Microservices Architecture Enables DevOps: an Experience Report on Migration to a Cloud-Native Architecture

This article reports on experiences and lessons learned during incremental migration and architectural refactoring of a commercial mobile back end as a service to microservices architecture. It explains how the researchers adopted DevOps and how this facilitated a smooth migration

Architecting Enterprise Applications for the Cloud: The Unicorn Universe Cloud Framework

© Springer International Publishing AG, part of Springer Nature 2018. Recent IT advances that include extensive use of mobile and IoT devices and wide adoption of cloud computing are creating a situation where existing architectures and software development frameworks no longer fully support the requirements of modern enterprise application. Furthermore, the separation of software development and operations is no longer practicable in this environment characterized by fast delivery and automated release and deployment of applications. This rapidly evolving situation requires new frameworks that support the DevOps approach and facilitate continuous delivery of cloud-based applications using micro-services and container-based technologies allowing rapid incremental deployment of application components. It is also becoming clear that the management of large-scale container-based environments has its own challenges. In this paper, we first discuss the challenges that developers of enterprise applications face today and then describe the Unicorn cloud framework (uuCloud) designed to support the development and deployment of cloud-based applications that incorporate mobile and IoT devices. We use a doctor surgery reservation application “Lekar” case study to illustrate how uuCloud is used to implement a large-scale cloud-based application

Antinociceptive effects of acetyl met-enkephalin derivatives following intrathecal administration in rat

Introduction: Intrathecal infusion of some enkephalin derivatives has been shown to restore analgesia in morphine tolerant patients with less adverse effects such as respiratory depression and constipation compared to morphine. Therefore developing new enkephalin derivatives is of central interest in pain management. In this study, antinociceptive effects of intrathecal administration of two novel acetyl met-enkephalin analogues were evaluated compared to met-enkephalin. Methods and Results: To permit the intrathecal administration of drugs into the lumbar subarachnoid space in adult Wistar rats, polyethylene (PE10) catheters were implanted in the L2 and L3 spinal segments in anesthetized animals. After a recovery time of 4-5 days, to protect the drugs from biodegradation, all rats were pretreated with peptidase inhibitors (APC) including Amastatin (A), Phosphoramidon (P) and captopril (C). Animals were dosed with intrathecal infusion of the analogues followed by tail flick latency test for an hour. Acetyl-Met-enk-CHO and Acetyl-Met-enk did not show significant antinociceptive effects in 10 nM (10-8 M) concentration. However Acetyl-Met-enk-CHO described discernible effects in 100 nm (10-7 M) in comparison with enkephalin. To estimate resistance against peptidase, molecular modeling was performed and showed compound Acetyl-Met-enk-CHO has low affinity to active site of aminopeptidase, dipeptidylcarboxypeptidase-I and neutral endopeptidase; the degrading endogenous enkephalin opioid peptides. Conclusions: According to our results, Acethyl-Met-enk-CHO may provide comparable analgesic effects with, although with 10 folds less potency. With likely resistance against endogenous peptidase, this molecule could be a valuable lead compound for further studies

Antinociceptive effects of acetyl Leu-enkephalin derivatives following intrathecal administration in rat

Introduction: Intrathecal infusion of some enkephalin derivatives has been shown to restore analgesia in morphine tolerant patients with less adverse effects such as respiratory depression and constipation compared to morphine. Therefore developing new enkephalin derivatives is of central interest in pain management. In this study, antinociceptive effects of intrathecal administration of two novel acetyl met-enkephalin analogues were evaluated compared to met-enkephalin. Methods and Results: To permit the intrathecal administration of drugs into the lumbar subarachnoid space in adult wistar rats, polyethylene (PE10) catheters were implanted in the L2 and L3 spinal segments in anesthetized animals. After a recovery time of 4-5 days, to protect the drugs from biodegradation, all rats were pretreated with peptidase inhibitors (APC) including Amastatin, Phosphoramidon and captopril. Animals were dosed with intrathecal infusion of the analogues followed by tail flick latency test for an hour. Acetyl-Leu-enk-CHO and Acetyl-Leu-enk did not show any significant antinociceptive effects in 10 nM (10-8 M) concentration. However Acetyl-Leu-enk demonstrated considerable effects in 100 nm (10-7 M) compared to Leu-enkephalin. Surprisingly, Acetyl-Met-Leu-enk-CHO antinociception did not improve but decreased with increasing intrathecal dosage to 100 nm, probably working as a partial agonist on opioid receptors. Conclusions: According to our results, Acetyl-Leu-enk may provide better analgesic effects, compared to Acetyl-Leu-enk-CHO. With likely reverse dose-response effects on tail flick test, Acetyl-Leu-enk-CHO might be considered as a particular ligand for opioid receptors without full agonistic effect for further studies

