Browsing by Author "Chen, Wei"
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Item An intrinsically disordered transcription activation domain increases the DNA binding affinity and reduces the specificity of NFκB p50/RelA(Elsevier, 2022) Baughman, Hannah E.R.; Narang, Dominic; Chen, Wei; Villagrán Suárez, Amalia C.; Lee, Joan; Bachochin, Maxwell J.; Gunther, Tristan R.; Wolynes, Peter G.; Komives, Elizabeth A.; Center for Theoretical Biological PhysicsMany transcription factors contain intrinsically disordered transcription activation domains (TADs), which mediate interactions with coactivators to activate transcription. Historically, DNA-binding domains and TADs have been considered as modular units, but recent studies have shown that TADs can influence DNA binding. Whether these results can be generalized to more TADs is not clear. Here, we biophysically characterized the NFκB p50/RelA heterodimer including the RelA TAD and investigated the TAD’s influence on NFκB–DNA interactions. In solution, we show the RelA TAD is disordered but compact, with helical tendency in two regions that interact with coactivators. We determined that the presence of the TAD increased the stoichiometry of NFκB–DNA complexes containing promoter DNA sequences with tandem κB recognition motifs by promoting the binding of NFκB dimers in excess of the number of κB sites. In addition, we measured the binding affinity of p50/RelA for DNA containing tandem κB sites and single κB sites. While the presence of the TAD enhanced the binding affinity of p50/RelA for all κB sequences tested, it also increased the affinity for nonspecific DNA sequences by over 10-fold, leading to an overall decrease in specificity for κB DNA sequences. In contrast, previous studies have generally reported that TADs decrease DNA-binding affinity and increase sequence specificity. Our results reveal a novel function of the RelA TAD in promoting binding to nonconsensus DNA, which sheds light on previous observations of extensive nonconsensus DNA binding by NFκB in vivo in response to strong inflammatory signals.Item Genotoxicity and Cytotoxicity of Cadmium Sulfide Nanomaterials to Mice: Comparison Between Nanorods and Nanodots(Mary Ann Liebert, Inc., 2014) Liu, Lu; Sun, Meiqing; Li, Qingzhao; Zhang, Hongmei; Alvarez, Pedro J.J.; Liu, Huajie; Chen, WeiCadmium sulfide (CdS) nanomaterials (such as CdS nanodots or nanorods) are widely used in optical, electronic, and biological applications. Large-scale production and use of these materials will likely result in accidental and incidental releases, which raise concerns about their potential environmental and human-health impacts. Most studies on toxicity of Cd-containing nanomaterials have focused on nanodots, and the relative toxicity of Cd containing nanorods is not well understood. Here, we compared genotoxicity and cytotoxicity of CdS nanorods (30-50nm diameter, 500-1100 nm length) and cubic CdS nanodots (3-5 nm) in mice by examining total cadmium accumulation in organs, acute toxicity, DNA damage, spermatozoon viability and abnormality, kidney and liver damage, and oxidative stress. Compared with (smaller) nanodots, nanorods resulted in relatively low bioaccumulation, acute toxicity, and damage to spermatozoa and the tested organs. Differences in toxicity between CdS nanodots and nanorods could not be fully explained by differences in their metal ion (Cd2 + ) release patterns, based on control tests with mice gavaged with dissolved CdCl2 at equivalent concentrations. This underscores that toxicity of metallic nanomaterials could not be solely predicted based either on their elemental composition or on the amount of ions released before receptor intake. Particle morphology (including size) may also need to be considered.Item Identification of Instantaneous Frequency and Damping From Transient Decay Data(ASME, 2020) Jin, Mengshi; Chen, Wei; Brake, Matthew R.W.; Song, HanwenJointed interfaces, damage, wear, or non-idealized boundary conditions often introduce nonlinear characteristics to assembled structures. Consequently, extensive research has been carried out regarding nonlinear system identification. The development of nonlinear system identification is also enabling the intentional application of nonlinearities towards practical fields such as vibration control and energy harvesting. This research proposes a nonlinear identification procedure that consists of two steps: first, the raw data is filtered by the Double Reverse Multimodal Decomposition method that involves system reconstruction, expansion, and filtering twice. Second, the Peak Finding and Fitting method is applied to the filtered signal to extract the instantaneous amplitude and frequency. The identification procedure is applied to the measured responses from a jointed structure to assess its efficacy. The results are compared with those obtained from other well-known methods—the Hilbert transform and zero-crossing methods. The comparison results indicate that the Peaking Finding and Fitting method extracts the amplitude of the response signal more