gebhart/patrepeval huggingface dataset:
Reciprocal Effect of Waardenburg Syndrome Mutations on DNA Binding by the Pax-3 Paired Domain and Homeodomain (1997)

The Pax-3 protein contains two DNA-binding domains, a paired domain and a homeodomain. Mutations in Pax-3 cause Waardenburg syndrome (WS) in humans and the mouse Splotch (Sp) phenotype. In the Sp-delayed mouse, a mutation in the Pax-3 paired domain (G9R) abrogates the DNA-binding activity of both the paired domain and the homeodomain, suggesting that they may functionally interact. To investigate this possibility further, we have analyzed the DNA-binding properties of additional point mutants in the Pax-3 paired domain and homeodomain that occur in WS patients (F12L, N14H, G15S, P17L, R23L, G48A, S51F and G66D in the paired domain, V47F and R53G in the homeodomain), the Pax-1 un mutation (G15A) and a substitution associated with Peters' anomaly in the PAX-6 gene (R23G). Within the paired domain, seven of 10 mutations were found to abrogate DNA-binding by the paired domain. Remarkably, these seven mutations also affected DNA binding by the homeodomain, causing either a complete loss (P17L and G66D), a reduction (R23G, R23L, G15S and G15A) or an increase in DNA-binding activity (N14H). In addition, the effect of paired domain mutations occurred at the level of monomer formation by the homeodomain, while the dimerization potential of this domain seemed unaffected in mutants where it could be analyzed. Furthermore, while both homeodomain mutations were found to abolish DNA binding by this domain, the R53G mutation also abrogated DNA binding by the paired domain. The important observation that independent mutations in either domain can affect DNA binding by the other in the intact Pax-3 protein strongly suggests that the two domains are not functionally independent but bind DNA through cooperative interactions. Modeling the deleterlous mutations on the three-dimensional structure of the paired domain of Drosophila Prd shows that these mutations cluster at the DNA interface, thus suggesting that a series of DNA contacts are essential for DNA binding by both the paired domain and the homeodomain of Pax-3.
Bayesian Uncertainty Quantification for Subsurface Inversion Using a Multiscale Hierarchical Model (2013)

We consider a Bayesian approach to nonlinear inverse problems in which the unknown quantity is a random field (spatial or temporal). The Bayesian approach contains a natural mechanism for regularization in the form of prior information, can incorporate information from heterogeneous sources and provide a quantitative assessment of uncertainty in the inverse solution. The Bayesian setting casts the inverse solution as a posterior probability distribution over the model parameters. The Karhunen-Loeve expansion is used for dimension reduction of the random field. Furthermore, we use a hierarchical Bayes’ model to inject multiscale data in the modeling framework. In this Bayesian framework, we show that this inverse problem is well-posed by proving that the posterior measure is Lipschitz continuous with respect to the data in total variation norm. Computational challenges in this construction arise from the need for repeated evaluations of the forward model (e.g., in the context of MCMC) and are compounded by high dimensionality of the posterior. We develop two-stage reversible jump MCMC that has the ability to screen the bad proposals in the first inexpensive stage. Numerical results are presented by analyzing simulated as well as real data from hydrocarbon reservoir. This article has supplementary material available online.
ChemInform Abstract: 1,2‐DIARYLETHYLENE‐DIENE EXCIPLEXES. SOLVENT‐INDUCED CHANGES IN CHEMICAL AND PHYSICAL PROCESSES (1977)

Abstract Die Fluoreszenz verschiedener 1,2‐Diaryläthylene (I)‐(III) kann durch konjugierte Diene wie (IV)‐(VII) gelöscht werden; dies führt zur Bildung von Cycloaddukten und zum Auftreten einer veränderten Fluoreszenz, was beides auf die intermediäre reversible (Temperaturabhängigkeit der Fluoreszenzlöschungs‐ Geschwindigkeitskonstanten) Bildung von Exciplexen zurückgeht.
Potential Influence of Surface Atomic Disorder on Fermi-level Pinning at Metal/SiGe Interface (2018)

The Schottky barrier heights (SBH) at metal/n-Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.55</sub> Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.45</sub> Schottky interface are reported as a function of work function of metals. In comparison of the pinning strength with metal/Si and metal/Ge, the result shows that a large amount of disorders and defects on SiGe do not have a significant effect on the Fermi level pinning (FLP), which may suggest that the intrinsic instead of extrinsic mechanism should be considered for the dominant mechanism of Fermi level pinning not only at metal/SiGe but also at metal/Si and Ge systems.
Pipeline Design and Verification in Bluenose II (2007)

