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1.
J Hazard Mater ; 458: 131747, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37454488

ABSTRACT

To assist in emergency preparedness for a biological agent terrorist attack or accidental pathogen release, potential contaminant levels and migration pathways of spores spread by urban stormwater were evaluated using a Storm Water Management Model (SWMM) of U.S. Coast Guard Base Elizabeth City, North Carolina. The high temporal-spatial resolution SWMM model was built using spore concentrations in stormwater runoff from asphalt, grass, and concrete collected from a point-scale field study. The subsequent modeled contamination scenarios included a notional plume release and point releases mimicking the field study under three rainfall conditions. The rainfall scenarios included a 6-hour natural rainfall event on Dec. 8, 2021 and two design storms (2-year and 100-year events). The observed spore concentrations from asphalt and concrete from the actual field experiment were applied to calibrate the washoff parameters in the SWMM model, using an exponential washoff function. The calibrated washoff coefficient (c1) and exponent (c2) were 0.01 and 1.00 for asphalt, 0.05 and 1.45 for grass, and 2.45 and 1.00 for concrete, respectively. The calibrated SWMM model simulated spore concentrations in runoff at times and magnitudes similar to the field study data. In the point release modeled scenario, the concrete surface generated 55.6% higher average spore concentrations than asphalt. Similarly, in the field experiment, a 175% (p < 0.05) higher average spore concentration in surface runoff was observed from concrete than from asphalt. This study demonstrates how SWMM may be used to evaluate spore washoff from urban surfaces under different precipitation amounts, intensities, and durations, and how visualized spatial migration pathways in stormwater runoff may be used for emergency planning and remediation.


Subject(s)
Water Pollutants, Chemical , Water , Rain , Water Pollutants, Chemical/analysis , Cities , Poaceae , Water Movements
2.
Polymers (Basel) ; 14(18)2022 Sep 17.
Article in English | MEDLINE | ID: mdl-36146034

ABSTRACT

Microplastics are harmful to both marine life and humans. Herein, a pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) technique for the detection of microplastics in aquatic shellfish is demonstrated. The organic matter in aquatic shellfish was removed by alkali digestion. Subsequently, using hexafluoroisopropanol as the extraction solvent, the extraction method was optimized. The influence of the digestion process on the nature of microplastics was investigated by analyzing the samples before and after the alkali treatment via infrared spectrometry, laser particle sizing, and scanning electron microscopy. Spiked recovery experiments and an analysis of actual samples were performed using PA6 and PA66 as analytes. A quantitative analysis of the characteristic ion fragment produced by high-temperature cracking was performed after chromatographic separation and mass spectrometry identification. The linear range of this method for PA6 and PA66 was 2-64 µg. The limits of detection of PA6 and PA66 were 0.2 and 0.6 µg, while the limits of quantitation were 0.6 and 2.0 µg, respectively. Recovery ranged from 74.4 to 101.62%, with a precision of 4.53-7.56%. The results suggest that the Py-GC/MS technique is suitable for the analysis and detection of trace microplastics in aquatic shellfish.

3.
Pest Manag Sci ; 78(10): 4314-4323, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35731693

ABSTRACT

BACKGROUND: A spider mite control method using night-time ultraviolet (UV)-B irradiation was recently developed for strawberry greenhouses (UV method). The control effect of this UV method is negatively affected by increasing temperature. Tetranychus urticae eggs are more resistant to a single dose of UV-B irradiation than Neoseiulus californicus eggs. By contrast, N. californicus can better survive nightly UV-B irradiation with the UV method compared with T. urticae. To elucidate the mechanism underlying these phenomena, we explored the hypotheses that higher temperature promotes photoenzymatic repair (PER) and that mortality is determined by UV-B susceptibility in the embryonic stage exposed to UV-B. RESULTS: PER efficacy was not promoted by increasing temperature. The lowest hatchability (around zero) of T. urticae eggs after a single dose of UV-B irradiation (0.288 and 0.432 kJ m-2 ) without photoreactivation was seen in the morphogenesis stages between "cleavage ended" and "eye points became colored". Based on these results, we developed a linear function of daily UV-B irradiance and deviation of cumulative irradiance during vulnerable embryonic developmental phases from 50% lethal dose (LD50 ) after a single dose of UV-B irradiation. The difference between T. urticae and N. californicus and changes in UV-B vulnerability due to temperature could be explained by this simple relationship. CONCLUSION: Slower development in T. urticae than N. californicus in nature and developmental delay under low temperatures increase the ovicidal effects of the UV method. This shows the advantage of the simultaneous use of the UV method and biological control, contributing to the development of integrated pest management. © 2022 Society of Chemical Industry.


