scholarly journals Spatio-Genetic and Phenotypic Modelling Elucidates Resistance and Re-Sensitisation to Treatment in Heterogeneous Melanoma

2018 ◽  
Author(s):  
Arran Hodgkinson ◽  
Laurent Le Cam ◽  
Dumitru Trucu ◽  
Ovidiu Radulescu
Keyword(s):  
Treatment Effectiveness ◽  
Rapid Development ◽  
Tumour Volume ◽  
Braf Inhibitors ◽  
Development Of Resistance ◽  
Time Space ◽  
Gradual Evolution ◽  
Cellular Population ◽  
Tumour Cell Population

AbstractAlthough novel targeted therapies have significantly improved the overall survival of patients with advanced melanoma, understanding and combatting drug resistance remains a major clinical challenge. Using partial differential equations, we describe the evolution of a cellular population through time, space, and phenotype dimensions, in the presence of various drug species. We then use this framework to explore models in which resistance is attained by either mutations (irreversible) or plasticity (reversible). Numerical results suggest that punctuated evolutionary assumptions are more consistent with results obtained from murine melanoma models than gradual evolution. Furthermore, in the context of an evolving tumour cell population, sequencing the treatment, for instance applying immunotherapy before BRAF inhibitors, can increase treatment effectiveness. However, drug strategies which showed success within a spatially homogeneous tumour environment were unsuccessful under heterogeneous conditions, suggesting that spatio-environmental heterogeneity may be the greatest challenge to tumour therapies. Plastic metabolic models are additionally capable of reproducing the characteristic resistant tumour volume curves and predicting re-sensitisation to secondary waves of treatment observed in patient derived xenograft (PDX) melanomas treated with MEK and BRAF inhibitors. Nevertheless, secondary relapse due to a pre-adapted subpopulation, remaining after the first wave of treatment, results in a more rapid development of resistance. Our model provides a framework through which tumour resistance can be understood and would suggest that carefully phased treatments may be able to overcome the development of long-term resistance in melanoma.

scholarly journals Space-Time Evolution of Subway Vulnerability Based on Hypergraph Space

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Kaihua Lu ◽  
Xiaoyan Gu
Keyword(s):  
Rapid Development ◽  
Efficiency Index ◽  
Development Stage ◽  
Space Structure ◽  
Normal Operation ◽  
Gradual Change ◽  
Time Space ◽  
Subway System ◽  
Main City

How to qualitatively and quantitatively evaluate the ability of the whole subway system to maintain the maximum normal operation has become a noteworthy topic. In this study, the hypergraph space structure of Nanjing subway network is used for research. This study uses the method of time-space evolution mechanism to dynamically and quantitatively analyze the gradual change characteristics of Nanjing subway system vulnerability under the influence of time and space. In addition, this study also makes static and dynamic comparative analysis on the vulnerability of a subway system by using connectivity rate and trip efficiency index, which provides new analysis methods and ideas for the study of a subway system network. The results show that although the overall structure of Nanjing’s subway network shows a loose trend, as Nanjing’s subway is still in a rapid development stage, it can be seen from the long-term planning of Nanjing’s subway that the construction of Nanjing’s subway ring line will be strengthened after the completion of the connection between the main city and the suburbs. Therefore, the vulnerability of the subway system should be reduced and the reliability will be improved.

Factors affecting resistance to insecticides in house-flies, Musca domestica L. (Diptera: Muscidae). I. Long-term control with bioresmethrin of flies with strong pyrethroid-resistance potential

1983 ◽  
Vol 73 (3) ◽  
pp. 481-489 ◽  
Author(s):  
I. Denholm ◽  
A. W. Farnham ◽  
Kate O'dell ◽  
R. M. Sawicki
Keyword(s):  
Musca Domestica ◽  
Pyrethroid Resistance ◽  
Rapid Development ◽  
Effective Control ◽  
Factors Affecting ◽  
House Flies ◽  
Development Of Resistance ◽  
Evolution Of Resistance ◽  
Pig Farm

AbstractThe assumption that by minimising contact with pyrethroids, satisfactory control of Musca domestica L. could be retained without eliciting resistance was tested on a pig farm in southern England where permethrin had failed through rapid development of resistance. Flies were satisfactorily controlled in enclosed buildings for 12 months by space spraying bioresmethrin (2 mg a.i./m3) at approximately fortnightly intervals when numbers reached an arbitrary nuisance level. Throughout this period, bioassays revealed no increase in tolerance of pyrethroids, although selection experiments in the laboratory confirmed the strong pyrethroid-resistance potential of the fly population. Thus effective control can be retained in spite of strong resistance potential when non-persistent insecticides are used intermittently. The results are discussed in the light of a published theoretical study of the influence of pesticide persistence on the evolution of resistance.

