A Minimal Mechanosensing Model Predicts Keratocyte Evolution on Flexible Substrates

A mathematical model is proposed for shape evolution and locomotion of fish epidermal keratocytes on elastic substrates. The model is based on mechanosensing concepts: cells apply contractile forces onto the elastic substrate, while cell shape evolution depends locally on the substrate stress generated by themselves or external mechanical stimuli acting on the substrate. We use the level set method to study the behaviour of the model numerically, and predict a number of distinct phenomena observed in experiments, such as (i) symmetry breaking from the stationary centrosymmetric to the well-known steadily propagating crescent shape, (ii) asymmetric bipedal oscillations and travelling waves in the lamellipodium leading edge, (iii) response to remote mechanical stress externally applied to the substrate (tensotaxis) and (iv) changing direction of motion towards an interface with a rigid substrate (durotaxis)

Artificial Intelligence and Machine Learning: A Perspective on Integrated Systems Opportunities and Challenges for Multi-Domain Operations

This paper provides a perspective on historical background, innovation and applications of Artificial Intelligence (AI) and Machine Learning (ML), data successes and systems challenges, national security interests, and mission opportunities for system problems. AI and ML today are used interchangeably, or together as AI/ML, and are ubiquitous among many industries and applications. The recent explosion, based on a confluence of new ML algorithms, large data sets, and fast and cheap computing, has demonstrated impressive results in classification and regression and used for prediction, and decision-making. Yet, AI/ML today lacks a precise definition, and as a technical discipline, it has grown beyond its origins in computer science. Even though there are impressive feats, primarily of ML, there still is much work needed in order to see the systems benefits of AI, such as perception, reasoning, planning, acting, learning, communicating, and abstraction. Recent national security interests in AI/ML have focused on problems including multidomain operations (MDO), and this has renewed the focus on a systems view of AI/ML. This paper will address the solutions for systems from an AI/ML perspective and that these solutions will draw from methods in AI and ML, as well as computational methods in control, estimation, communication, and information theory, as in the early days of cybernetics. Along with the focus on developing technology, this paper will also address the challenges of integrating these AI/ML systems for warfare

MOLECULAR ANALYSIS OF THE CAMP- RESPONSE ELEMENT [CRE] ELEMENTS IN THE PROMOTER REGION AND EXON 1 OF THE SURVIVAL OF MOTOR NEURON 2 [SMN2] GENE IN MALAYSIAN SPINAL MUSCULAR ATROPHY PATIENTS; TO ELUCIDATE THEIR ROLE IN CIRCUMSCRIBING THE CLINICAL SEVERITY

Objective: In the Spinal muscular atrophy [SMA] genes [SMN1 and SMN2 genes]; the CRE-II elements at -400 bp in the promoter region of the SMN genes and CRE-I element at +108 bp in the exon 1 of the SMN genes, are reported to have a role in c-AMP induce expression of the SMN genes through its binding affinity to CREB-1. This study was designed to determine the role of CRE sites in the circumscribing the clinical severity of SMA. Methods: Direct sequencing was performed for the PCR products of the promoter regions of the SMA patients with homozygous deletion of SMN1, different copy number of SMN2 and NAIP non deletion. Results: No variation among the CRE-I and CRE-II sites was found in all the clinical types as compare to normal healthy control showing no role of CRE sites in circumscribing the clinical severity of SMA. Conclusion: There was no sequence variation found in the CRE binding sites in the three different clinical types of SMA reflecting no role of CRE binding sites in circumscribing the clinical severity of SMA

A successful full term delivery in a case of robotic assisted insertion of transabdominal cerclage in an obese woman with multiple uterine fibroids

Cervical incompetence is not an uncommon presentation in an obstetric emergency unit. Some of these patients will be managed with a cervical cerclage. While the management of patients presenting with first time cervical incompetence is relatively established, the management of patient with repeated cervical incompetence might require an abdominal cerclage. Abdominal cerclages can be inserted traditionally via laparotomy or via a minimally invasive approach (MIS). We present a case of an obese patient presenting with 3 previous second trimester miscarriages despite 2 cervical cerclage complicated by multiple uterine fibroids who underwent a robotic assisted insertion of transabdominal cerclage (RTAC) pre-pregnancy. She subsequently conceived spontaneously and carried the pregnancy to term and delivered a healthy baby via caesarean section. There have been multiple published studies showing that an MIS approach for abdominal cerclage insertion is safe and viable. Robotic assisted procedures allow for better visualisation and manipulation of tissue especially in patients anticipating a complex procedure. For our patient we feel that a robotic assisted procedure would be more beneficial given her profile and the complexity of her case

A Minimal Mechanosensing Model Predicts Keratocyte Evolution on Flexible Substrates

