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1.
Phys Rev Lett ; 117(6): 061801, 2016 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-27541458

RESUMO

Any new particle charged under SU(3)_{C} and carrying an electric charge will leave an imprint in the diphoton invariant mass spectrum, as it can mediate the gg→γγ process through loops. The combination of properties of loop functions, threshold resummation, and gluon parton distribution functions can result in a peaklike feature in the diphoton invariant mass around twice the mass of a given particle even if the particle is short lived, and thus it does not form a narrow bound state. Using a recent ATLAS analysis, we set upper limits on the combined SU(3)_{C} and electric charge of new particles and indicate future prospects. We also discuss the possibility that the excess of events in the diphoton invariant mass spectrum around 750 GeV originates from loops of a particle with a mass of around 375 GeV.

2.
Phys Rev Lett ; 117(25): 251801, 2016 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-28036199

RESUMO

We present a new solution to the electroweak hierarchy problem. We introduce N copies of the standard model with varying values of the Higgs mass parameter. This generically yields a sector whose weak scale is parametrically removed from the cutoff by a factor of 1/sqrt[N]. Ensuring that reheating deposits a majority of the total energy density into this lightest sector requires a modification of the standard cosmological history, providing a powerful probe of the mechanism. Current and near-future experiments can explore much of the natural parameter space. Furthermore, supersymmetric completions that preserve grand unification predict superpartners with mass below m_{W}M_{pl}/M_{GUT}∼10 TeV.

3.
Nicotine Tob Res ; 18(10): 2013-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27117284

RESUMO

BACKGROUND: Cigarette pricing policy is one tool for controlling smoking behavior on a national scale. It is unclear, however, what effects such policy has on adolescents and which characteristic subgroups of adolescents are more or less sensitive to cigarette pricing policy. MATERIALS AND METHODS: Our data came from the 2013 Korea Youth Risk Behavior Web-based Survey. The dependent variable was whether or not a participant was classified as a "persistent smokers," defined as a smoker who would continue smoking despite any price increase. Other variables of interest were smoking days (quantity), previous attempts to stop smoking, and previous education on smoking cessation. The statistical analysis was performed using weighted data and the SURVEYFREQ and SURVEYLOGISTIC procedures in SAS 9.3. RESULTS: Among 7094 adolescent smokers (5349 males and 1745 females), 19.9% of males and 25.1% of females reported as persistent smokers. Compared with light smokers, heavy smokers are more likely to be persistent smokers (male: odds ratio [OR] = 2.45, 95% confidence interval [CI] = 2.04-2.95, P value < .001; female: OR = 3.23, 95% CI = 2.44-4.27, P value < .001). When we stratified the data by household income, previous attempts to stop smoking, and previous education on smoking cessation, that trend remained statistically significant. CONCLUSIONS: Because heavier smokers with higher risk of health-related consequences were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional cessation policy is needed along with pricing policy for adolescents with heavier smoking behavior in Korea. IMPLICATION: This study shows that heavy smokers are more likely to be persistent smokers despite the cigarette price increase policy, compared with light smokers in Korean adolescents. Because heavier smokers were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional tobacco control policies should be evaluated and effective ones implemented in addition to cigarette prices to reduce smoking among regular adolescent smokers.


Assuntos
Comportamento do Adolescente , Comércio/economia , Prevenção do Hábito de Fumar , Impostos/economia , Produtos do Tabaco/economia , Adolescente , Feminino , Humanos , Masculino , República da Coreia , Fumar/economia , Abandono do Hábito de Fumar/métodos , Inquéritos e Questionários
4.
Phys Rev Lett ; 113(5): 051801, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25126909

RESUMO

We discuss an extension of the standard model by fields not charged under standard model gauge symmetry in which the electroweak symmetry breaking is driven by the Higgs quartic coupling itself without the need for a negative mass term in the potential. This is achieved by a scalar field S with a large coupling to the Higgs field at the electroweak scale which is driven to very small values at high energies by the gauge coupling of a hidden symmetry under which S is charged. This model can remain perturbative all the way to the Planck scale. The Higgs boson is fully standard-model-like in its couplings to fermions and gauge bosons. However, the effective cubic and quartic self-couplings of the Higgs boson are significantly enhanced.