Subject(s)
Fragaria , Tetranychidae , Animals , Pest Control, Biological , Predatory Behavior , Temperature , Tetranychidae/physiology , Tick Control/methods , Ultraviolet Rays
4.
Nat Cell Biol ; 24(2): 230-241, 2022 02.
Article in English | MEDLINE | ID: mdl-35145222

ABSTRACT

Many cancers have an unusual dependence on glutamine. However, most previous studies have focused on the contribution of glutamine to metabolic building blocks and the energy supply. Here, we report that cancer cells with aberrant expression of glutamate decarboxylase 1 (GAD1) rewire glutamine metabolism for the synthesis of γ-aminobutyric acid (GABA)-a prominent neurotransmitter-in non-nervous tissues. An analysis of clinical samples reveals that increased GABA levels predict poor prognosis. Mechanistically, we identify a cancer-intrinsic pathway through which GABA activates the GABAB receptor to inhibit GSK-3ß activity, leading to enhanced ß-catenin signalling. This GABA-mediated ß-catenin activation both stimulates tumour cell proliferation and suppresses CD8+ T cell intratumoural infiltration, such that targeting GAD1 or GABABR in mouse models overcomes resistance to anti-PD-1 immune checkpoint blockade therapy. Our findings uncover a signalling role for tumour-derived GABA beyond its classic function as a neurotransmitter that can be targeted pharmacologically to reverse immunosuppression.


Subject(s)
Cell Proliferation , Neoplasms/metabolism , Tumor Escape , Tumor Microenvironment/immunology , beta Catenin/metabolism , gamma-Aminobutyric Acid/metabolism , A549 Cells , Animals , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , HCT116 Cells , HEK293 Cells , HT29 Cells , Humans , Immune Checkpoint Inhibitors/pharmacology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Mice, Inbred C57BL , Mice, Nude , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/pathology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Receptors, GABA-B/metabolism , Tumor Burden , Tumor Escape/drug effects , Wnt Signaling Pathway , Xenograft Model Antitumor Assays , beta Catenin/genetics
5.
PLoS One ; 16(4): e0248489, 2021.
Article in English | MEDLINE | ID: mdl-33844687

ABSTRACT

Accurate streamflow prediction plays a pivotal role in hydraulic project design, nonpoint source pollution estimation, and water resources planning and management. However, the highly non-linear relationship between rainfall and runoff makes prediction difficult with desirable accuracy. To improve the accuracy of monthly streamflow prediction, a seasonal Support Vector Regression (SVR) model coupled to the Soil and Water Assessment Tool (SWAT) model was developed for 13 subwatersheds in the Illinois River watershed (IRW), U.S. Terrain, precipitation, soil, land use and land cover, and monthly streamflow data were used to build the SWAT model. SWAT Streamflow output and the upstream drainage area were used as two input variables into SVR to build the hybrid SWAT-SVR model. The Calibration Uncertainty Procedure (SWAT-CUP) and Sequential Uncertainty Fitting-2 (SUFI-2) algorithms were applied to compare the model performance against SWAT-SVR. The spatial calibration and leave-one-out sampling methods were used to calibrate and validate the hybrid SWAT-SVR model. The results showed that the SWAT-SVR model had less deviation and better performance than SWAT-CUP simulations. SWAT-SVR predicted streamflow more accurately during the wet season than the dry season. The model worked well when it was applied to simulate medium flows with discharge between 5 m3 s-1 and 30 m3 s-1, and its applicable spatial scale fell between 500 to 3000 km2. The overall performance of the model on yearly time series is "Satisfactory". This new SWAT-SVR model has not only the ability to capture intrinsic non-linear behaviors between rainfall and runoff while considering the mechanism of runoff generation but also can serve as a reliable regional tool for an ungauged or limited data watershed that has similar hydrologic characteristics with the IRW.