As digital hardware circuits get more complex, it becomes more difficult and time consuming to verify a design. Although time to market is crucial, adequate time should be spent on verification since a bug found after manufacturing is expensive to fix and will cause further delay to market. Techniques in formal methods such as model checking allow the discovery of subtle design bugs. However, formal verification usually requires specialized expertise. Bluenose II aims to address these issues by raising design abstraction to increase productivity and reduce verification effort, focusing on pipelined circuits in particular.
1.7 kW power booster TWT at 35 GHz (2014)

Summary form only given. The development of a broadband multi-kW Ka-band PPM focused TWT driver-booster combination is reported. The driver is an existing broadband coupled-cavity TWT <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> , employing a 2 stage depressed collector. The power booster is a newly designed sever-less folded waveguide TWT designed to provide 3-4 dB of additional gain <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The booster also uses a 2 stage depressed collector and a slightly modified version of the same electron gun used in the driver. In order to accommodate the high power output of the booster over the full operating band, a new racetrack window was successfully designed built and tested. The maximum booster output power of ~ 1.75 kW at ~ 750 Watt CC-TWT input power at 35 GHz has been demonstrated. The booster output power of 1.5 kW over 5 GHz and of 1.25 kW over 7 GHz centered at 35 GHz has been measured. Beam current interception of ~ 7% has been observed in the power booster when operating > 1 kW, thus preventing a CW operation of the booster. The predictions from the 2.5D large signal TESLA-FW simulation code <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> are in very good agreement with the measured data.
Nanopore Detection of 8-Oxoguanine in the Human Telomere Repeat Sequence (2015)

The human telomere repeat sequence 5'-TTAGGG-3' is a hot spot for oxidation at guanine, yielding 8-oxo-7,8-dihydroguanine (OG), a biomarker of oxidative stress. Telomere shortening resulting from oxidation will ultimately induce cellular senescence. In this study, α-hemolysin (α-HL) nanopore technology was applied to detect and quantify OG in the human telomeric DNA sequence. This repeat sequence adopts a basket G-quadruplex in the NaCl electrolyte used for analysis that enters the α-HL channel, slowly unfolds, and translocates. The basket fold containing OG disrupts the structure, leading to >10× increase in the unfolding kinetics without yielding a detectable current pattern. Therefore, detection of OG with α-HL required labeling of OG with aminomethyl-[18-crown-6] using a mild oxidant. The labeled OG yielded a pulse-like signal in the current vs time trace when the DNA strand was electrophoretically passed through α-HL in NaCl electrolyte. However, the rate of translocation was too slow using NaCl salts, leading us to further refine the method. A mixture of NH4Cl and LiCl electrolytes induced the propeller fold that unravels quickly outside the α-HL channel. This electrolyte allowed observation of the labeled OG, while providing a faster recording of the currents. Lastly, OG distributions were probed with this method in a 120-mer stretch of the human telomere sequence exposed to the cellular oxidant (1)O2. Single-molecule profiles determined the OG distributions to be random in this context. Application of the method in nanomedicine can potentially address many questions surrounding oxidative stress and telomere attrition observed in various disease phenotypes including prostate cancer and diabetes.
Reduction of persistent photoconductivity in ZnO thin film transistor-based UV photodetector (2012)

We report a ZnO-based thin film transistor UV photodetector with a back gate configuration. The thin-film transistor (TFT) aspect ratio W/L is 150 μm/5 μm and has a current on-off ratio of 1010. The detector shows UV-visible rejection ratio of 104 and cut-off wavelength of 376 nm. The device has low dark current of 5 × 10−14 A. The persistent photoconductivity is suppressed through oxygen plasma treatment of the channel surface which significantly reduces the density of oxygen vacancy confirmed by XPS measurements. The proper gate bias-control further reduces recovery time. The UV-TFT configuration is particularly suitable for making large-area imaging arrays.
SELECTION OF CONTROL SPEEDS IN DYNAMIC INTELLIGENT SPEED ADAPTATION SYSTEM: A PRELIMINARY ANALYSIS (2007)

