Performance and cost trade-off in Tracking Area reconfiguration: A Pareto-optimization approach

Tracking Area (TA) design is one of the key tasks in location management of Long Term Evolution (LTE) networks. TA enables to trace and page User Equipments (UEs). As UEs distribution and mobility patterns change over time, TA design may have to undergo revisions. For revising the TA design, the cells to be reconfigured typically have to be temporary torn down. Consequently, this will result in service interruption and “cost”. There is always a trade-off between the performance in terms of the overall signaling overhead of the network and the reconfiguration cost. In this paper, we model this trade-off as a bi-objective optimization problem to which the solutions are characterized by Pareto-optimality. Solving the problem delivers a host of potential trade-offs among which the selection can be based on the preferences of a decision maker. An integer programming model has been developed and applied to the problem. Solving the integer programming model for various cost budget levels leads to an exact scheme for Pareto-optimization. In order to deliver Pareto-optimal solutions for large networks in one single run, a Genetic Algorithm (GA) embedded with Local Search (LS) is applied. Unlike many commonly adopted approaches in multi-objective optimization, our algorithm does not consider any weighted combination of the objectives. Comprehensive numerical results are presented in this study, using large-scale realistic or real-life network scenarios. The experiments demonstrate the effectiveness of the proposed approach.     

P16 and HPV Genotype Significance in HPV-Associated Cervical Cancer—A Large Cohort of Two Tertiary Referral Centers

The expression of p16 is a good surrogate of human papillomavirus (HPV) infection in HPV-associated cancers. The significance of p16 expression, HPV genotype and genera in the outcome of patients with HPV-associated cervical cancer (CC) is unclear. Our aim is to ascertain the prognostic significance of these factors. Data from 348 patients (median age: 47.5 years old) with CC, diagnosed in two referral centers, were retrospectively collected. Advanced disease (FIGO2018 IB2-IV) was present in 68% of patients. A single HPV genotype was identified in 82.8% of patients. The most common HPVs were HPV16 (69%) and HPV18 (14%). HPV genera reflected this distribution. HPV16 tumors presented at an earlier stage. P16 was negative in 18 cases (5.2%), 83.3% of which were squamous cell carcinomas. These cases occurred in older patients who tended to have advanced disease. In the univariate analysis, HPV16 (HR: 0.58; p = 0.0198), α-9 genera (HR: 0.37; p = 0.0106) and p16 overexpression (HR: 0.54; p = 0.032) were associated with better survival. HPV16 (HR: 0.63; p = 0.0174) and α-9 genera (HR: 0.57; p = 0.0286) were associated with less relapse. In the multivariate analysis, only the International Federation of Gynecology and Obstetrics (FIGO) stage retained an independent prognostic value. HPV16, α-9 genera and p16 overexpression were associated with better survival, although not as independent prognostic factors. Patients with p16-negative HPV-associated CC were older, presented with advanced disease and had worse prognosis.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances,Challenges and Future Prospects

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges.     

Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Thermal evaluation of the use of porous ceramic plates on ventilated façades—part II: Thermal behavior

The effects of porous ceramic plates on the thermal behavior of ventilated façades were evaluated, and the results are presented herein. Thermal behavior in a ventilated façade of specimens containing 40 wt% of lime mud and a firing temperature of 1100°C was evaluated and compared with a commercial porcelain ceramic tile, which was the reference material. An experimental apparatus was designed to evaluate the thermal performance of the studied ventilated façades. The results revealed that the ventilated façade composed of the studied porous ceramic tiles produced a greater reduction in temperature between the external environmental and the interior of a box representing a building (ΔT5) of 65.7°C, compared with the façade composed of the commercial porcelain ceramic tiles (ΔT5 = 56.0°C) and even the traditional façade (ΔT5 = 49.1°C). Thus, porous ceramic tiles based on byproducts are promising candidates for ventilated façade systems.     