Subject(s)
Forecasting/methods , Hydrology/methods , Water Movements , Calibration , Environmental Monitoring/methods , Estuaries , Illinois , Models, Theoretical , Rivers , Spatial Analysis , Support Vector Machine , Water
6.
Pest Manag Sci ; 77(2): 851-859, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32949092

ABSTRACT

BACKGROUND: A new physical control method using ultraviolet-B (UV-B) lamps and light-reflecting sheets (UV method) significantly suppressed a spider mite population on greenhouse strawberries. Although UV-B radiation may adversely affect the survival of phytoseiid mites, previous research has suggested that Neoseiulus californicus can improve its survival on exposure to UV-B irradiation by consuming antioxidants contained in tea and peach pollen. In this study, we evaluated strawberry pollen as an alternative food source for N. californicus and examined whether antioxidants in the pollen mitigated UV-B damage to N. californicus. RESULTS: The fecundity of N. californicus females reared on Tetranychus urticae decreased on shifting their diet to pollen. By contrast, females reared continuously on strawberry pollen produced as many eggs as females reared continuously on T. urticae. Survival and fecundity after UV-B irradiation were higher in females on the pollen diet. Oxygen radical absorbance capacity analysis revealed that the high antioxidant activity of strawberry pollen was due to four hydroxycinnamoyl spermidine derivatives. CONCLUSION: Strawberry pollen was an adequate alternative food source for N. californicus. Feeding on strawberry pollen, which contains spermidine derivatives with high antioxidant activity, mitigated UV-B damage. This shows the potential of combining the UV-method with N. californicus for controlling T. urticae in strawberries.


Subject(s)
Fragaria , Mites , Tetranychidae , Animals , Female , Pest Control, Biological , Pollen , Predatory Behavior
7.
Geosciences (Basel) ; 10(25): 1-36, 2020 Jan 11.
Article in English | MEDLINE | ID: mdl-32983579

ABSTRACT

Watershed-scale nonpoint source (NPS) pollution models have become important tools to understand, evaluate, and predict the negative impacts of NPS pollution on water quality. Today, there are many NPS models available for users. However, different types of models possess different form and structure as well as complexity of computation. It is difficult for users to select an appropriate model for a specific application without a clear understanding of the limitations or strengths for each model or tool. This review evaluates 14 more commonly used watershed-scale NPS pollution models to explain how and when the application of these different models are appropriate for a given effort. The models that are assessed have a wide range of capacities that include simple models used as rapid screening tools (e.g., Long-Term Hydrologic Impact Assessment (L-THIA) and Nonpoint Source Pollution and Erosion Comparison Tool (N-SPECT/OpenNSPECT)), medium-complexity models that require detail data input and limited calibration (e.g., Generalized Watershed Loading Function (GWLF), Loading Simulation Program C (LSPC), Source Loading and Management Model (SLAMM), and Watershed Analysis Risk Management Frame (WARMF)), complex models that provide sophisticated simulation for NPS pollution processes with intensive data and rigorous calibration (e.g., Agricultural Nonpoint Source pollution model (AGNPS/AnnAGNPS), Soil and Water Assessment Tool (SWAT), Stormwater Management Model (SWMM), and Hydrologic Simulation Program Fortran (HSPF)), and modeling systems that integrate various sub-models and tools, and contain the highest complexity to solve all phases of hydrologic, hydraulic, and chemical dynamic processes (e.g., Automated Geospatial Watershed Assessment Tool (AGWA), Better Assessment Science Integrating Point and Nonpoint Sources (BASINS) and Watershed Modeling System (WMS)). This assessment includes model intended use, components or capabilities, suitable land-use type, input parameter type, spatial and temporal scale, simulated pollutants, strengths and limitations, and software availability. Understanding the strengths and weaknesses of each watershed-scale NPS model will lead to better model selection for suitability and help to avoid misinterpretation or misapplication in practice. The article further explains the crucial criteria for model selection, including spatial and temporal considerations, calibration and validation, uncertainty analysis, and future research direction of NPS pollution models. The goal of this work is to provide accurate and concise insight for watershed managers and planners to select the best-suited model to reduce the harm of NPS pollution to watershed ecosystems.