accurately. Consequently, this yields a higher signal-to-noise ratio in the extracted damping values. As a recommended last step, uncertainty assessment is conducted to calculate the 95% confidence intervals of the nonlinear properties of the system.Item Impact of air pollution on human activities: Evidence from nine million mobile phone users(Public Library of Science, 2021) Chen, Wei; He, YingHua; Pan, ShiyuanTo measure the effects of air pollution on human activities, this study applies statistical/econometric modeling to hourly data of 9 million mobile phone users from six cities in China’s Zhejiang Province from December 18 to 21, 2013. Under a change in air quality from “Good” (Air Quality Index, or AQI, between 51 and 100) to “Heavily Polluted” (AQI between 201 to 300), the following effects are demonstrated. (i) Consistent with the literature, for every one million people, 1, 482 fewer individuals are observed at parks, 95% confidence interval or CI (−2, 229, −735), which represents a 15% decrease. (ii) The number of individuals at shopping malls has no statistically significant change. (iii) Home is the most important location under worsening air quality, and for every one million people, 63, 088 more individuals are observed at home, 95% CI (47, 815, 78, 361), which represents a 19% increase. (iv) Individuals are on average 633 meters closer to their home, 95% CI (529, 737); as a benchmark, the median distance from home ranges from 300 to 1900 meters across the cities in our sample. These effects are not due to weather or government regulations. We also provided provisional evidence that individuals engage in inter-temporal activity substitutions within a day, which leads to mitigated (but not nullified) effects of air pollution on daily activities.Item Impact of irreversible sorption on sediment quality(2000) Chen, Wei; Tomson, Mason B.Irreversible sorption has been widely observed for hydrophobic organic contaminants in natural sediments. It is a complicated process and impacts sediment quality and contaminated sediment management. In this research, experiments were conducted to further understand the nature of irreversible sorption and the mechanism(s) controlling this process. The unique characteristics of the irreversible compartment were delineated with the sorption and desorption of five chlorinated benzenes in four natural sediments. It was observed that each chemical-sediment combination exhibited a fixed amount of maximum irreversible sorption capacity, qirrmax . However, the organic carbon based partition coefficient associated with the irreversible compartment was essentially constant for different chemical-sediment combinations--- Kirroc=105.42+/-0.17 . The desorption behaviors were modeled with an irreversible sorption model, in which a Langmurian-type expression (representing the irreversible fraction) was added to the linear model. For the sorption and desorption of different compounds in the same sediment qirrmax seems to be related to both Kow and solubility. For sorption and desorption of the same compound in different sediments qirrmax depends mainly on sediment organic carbon content (foc), but may also be affected by the origin of the sediments. The release from the irreversible compartment was not affected by a number of factors, such as extended desorption time, competitive sorption, caustic treatment of sediments, and external mechanic forces. Many observations in this research suggest that sorption and desorption of hydrophobic organic contaminants in natural sediments are not controlled by the same mechanism, and irreversible sorption may be partly due to the association of organic sorbate molecules to some highly insoluble and hydrophobic materials in sediments. Irreversible sorption greatly affects the fate and transport of contaminants in surface and subsurface environments---it causes contaminants to persist in soils and sediments, and it also reduces the efficiency of pump and treat and bioremediation. Nevertheless, the same process could also greatly reduce the ecological and human-health risks of contaminated sediments. Thus, it is necessary to establish risk-based sediment quality standards, which could be of enormous economical impact. Also, to quantitatively address the impact of irreversible sorption on sediment quality, a one-dimensional solute-transport model was developed. This simple model could provide valuable support for environmental decision making.Item Magnetic Fields and Accretion on T Tauri Stars(2015-04-20) Chen, Wei; Johns-Krull, Christopher M; Hartigan, Patrick M; Lenardic, AdrianIn this thesis, we study magnetic properties of Classical T Tauri Stars (CTTSs) using diffferent analysis methods from different angles. We first implement a least-squares deconvolution (LSD) code to enhance the signal-to-noise ratio of the observed data and therefore the ability to detect weak magnetic signatures in the polarized spectra. We compare our code to another LSD code by analyzing the same spectra with the same line list, and the good agreement confirms that our code performs