Intelligent speed adaptation (ISA) has been shown to be an effective measure for road safety improvement. Recently, there has been an increasing interest in using ISA systems, particularly with the dynamic speed control, to manage congestion and reduce energy/emissions. The effectiveness of the dynamic ISA system relies on its speed control strategies. This paper presents the development of a preliminary method to determine control speeds of the dynamic ISA system. The initial results show reasonable control speeds under various levels of freeway congestion as categorized by freeway level of service.
Evolving Energy Efficient Convolutional Neural Networks (2019)

As deep neural networks have been deployed in more and more applications over the past half decade and are finding their way into an ever increasing number of operational systems, their energy consumption becomes a concern whether running in the datacenter or on edge devices. Hyperparameter optimization and automated network design for deep learning is a quickly growing field, but much of the focus has remained only on optimizing for the performance of the machine learning task. In this work, we demonstrate that the best performing networks created through this automated network design process have radically different computational characteristics (e.g. energy usage, model size, inference time), presenting the opportunity to utilize this optimization process to make deep learning networks more energy efficient and deployable to smaller devices. Optimizing for these computational characteristics is critical as the number of applications of deep learning continues to expand.
Constitutive CCND1/CDK2 Activity Substitutes for p53 Loss, or MYC or Oncogenic RAS Expression in the Transformation of Human Mammary Epithelial Cells (2013)

Cancer develops following the accumulation of genetic and epigenetic alterations that inactivate tumor suppressor genes and activate proto-oncogenes. Dysregulated cyclin-dependent kinase (CDK) activity has oncogenic potential in breast cancer due to its ability to inactivate key tumor suppressor networks and drive aberrant proliferation. Accumulation or over-expression of cyclin D1 (CCND1) occurs in a majority of breast cancers and over-expression of CCND1 leads to accumulation of activated CCND1/CDK2 complexes in breast cancer cells. We describe here the role of constitutively active CCND1/CDK2 complexes in human mammary epithelial cell (HMEC) transformation. A genetically-defined, stepwise HMEC transformation model was generated by inhibiting p16 and p53 with shRNA, and expressing exogenous MYC and mutant RAS. By replacing components of this model, we demonstrate that constitutive CCND1/CDK2 activity effectively confers anchorage independent growth by inhibiting p53 or replacing MYC or oncogenic RAS expression. These findings are consistent with several clinical observations of luminal breast cancer sub-types that show elevated CCND1 typically occurs in specimens that retain wild-type p53, do not amplify MYC, and contain no RAS mutations. Taken together, these data suggest that targeted inhibition of constitutive CCND1/CDK2 activity may enhance the effectiveness of current treatments for luminal breast cancer.
Direct observation of dipolar chains in ferrofluids in zero field using cryogenic electron microscopy (2003)

The particle structure of ferrofluids is studied in situ, by cryogenic electron microscopy, on vitrified films of iron and magnetite dispersions. By means of synthesis of iron colloids with controlled particle size and different types of surfactant, dipolar particle interactions can be varied over a broad range, which significantly influences the ferrofluid particle structure. Our experiments on iron dispersions (in contrast to magnetite dispersions) for the first time demonstrate, in ferrofluids in zero field, a transition with increasing particle size from separate particles to linear chains of particles (Butter K, Bomans P H, Frederik P M, Vroege G J and Philipse A P 2003 Nature Mater. 2 88). These chains, already predicted theoretically by de Gennes and Pincus (de Gennes P G and Pincus P A 1970 Phys. Kondens. Mater. 11 189), very much resemble the fluctuating chains found in simulations of dipolar fluids (Weis J J 1998 Mol. Phys. 93 361, Chantrell R W, Bradbury A, Popplewell J and Charles S W 1982 J. Appl. Phys. 53 2742). Decreasing the range of steric repulsion between particles by employing a thinner surfactant layer is found to change particle structures as well. The dipolar nature of the aggregation is confirmed by the alignment of existing chains and individual particles in the field direction upon vitrification of dispersions in a saturating magnetic field. Frequency-dependent susceptibility measurements indicate that particle structures in truly three-dimensional ferrofluids are qualitatively similar to those in liquid films.
A surgical case of complex-type pulmonary arteriovenous fistula (2018)

