing the device's functionality should be able to interact with different AASs. In this work, we investigate the integration of the Programmable Logic Controller (PLC) runtime systems into the I4.0 middleware. For doing this, we specify the function blocks (FBs) for connecting the PLCs with AASs and other I4.0 components, such as registry and discovery server. We analyze the requirements of such FBs while focusing on REST/HTTP- and OPC UA-based AASs, and provide interface specification for IEC 61499- and IEC 61131-3-based FBs. Furthermore, we implemented an FB library that enables communication with an AAS from the respective control applications. Those FBs allow accessing properties and invoking operations of remote AASs, as well as hosting AASs submodels. Common functionalities, such as registering the runtime system at the registry component, or finding AASs, are also supported. The results obtained in this paper will ease interaction with the complex AAS structure from the low-level devices.

Engineering distributed control systems is a complex task, where the complexity and, thus, costs of the software development are growing rapidly. To keep the software complexity at an acceptable level and save time for development and subsequent maintenance, new solutions are sorely needed. In this paper, we investigate the advantages of using skills - universal control device interfaces - for generating complex logic in distributed control environments. By enriching a skill interface with the information about the dynamic behavior of a component under control, we compose the functionalities of individual control devices. The logic, required for such composition, is automatically derived from the interface description and the production plan, identifying the required skill sequence. The evaluation, executed using two industrial demonstrators, shows that the approach successfully handles different behavioral models and is capable of generating fault-tolerant orchestrators, including error handling scenarios. Overall, for developing a complex logic in a distributed skill-based automation system, the proposed approach shows significant savings in development time allowing to automate the skill composition task.