5.
Mult Scler Relat Disord ; 88: 105751, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38968925

RESUMO

BACKGROUND: The hit-hard-and-early (HHAE) strategy where treatment is initiated with high-efficacy therapies opposed to low-efficacy therapies presents a potential paradigm shift in multiple sclerosis (MS) management. This study aimed to assess the adoption of the HHAE strategy in Germany and the United States (US) from 2020 to 2022 based on real-world data. METHODS: The analysis was based on longitudinal, patient-level data from Germany and the US. For Germany, data was extracted from the Permea platform covering approximately 44 % of all German community pharmacy dispensing. For the US, data from the Komodo Healthcare Map™ was utilized, covering medical benefit data from around 88 % of the US patient population. Patients ≥18 years old and who had at least 2 prescriptions for MS-related disease-modifying drugs (DMDs) between January 2020 and December 2022 were included. To approximate therapy beginners, a washout period of one year before treatment start was applied, excluding all patients who had an MS-related DMD prescription or claim in 2019. Cohort entry date was the day of the first MS-related DMD dispense or claim. DMDs were classified as high-efficacy and low-efficacy based on the Multiple Sclerosis Therapy Consensus Group (MSTCG). Group differences were assessed with two-sided χ2-square and t-tests. RESULTS: 29,604 MS therapy beginners were identified in the German and 49,791 MS therapy beginners were identified in the US dataset. 29.6 % of MS therapy beginners in Germany and 61.6 % in the US followed the HHAE strategy. Between 2020 and 2022, a significant 14 % increase in the HHAE strategy was observed in both countries (p < 0.0001). High-efficacy therapy beginners switched from their initially prescribed therapy less frequently than low-efficacy therapy beginners: 6.9 % of high-efficacy vs. 19.5 % of low-efficacy therapy beginners in Germany (p < 0.0001) and 5.5 % of high-efficacy vs. 25.0 % low-efficacy therapy beginners in the US (p < 0.0001) switched from their first prescribed DMD. CONCLUSION: Between 2020 and 2022, the adoption of the HHAE strategy increased in both countries, with the US exhibiting nearly double the adoption rates. High-efficacy therapy beginners were less likely to switch from their initially prescribed medication than low-efficacy therapy beginners. Real world evidence can provide valuable insights into rapidly changing treatment patterns in patients with MS.


Assuntos
Esclerose Múltipla , Humanos , Alemanha , Estados Unidos , Esclerose Múltipla/terapia , Esclerose Múltipla/tratamento farmacológico , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Fatores Imunológicos/uso terapêutico , Estudos Longitudinais , Adulto Jovem
6.
Chem Sci ; 15(17): 6349-6362, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38699251

RESUMO

Careful control of electronic properties, structural order, and solubility of π-conjugated polymers is central to the improvement of organic photovoltaic (OPV) performance. In this work, we designed and synthesized a series of naphthobisthiadiazole-quaterthiophene copolymers by systematically replacing the alkyl groups with ester groups and changing the position of the fluorine groups in the quaterthiophene moiety. These alterations lowered the HOMO and LUMO energy levels and systematically varied the combination of intramolecular noncovalent interactions such as O⋯S and F⋯S interactions in the backbone. More importantly, although the introduction of such noncovalent interactions often lowers the solubility owing to the interlocking of backbone linkages, we found that careful design of the noncovalent interactions afforded polymers with relatively high solubility and high crystallinity at the same time. As a result, the power conversion efficiency of OPV cells that used fullerene (PC61BM) and nonfullerene (Y12) as the acceptor was improved. Our work offers important information for the development of high-performance π-conjugated polymers for OPVs.