1-Benzyl-2-(4-chloro­phen­yl)-4,5-di­phenyl-1H-imidazole

The mol­ecular conformation of the title compound, C28H21ClN2, is stabilized by an intra­molecular C—H⋯N hydrogen bond. It has many pharmacological properties, such as being an inhibitor of P38 MAP Kinase, and can play an important role in biochemical processes

DevOps Adoption Benefits and Challenges in Practice: A Case Study

DevOps is an approach in which traditional software engineering roles are merged and communication is enhanced to improve the production release frequency and maintain software quality. There seem to be benefits in adopting DevOps but practical industry experiences have seldom been reported. We conducted a qualitative multiple-case study and interviewed the representatives of three software development organizations in Finland. The responses indicate that with DevOps, practitioners can increase the frequency of releases and improve test automation practices. DevOps was seen to encourage collaboration between departments which boosts communication and employee welfare. Continuous releases enable a more experimental approach and rapid feedback collection. The challenges include communication structures that hinder cross-department collaboration and having to address the cultural shift. Dissimilar development and production environments were mentioned as some of the technical barriers. DevOps might not also be suitable for all industries. Ambiguity in the definition of DevOps makes adoption difficult since organizations might not know which practices they should implement for DevOps.Peer reviewe

Monomethyl Auristatin E, a Potent Cytotoxic Payload for Development of Antibody-Drug Conjugates against Breast Cancer

Background: Breast cancer is a heterogeneous disease characterized by differential responses to targeted and chemotherapeutic agents. Antibody-drug conjugates are one of the promising strategies for the treatment of breast cancer. Monomethyl auristatin E (MMAE) is a highly potent microtubule inhibitor and a common payload used for development of antibody-drug conjugates. The purpose of this study was to investigate the cytotoxic effects of MMAE on breast cancer cell lines.Materials and Methods: MDA-MB-468 and MDA-MB-453 cells were treated with MMAE at various concentrations (1, 10, 100, and 1000 ng/ml), and cytotoxicity was measured after 48 and 72 hours using an MTT assay.Results: Our findings indicated that MMAE possesses dose- and time-dependent cytotoxic activities against human breast cancer cells. The morphological features of the treated cells were supportive of the cytotoxic activity of MMAE. The results of the MTT assay showed that MMAE has a significant cytotoxicity against MDA-MB-468 and, to a lesser degree, MDA-MB-453 cells.Conclusion: MMAE can be used as a highly cytotoxic payload for development of antibody-drug conjugates against breast cancer

Monomethyl auristatin E Exhibits Potent Cytotoxic Activity against Human Cancer Cell Lines SKBR3 and HEK293

Background: Monomethyl auristatin E (MMAE) is a synthetic analog of dolastatin 10, a compound originally isolated from the marine mollusk. MMAE, as a highly potent microtubule inhibitor, exerts its potent cytotoxic effect by inhibiting microtubule assembly, tubulin-dependent GTP hydrolysis and microtubes polymerization. This molecule, by itself, lacks the tumor specificity required to elicit therapeutic benefit. Nevertheless, the extremely cytotoxic potential of MMAE could be harnessed in the form of MMAE-antibody conjugates. The aim of the present study was to evaluate the cytotoxic activity of MMAE against breast (SKBR3) and kidney (HEK293) cancer cell lines in an in vitro cell-based assay.Materials and Methods: SKBR3 and HEK293 cells were treated with different concentrations ranging from 0.002048, 0.01024, 0.0512, 0.256, 1.28, 6.4, 32, 160, 800 and 4000 nM of MMAE, and cell viability was determined after 72 hours using an MTT colorimetric assay. The effect of MMAE was regularly monitored by direct observation using an invert microscope.Results: Microscopic observation showed that there was a concentration-dependent increase in cell death. Results from the MTT assay revealed a statistically significant loss of viability (P<0.0001) at concentrations ranging from 0.01024 to 4000 nM in SKBR3 cells, and 0.0512 to 4000 nM in HEK293 cells. Our findings showed that MMAE inhibited the growth of SKBR3 and HEK293 cells in a concentration-dependent manner, with IC50 values of 3.27 ± 0.42 and 4.24 ± 0.37 nM, respectively.Conclusion: MMAE was able to significantly inhibit cell growth at nanomolar concentrations, emphasizing its great potential for the development of antibody-drug conjugates