症例は70歳，女性．近医で胸部異常陰影と低酸素血症を指摘され当院呼吸器内科紹介となった．胸部造影CTでは左舌区に複雑型肺動静脈瘻を認め，縦隔型舌区肺動脈より1本，葉間から分岐するA4，A5，A8よりそれぞれ1本ずつ流入動脈を認めた．放射線科よりコイル塞栓術は困難と判断され，手術目的に当科紹介となった．手術は左上葉切除を施行した．術前検査でシャント率31.4%，動脈血酸素分50.2 mmHgであったが，術後には9.5%，動脈血酸素分圧も89.7 mmHgと著明に改善した．複雑型肺動静脈瘻に対して手術が有効であった一例を経験したので，文献的考察を加え報告する．
Supplementary Data from Dual PI3K/mTOR Inhibition in Colorectal Cancers with APC and PIK3CA Mutations (2023)

&lt;p&gt;S1. AP spheroids were plated and allowed to mature for 48 hours. S2. To address the issue of potentially slower growth of the spheres with the largest initial sizes, a change-point analysis was performed. S3. AP mice were treated with control (A) or BEZ235 (B) for 14 days. S4. AP mice were treated with BEZ235 or control for 14 days. S5. AP spheroids were treated with NVP-BYL719, BEZ235, LY3023414, or control for 24 hours. S5. AP spheroids were treated with NVP-BYL719, BEZ235, LY3023414, or control for 24 hours. Supplementary Table S1. AP spheroids were treated with NVP-BYL719, GDC0941, BEZ235, LY3023414, or control for 48 hours. Supplemental Table S2. AP mice were treated with BEZ235, LY3023414 or control for 14 days.&lt;/p&gt;
TLR4 (Toll-Like Receptor 4)-Dependent Signaling Drives Extracellular Catabolism of LDL (Low-Density Lipoprotein) Aggregates (2019)

We present a mechanism in which interaction of macrophages with agLDL initiates a TLR4 signaling pathway, resulting in formation of the lysosomal synapse, catabolism of agLDL, and lipid accumulation in vitro and in vivo.
Oxysterols Inhibit Phosphatidylcholine Synthesis via ERK Docking and Phosphorylation of CTP:Phosphocholine Cytidylyltransferase (2005)

Surfactant deficiency contributes to acute lung injury and may result from the elaboration of bioactive lipids such as oxysterols. We observed that the oxysterol 22-hydroxycholesterol (22-HC) in combination with its obligate partner, 9-cis-retinoic acid (9-cis-RA), decreased surfactant phosphatidylcholine (PtdCho) synthesis by increasing phosphorylation of the regulatory enzyme CTP:phosphocholine cytidylyltransferase-alpha (CCTalpha). Phosphorylation of CCTalpha decreased its activity. 22-HC/9-cis-RA inhibition of PtdCho synthesis was blocked by PD98059 or dominant-negative ERK (p42 kinase). Overexpression of constitutively active MEK1, the kinase upstream of p42 kinase, increased CCTalpha phosphorylation. Expression of truncated CCTalpha mutants lacking proline-directed sites within the C-terminal phosphorylation domain partially blocked oxysterol-mediated inhibition of PtdCho synthesis. Mutagenesis of Ser315 within CCTalpha was both required and sufficient to confer significant resistance to 22-HC/9-cis-RA inhibition of PtdCho synthesis. A novel putative ERK-docking domain N-terminal to this phosphoacceptor site was mapped within the CCTalpha membrane-binding domain (residues 287-300). The results are the first demonstration of a physiologically relevant phosphorylation site and docking domain within CCTalpha that serve as targets for ERKs, resulting in inhibition of surfactant synthesis.
Polyomavirus T Antigen Induces <i>APOBEC3B</i> Expression Using an LXCXE-Dependent and TP53-Independent Mechanism (2019)