7.
Mol Cell Proteomics ; 10(11): M111.008433, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21832255

RESUMO

Epithelial-mesenchymal transition (EMT), whether in developmental morphogenesis or malignant transformation, prominently involves modified cell motility behavior. Although major advances have transpired in understanding the molecular pathways regulating the process of EMT induction per se by certain environmental stimuli, an important outstanding question is how the activities of signaling pathways governing motility yield the diverse movement behaviors characteristic of pre-induction versus postinduction states across a broad landscape of growth factor contexts. For the particular case of EMT induction in human mammary cells by ectopic expression of the transcription factor Twist, we found the migration responses to a panel of growth factors (EGF, HRG, IGF, HGF) dramatically disparate between confluent pre-Twist epithelial cells and sparsely distributed post-Twist mesenchymal cells-but that a computational model quantitatively integrating multiple key signaling node activities could nonetheless account for this full range of behavior. Moreover, motility in both conditions was successfully predicted a priori for an additional growth factor (PDGF) treatment. Although this signaling network state model could comprehend motility behavior globally, modulation of the network interactions underlying the altered pathway activities was identified by ascertaining differences in quantitative topological influences among the nodes between the two conditions.


Assuntos
Mama/citologia , Movimento Celular , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteínas Nucleares/metabolismo , Transdução de Sinais , Proteína 1 Relacionada a Twist/metabolismo , Linhagem Celular , Simulação por Computador , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Transição Epitelial-Mesenquimal , Receptores ErbB/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Análise dos Mínimos Quadrados , Modelos Biológicos , Análise Multivariada , Fenótipo , Fosforilação , Mapas de Interação de Proteínas
8.
Adv Sci (Weinh) ; 10(5): e2205682, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36529702

RESUMO

In π $\upi$ -conjugated polymers, a highly ordered backbone structure and solubility are always in a trade-off relationship that must be overcome to realize highly efficient and solution-processable organic photovoltaics (OPVs). Here, it is shown that a π $\upi$ -conjugated polymer based on a novel thiazole-fused ring, thieno[2',3':5,6]benzo[1,2-d:4,3-d']bisthiazole (TBTz) achieves both high backbone order and high solubility due to the structural feature of TBTz such as the noncovalent interlocking of the thiazole moiety, the rigid and bent-shaped structure, and the fused alkylthiophene ring. Furthermore, based on the electron-deficient nature of these thiazole-fused rings, the polymer exhibits deep HOMO energy levels, which lead to high open-circuit voltages (VOC s) in OPV cells, even without halogen substituents that are commonly introduced into high-performance polymers. As a result, when the polymer is combined with a typical nonfullerene acceptor Y6, power conversion efficiencies of reaching 16% and VOC s of more than 0.84 V are observed, both of which are among the top values reported so far for "halogen-free" polymers. This study will serve as an important reference for designing π $\upi$ -conjugated polymers to achieve highly efficient and solution-processable OPVs.

9.
Expert Rev Proteomics ; 8(5): 565-75, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21999828

RESUMO

While proteomic methods have illuminated many areas of biological protein space, many fundamental questions remain with regard to systems-level relationships between mRNAs, proteins and cell behaviors. While mass spectrometric methods offer a panoramic picture of the relative expression and modification of large numbers of proteins, they are neither optimal for the analysis of predefined targets across large numbers of samples nor for assessing differences in proteins between individual cells or cell compartments. Conversely, traditional antibody-based methods are effective at sensitively analyzing small numbers of proteins across small numbers of conditions, and can be used to analyze relative differences in protein abundance and modification between cells and cell compartments. However, traditional antibody-based approaches are not optimal for analyzing large numbers of protein abundances and modifications across many samples. In this article, we will review recent advances in methodologies and philosophies behind several microarray-based, intermediate-level, 'protein-omic' methods, including a focus on reverse-phase lysate arrays and micro-western arrays, which have been helpful for bridging gaps between large- and small-scale protein analysis approaches and have provided insight into the roles that protein systems play in several biological processes.