8.
Sci China Life Sci ; 63(3): 332-342, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32060861

ABSTRACT

Cellular senescence (CS) is a state of stable cell cycle arrest characterized by the production and secretion of inflammatory molecules. Early studies described oncogene-induced senescence (OIS) as a barrier to tumorigenesis, such that the therapeutic induction of CS might represent a rational anti-cancer strategy. Indeed, the validity of this approach has been borne out by the development and approval of the cyclin-dependent kinase (CDK) inhibitor palbociclib for the treatment of breast cancer. Apart from tumors, senescent cells have also been shown to accumulate during natural mammalian aging, where they produce detrimental effects on the physiology of surrounding tissues. Thus, pharmacological senescent cell depletion has been proposed as an approach to delay age-related functional decline; this has been formally demonstrated in animal models. In this review article, we describe the current mechanistic understanding of cellular senescence at the molecular level and how it informs the development of new therapeutic strategies to combat cancer and aging.


Subject(s)
Aging/drug effects , Antineoplastic Agents/pharmacology , Cellular Senescence/drug effects , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyridines/pharmacology , Animals , Antineoplastic Agents/metabolism , Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Cell Transformation, Neoplastic/drug effects , Cyclin-Dependent Kinases/antagonists & inhibitors , Drug Discovery , Female , Humans , Piperazines/metabolism , Protein Kinase Inhibitors/metabolism , Pyridines/metabolism
9.
Photochem Photobiol ; 96(4): 877-882, 2020 07.
Article in English | MEDLINE | ID: mdl-31886904

ABSTRACT

The two-spotted spider mite, Tetranychus urticae, is an economically important agricultural pest. A novel physical control method involving daily nighttime UV-B irradiation was recently developed for use in strawberry greenhouses. However, the overlapping of leaves after March prevents direct irradiation to T. urticae on the lower leaf surface, decreasing control effect. Excessive UV-B irradiation causes leaf sunscald in winter. Therefore, optimization of UV-B irradiance and a compensatory control agent are desired. Temperature may affect the survival of organisms exposed to UV-B, although the temperature dependence of UV-B damage is controversial. A phytoseiid mite, Neoseiulus californicus, is a prominent predator but vulnerable to a single UV-B irradiation. We compared dose-response and temperature dependence of UV-B damage between T. urticae and N. californicus eggs under daily nighttime UV-B irradiation. Unexpectedly, N. californicus showed greater resistance to UV-B than T. urticae, and the mortality was increased and decreased at low and high temperatures, respectively. This makes possible the application of UV-B doses that are lethal for spider mites but safe for phytoseiid mites. Overall, we concluded that combined use of phytoseiid mites with UV-B lamps is advantageous to spider mite management in strawberry greenhouses.


Subject(s)
Ovum , Predatory Behavior , Temperature , Tetranychidae/physiology , Ultraviolet Rays , Animals , Dose-Response Relationship, Radiation , Fragaria/parasitology , Plant Leaves/parasitology , Tetranychidae/radiation effects
10.
Water (Basel) ; 12(1): 39, 2019 Dec 20.
Article in English | MEDLINE | ID: mdl-32983578