scholarly journals Consistent Long-Term Monthly Coastal Wetland Vegetation Monitoring Using a Virtual Satellite Constellation

2021 ◽  
Vol 13 (3) ◽  
pp. 438
Author(s):  
Subrina Tahsin ◽  
Stephen C. Medeiros ◽  
Arvind Singh
Keyword(s):  
Vegetation Index ◽  
Coastal Wetland ◽  
Thermal Emission ◽  
Mean Squared Error ◽  
Wetland Vegetation ◽  
Coefficient Of Determination ◽  
Landsat 8 ◽  
Vegetation Monitoring ◽  
Time Space

Long-term monthly coastal wetland vegetation monitoring is the key to quantifying the effects of natural and anthropogenic events, such as severe storms, as well as assessing restoration efforts. Remote sensing data products such as Normalized Difference Vegetation Index (NDVI), alongside emerging data analysis techniques, have enabled broader investigations into their dynamics at monthly to decadal time scales. However, NDVI data suffer from cloud contamination making periods within the time series sparse and often unusable during meteorologically active seasons. This paper proposes a virtual constellation for NDVI consisting of the red and near-infrared bands of Landsat 8 Operational Land Imager, Sentinel-2A Multi-Spectral Instrument, and Advanced Spaceborne Thermal Emission and Reflection Radiometer. The virtual constellation uses time-space-spectrum relationships from 2014 to 2018 and a random forest to produce synthetic NDVI imagery rectified to Landsat 8 format. Over the sample coverage area near Apalachicola, Florida, USA, the synthetic NDVI showed good visual coherence with observed Landsat 8 NDVI. Comparisons between the synthetic and observed NDVI showed Root Mean Squared Error and Coefficient of Determination (R2) values of 0.0020 sr−1 and 0.88, respectively. The results suggest that the virtual constellation was able to mitigate NDVI data loss due to clouds and may have the potential to do the same for other data. The ability to participate in a virtual constellation for a useful end product such as NDVI adds value to existing satellite missions and provides economic justification for future projects.

scholarly journals COVD-01. VINBLASTINE MONOTHERAPY INDUCTION FOR LOCALISED CNS GERMINOMA DURING THE COVID-19 PANDEMIC

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii282-iii282
Author(s):  
Rafael Moleron ◽  
Sara Stoneham ◽  
Thankamma Ajithkumar ◽  
Justin Cross ◽  
James Nicholson ◽  
...  
Keyword(s):  
Germ Cell ◽  
Treatment Options ◽  
Single Agent ◽  
Germ Cell Tumour ◽  
Research Priorities ◽  
Tumour Volume ◽  
Cell Tumour ◽  
Low Grade ◽  
Testicular Seminoma

Abstract INTRODUCTION Patients with localised CNS-germinoma have excellent survival. More recently, intensive inpatient chemotherapy (carboPEI=carboplatin/etoposide/ifosfamide in Europe) has been effectively employed to reduce radiotherapy fields and/or dose. Current research priorities focus on reducing treatment burden and long-term sequelae. Of note, outpatient-based single-agent carboplatin chemotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology) [Alifrangis,EJC,2020]. Recently, successful vinblastine monotherapy was reported in localised CNS-germinoma [Murray,Neurooncol-Adv,2020]. METHODS Due to the COVID-19 pandemic, adapted UK guidelines for germ-cell-tumour management were distributed, including potential non-standard treatment options that would reduce hospital visits/admissions. A 30-year-old patient presented with a 32mmx30mmx35mm diameter solid+multi-cystic localised pineal CNS lesion, consistent radiologically with a germ-cell-tumour with prominent teratoma component. Investigation revealed negative AFP/HCG markers and biopsy-proven pure germinoma. After appropriate consent, the patient commenced 12-week induction with weekly vinblastine monotherapy (low-grade-glioma dosing [Lassaletta,JCO,2016]), with wk6&12 MRI re-assessment prior to definitive radiotherapy. RESULTS Vinblastine was well-tolerated. After initial 4mg/m2 test-dosing (wk1), standard 6mg/m2 was delivered for wk2, but resulted in asymptomatic neutropenia (nadir 0.3x10^9/l) and missed dosing at wk3. Subsequent doses were 4mg/m2, with no further neutropenia. As expected, MRI showed moderate 40% tumour volume reduction by wk12. Surgical resection of the residual presumed teratoma component was undertaken prior to radiotherapy. CONCLUSION Patients with CNS-germinoma have excellent outcomes and reduction of treatment-effects remains a priority. The exquisite chemosensitivity of germinoma, excellent results from monotherapy for metastatic testicular disease, and early promise of vinblastine monotherapy lend itself to further exploration for CNS-germinoma.