Assuntos
Espectrometria de Massas/métodos , Proteínas/análise , Proteômica/métodos , RNA Mensageiro/análise , Animais , Fenômenos Fisiológicos Celulares , Biologia Computacional , Estudo de Associação Genômica Ampla/métodos , Humanos , Análise Serial de Proteínas/métodos , Proteínas/imunologia , Locos de Características Quantitativas , Biologia de Sistemas/métodos
10.
ACS Appl Mater Interfaces ; 13(33): 39322-39330, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34374522

RESUMO

One of the most challenging issues facing the organic photovoltaic community is to realize a high fill factor (FF) even with thick active layers. This is because the thick active layer is beneficial for photon absorption but makes charge collection difficult, which is primarily restricted by nongeminate recombination in solar cells. In this work, we have studied nongeminate recombination in four kinds of polymer solar cells based on blends of donor-conjugated polymers with different crystallinities and acceptor-conjugated polymers with a naphthalene diimide unit by using transient photovoltage and photocurrent techniques. As a result, we find that nongeminate recombination is considerably suppressed with an increasing degree of crystallinity of donor polymers, leading to a high FF of more than 0.6 even with an active layer thickness of 300 nm. The origin of such a phenomenon is further discussed in terms of variations in the states of mixed phases with a cascaded energy structure between crystalline domains and amorphous domains evaluated by conductive atomic force microscopy.

11.
ACS Appl Mater Interfaces ; 13(47): 56420-56429, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34783522

RESUMO

Achieving both the backbone order and solubility of π-conjugated polymers, which are often in a trade-off relationship, is imperative for maximizing the performance of organic solar cells. Here, we studied three different π-conjugated polymers based on thiazolothiazole (PSTz1 and POTz1) and benzobisthiazole (PNBTz1) that were combined with a benzodithiophene unit in the backbone, where PNBTz1 was newly synthesized. Because of the steric hindrance between the side chains located on neighboring heteroaromatic rings, POTz1 had a much less coplanar backbone than PSTz1 in which such a steric hindrance is absent. However, POTz1 showed higher photovoltaic performance in solar cells that used Y6 as the acceptor material. This was likely due to the significantly higher solubility of POTz1 than PSTz1, resulting in a better morphology. Interestingly, PNBTz1 was found to have markedly higher backbone coplanarity than POTz1, despite having similar steric hindrance between the side chains, most likely owing to the more extended π-electron system, whereas PNBTz1 had good solubility comparable to POTz1. As a result, PNBTz1 exhibited higher photovoltaic performance than POTz1 in the Y6-based cells: specifically, the fill factor was significantly enhanced. Our results indicate that the backbone order and solubility can be achieved by the careful molecular design, which indeed leads to higher photovoltaic performance.

12.
Spine Surg Relat Res ; 5(2): 91-97, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842716

RESUMO

INTRODUCTION: Despite technical developments in decompression without fusion, many studies still assert that instability could be increased in patients with spinal stenosis and lumbar degenerative spondylolisthesis after spinal decompression surgery without fusion. Thus, this study aimed to describe and assess the clinical outcomes of the semi-circumferential decompression (SCD) technique used for microsurgical en-bloc total ligamentum flavectomy with preservation of the facet joint in treating patients who have lumbar spinal stenosis with two-level degenerative spondylolisthesis. METHODS: We retrospectively analyzed the clinical and radiologic outcomes of 14 patients who had spinal stenosis with two-level Meyerding grade I degenerative spondylolisthesis. We evaluated improvements in back pain and radiating pain using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). We have also examined the occurrence of spinal instability on a radiological exam using slip percentage and slip angle. RESULTS: The mean VAS score of back pain and radiating pain has been determined to decrease significantly from 6.7 to 3.3 and from 8.6 to 2.7, respectively. Meanwhile, the ODI score significantly improved from 27.3 preoperatively to 9.8 postoperatively. Statistically significant change was not observed in the slip percentage in both upper and lower levels. Dynamic slip percentage, which is defined as the difference in the slip percentage between flexion and extension, also did not significantly change. No statistically significant change was found in the slip angle and dynamic slip angle. CONCLUSIONS: SCD is a recommendable procedure that can improve clinical results. This procedure does not cause spinal instability when treating patients who have spinal stenosis with two-level degenerative spondylolisthesis.

