Performance Evaluation of Optimized Predictive Model for Software Defined Network Traffic Management using Machine Learning

Communication channel is essential in any type of engagement for delivering and receiving data via the internet. To determine the most efficient and safe way through which network data may travel while minimizing the danger of network breaches or cyber-attacks. The objective is to build an optimized network traffic management predictive model that can predict the ideal path in real-time while accounting through the dynamic nature of software defined network traffic and the continuously changing danger of landscaping. To design a robust model of the data and scalable system that can suggest accurate suggestions of route to the network managers, a thorough grasp of network’s infrastructure, data analysis, and machine learning techniques are applied. Choosing the optimum path route data from the sdn based network traffic dataset, the model suggests an optimal path to avoid network communication traffic and congestion. Here nine Machine Learning algorithms are explored and analysed their performance by using the percentage split, resampling and cross validation which originally recorded as 92.76% and after training with cross validation it improved to 98.40% providing the best optimal path with minimum congestions. Building the optimized network traffic management model not only provide network security but also contribute to environmental sustainability. Their capacity to properly filter and manage network traffic helps to decrease energy usage by predicting the optimal routes for software defined network traffic

Regulation of NMDA-type glutamate receptors and MDR1 by two members of the EF-hand protein family

EF-hand proteins are a conserved family of proteins that are modulated by divalent cations and regulate diverse cellular activities. In the present study we characterized the molecular determinants of myosin regulatory light chain (RLC) interaction with several subunits of the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Myosin RLC is an EF-hand protein that is traditionally considered an integral component of the myosin II complex. We show that this light chain is important for trafficking of NMDA receptors and that this function is likely independent of the myosin II complex. In addition, we studied the interaction of myosin RLC with a second non-myosin target, multi-drug resistance protein 1 (MDR1) also known as P-glycoprotein. Finally, we characterized a previously undescribed calcium-dependent calmodulin binding site on the NMDAR 2A (NR2A) subunit of the NMDA receptor. Calmodulin is structurally-related to myosin RLC and also considered an EF-hand protein. Myosin II motors are hexameric complexes containing two heavy chains that each bind a pair of light chains: one essential light chain and one RLC. Alternative binding partners have been described for both light chains of myosin II raising the possibility that myosin RLC, like other EF-hand proteins, may adopt conformations that can be distinguished from conventional myosin RLC-heavy chain interactions. In this study, we mapped the myosin RLC binding site to a 30-37 amino acid region of the C-termini of NR1 and NR2 subunits. Myosin RLC-NMDA receptor subunit interactions could be distinguished from the prototypical interaction of myosin RLC with the neck region of non-muscle myosin II-B heavy chain. NMDA-myosin RLC interactions were maintained in the absence of the fourth EF-hand domain and did not require the addition of magnesium. We report that sequence similarity in the "GxxxR" portion of the incomplete IQ2 motif found in nonmuscle myosin II heavy chain isoforms likely contributes to the recognition of NR2A as a non-myosin target of the myosin RLC. We report that myosin RLC-NR2A interactions likely occur in the Golgi complex and this interaction is important in forward trafficking of NR1/NR2A receptors. We suggest that a role for myosin RLC in protein trafficking in polarized cells is distinct from the typical interaction of myosin RLC as a component of the myosin II complex. Like glutamate receptor subunits, MDR1 is also a membrane-bound protein expressed in polarized cells. MDR1 is a drug efflux transporter that consists of two homologous halves, each consisting of six membrane-spanning domains plus a nucleotide binding domain linked by an intracellular linker region. The linker region of MDR1 is a determinant of cell surface expression and directly interacts with intracellular cytoskeletal, regulatory, and motor proteins. A previous study documented a direct interaction between myosin RLC and the linker region of a related ABC transporter, bile salt export protein (BSEP), and established a role for myosin in BSEP trafficking. We found that myosin RLC interacts with MDR1 via the amino terminal of the light chain as observed with NMDA receptor subunits. This interaction of myosin RLC with both of its binding partners (MDR1 and NMDA receptor subunits) is decreased upon phosphorylation of specific residues in the amino terminal of the light chain. We used Madin-Darby canine kidney (MDCK) cells stably expressing MDR1 (MDCKII-MDR1) as a model system to study the functional consequences of perturbing the phosphorylation state of myosin RLC in intact cells. Treatment of polarized MDCKII-MDR1 monolayers with ML-7, a pharmacologic inhibitor of myosin light chain kinase, increased the permeability of [³H]-digoxin (a well-known substrate of MDR1) and decreased apical expression of MDR1 in MDCKII-MDR1 cells. The combination of NR1 splice variants and NR2 subunits imparts differing physiological and pharmacological properties on NMDA receptor assemblies. The NR2 C-termini of NMDA receptors are approximately 600 amino acids long and the middle region of NR2A C-terminus (NR2A (875-1029)) bears only 29% sequence similarity with the corresponding region in the NR2B subunit. We used a proteomics approach to uncover proteins that may interact with this region from mouse brain homogenates both in the presence and absence of calcium. Calmodulin was found to interact with NR2A (875-1029) in a calcium-dependent manner. The binding affinity of calmodulin for the NR2A subunit was found to be 5.2 ± 2.4 nM, which is comparable to the affinity of a previously described binding site of calmodulin on the NR1 subunit. We found that tryptophan at position W1014 in NR2A C-terminal is critical for interaction with calmodulin. We also confirm in our studies that calmodulin is not a binding partner of the NR2B subunit of the NMDA receptor. Together our studies provide insight to the interaction of two EF-hand proteins with target proteins. For the first time we provide a functional role of myosin RLC in trafficking of NMDA receptors to the plasma membrane. We also show that myosin RLC can influence cell surface expression of MDR1 and as a consequence alter the transport properties of MDR1 as a drug efflux transporter. This study will contribute to our understanding of the mechanisms that underlie increased expression of MDR proteins associated with drug refractory conditions. In addition, we characterized a novel calmodulin binding site on the NR2A subunit of the NMDA receptor. This previously undescribed calmodulin binding site within the NR2A C-terminus potentially highlights an important distinction between Ca²⁺/calmodulin regulation of NR2A versus NR2B containing complexes