scholarly journals Time-Based Corporate-Social-Responsibility Evaluation Model Taking Chinese Listed Forestry Companies as an Example

2021 ◽  
Vol 13 (14) ◽  
pp. 7971
Author(s):  
Xinfei Li ◽  
Baodong Cheng ◽  
Heng Xu
Keyword(s):  
Corporate Social Responsibility ◽  
Social Responsibility ◽  
Evaluation Model ◽  
Rapid Development ◽  
Entropy Method ◽  
Static State ◽  
Different Types ◽  
Normative Constraints ◽  
Corporate Social

With the rapid development of the economy, corporate social responsibility (CSR) is receiving increasing attention from companies themselves, but also increasing attention from society as a whole. How to reasonably evaluate the performance of CSR is a current research hotspot. Existing corporate-social-responsibility evaluation methods mostly focus on the static evaluation of enterprises in the industry, and do not take the time factor into account, which cannot reflect the performance of long-term CSR. On this basis, this article proposes a time-based entropy method that can evaluate long-term changes in CSR. Studies have shown that the completion of CSR in a static state does not necessarily reflect the dynamic and increasing trend of CSR in the long term. Therefore, the assessment of CSR should consider both the static and dynamic aspects of a company. In addition, the research provides the focus of different types of forestry enterprises in fulfilling CSR in the long term, and provides a clearer information path for the standard identification and normative constraints of different types of forestry enterprises CSR.

scholarly journals Moderate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yun C. Chang ◽  
Ami Khanal Lamichhane ◽  
Hongyi Cai ◽  
Peter J. Walter ◽  
John E. Bennett ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
High Frequency ◽  
Antifungal Agent ◽  
Inhibitory Concentration ◽  
Glucuronic Acid ◽  
Rapid Development ◽  
Acid Synthesis ◽  
Transcriptional Factor ◽  
Development Of Resistance ◽  
Acid Accumulation

AbstractThe antifungal agent 5-fluorocytosine (5-FC) is used for the treatment of several mycoses, but is unsuitable for monotherapy due to the rapid development of resistance. Here, we show that cryptococci develop resistance to 5-FC at a high frequency when exposed to concentrations several fold above the minimal inhibitory concentration. The genomes of resistant clones contain alterations in genes relevant as well as irrelevant for 5-FC resistance, suggesting that 5-FC may be mutagenic at moderate concentrations. Mutations in FCY2 (encoding a known permease for 5-FC uptake), FCY1, FUR1, UXS1 (encoding an enzyme that converts UDP-glucuronic acid to UDP-xylose) and URA6 contribute to 5-FC resistance. The uxs1 mutants accumulate UDP-glucuronic acid, which appears to down-regulate expression of permease FCY2 and reduce cellular uptake of the drug. Additional mutations in genes known to be required for UDP-glucuronic acid synthesis (UGD1) or a transcriptional factor NRG1 suppress UDP-glucuronic acid accumulation and 5-FC resistance in the uxs1 mutants.

Measuring Dynamic Sales Impacts of LBA Using Wireless Communication Technology

2013 ◽  
Vol 662 ◽  
pp. 896-901
Author(s):  
Zong Jin Liu ◽  
Yang Yang ◽  
Zheng Fang ◽  
Yan Yan Xu
Keyword(s):  
Wireless Communication ◽  
Error Correction ◽  
Communication Technology ◽  
Dynamic Error ◽  
Rapid Development ◽  
Vector Autoregressive ◽  
Vector Error Correction ◽  
Vector Error ◽  
Equilibrium Relationship

