The Vital Role of Blood Flow-Induced Proliferation and Migration in Capillary Network Formation in a Multiscale Model of Angiogenesis

Sprouting angiogenesis and capillary network formation are tissue scale phenomena. There are also sub-scale phenomena involved in angiogenesis including at the cellular and intracellular (molecular) scales. In this work, a multiscale model of angiogenesis spanning intracellular, cellular, and tissue scales is developed in detail. The key events that are considered at the tissue scale are formation of closed flow path (that is called loop in this article) and blood flow initiation in the loop. At the cellular scale, growth, migration, and anastomosis of endothelial cells (ECs) are important. At the intracellular scale, cell phenotype determination as well as alteration due to blood flow is included, having pivotal roles in the model. The main feature of the model is to obtain the physical behavior of a closed loop at the tissue scale, relying on the events at the cellular and intracellular scales, and not by imposing physical behavior upon it. Results show that, when blood flow is considered in the loop, the anastomosed sprouts stabilize and elongate. By contrast, when the loop is modeled without consideration of blood flow, the loop collapses. The results obtained in this work show that proper determination of EC phenotype is the key for its survival.     

Strategies toward rheumatoid arthritis therapy; the old and the new

Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease-modifying antirheumatic drugs (DMARDs), administered as first-line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti-CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor-α (TNF-α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin-1 (IL-1), anakinra, and costimulation blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF-α inhibitors, JAK inhibitors, anti-interleukin-6-receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat-to-target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation.     

Identification and functional characterization of the CVOMTs and EOMTs genes promoters from Ocimum basilicum L.

Plant Cell, Tissue and Organ Culture (PCTOC) - Methyl chavicol and methyl eugenol are important phenylpropanoid compounds previously purified from basil. These compounds are significantly enhanced...     

Variable impact transportation (VIT) model for energy and environmental impact of hauling truck operation

Purpose

Fuel economy and emissions of heavy-duty trucks greatly vary based on vehicular/environmental conditions. Large-scale infrastructure construction projects require a large amount of material/equipment transportation. Single-parameter generic hauling models may not be the best option for an accurate estimation of hauling contribution in life cycle assessment (LCA) involving construction projects; therefore, more precise data and parameterized models are required to represent this contribution. This paper discusses key environmental/operational variables and their impact on transportation of materials and equipment; a variable-impact transportation (VIT) model accounting for these variables was developed to predict environmental impacts of hauling.

Methods

The VIT model in the form of multi-nonlinear regression equations was developed based on simulations using the U.S. Environmental Protection Agency (EPA)’s Motor Vehicle Emission Simulator (MOVES) to compute all the impact categories in EPA’s TRACI 2.1 and energy consumption of transportation. Considering actual driving cycles of hauling trucks recorded during a pavement rehabilitation project, the corresponding environmental impacts were calculated, and sensitivity analyses were performed. In addition, an LCA case study based on historical pavement reconstruction projects in Illinois was conducted to analyze the contribution of transportation and variability of its impacts during the pavements’ life cycle.

Results and discussion

The importance of vehicle driving cycles was realized from simulation results. The case study results showed that considering driving cycles using the VIT model could increase the contribution of hauling in total life cycle Global Warming Potential (GWP) and total life cycle GWP itself by 2–4 and 3–5%, respectively. In addition to GWP, ranges of other hauling-related impact categories including Smog, Ozone Depletion, Acidification, and Primary Energy Demand from fuel were presented based on the case study. Ozone Depletion ranged from 9 to 45%, and Smog ranged from 11 to 48% of the total relevant life cycle impacts. The GWP contribution of hauling in pavement LCA ranged between 5 and 32%. The results indicate that the contribution of hauling transportation can be significant in pavement LCA.

Conclusions

For large-scale roadway infrastructure construction projects that need a massive amount of material transportation, high fidelity models and data should be used especially for comparative LCAs that can be used as part of decision making between alternatives. The VIT model provides a simple analytical platform to include the critical vehicular/operational variables without any dependence on an external software; the model can also be incorporated in those studies where some of the transportation activity data are available.

     

Environmental and economic impact of using new-generation wide-base tires

Purpose

New-generation wide-base tire (NG-WBT) is known for improving fuel economy and at the same time for potentially causing a greater damage to pavement. No study has been conducted to evaluate the net environmental saving of the combined system of pavements and NG-WBT. This study adopted a holistic approach (life cycle assessment [LCA] and life cycle costing [LCC]) to quantitatively evaluate the environmental and economic impact of using NG-WBT.