ABSTRACT

Soil erosion and lake sediment loading are primary concerns of watershed managers around the world. In the Xinjiang River Basin of China, severe soil erosion occurs primarily during monsoon periods, resulting in sediment flow into Poyang Lake and subsequently causing lake water quality deterioration. Here, we identified high-risk soil erosion areas and conditions that drive sediment yield in a watershed system with limited available data to guide localized soil erosion control measures intended to support reduced sediment load into Poyang Lake. We used the Soil and Water Assessment Tool (SWAT) model to simulate monthly and annual sediment yield based on a calibrated SWAT streamflow model, identified where sediment originated, and determined what geographic factors drove the loading within the watershed. We applied monthly and daily streamflow discharge (1985-2009) and monthly suspended sediment load data (1985-2001) to Meigang station to conduct parameter sensitivity analysis, calibration, validation, and uncertainty analysis of the model. The coefficient of determination (R 2), Nash-Sutcliffe efficiency (NSE), percent bias (PBIAS), and RMSE -observation's standard deviation ratio (RSR) values of the monthly sediment load were 0.63, 0.62, 3.8%, and 0.61 during calibration, respectively. Spatially, the annual sediment yield rate ranged from 3 ton ha-1year-1 on riparian lowlands of the Xinjiang main channel to 33 ton ha-1year-1 on mountain highlands, with a basin-wide mean of 19 ton ha-1year-1. The study showed that 99.9% of the total land area suffered soil loss (greater than 5 ton ha-1year-1). More sediment originated from the southern mountain highlands than from the northern mountain highlands of the Xinjiang river channel. These results suggest that specific land use types and geographic conditions can be identified as hotspots of sediment source with relatively scarce data; in this case, orchards, barren lands, and mountain highlands with slopes greater than 25° were the primary sediment source areas. This study developed a reliable, physically-based streamflow model and illustrates critical source areas and conditions that influence sediment yield.

11.
Nat Commun ; 9(1): 4274, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30323337

ABSTRACT

Intrinsic resistance to anti-HER2 therapy in breast cancer remains an obstacle in the clinic, limiting its efficacy. However, the biological basis for intrinsic resistance is poorly understood. Here we performed a CRISPR/Cas9-mediated loss-of-function genetic profiling and identified TALDO1, which encodes the rate-limiting transaldolase (TA) enzyme in the non-oxidative pentose phosphate pathway, as essential for cellular survival following pharmacological HER2 blockade. Suppression of TA increases cell susceptibility to HER2 inhibition in two intrinsically resistant breast cancer cell lines with HER2 amplification. Mechanistically, TA depletion combined with HER2 inhibition significantly reduces cellular NADPH levels, resulting in excessive ROS production and deficient lipid and nucleotide synthesis. Importantly, higher TA expression correlates with poor response to HER2 inhibition in a breast cancer patient cohort. Together, these results pinpoint TA as a novel metabolic enzyme possessing synthetic lethality with HER2 inhibition that can potentially be exploited as a biomarker or target for combination therapy.


Subject(s)
Breast Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Receptor, ErbB-2/genetics , Synthetic Lethal Mutations/genetics , Transaldolase/genetics , Breast Neoplasms/metabolism , CRISPR-Cas Systems , Cell Death/drug effects , Cell Line, Tumor , Female , Genetic Testing , HEK293 Cells , Humans , Lapatinib/pharmacology , Metabolic Flux Analysis , NADP/metabolism , Pentose Phosphate Pathway
12.
Cell Res ; 28(6): 625-643, 2018 06.
Article in English | MEDLINE | ID: mdl-29808012

ABSTRACT

Cellular senescence is a fundamental cell fate playing a significant role throughout the natural aging process. However, the molecular determinants distinguishing senescence from other cell-cycle arrest states such as quiescence and post-mitotic state, and the specified mechanisms underlying cell-fate decisions towards senescence versus cell death in response to cellular stress stimuli remain less understood. Employing multi-omics approaches, we revealed that switching off the specific mitochondrial processing machinery involving the peptidase IMMP2L serves as the foundation of the senescence program, which was also observed during the mammalian aging process. Mechanistically, we demonstrate that IMMP2L processes and thus activates at least two substrates, mitochondrial metabolic enzyme glycerol-3-phosphate dehydrogenase (GPD2) and cell death regulator apoptosis-inducing factor (AIF). For cells destined to senesce, concerted shutdown of the IMMP2L-GPD2 and IMMP2L-AIF signaling axes collaboratively drives the senescent process by reprogramming mitochondria-associated redox status, phospholipid metabolism and signaling network, and simultaneously blocking cell death under oxidative stress conditions.