similarly with other state of the art LSD codes. We have also tested the instrument we use to collect the spectropolarimetric data presented in this thesis. The intrument do produce spurious signals but at a very low level, posing no problem in our analysis. The polarization efficiency of the instrument is also high. We then studied the CTTS BP Tau and found field configuration not consistent with other results in the literature, which may simply be due to the temporal variability given the observations were taken 8 years apart. Next, we detect extremely high levels of polarization on TW Hya in the 2013 epoch, which motivated us do a thorough magnetic variability study. We find that the field geometry does have changed, indicating a dynamo origin of these fields. We also try to use the rotational modulation of 6 CTTSs to locate the accretion spots. Some of the stars have shown definte change over the years while some remain similar.Item Magnetically Controlled Accretion on the Classical T Tauri Stars GQ Lupi and TQ Hydrae(The American Astronomical Society, 2013) Johns-Krull, Christopher M.; Chen, Wei; Valenti, Jeff A.; Jeffers, Sandra V.; Piskunov, Nikolai E.; Kochukhov, Oleg; Makaganiuk, V.; Stempels, H.C.; Snik, Frans; Keller, Christoph; Rodenhuis, M.We present high spectral resolution (R ≈ 108,000) Stokes V polarimetry of the classical T Tauri stars (CTTSs) GQ Lup and TW Hya obtained with the polarimetric upgrade to the HARPS spectrometer on the ESO 3.6 m telescope. We present data on both photospheric lines and emission lines, concentrating our discussion on the polarization properties of the He i emission lines at 5876 Å and 6678 Å. The He i lines in these CTTSs contain both narrow emission cores, believed to come from near the accretion shock region on these stars, and broad emission components which may come from either a wind or the large-scale magnetospheric accretion flow.We detect strong polarization in the narrow component of the two He i emission lines in both stars. We observe a maximum implied field strength of 6.05 ± 0.24 kG in the 5876 Å line of GQ Lup, making it the star with the highest field strength measured in this line for a CTTS. We find field strengths in the two He i lines that are consistent with each other, in contrast to what has been reported in the literature on at least one star. We do not detect any polarization in the broad component of the He i lines on these stars, strengthening the conclusion that they form over a substantially different volume relative to the formation region of the narrow component of the He i lines.Item Measurement and identification of the nonlinear dynamics of a jointed structure using full-field data, Part I: Measurement of nonlinear dynamics(Elsevier, 2022) Chen, Wei; Jana, Debasish; Singh, Aryan; Jin, Mengshi; Cenedese, Mattia; Kosova, Giancarlo; Brake, Matthew R.W.; Schwingshackl, Christoph W.; Nagarajaiah, Satish; Moore, Keegan J.; Noël, Jean-PhilippeJointed structures are ubiquitous constituents of engineering systems; however, their dynamic properties (e.g., natural frequencies and damping ratios) are challenging to identify correctly due to the complex, nonlinear nature of interfaces. This research seeks to extend the efficacy of traditional experimental methods for linear system identification (such as impact testing, shaker ringdown testing, random excitation, and force or amplitude-control stepped sine testing) on nonlinear jointed systems, e.g., the half Brake–Reuß beam, by augmenting them with full-field data collected by high-speed videography. The full-field response is acquired using high-speed cameras combined with Digital Image Correlation (DIC), which enables studying the spatial–temporal dynamic characteristics of the system. As this is a video-based experiment, additional constraints are attached to the beam at the node points to remove the rigid body motion, which ensures that the beam is in the view of the camera during the entire test. The use of a video-based method introduces new sources of experimental error, such as noise from the high-speed camera’s fan and electrical noise, and so the measurement accuracy of DIC is validated using accelerometer data. After validating the DIC data, the measurements are recorded for several types of excitation, including hammer testing, shaker ringdown testing, fixed sine testing, and stepped sine testing. Using the DIC data to augment standard nonlinear system identification techniques, modal coupling and the mode shapes’ evolution are investigated. The suitability of videography methods for nonlinear system identification of nonlinear beams is explored for the first time in this paper, and recommendations for techniques to facilitate this process are made. This article focuses on developing an accurate data collection methodology as well as recommendations for nonlinear testing with DIC, which paves the way for video-based investigation of nonlinear system identification. In Part-II (Jin et al., 2021) of this work, the same data set is used for a rigorous assessment of nonlinear system identification