13.
ACS Appl Mater Interfaces ; 13(33): 39178-39185, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34379385

RESUMO

This work reports strategies for improving the power conversion efficiency (PCE) by capitalizing on temporal changes through the storage effect and immediate improvements by interface passivation. It is demonstrated that both strategies can be combined as shown by PCE improvement in passivated perovskite solar cells (PSCs) upon ambient storage because of trap density reduction. By analyzing the dominant charge recombination process, we find that lead-related traps in perovskite bulk, rather than at the surface, are the recombination centers in both as-fabricated and ambient-stored passivated PSCs. This emphasizes the necessity to reduce intrinsic defects in the perovskite bulk. Furthermore, storage causes temporal changes in band alignment even in passivated PSCs, contributing to PCE improvement. Building on these findings, composition engineering was employed to produce further immediate PCE improvements because of defect reduction in the bulk, achieving a PCE of 22.2%. These results show that understanding the dominant recombination mechanisms within a PSC is important to inform strategies for producing immediate and temporal PCE enhancements either by interface passivation, storage, composition engineering, or a combination of them all to fabricate highly efficient PSCs.

14.
Chem Asian J ; 15(6): 796-801, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32012465

RESUMO

Herein, the hole transport in a quinoxaline-thiophene based conjugated polymer (PTQ1) mixed with an insulating polystyrene (PS) was studied by macroscopic and local current density-voltage characteristics measurements. As a result, we found that the hole conductivity in PTQ1 : PS blends increases as the weight ratio of PTQ1 is reduced down to 20 wt%. This is mainly ascribed to increases in mobility because the charge carrier density would be constant in the insulating PS matrix. With decreasing PTQ1 weight ratio in the blends, the absorption bandwidth of PTQ1 and additional emission due to excimer decreased, suggesting that interchain interactions are suppressed. By measuring the temperature-dependent conductivity, we also found that the activation energy for the hole conductivity is smaller in PTQ1 : PS blends than in PTQ1 neat films. These findings suggest that trap sites decrease because of the suppressed interaction between PTQ1 chains in blend films. We also measured conductive atomic force microscope images of the blend films to clarify the local conductive property. For PTQ1 neat films, a low conductive image was observed over the entire film. For PTQ1 : PS blends, on the other hand, many highly conductive spots were locally found. We thus conclude that the dilution of PTQ1 chains in the PS matrix leads to a lower formation of trap sites, resulting in more conductive transport in PTQ1 : PS blends than in PTQ1 neat films.

15.
Nanomaterials (Basel) ; 10(2)2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32013188

RESUMO

Abstract: A non-fullerene molecule named Y6 was incorporated into a binary blend of PBDB-T and IT-M to further enhance photon harvesting in the near-infrared (near-IR) region. Compared with PBDB-T/IT-M binary blend devices, PBDB-T/IT-M/Y6 ternary blend devices exhibited an improved short-circuit current density (JSC) from 15.34 to 19.09 mA cm-2. As a result, the power conversion efficiency (PCE) increased from 10.65% to 12.50%. With an increasing weight ratio of Y6, the external quantum efficiency (EQE) was enhanced at around 825 nm, which is ascribed to the absorption of Y6. At the same time, EQE was also enhanced at around 600-700 nm, which is ascribed to the absorption of IT-M, although the optical absorption intensity of IT-M decreased with increasing weight ratio of Y6. This is because of the efficient energy transfer from IT-M to Y6, which can collect the IT-M exciton lost in the PBDB-T/IT-M binary blend. Interestingly, the EQE spectra of PBDB-T/IT-M/Y6 ternary blend devices were not only increased but also red-shifted in the near-IR region with increasing weight ratio of Y6. This finding suggests that the absorption spectrum of Y6 is dependent on the weight ratio of Y6, which is probably due to different aggregation states depending on the weight ratio. This aggregate property of Y6 was also studied in terms of surface energy.