Subject(s)
Apoptosis Inducing Factor/metabolism , Cellular Senescence , Endopeptidases/metabolism , Glycerolphosphate Dehydrogenase/metabolism , Signal Transduction , Aging , Animals , Cell Death , Cell Line , HEK293 Cells , HeLa Cells , Humans , Mice, Inbred C57BL , Oxidative Stress
13.
EMBO Rep ; 19(6)2018 06.
Article in English | MEDLINE | ID: mdl-29777051

ABSTRACT

Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor CD36 is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli. Moreover, ectopic CD36 expression in dividing mammalian cells is sufficient to initiate the production of a large subset of the known SASP components via activation of canonical Src-p38-NF-κB signaling, resulting in the onset of a full senescent state. The secretome is further shown to be ligand-dependent, as amyloid-beta (Aß) is sufficient to drive CD36-dependent NF-κB and SASP activation. Finally, loss-of-function experiments revealed a strict requirement for CD36 in secretory molecule production during conventional senescence reprogramming. Taken together, these results uncover the Aß-CD36-NF-κB signaling axis as an important regulator of the senescent cell fate via induction of the SASP.


Subject(s)
Amyloid beta-Protein Precursor/metabolism , CD36 Antigens/physiology , Cellular Senescence/physiology , NF-kappa B/metabolism , CD36 Antigens/genetics , Cells, Cultured , Cellular Senescence/genetics , Fibroblasts/metabolism , Humans , Loss of Function Mutation , Signal Transduction
14.
Cell Discov ; 3: 17019, 2017.
Article in English | MEDLINE | ID: mdl-28626588

ABSTRACT

Cellular senescence is a cell fate characterized by an irreversible cell cycle arrest, but the molecular mechanism underlying this senescence hallmark remains poorly understood. Through an unbiased search for novel senescence regulators in airway basal cells, we discovered that the epigenetic regulator ubiquitin-like with PHD and ring finger domain-containing protein 1 (UHRF1) is critical for regulating cell cycle progression. Upon injury, basal cells in the mouse airway rapidly induce the expression of UHRF1 in order to stimulate stem cell proliferation and tissue repair. Targeted depletion of Uhrf1 specifically in airway basal cells causes a profound defect in cell cycle progression. Consistently, cultured primary human basal cells lacking UHRF1 do not exhibit cell death or differentiation phenotypes but undergo a spontaneous program of senescence. Mechanistically, UHRF1 loss induces G1 cell cycle arrest by abrogating DNA replication factory formation as evidenced by loss of proliferating cell nuclear antigen (PCNA) puncta and an inability to enter the first cell cycle. This proliferation defect is partially mediated by the p15 pathway. Overall, our study provides the first evidence of an indispensable role of UHRF1 in somatic stem cells proliferation during the process of airway regeneration.

15.
J Biol Chem ; 292(2): 748-759, 2017 Jan 13.
Article in English | MEDLINE | ID: mdl-27903634

ABSTRACT

Targeted inhibitors of the human epidermal growth factor receptor 2 (HER2), such as trastuzumab and lapatinib, are among the first examples of molecularly targeted cancer therapy and have proven largely effective for the treatment of HER2-positive breast cancers. However, approximately half of those patients either do not respond to these therapies or develop secondary resistance. Although a few signaling pathways have been implicated, a comprehensive understanding of mechanisms underlying HER2 inhibitor drug resistance is still lacking. To address this critical question, we undertook a concerted approach using patient expression data sets, HER2-positive cell lines, and tumor samples biopsied both before and after trastuzumab treatment. Together, these methods revealed that high expression and activation of a specific subset of receptor tyrosine kinases (RTKs) was strongly associated with poor clinical prognosis and the development of resistance. Mechanistically, these RTKs are capable of maintaining downstream signal transduction to promote tumor growth via the suppression of cellular senescence. Consequently, these findings provide the rationale for the design of therapeutic strategies for overcoming drug resistance in breast cancer via combinational inhibition of the limited number of targets from this specific subset of RTKs.


