RESUMO
Hepatocellular carcinoma is one of the top causes of cancer-related death globally. SIRT3 belongs to the Sirtuin family of proteins, a collection of NAD+-dependent enzymes that play a role in controlling several cellular functions, including metabolism, aging, and stress response. SIRT3 expression has been discovered to be often downregulated in HCC tissues relative to normal liver tissues. Hence, SIRT3 may function as a tumor suppressor in HCC. In the present study, pharmacophore-based virtual screening of a small molecule database was performed initially, and then the screened hits were docked to the active site of SIRT3 to choose the best binding modes. One co-crystal ligand (PDB name: 1NQ) was utilized as a template to generate pharmacophore model query. A total of 0.2 million compounds from the VITAS-M Lab database were downloaded and prepared for virtual screening. Following database preparation, ligand-based virtual screening was performed using the pharmacophore query model generated in the previous phase. The compounds with the same pharmacophoric characteristics as the query at the same distance were screened. There were a total of 74 hits that matched the query model. These compounds were then docked to the SIRT3 using the standard precision protocol of the glide tool. To select hits with high binding affinities, a threshold of -8 kcal/mol was used. Based on the glide gscore, two hits were chosen. These two hits were selected to investigate the stability of the protein-ligand complex by molecular dynamics simulation. All of these findings indicate that the selected hit compounds C1 and C2 can serve as lead compounds in inhibiting the biological activity of SIRT3 requiring further detailed investigations.Communicated by Ramaswamy H. Sarma.
RESUMO
Computer Security Incident Response Teams (CSIRTs) or Computer Emergency Response Teams (CERTs) are an integral part of incident handling capabilities and are increasingly demanded by organizations such as critical infrastructures. They can hold many different skills and are of great interest to organizations in terms of cyber security and, more concretely, cyber incident management. This contribution seeks to analyze the extent to which their activity is regulated under Swiss law, considering that private CSIRTs are not regulated in the same way as governmental and national CSIRTs such as the Computer Emergency Response Team of the Swiss government and official national CERT of Switzerland (GovCERT).
RESUMO
Computer security incident response teams (CSIRTs) respond to a computer security incident when the need arises. Failure of these teams can have far-reaching effects for the economy and national security. CSIRTs often have to work on an ad hoc basis, in close cooperation with other teams, and in time constrained environments. It could be argued that under these working conditions CSIRTs would be likely to encounter problems. A needs assessment was done to see to which extent this argument holds true. We constructed an incident response needs model to assist in identifying areas that require improvement. We envisioned a model consisting of four assessment categories: Organization, Team, Individual and Instrumental. Central to this is the idea that both problems and needs can have an organizational, team, individual, or technical origin or a combination of these levels. To gather data we conducted a literature review. This resulted in a comprehensive list of challenges and needs that could hinder or improve, respectively, the performance of CSIRTs. Then, semi-structured in depth interviews were held with team coordinators and team members of five public and private sector Dutch CSIRTs to ground these findings in practice and to identify gaps between current and desired incident handling practices. This paper presents the findings of our needs assessment and ends with a discussion of potential solutions to problems with performance in incident response.