Methods

The net effect of different levels of market penetration of NG-WBT on energy consumption, global warming potential (GWP), and cost based on the fatigue cracking and rutting performance of two different asphalt concrete (AC) pavement structures was evaluated. The performance of pavements was determined based on pavement design lives; pavement surface characteristics, and pavement critical strain responses obtained from the artificial neural network (ANN) based on finite element (FE) simulations were used to calculate design lives of pavements. Based on the calculated design lives, life cycle inventory (LCI) and cost databases, and rolling resistance (RR) models previously developed by the University of Illinois at Urbana-Champaign (UIUC) were used to calculate the environmental and economic impact of the combined system.

Results and discussion

The fuel economy improvement using NG-WBT is 1.5% per axle. Scenario-based case studies were conducted. Considering 0% NG-WBT market penetration (or 100% standard dual tire assembly [DTA]) as a baseline, scenario 1 assumed the same fatigue and rutting potential between NG-WBT and DTA; therefore, the only difference came from fuel economy improvement of using NG-WBT. In scenario 2, pavement fatigue cracking potential determined the pavement design life; both thick and thin AC overlay sections experienced positive net environmental savings, but mixed net economic savings. In scenario 3, pavement rutting potential determined the pavement design life; the thick AC overlay section experienced positive net environmental savings, but mixed net economic savings. The thin section experienced negative net environmental and economic savings.

Conclusions

The outcomes of scenario-based case studies indicated that NG-WBT can result in significant savings in life cycle energy consumption and cost, and GWP; however, these benefits were sensitive to the method used to determine the pavement performance; especially, a small change in pavement strain can result in significant change in pavement life. In addition, the effect of fuel price/economy improvement, discount rate, and International Roughness Index (IRI) threshold values was studied in the sensitivity analyses.

     

Comparison of outcomes of percutaneous coronary intervention on proximal versus non-proximal left anterior descending coronary artery, proximal left circumflex, and proximal right coronary artery: A cross-sectional study

Background

There have been few prospective studies examining the utility of routine exercise treadmill testing (ETT) early after percutaneous coronary intervention (PCI). The objective of this study was to examine the impact of a routine ETT strategy early after PCI on follow-up cardiac events and procedures.

Methods

We examined 136 patients who underwent routine ETT at 6 weeks post-PCI in the ADORE trial. The ETT was classified as positive, indeterminate, or negative. The Duke Treadmill Score (DTS) was calculated for all patients. Follow-up occurred at 9 months.

Results

ETT results at 6 weeks were: 32 (23.5%) positive, 24 (17.6%) indeterminate and 80 (58.8%) negative. At 9 months, the composite event rate was 21.9% in those with a positive ETT, 20.8% in those with an indeterminate ETT and 12.5% in those with a negative ETT (p = 0.25 positive vs. negative ETT). The sensitivity of early ETT for predicting clinical events was 41.2%, the specificity was 73.3%, the positive predictive value was 21.9% and the negative predictive value was 87.5%. At 9 months, the cardiac procedure rate was 18.8% in those with a positive test, 13.0% in those with an indeterminate test, and 6.3% in those with a negative test (p = 0.07 positive vs. negative ETT). In a multivariate logistic regression model, coronary stenting during PCI and a ≥ 85% MPHR achieved were found to be inversely associated with clinical events. However, the DTS did not independently predict clinical events.

Conclusion

Although the statistical power of the study was limited by the small number of clinical events (particularly MI and death), the results of this study support the ACC/AHA guidelines that exercise treadmill testing should not be used routinely after PCI.     

Biological Role of Pigment Production for the Bacterial Phytopathogen Pantoea stewartii subsp. stewartii

Pantoea stewartii subsp. stewartii, the causal agent of Stewart's wilt of sweet corn, produces a yellow carotenoid pigment. A nonpigmented mutant was selected from a bank of mutants generated by random transposon mutagenesis. The transposon insertion site was mapped to the crtB gene, encoding a putative phytoene synthase, an enzyme involved in the early steps of carotenoid biosynthesis. We demonstrate here that the carotenoid pigment imparts protection against UV radiation and also contributes to the complete antioxidant pathway of P. stewartii. Moreover, production of this pigment is regulated by the EsaI/EsaR quorum-sensing system and significantly contributes to the virulence of the pathogen in planta.