Subject(s)
Breast Neoplasms , Drug Resistance, Neoplasm , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Quinazolines/pharmacology , Signal Transduction , Trastuzumab/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Female , Humans , Lapatinib , Receptor, ErbB-2 , Signal Transduction/drug effects , Signal Transduction/genetics
16.
PLoS One ; 11(10): e0165512, 2016.
Article in English | MEDLINE | ID: mdl-27792784

ABSTRACT

After any distribution of secret sharing shadows in a threshold changeable secret sharing scheme, the threshold may need to be adjusted to deal with changes in the security policy and adversary structure. For example, when employees leave the organization, it is not realistic to expect departing employees to ensure the security of their secret shadows. Therefore, in 2012, Zhang et al. proposed (t → t', n) and ({t1, t2,⋯, tN}, n) threshold changeable secret sharing schemes. However, their schemes suffer from a number of limitations such as strict limit on the threshold values, large storage space requirement for secret shadows, and significant computation for constructing and recovering polynomials. To address these limitations, we propose two improved dealer-free threshold changeable secret sharing schemes. In our schemes, we construct polynomials to update secret shadows, and use two-variable one-way function to resist collusion attacks and secure the information stored by the combiner. We then demonstrate our schemes can adjust the threshold safely.


Subject(s)
Computer Security , Models, Theoretical , Internet
17.
Cancer Cell ; 29(1): 49-60, 2016 Jan 11.
Article in English | MEDLINE | ID: mdl-26766590

ABSTRACT

The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit the hypoxic microenvironment via suppressing the expression of an epigenetic regulator KDM1B and modulating activities of multiple pathways. Interestingly, biogenesis of miR-215 and several miRNAs is accelerated post-transcriptionally by hypoxia-inducible factors (HIFs) through HIF-Drosha interaction. Moreover, miR-215 expression correlates inversely with KDM1B while correlating positively with HIF1α and GBM progression in patients. These findings reveal a direct role of HIF in regulating miRNA biogenesis and consequently activating the miR-215-KDM1B-mediated signaling required for GIC adaptation to hypoxia.


Subject(s)
Gene Expression Regulation, Neoplastic/genetics , Glioma/genetics , MicroRNAs/genetics , Oxidoreductases, N-Demethylating/genetics , Tumor Microenvironment/genetics , Animals , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Cell Hypoxia , Cell Line, Tumor , Humans , Mice, Nude , Neoplasm Recurrence, Local/genetics
18.
Comput Intell Neurosci ; 2015: 918305, 2015.
Article in English | MEDLINE | ID: mdl-26413090

ABSTRACT

Lithium-ion batteries are widely used in many electronic systems. Therefore, it is significantly important to estimate the lithium-ion battery's remaining useful life (RUL), yet very difficult. One important reason is that the measured battery capacity data are often subject to the different levels of noise pollution. In this paper, a novel battery capacity prognostics approach is presented to estimate the RUL of lithium-ion batteries. Wavelet denoising is performed with different thresholds in order to weaken the strong noise and remove the weak noise. Relevance vector machine (RVM) improved by differential evolution (DE) algorithm is utilized to estimate the battery RUL based on the denoised data. An experiment including battery 5 capacity prognostics case and battery 18 capacity prognostics case is conducted and validated that the proposed approach can predict the trend of battery capacity trajectory closely and estimate the battery RUL accurately.


Subject(s)
Algorithms , Biological Evolution , Electric Power Supplies , Lithium/chemistry , Wavelet Analysis , Humans , Models, Theoretical , Support Vector Machine
20.
Food Chem ; 135(4): 2222-8, 2012 Dec 15.
Article in English | MEDLINE | ID: mdl-22980794

ABSTRACT

Immunosenescence, the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main factor responsible for infections, cancer and autoimmune conditions in the elderly. Senescence-accelerated mouse (SAM) was used to study the protective effects of Pu-erh tea in the elderly. The senile-prone sub-strain, SAM-P8 mice were administered individually with ripened or crude Pu-erh tea at 125, 250 or 500mg/kg. The results showed that Pu-erh tea significantly increased the fractions of naïve T lymphocytes, CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood, but decreased the levels of IL-6 in aged mice. These data suggested that the Pu-erh tea reversed the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine. Thus, long term drinking of Pu-erh tea may be beneficial for the aged population in terms of increasing the body's resistance to infection and cancer.


Subject(s)
Aging/drug effects , Aging/immunology , Camellia sinensis/chemistry , Cytokines/immunology , Plant Extracts/administration & dosage , Tea/chemistry , Animals , Disease Models, Animal , Humans , Inflammation , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Male , Mice , Polyphenols/administration & dosage , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
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