16.
Nat Commun ; 11(1): 3008, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546736

RESUMO

The toxicity of lead perovskite hampers the commercialization of perovskite-based photovoltaics. While tin perovskite is a promising alternative, the facile oxidation of tin(II) to tin(IV) causes a high density of defects, resulting in lower solar cell efficiencies. Here, we show that tin(0) nanoparticles in the precursor solution can scavenge tin(IV) impurities, and demonstrate that this treatment leads to effectively tin(IV)-free perovskite films with strong photoluminescence and prolonged decay lifetimes. These nanoparticles are generated by the selective reaction of a dihydropyrazine derivative with the tin(II) fluoride additive already present in the precursor solution. Using this nanoparticle treatment, the power conversion efficiency of tin-based solar cells reaches 11.5%, with an open-circuit voltage of 0.76 V. Our nanoparticle treatment is a simple and broadly effective method that improves the purity and electrical performance of tin perovskite films.

17.
Biophys J ; 95(8): 4013-24, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18621811

RESUMO

Cell migration plays a critical role in a wide variety of physiological and pathological phenomena as well as in scaffold-based tissue engineering. Cell migration behavior is known to be governed by biochemical stimuli and cellular interactions. Biophysical processes associated with interactions between the cell and its surrounding extracellular matrix may also play a significant role in regulating migration. Although biophysical properties of two-dimensional substrates have been shown to significantly influence cell migration, elucidating factors governing migration in a three-dimensional environment is a relatively new avenue of research. Here, we investigate the effect of the three-dimensional microstructure, specifically the pore size and Young's modulus, of collagen-glycosaminoglycan scaffolds on the migratory behavior of individual mouse fibroblasts. We observe that the fibroblast migration, characterized by motile fraction as well as locomotion speed, decreases as scaffold pore size increases across a range from 90 to 150 mum. Directly testing the effects of varying strut Young's modulus on cell motility showed a biphasic relationship between cell speed and strut modulus and also indicated that mechanical factors were not responsible for the observed effect of scaffold pore size on cell motility. Instead, in-depth analysis of cell locomotion paths revealed that the distribution of junction points between scaffold struts strongly modulates motility. Strut junction interactions affect local directional persistence as well as cell speed at and away from the junctions, providing a new biophysical mechanism for the governance of cell motility by the extracellular microstructure.


Assuntos
Comunicação Celular , Movimento Celular , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Alicerces Teciduais , Animais , Comunicação Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Colágeno/metabolismo , Reagentes de Ligações Cruzadas/farmacologia , Elasticidade/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Glicosaminoglicanos/metabolismo , Camundongos , Modelos Biológicos , Porosidade/efeitos dos fármacos
18.
Mol Pharmacol ; 73(6): 1668-78, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18349105

RESUMO

Small-molecule kinase inhibitors often modulate signaling pathways other than the one targeted, whether by direct "off-target" effects or by indirect "pathway cross-talk" effects. The presence of either or both of these classes of complicating factors impedes the predictive understanding of kinase inhibitor consequences for cell phenotypic behaviors involved in drug efficacy responses. To address this problem, we offer an avenue toward comprehending how kinase inhibitor modulations of cell signaling networks lead to altered cell phenotypic responses by applying a quantitative, multipathway computational modeling approach. We show that integrating measurements of signals across three key kinase pathways involved in regulating migration of human mammary epithelial cells, downstream of ErbB system receptor activation by epidermal growth factor (EGF) or heregulin (HRG), significantly improves prediction of cell migration changes resulting from treatment with the small-molecule inhibitors 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 2'-amino-3'-methoxyflavone (PD98059) for both normal and HER2-overexpressing cells. These inhibitors are primarily directed toward inhibition of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) but are known to exhibit off-target effects; moreover, complex cross-talk interactions between the PI3K/Akt and MEK/extracellular signal-regulated kinase (Erk) pathways are also appreciated. We observe here that treatment with LY294002 reduces migration of HRG-stimulated cells but not EGF-stimulated cells, despite comparable levels of reduction of Akt phosphorylation under both conditions, demonstrating that the target inhibition effect is not unilaterally predictive of efficacy against cell phenotypic response. Consequent measurement of levels of Erk and p38 phosphorylation, along with those for EGF receptor phosphorylation, after LY294002 treatment revealed unintended modulation of these nontargeted pathways. However, when these measurements were incorporated into a partial least-squares regression model, the cell migration responses to treatment were successfully predicted. Similar success was found for the same multipathway model in analogously predicting PD98059 treatment effects on cell migration. We conclude that a quantitative, multipathway modeling approach can provide a significant advance toward comprehending kinase inhibitor efficacy in the face of off-target and pathway cross-talk effects.