with full-field DIC data.Item Measurement and identification of the nonlinear dynamics of a jointed structure using full-field data; Part II - Nonlinear system identification(Elsevier, 2022) Jin, Mengshi; Kosova, Giancarlo; Cenedese, Mattia; Chen, Wei; Singh, Aryan; Jana, Debasish; Brake, Matthew R.W.; Schwingshackl, Christoph W.; Nagarajaiah, Satish; Moore, Keegan J.; Noël, Jean-PhilippeThe dynamic responses of assembled structures are greatly affected by the mechanical joints, which are often the cause of nonlinear behavior. To better understand and, in the future, tailor the nonlinearities, accurate methods are needed to characterize the dynamic properties of jointed structures. In this paper, the nonlinear characteristics of a jointed beam is studied with the help of multiple identification methods, including the Hilbert Transform method, Peak Finding and Fitting method, Dynamic Mode Decomposition method, State-Space Spectral Submanifold, and Wavelet-Bounded Empirical Mode Decomposition method. The nonlinearities are identified by the responses that are measured via accelerometers in a series of experiments that consist of hammer testing, shaker ringdown testing, and response/force-control stepped sine testing. In addition to accelerometers, two high-speed cameras are used to capture the motion of the whole structure during the shaker ringdown testing. Digital Image Correlation (DIC) is then adopted to obtain the displacement responses and used to determine the mode shapes of the jointed beam. The accuracy of the DIC data is validated by the comparison between the identification results of acceleration and displacement signals. As enabled by full-field data, the energy-dependent characteristics of the structure are also presented. The setup of the different experiments is described in detail in Part I (Chen et al., 2021) of this research. The focus of this paper is to compare nonlinear system identification methods applied to different measurement techniques and to exploit the use of high spatial resolution data.Item Single-molecule conformational dynamics of a transcription factor reveals a continuum of binding modes controlling association and dissociation(Oxford University Press, 2021) Chen, Wei; Lu, Wei; Wolynes, Peter G; Komives, Elizabeth A; Center for Theoretical Biological PhysicsBinding and unbinding of transcription factors to DNA are kinetically controlled to regulate the transcriptional outcome. Control of the release of the transcription factor NF-κB from DNA is achieved through accelerated dissociation by the inhibitor protein IκBα. Using single-molecule FRET, we observed a continuum of conformations of NF-κB in free and DNA-bound states interconverting on the subseconds to minutes timescale, comparable to in vivo binding on the seconds timescale, suggesting that structural dynamics directly control binding kinetics. Much of the DNA-bound NF-κB is partially bound, allowing IκBα invasion to facilitate DNA dissociation. IκBα induces a locked conformation where the DNA-binding domains of NF-κB are too far apart to bind DNA, whereas a loss-of-function IκBα mutant retains the NF-κB conformational ensemble. Overall, our results suggest a novel mechanism with a continuum of binding modes for controlling association and dissociation of transcription factors.Item Sorption and desorption of hydrocarbons to and from historically contaminated Lake Charles sediments(1997) Chen, Wei; Tomson, Mason B.The sorption and desorption behaviors of chlorinated hydrocarbons and naphthalene to and from Lake Charles sediments were studied. The sorption of 1,2- dichlorobenzene, 1,2,4-trichlorobenzene, and naphthalene was determined to be linear via hydrophobic effect, and the partition coefficients of these compounds were in the range of literature reported values. The desorption of chlorinated hydrocarbons and naphthalene were studied with two systems--a desorption with continuous removal of aqueous phase contaminants and a desorption by the repetitive water extraction. The desorption of both historically-existed and newly-added compounds showed great deviations from the equilibrium conditions. A biphasic desorption, with a labile phase and a resistant phase, has been observed to exist for both freshly- and aged-contaminated sediments. The desorption from the irreversible compartment reached a near-constant concentration, which was orders of magnitude lower than that predicted by equilibrium equations. The size of the resistant fractions seemed highly related to the initial solid phase concentration. Several factors, including pH, temperature, and competitive sorption, were found to significantly affect the release of historically-existed contaminants from the sediments. The laboratory observations in this study agreed well with other laboratory and field observations. The existence of the irreversible fraction may have a significant impact on regulatory, modeling and remediation activities.Item Spectropolarimetry of the Classical T Tauri Star BP Tau(The American Astronomical Society, 2013) Chen, Wei; Johns-Krull, Christopher M.