Consequences of different cutting regimes on regrowth and nutrient stoichiometry of Sparganium erectum L. and Potamogeton natans L.

Aquatic vegetation forms an essential component in freshwater ecosystems but due to changed environmental and anthropogenic conditions often needs management to reduce nuisance for human land‐use. In this paper, the authors looked at the regrowth of two macrophyte species (Potamogeton natans and Sparganium erectum) in two lowland rivers under different cutting treatments. After an initial cross‐sectional transect was manually removed from bank to bank at the beginning of the growth season, a monthly repetitive removal of biomass in plots on that transect was done during the rest of the growth season (testing frequency of mowing). Additional new transects were also cut in subsequent months (testing timing of mowing). Finally, biomass was repetitively removed in plots in those additional transects too (testing frequency of mowing × timing of mowing). The biomass at the end of the growth season was analysed for C, N, P, and Si. It was demonstrated that timing and frequency of vegetation cutting has an important effect on the capacity and rate of species' recovery and therefore on the efficiency of the applied management. Nutrient stoichiometry of the regrown biomass was directly affected by cutting. Caused by differences in the applied timing and frequency of the cutting, C/N and N/P ratios and BSi concentrations were highly variable. Yet, overall, there was a clear tendency towards a higher C/N ratio and BSi concentration and lower N/P ratio in biomass that recovered after cutting. This human impact on the quantity and quality of autochthonous organic matter may have knock‐on effects on the decomposers food web and mineralization process.     

Evaluation and characterization of ammoniumpolyphosphate–pentaerythritol‐based systems for intumescent coatings

Intumescent coatings are increasingly used as a method of passive fire protection on steel constructions. By forming a carbon network and releasing a blowing agent, the thin intumescent film swells 100‐fold at elevated temperatures. The highly insulating foam effectively prevents the load bearing steel from reaching its critical temperature at which it looses its mechanical properties and collapses. The role of the carbon donor in intumescent coatings has been studied. Comparison in temperature development, foaming ratios, and rheological behavior has been performed between formulations containing pentaerythritol (penta), di–penta, and tri–penta. A simulated fire test, in which the temperature development during intumescence was studied, showed that the formulations containing penta were considerably more efficient in keeping a low temperature throughout the process. A more rapid temperature development was displayed when using di–penta and tri–penta as the carbon donor. Rheometer tests indicate that penta formulations enter the intumescent process at a lower temperature and stays in it for a longer time than di–penta and tri–penta formulations. Furthermore, the crossover temperature and maximum phase angle are shifted towards higher temperatures by replacing penta with di–penta and with tri–penta in the formulations, respectively. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 748–753, 2007     

Influence of Pt Loading on Al2O3 for the Low Temperature Combustion of Methanol with and Without a Trace Amount of Ammonia

Pt/Al₂O₃ catalysts with platinum contents of 0.1, 1.0 and 3.0 wt% were used for the low temperature combustion of methanol in the absence and the respective presence of a trace amount of ammonia. It is observed that ammonia inhibits the combustion of methanol, which is due to competition between methanol and ammonia for the same sites. For a fixed space velocity and without ammonia in the gas, the performances of the catalysts increase up to a Pt loading of 1.0 wt%. In the presence of ammonia, however, no upper limit of performance is observed with increased Pt content. The results are discussed in terms of both Pt–support interface and the Pt surface being active.     

EVALUATION OF A METHOD FOR MEASURING MIXING TIME USING NUMERICAL SIMULATION AND EXPERIMENTAL DATA

A method for measuring mixing performance in large-scale vessels is investigated. The method is evaluated experimentally in a pilotscale reactor and by using a model based on the three-dimensional calculation of the flow field. The method is based on injection of a tracer and measuring the concentration with several detectors at different locations. The mixing performance is measured as the decay rate of the difference between the concentration at the detectors and the final concentration.

The model predicts a strong dependence on injection point. The assumption of a first-order decay rate of the concentration deviation is more appropriate for some injection points.