Because of rapid development of wireless communication technology, there is an increasing adoption of mobile advertising, such as location based advertising (LBA). To what extent can LBA improve advertising effectiveness is an important topic in the field of wireless communication technology research. Most researches quantify long term impacts of advertisings by VAR (Vector Autoregressive) model. However, compared to VAR model, VECM (Vector Error Correction Model) is a better method in that it allows one to estimate both a long-term equilibrium relationship and a short-term dynamic error correction process. In this study, we employ VECM to explore LBA’s (Location Based Advertising) and PUA’s (Pop-up Advertising) sales impact in both short and long terms. The developed VECM reveals that LBA’s sales impact is about more than2 times as big as PUA’s in short dynamic term and nearly 6 times bigger than PUA’s in long equilibrium term. These findings add to advertising and VECM literatures. These results can give managers more confident to apply wireless communication technology to advertising.

The PLC Research in the Program Control System of Thermal Power Coal Handling

2012 ◽  
Vol 548 ◽  
pp. 812-816
Author(s):  
Xiao Min Chen ◽  
Xi Yan Liu
Keyword(s):  
Power Plants ◽  
Rapid Development ◽  
Thermal Power ◽  
Chinese Economy ◽  
Power Requirement ◽  
Handling System ◽  
Human Power ◽  
Material Resources ◽  
Electricity System

With the rapid development of Chinese economy, the thermal power requirement is increasing not only in industry but also for the civil use in recent years. In China, the main fuel of thermal power is coal. Coal handling system places the consequence in the whole generate electricity system and has significant meaning to the power plant operation. The coal handling system of the thermal power plants has many types of equipment. The environment is vile with complicated control. If we control this system through manual mode, there will appear the imponderable questions. This article through the research of the coal handling system by the management of PLC can determine the long-term safe operation and reduce a mass of human power and material resources. It has the fundamental practical meaning and research value.

scholarly journals Spatial and Temporal Changes in PD-L1 Expression in Cancer: The Role of Genetic Drivers, Tumor Microenvironment and Resistance to Therapy

2020 ◽  
Vol 21 (19) ◽  
pp. 7139 ◽  
Author(s):  
Elena Shklovskaya ◽  
Helen Rizos
Keyword(s):  
Tumor Microenvironment ◽  
Patient Outcomes ◽  
Cytotoxic T Lymphocyte ◽  
Cell Types ◽  
Development Of Resistance ◽  
Improve Patient Selection ◽  
Potential Biomarker ◽  
Programmed Cell Death 1 ◽  
Tumor Biopsies

Immunotherapies blocking immune inhibitory receptors programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) on T-cells have dramatically improved patient outcomes in a range of advanced cancers. However, the lack of response, and the development of resistance remain major obstacles to long-term improvements in patient outcomes. There is significant interest in the clinical use of biomarkers to improve patient selection, and the expression of PD-1 ligand 1 (PD-L1) is often reported as a potential biomarker of response. However, accumulating evidence suggests that the predictive value of PD-L1 expression in tumor biopsies is relatively low due, in part, to its complex biology. In this review, we discuss the biological consequences of PD-L1 expression by various cell types within the tumor microenvironment, and the complex mechanisms that regulate PD-L1 expression at the genomic, transcriptomic and proteomic levels.

scholarly journals Customer Segmentation Through Path Reconstruction

2020 ◽  
Author(s):  
Santiago García
Keyword(s):  
Rapid Development ◽  
Customer Segmentation ◽  
Smart Phones ◽  
Indoor Environments ◽  
Flow Conditions ◽  
Gps Receivers ◽  
Current State ◽  
Different Types

With the rapid development of smart phones, tablets and their operative systems, many positioning enabled sensors have been built into these devices. Users can now accurately fix their location according to the function of GPS receivers. For indoor environments, as in the case we are studying, WiFi based positioning is preferred to GPS due to the attenuation or obstruction of signals. This paper deals with the automatic classification of customers in a Sports Shop Center on the basis of their movements around the shop's premises. To achieve this goal, we start by collecting (x,y) coordinates from customers while they visit the store. Consequently, any costumer's path through the shop is formed by a list of coordinates, obtained with a frequency of one measurement per minute. Then, a guess about the full trajectory is constructed and a number of parameters about these trajectories is calculated before performing an Unsupervised Learning Clustering Process. As a result, we can identify several types of customers, and the dynamics of their behavior inside the shop. This information is of great value to the company, to be used both in the long term and also in short periods of time, monitoring the current state of the shop at any moment, identifying different types of situation appearing during restricted periods, or predicting customer flow conditions

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