On Solution of Interval Valued Intuitionistic Fuzzy Assignment Problem Using Similarity Measure and Score Function

The primary objective of the paper is to propose a new method for solving assignment problem under uncertain situation. In the classical assignment problem ( ), denotes the cost for assigning the job to the person which is deterministic in nature. Here in some uncertain situation, we have assigned a cost in the form of composite relative degree instead of and this replaced cost is in the maximization form. In this paper, it has been solved and validated by the two proposed algorithms, a new mathematical formulation of assignment problem has been presented where the cost has been considered to be an IVIFN and the membership of elements in the set can be explained by positive and negative evidences. To determine the composite relative degree of similarity of the concept of similarity measure and the score function is used for validating the solution which is obtained by Composite relative similarity degree method. Further, hypothetical numeric illusion is conducted to clarify the method's effectiveness and feasibility developed in the study. Finally, conclusion and suggestion for future work are also proposed

On Solution of Interval Valued Intuitionistic Fuzzy Assignment Problem Using Similarity Measure and Score Function

The primary objective of the paper is to propose a new method for solving assignment problem under uncertain situation. In the classical assignment problem ( ), denotes the cost for assigning the job to the person which is deterministic in nature. Here in some uncertain situation, we have assigned a cost in the form of composite relative degree instead of and this replaced cost is in the maximization form. In this paper, it has been solved and validated by the two proposed algorithms, a new mathematical formulation of assignment problem has been presented where the cost has been considered to be an IVIFN and the membership of elements in the set can be explained by positive and negative evidences. To determine the composite relative degree of similarity of the concept of similarity measure and the score function is used for validating the solution which is obtained by Composite relative similarity degree method. Further, hypothetical numeric illusion is conducted to clarify the method's effectiveness and feasibility developed in the study. Finally, conclusion and suggestion for future work are also proposed

On Solution of Interval Valued Intuitionistic Fuzzy Assignment Problem Using Similarity Measure and Score Function

The primary objective of the paper is to propose a new method for solving assignment problem under uncertain situation. In the classical assignment problem ( ), denotes the cost for assigning the job to the person which is deterministic in nature. Here in some uncertain situation, we have assigned a cost in the form of composite relative degree instead of and this replaced cost is in the maximization form. In this paper, it has been solved and validated by the two proposed algorithms, a new mathematical formulation of assignment problem has been presented where the cost has been considered to be an IVIFN and the membership of elements in the set can be explained by positive and negative evidences. To determine the composite relative degree of similarity of the concept of similarity measure and the score function is used for validating the solution which is obtained by Composite relative similarity degree method. Further, hypothetical numeric illusion is conducted to clarify the method's effectiveness and feasibility developed in the study. Finally, conclusion and suggestion for future work are also proposed

Zwitterionic Chitosan Derivative, a New Biocompatible Pharmaceutical Excipient, Prevents Endotoxin-Mediated Cytokine Release

Chitosan is a cationic polymer of natural origin and has been widely explored as a pharmaceutical excipient for a broad range of biomedical applications. While generally considered safe and biocompatible, chitosan has the ability to induce inflammatory reactions, which varies with the physical and chemical properties. We hypothesized that the previously reported zwitterionic chitosan (ZWC) derivative had relatively low pro-inflammatory potential because of the aqueous solubility and reduced amine content. To test this, we compared various chitosans with different aqueous solubilities or primary amine contents with respect to the intraperitoneal (IP) biocompatibility and the propensity to induce pro-inflammatory cytokine production from macrophages. ZWC was relatively well tolerated in ICR mice after IP administration and had no pro-inflammatory effect on naïve macrophages. Comparison with other chitosans indicates that these properties are mainly due to the aqueous solubility at neutral pH and relatively low molecular weight of ZWC. Interestingly, ZWC had a unique ability to suppress cytokine/chemokine production in macrophages challenged with lipopolysaccharide (LPS). This effect is likely due to the strong affinity of ZWC to LPS, which inactivates the pro-inflammatory function of LPS, and appears to be related to the reduced amine content. Our finding warrants further investigation of ZWC as a functional biomaterial