Assuntos
Movimento Celular/fisiologia , Células Epiteliais/metabolismo , Glândulas Mamárias Humanas/metabolismo , Receptor Cross-Talk/fisiologia , Receptor ErbB-2/biossíntese , Transdução de Sinais/fisiologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Humanos , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/efeitos dos fármacos , Valor Preditivo dos Testes , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptor Cross-Talk/efeitos dos fármacos , Receptor ErbB-2/genética , Transdução de Sinais/efeitos dos fármacos
19.
Mol Syst Biol ; 2: 54, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17016520

RESUMO

Although human epidermal growth factor receptor 2 (HER2) overexpression is implicated in tumor progression for a variety of cancer types, how it dysregulates signaling networks governing cell behavioral functions is poorly understood. To address this problem, we use quantitative mass spectrometry to analyze dynamic effects of HER2 overexpression on phosphotyrosine signaling in human mammary epithelial cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). Data generated from this analysis reveal that EGF stimulation of HER2-overexpressing cells activates multiple signaling pathways to stimulate migration, whereas HRG stimulation of these cells results in amplification of a specific subset of the migration signaling network. Self-organizing map analysis of the phosphoproteomic data set permitted elucidation of network modules differentially regulated in HER2-overexpressing cells in comparison with parental cells for EGF and HRG treatment. Partial least-squares regression analysis of the same data set identified quantitative combinations of signals within the networks that strongly correlate with cell proliferation and migration measured under the same battery of conditions. Combining these modeling approaches enabled association of epidermal growth factor receptor family dimerization to activation of specific phosphorylation sites, which appear to most critically regulate proliferation and/or migration.


Assuntos
Mama/citologia , Células Epiteliais/efeitos dos fármacos , Fosfotirosina/fisiologia , Processamento de Proteína Pós-Traducional , Receptor ErbB-2/fisiologia , Transdução de Sinais , Algoritmos , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Divisão Celular/fisiologia , Linhagem Celular/efeitos dos fármacos , Linhagem Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Movimento Celular/fisiologia , Dimerização , Fator de Crescimento Epidérmico/farmacologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Receptores ErbB/química , Receptores ErbB/genética , Receptores ErbB/fisiologia , Feminino , Expressão Gênica , Genes erbB-1 , Genes erbB-2 , Humanos , Análise dos Mínimos Quadrados , Espectrometria de Massas , Neuregulina-1/farmacologia , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Receptor ErbB-2/biossíntese , Receptor ErbB-2/química , Proteínas Recombinantes de Fusão/fisiologia , Transdução de Sinais/efeitos dos fármacos
20.
ACS Appl Mater Interfaces ; 9(23): 19988-19997, 2017 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-28553705

RESUMO

Herein, the open-circuit voltage (VOC) loss in both polymer solar cells and perovskite solar cells is quantitatively analyzed by measuring the temperature dependence of VOC to discuss the difference in the primary loss mechanism of VOC between them. As a result, the photon energy loss for polymer solar cells is in the range of about 0.7-1.4 eV, which is ascribed to temperature-independent and -dependent loss mechanisms, while that for perovskite solar cells is as small as about 0.5 eV, which is ascribed to a temperature-dependent loss mechanism. This difference is attributed to the different charge generation and recombination mechanisms between the two devices. The potential strategies for the improvement of VOC in both solar cells are further discussed on the basis of the experimental data.

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