APOBEC3B is a single-stranded DNA cytosine deaminase with beneficial innate antiviral functions. However, misregulated APOBEC3B can also be detrimental by inflicting APOBEC signature C-to-T and C-to-G mutations in genomic DNA of multiple cancer types. Polyomavirus and papillomavirus oncoproteins induce APOBEC3B overexpression, perhaps to their own benefit, but little is known about the cellular mechanisms hijacked by these viruses to do so. Here we investigate the molecular mechanism of APOBEC3B upregulation by the polyomavirus large T antigen. First, we demonstrate that the upregulated APOBEC3B enzyme is strongly nuclear and partially localized to virus replication centers. Second, truncated T antigen (truncT) is sufficient for APOBEC3B upregulation, and the RB-interacting motif (LXCXE), but not the p53-binding domain, is required. Third, genetic knockdown of RB1 alone or in combination with RBL1 and/or RBL2 is insufficient to suppress truncT-mediated induction of <i>APOBEC3B</i> Fourth, CDK4/6 inhibition by palbociclib is also insufficient to suppress truncT-mediated induction of <i>APOBEC3B</i> Last, global gene expression analyses in a wide range of human cancers show significant associations between expression of <i>APOBEC3B</i> and other genes known to be regulated by the RB/E2F axis. These experiments combine to implicate the RB/E2F axis in promoting <i>APOBEC3B</i> transcription, yet they also suggest that the polyomavirus RB-binding motif has at least one additional function in addition to RB inactivation for triggering <i>APOBEC3B</i> upregulation in virus-infected cells.<b>IMPORTANCE</b> The APOBEC3B DNA cytosine deaminase is overexpressed in many different cancers and correlates with elevated frequencies of C-to-T and C-to-G mutations in 5'-TC motifs, oncogene activation, acquired drug resistance, and poor clinical outcomes. The mechanisms responsible for APOBEC3B overexpression are not fully understood. Here, we show that the polyomavirus truncated T antigen (truncT) triggers APOBEC3B overexpression through its RB-interacting motif, LXCXE, which in turn likely modulates the binding of E2F family transcription factors to promote <i>APOBEC3B</i> expression. This work strengthens the mechanistic linkage between active cell cycling, APOBEC3B overexpression, and cancer mutagenesis. Although this mutational mechanism damages cellular genomes, viruses may leverage it to promote evolution, immune escape, and pathogenesis. The cellular portion of the mechanism may also be relevant to nonviral cancers, where genetic mechanisms often activate the RB/E2F axis and APOBEC3B mutagenesis contributes to tumor evolution.
Special Populations and Pharmacogenetic Issues in Tuberculosis Drug Development and Clinical Research (2015)

Special populations, including children and pregnant women, have been neglected in tuberculosis drug development. Patients in developing countries are inadequately represented in pharmacology research, and postmarketing pharmacovigilance activities tend to be rudimentary in these settings. There is an ethical imperative to generate evidence at an early stage to support optimal treatment in these populations and in populations with common comorbid conditions, such as diabetes and human immunodeficiency virus (HIV) infection. This article highlights the research needed to support equitable access to new antituberculosis regimens. Efficient and opportunistic pharmacokinetic study designs, typically using sparse sampling and population analysis methods, can facilitate optimal dose selection for children and pregnant women. Formulations suitable for children should be developed early and used in pharmacokinetic studies to guide dose selection. Drug-drug interactions between commonly coprescribed medications also need to be evaluated, and when these are significant, alternative approaches should be sought. A potent rifamycin-sparing regimen could revolutionize the treatment of adults and children requiring a protease inhibitor as part of antiretroviral treatment regimens for HIV infection. A sufficiently wide formulary of drugs should be developed for those with contraindications to the standard approaches. Because genetic variations may influence an individual's response to tuberculosis treatment, depending on the population being treated, it is important that samples be collected and stored for pharmacogenetic study in future clinical trials.
A simple method to determine mineralization of 14C-labeled compounds in soil (2014)

Degradation of organic compounds in soil is often determined by measuring the decrease of the parent compound and analyzing the occurrence of its metabolites. However, determining carbon species as end products of parent compound dissipation requires using labeled materials that allow more accurate determination of the environmental fate of the compound of interest. The current conventional closed system widely used to monitor degradation of (14) C-labeled compounds in soil is complex and expensive and requires a specialized apparatus and facility. In the present study, the authors describe a simple system that facilitates measurement of mineralization of (14) C-labeled compounds applied to soil samples. In the system, soda lime pellets to trap mineralized (14) C-carbon species, including carbon dioxide, were placed in a cup, which was then inserted above the treated soil sample in a tube. Mineralization of [(14) C]2,4-D applied to soil samples in the simple system was compared with that in the conventional system. The simple system provided an equivalent detection of (14) C-carbon species mineralized from the parent compound. The results demonstrate that this cost- and space-effective simple system is suitable for examining degradation and mineralization of (14) C-labeled compounds in soil and could potentially be used to investigate their mineralization in other biological matrices.
Theory to predict particle migration and margination in the pressure-driven channel flow of blood (2017)

A coarse-grained theory quickly and accurately estimates the cross-flow transport of red blood cells and platelets in pressure-driven channel flow. The deformability-induced cell migration and shear-induced diffusion are the keys to understanding blood suspensions at low Reynolds number.