A mathematical model is proposed for shape evolution and locomotion of fish epidermal keratocytes on elastic substrates. The model is based on mechanosensing concepts: cells apply contractile forces onto the elastic substrate, while cell shape evolution depends locally on the substrate stress generated by themselves or external mechanical stimuli acting on the substrate. We use the level set method to study the behaviour of the model numerically, and predict a number of distinct phenomena observed in experiments, such as (i) symmetry breaking from the stationary centrosymmetric to the well-known steadily propagating crescent shape, (ii) asymmetric bipedal oscillations and travelling waves in the lamellipodium leading edge, (iii) response to remote mechanical stress externally applied to the substrate (tensotaxis) and (iv) changing direction of motion towards an interface with a rigid substrate (durotaxis)

Effect of stacking fault energy on the dynamic recrystallization during hot working of FCC metals: a study using processing maps

The influence of stacking fault energy (SFE) on the mechanism of dynamic recrystallization (DRX) during hot deformation of FCC metals is examined in the light of results from the power dissipation maps. The DRX domain for high SFE metals like Al and Ni occurred at homologous temperature below 0·7 and strain rates of 0·001 s−1 while for low SFE metals like Cu and Pb the corresponding values are higher than 0·8 and 100 s−1. The peak efficiencies of power dissipation are 50% and below 40% respectively. A simple model which considers the rate of interface formation (nucleation) involving dislocation generation and simultaneous recovery and the rate of interface migration (growth) occurring with the reduction in interface energy as the driving force, has been proposed to account for the effect of SFE on DRX. The calculations reveal that in high SFE metals, interface migration controls DRX while the interface formation is the controlling factor in low SFE metals. In the latter case, the occurrence of flow softening and oscillations could be accounted for by this model

Molecular analysis of promoter region of the SMN2 gene in the patients of spinal musculatr atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by the absence of the full length SMN protein (FL-SMN) as a result of mutation or deletion of SMN1 gene. The isoform to this gene, SMN2 gene, with mutation in 1 base pair, encodes for 10% of FL-SMN protein and is reported to decrease the severity of the disease when there is an increase gene dosage. There are 3 clinical types of SMA; type I, type II and type III. Type I SMA is the most severe type and only a small amount of FL-SMN protein is present in these individuals. We postulated that the difference in the promoter region of SMN2 gene produces the different level of FL-SMN protein. To verify this hypothesis, the DNA samples of 69 SMA patients who were referred to the Human Genome Center, USM were extracted from their blood. The SMN1 deletion analysis was performed, followed by the SMN2 copy no. analysis and NAIP deletion analysis to remove any clinical bias as NAIP gene deletion and SMN2 copy number have been reported to be associated with SMA disease severity. Only 10 SMA patients from different clinical types (type I=2, type II=3, type III=5) with homozygous deletion of the SMN1 and 2 copies of the SMN2 and deletion in NAIP were finally recruited. Primers were designed for the amplification of the SMN2 promoter region. Bioinformatics analysis was performed to identify the crucial transcription factor binding sites within the reported ~4.6 kb promoter region. As the core promoter region is still unknown (unreported), we analyzed 15 ORFs and 24 nested ORFs with 15 TATA boxes reflecting the diverse functional integrity of this region. The promoter prediction and core promoter prediction was also performed. Based on the bioinformatics analysis and the designed primers, PCR amplification was done for different regions in the promoter and the PCR products were subjected to direct DNA sequencing. The results were analyzed by Vector NTI suite 9, ClustalX and Gene Doc softwares. The molecular analysis confirmed the absence of any mutation in the promoter region of the SMN2 gene between normal healthy individuals (total 2) and SMA patients. In 4 patients and 1 normal healthy individual the CA repeats were found to be increased which we think cause no effect in disease progression and severity. In conclusion, there was no mutation found in the promoter region of the SMN2 gene among the SMA patients of different clinical types and normal controls. Further analysis involving the cloning of the promoter regions with highest probability of involvement in expression of the SMN2 gene using luciferase assay is ongoing. The results will be useful for the subsequent phase of the study involving the transcription initiation of the SMN2 gene

Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition

The Akt family of kinases are activated by growth factors and regulate pleiotropic cellular activities. In this study, we provide evidence for isoform-specific positive and negative roles for Akt1 and -2 in regulating growth factor–stimulated phenotypes in breast epithelial cells. Insulin-like growth factor-I receptor (IGF-IR) hyperstimulation induced hyperproliferation and antiapoptotic activities that were reversed by Akt2 down-regulation. In contrast, Akt1 down-regulation in IGF-IR–stimulated cells promoted dramatic neomorphic effects characteristic of an epithelial–mesenchymal transition (EMT) and enhanced cell migration induced by IGF-I or EGF stimulation. The phenotypic effects of Akt1 down-regulation were accompanied by enhanced extracellular signal–related kinase (ERK) activation, which contributed to the induction of migration and EMT. Interestingly, down-regulation of Akt2 suppressed the EMT-like morphological conversion induced by Akt1 down-regulation in IGF-IR–overexpressing cells and inhibited migration in EGF-stimulated cells. These results highlight the distinct functions of Akt isoforms in regulating growth factor–stimulated EMT and cell migration, as well as the importance of Akt1 in cross-regulating the ERK signaling pathway