Towards policy-aware edge computing architectures

Cloud computing offers an economical and elastic means to handle the storage and computation needs of the Internet of Things (IoT). However, storage and retrieval from the cloud could potentially violate policies, especially those pertaining to data privacy. Edge computing as a paradigm is a suitable way to overcome these issues. This poster presents an edge computing architecture that enables policy-aware normalization and filtration of the data that is sent to cloud services to preserve policies. We use a secure and encrypted channel to transmit the data generated by the IoT devices to the dedicated computing units at the edge of the network. Our architecture offers programmers the ability to configure the system easily and perform a predetermined set of computation tasks on the data, e.g., tasks to uphold privacy policies such as blurring faces, license plates, etc

Delayed Cutaneous Wound Healing and Aberrant Expression of Hair Follicle Stem Cell Markers in Mice Selectively Lacking Ctip2 in Epidermis

Background: COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep-/-) mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB) establishment during development, similar to what was observed in Ctip2 null (Ctip2(-/-)) mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing. Methodology/Principal Findings: Full thickness excisional wound healing experiments were performed on Ctip2(L2/L2) and Ctip2(ep-/-) animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC) and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2(ep-/-) mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA) in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF) stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair. Conclusions/Significance: Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure

Safety, tolerability, and potential clinical activity of a glucocorticoid-induced TNF receptor-related protein agonist alone or in combination with nivolumab for patients with advanced solid tumors: a phase 1/2a dose-escalation and cohort-expansion clinical trial

Importance: Multiple immunostimulatory agonist antibodies have been clinically tested in solid tumors to evaluate the role of targeting glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein in anticancer treatments. Objective: To evaluate the safety and activity of the fully human glucocorticoid-induced TNF receptor-related protein agonist IgG1 monoclonal antibody BMS-986156 with or without nivolumab in patients with advanced solid tumors. Design, Setting, and Participants: This global, open-label, phase 1/2a study of BMS-986156 with or without nivolumab enrolled 292 patients 18 years or older with advanced solid tumors and an Eastern Cooperative Oncology Group performance status of 1 or less. Prior checkpoint inhibitor therapy was allowed. Monotherapy and combination dose-escalation cohorts ran concurrently to guide expansion doses beginning October 16, 2015; the study is ongoing. Interventions: The protein agonist BMS-986156 was administered intravenously at a dose of 10, 30, 100, 240, or 800 mg every 2 weeks as monotherapy, and in the combination group 30, 100, 240, or 800 mg plus 240 mg of nivolumab every 2 weeks; same-dose cohorts were pooled for analysis. One cohort also received 480 mg of BMS-986156 plus 480 mg of nivolumab every 4 weeks. Main Outcomes and Measures: The primary end points were safety, tolerability, and dose-limiting toxic effects. Additional end points included antitumor activity per Response Evaluation Criteria in Solid Tumors, version 1.1, and exploratory biomarker analyses. Results: With a follow-up range of 1.4 to 101.7 weeks (follow-up ongoing), 34 patients (16 women and 18 men; median age, 56.6 years [range, 28-75 years]) received monotherapy (4 patients completed initial treatment), and 258 patients (140 women and 118 men; median age, 60 years [range, 21-87 years]) received combination therapy (65 patients completed initial treatment). No grade 3 to 5 treatment-related adverse events occurred with BMS-986156 monotherapy; grade 3 to 4 treatment-related adverse events occurred in 24 patients (9.3%) receiving BMS-986156 plus nivolumab, with no grade 5 treatment-related adverse events. One dose-limiting toxic effect (grade 4 elevated creatine phosphokinase levels) occurred in a patient receiving 800 mg of BMS-986156 plus 240 mg of nivolumab every 2 weeks; BMS-986156 with or without nivolumab exhibited linear pharmacokinetics with dose-related increase after a single dose. Peripheral T-cell and natural killer-cell proliferation increased after administration of BMS-986156 with or without nivolumab. No consistent and significant modulation of intratumoral CD8+ T cells and FoxP3+ regulatory T cells was observed. No responses were seen with BMS-986156 alone; objective response rates ranged from 0% to 11.1% (1 of 9) across combination therapy cohorts, with a few responses observed in patients previously treated with anti-programmed death receptor (ligand) 1 therapy. Conclusions and Relevance: Based on this cohort, BMS-986156 appears to have had a manageable safety profile, and BMS-986156 plus nivolumab demonstrated safety and efficacy comparable to historical data reported for nivolumab monotherapy. Trial Registration: ClinicalTrials.gov identifier: NCT02598960

Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME