gebhart/patrepeval huggingface dataset:
Single Strand Targeted Triplex Formation: Physicochemical and Biochemical Properties of Foldback Triplexes (1996)

Oligodeoxyribonucleotides containing both Watson-Crick and Hoogsteen hydrogen bonding domains joined by a nucleotide loop (FTFOs) are studied for their binding affinity and specificity to the DNA and RNA single-stranded targets. Thermal denaturation studies reveal that FTFOs have high binding affinity for their targets than do antisense (duplex forming) and antigene (triplex forming) oligonucleotides, because of involvement of both the Watson-Crick and Hoogsteen domains in the interaction. Studies with FTFOs containing different sizes and sequences of loops show that 4-6 bases long loops are optimum for binding; loop sequence does not have a dramatic effect on binding. The FTFOs have greater sequence specificity than do antisense and antigene oligonucleotides because they read the target sequence twice. SI-, PI- and mung bean nuclease protection assays show that the DNA FTFO forms a stable triplex with the DNA target strand, but a weak or no triplex with the RNA target strand. Gel mobility shift assay is used to determine binding of FTFOs to DNA and RNA targets. The circular dichroism (CD) spectrum of the foldback triplex formed with the DNA target strand resembles the B-DNA spectrum, suggesting that the triplex has a B-type of conformation.
Profiling copy number variation and disease associations from 50,726 DiscovEHR Study exomes (2017)

Abstract Copy number variants (CNVs) are a substantial source of genomic variation and contribute to a wide range of human disorders. Gene-disrupting exonic CNVs have important clinical implications as they can underlie variability in disease presentation and susceptibility. The relationship between exonic CNVs and clinical traits has not been broadly explored at the population level, primarily due to technical challenges. We surveyed common and rare CNVs in the exome sequences of 50,726 adult DiscovEHR study participants with linked electronic health records (EHRs). We evaluated the diagnostic yield and clinical expressivity of known pathogenic CNVs, and performed tests of association with EHR-derived serum lipids, thereby evaluating the relationship between CNVs and complex traits and phenotypes in an unbiased, real-world clinical context. We identified CNVs from megabase to exon-level resolution, demonstrating reliable, high-throughput detection of clinically relevant exonic CNVs. In doing so, we created a catalog of high-confidence common and rare CNVs and refined population frequency estimates of known and novel gene-disrupting CNVs. Our survey among an unselected clinical population provides further evidence that neuropathy-associated duplications and deletions in 17p12 have similar population prevalence but are clinically under-diagnosed. Similarly, adults who harbor 22q11.2 deletions frequently had EHR documentation of neurodevelopmental/neuropsychiatric disorders and congenital anomalies, but not a formal genetic diagnosis (i.e., deletion). In an exome-wide association study of lipid levels, we identified a novel five-exon duplication within LDLR segregating in a large kindred with features of familial hypercholesterolemia. Exonic CNVs provide new opportunities to understand and diagnose human disease.
Association of declining PSA values with a lower risk of progression in the Canary Prostate Cancer Active Surveillance Study (PASS). (2013)

88 Background: Active Surveillance of men with low risk prostate cancer entails uncertainty for the patient and physician in determining risk of progression. While PSA determinations are frequently measured in men on active surveillance, no study thus far has found PSA velocity (PSAV) or PSA doubling times that identify patients at risk for clinical progression. However, based on observations in PASS, we hypothesized that men with negative PSAV might be at decreased risk for progression. Methods: From 723 PASS participants, we identified 396 who had at least 5 PSA values over 12-24 months after their diagnosis and prior to progression or last follow-up. Of the 396 patients, 56 progressed as defined by increase in Gleason score or increase in tumor involvement of the core biopsies to ≥ 34%, or increase in clinical stage while 340 men had no progression. PSAV is the slope of the log(PSA) values over time. ROC analysis was used with PSAV as the predictor of biopsy/clinical progression. Results: PSAV was mildly associated with clinical/biopsy progression with an AUC of 0.62 (95% CI: 0.54-0.70). Interestingly, by thresholding PSAV at 0, 150 of 396 men had negative a PSAV. Subjects with with a negative PSAV had a much lower rate of progression while on active surveillance. PSAV&lt;0 had a negative predictive value for progression of 0.93 (95% CI: 0.88-0.97). The progression rate for those with negative PSA velocity was 11/150 ≈ 0.07, or 7% and 18% (45/246) for those with positive PSA velocity. Viewed another way, men with PSAV&lt;0 had a 0.4 fold relative risk of progression compared to men with a positive PSAV or were 60% less likely to have clinical/grade progression than those with positive PSA velocity (95% CI: 0.21-0.75). Conclusions: Declining PSAV in men on active surveillance for clinically localized prostate cancer is associated with a lower risk of clinical progression. Clinical trial information: NCT00756665.
Comparative Evaluation of Covalent Docking Tools (2018)

Increased interest in covalent drug discovery led to the development of computer programs predicting binding mode and affinity of covalent inhibitors. Here we compare the performance of six covalent docking tools, AutoDock4, CovDock, FITTED, GOLD, ICM-Pro, and MOE, for reproducing experimental binding modes in an unprecedently large and diverse set of covalent complexes. It was found that 40-60% of the top scoring ligand poses are within 2.0 Å RMSD from the experimental binding mode. This rate showed program dependent increase and achieved 50-90% when the best RMSD among the top ten scoring poses was considered. This performance is comparable to that of noncovalent docking tools and therefore suggests that anchoring the ligand does not necessarily improve the accuracy of the prediction. The effect of various ligand and protein features on the docking performance was investigated. At the level of warhead chemistry, higher success rate was found for Michael additions, nucleophilic additions and nucleophilic substitutions than for ring opening reactions and disulfide formation. Increasing ligand size and flexibility generally affects pose predictions unfavorably, although AutoDock4, FITTED, and ICM-Pro were found to be less sensitive up to 35 heavy atoms. Increasing the accessibility of the target cysteine tends to result in improved binding mode predictions. Docking programs show protein dependent performance suggesting a target-dependent choice of the optimal docking tool. It was found that noncovalent docking into Cys/Ala mutated proteins by ICM-Pro and Glide reproduced experimental binding modes with only slightly lower performance and at a significantly lower computational expense than covalent docking did. Overall, our results highlight the key factors influencing the docking performance of the investigated tools and they give guidelines for selecting the optimal combination of warheads, ligands, and tools for the system investigated. Results also identify the most important aspects to be considered for developing improved protocols for docking and virtual screening of covalent ligands.
Sparse Phase Retrieval via Truncated Amplitude Flow (2016)

This paper develops a novel algorithm, termed \emph{SPARse Truncated Amplitude flow} (SPARTA), to reconstruct a sparse signal from a small number of magnitude-only measurements. It deals with what is also known as sparse phase retrieval (PR), which is \emph{NP-hard} in general and emerges in many science and engineering applications. Upon formulating sparse PR as an amplitude-based nonconvex optimization task, SPARTA works iteratively in two stages: In stage one, the support of the underlying sparse signal is recovered using an analytically well-justified rule, and subsequently, a sparse orthogonality-promoting initialization is obtained via power iterations restricted on the support; and, in the second stage, the initialization is successively refined by means of hard thresholding based gradient-type iterations. SPARTA is a simple yet effective, scalable, and fast sparse PR solver. On the theoretical side, for any $n$-dimensional $k$-sparse ($k\ll n$) signal $\bm{x}$ with minimum (in modulus) nonzero entries on the order of $(1/\sqrt{k})\|\bm{x}\|_2$, SPARTA recovers the signal exactly (up to a global unimodular constant) from about $k^2\log n$ random Gaussian measurements with high probability. Furthermore, SPARTA incurs computational complexity on the order of $k^2n\log n$ with total runtime proportional to the time required to read the data, which improves upon the state-of-the-art by at least a factor of $k$. Finally, SPARTA is robust against additive noise of bounded support. Extensive numerical tests corroborate markedly improved recovery performance and speedups of SPARTA relative to existing alternatives.
A Strategy to Design Hyperpolarized 13C Magnetic Resonance Probes Using [1‐13C]α‐Amino Acid as a Scaffold Structure (2017)

Hyperpolarization is an emerging method that dramatically enhances NMR signal intensity. As a result of their increased sensitivity, hyperpolarized (HP) NMR molecular probes can be used to perform time-resolved spectroscopy and imaging in vitro and in vivo. It is, however, challenging to design such probes de novo. Herein, the [1-<sup>13</sup> C]α-amino acid is reported as a scaffold structure to design HP <sup>13</sup> C NMR molecular probes. The [1-<sup>13</sup> C]α-amino acid can be converted to various HP <sup>13</sup> C chemical probes that show sufficient chemical shift change by altering the chemical state of the α nitrogen upon interaction with the target. Several previously reported HP probes could be explained by this design principle. To demonstrate the versatility of this approach, two α-amino-acid-based HP <sup>13</sup> C chemical probes, sensitive to pH and Ca<sup>2+</sup> ion, were developed and used to detect targets.
Hydrodynamic drift ratchet scalability (2016)

The hydrodynamic drift ratchet provides a novel means to continuously separate particles at the microscale, based on particle size. Separation arises from a combination of diffusion and particle‐wall hydrodynamic interactions. As there are currently no verified experiments, our aim is to determine numerically how these systems scale so that appropriate experiments can be designed. Using nondimensional variables, we derive the correct scaling parameters governing drift ratchets by simulating individual particle motion using a model that treats the particle dynamics at pore walls as elastic reflections. While our model does not quantitatively resolve the detailed hydrodynamic interactions, we show that it does recover the correct scaling behavior for these interactions. Our simulations demonstrate that the drift velocity relative to the characteristic pore size is independent of pore size if all the relevant nondimensional groups remain constant. Dynamic similarity can be used to facilitate the appropriate design and testing protocols for experiments. © 2016 American Institute of Chemical Engineers AIChE J , 63: 2358–2366, 2017
Plasmon-enhanced fluorescence in gold nanorod-quantum dot coupled systems (2019)

Plasmon-exciton coupling is of great importance to many optical devices and applications. One of the coupling manifestations is plasmon-enhanced fluorescence. Although this effect is demonstrated in numerous experimental and theoretical works, there are different particle shapes for which this effect is not fully investigated. In this work electrostatic complexes of gold nanorods and CdSe/CdZnS quantum dots were studied. Double-resonant gold nanorods have an advantage of the simultaneous enhancement of the absorption and emission when the plasmon bands match the excitation and fluorescence wavelengths of an emitter. A relationship between the concentration of quantum dots in the complexes and the enhancement factor was established. It was demonstrated that the enhancement factor is inversely proportional to the concentration of quantum dots. The maximal fluorescence enhancement by 10.8 times was observed in the complex with the smallest relative concentration of 2.5 quantum dots per rod and approximately 5 nm distance between them. Moreover, the influence of quantum dot location on the gold nanorod surface plays an important role. Theoretical study and experimental data indicate that only the position near the nanorod ends provides the enhancement. At the same time, the localization of quantum dots on the sides of the nanorods leads to the fluorescence quenching.
A note on the conformational flexibility of the antiestrogenic drug tamoxifen: preferred conformations in the free state and bound to the protein calmodulin (1992)

The conformational properties of the antiestrogenic drug tamoxifen, a triphenylbut-1-ene derivative, have been studied using molecular mechanics. Four distinct conformers have been identified, and the energy barriers between them have been established. The orientation of the ethyl group substituent has been examined in particular, since the lowest-energy conformers have this group orientated 180 degrees away from its position in the crystal structures of tamoxifen and its derivatives. These differences have implications for the interactions of tamoxifen with the calcium-binding protein calmodulin; relevant results from a molecular-modelling study of this protein-drug complex are presented.
Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression profiles in tracheal aspirates do not adequately reflect tracheal or lung tissue profiles in neonatal respiratory distress: Observations from an animal model (2005)

The MMP/TIMP profiles in TA do not adequately represent the profiles in either trachea or lung. Thus, MMP/TIMP profiles from TA are limited and should be interpreted for trends rather than actual tissue levels.
Detection of Specific Binding to HER2 Receptors by in vivo Fluorescence Lifetime Imaging (2012)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text Y. Ardeshirpour, V. Chernomordik, M. Hassan, R. Zielinski, G. Griffiths, O. Vasalatiy, A. V. Smirnov, J. R. Knutson, S. Achilefu, J. Capala, and A. Gandjbakhche, "Detection of Specific Binding to HER2 Receptors by in vivo Fluorescence Lifetime Imaging," in Biomedical Optics and 3-D Imaging, OSA Technical Digest (Optica Publishing Group, 2012), paper BTu3A.24. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Temperature dependence (4K to 300K) of the electrical resistivity of methane grown carbon fibers (1987)

Experimental measurements of the electrical resistivity vs temperature of methane vapor grown carbon fibers are presented. The fibers are heat treated from 1100 C (as-grown) to 3000 C. Data are fit to a standard two band model, which yields values for boundary scattering limited electron mobility, in-plane mean free path, energy band overlap, and total carrier density. The data are also fit to an ellipsoidal band model, where data fits yield effective masses, band overlap, Fermi velocity, phonon contributions to scattering, and ionized impurity scattering rates.
Linear Integration of Sensory Evidence over Space and Time Underlies Face Categorization (2021)

Visual object recognition relies on elaborate sensory processes that transform retinal inputs to object representations, but it also requires decision-making processes that read out object representations and function over prolonged time scales. The computational properties of these decision-making processes remain underexplored for object recognition. Here, we study these computations by developing a stochastic multifeature face categorization task. Using quantitative models and tight control of spatiotemporal visual information, we demonstrate that human subjects (five males, eight females) categorize faces through an integration process that first linearly adds the evidence conferred by task-relevant features over space to create aggregated momentary evidence and then linearly integrates it over time with minimum information loss. Discrimination of stimuli along different category boundaries (e.g., identity or expression of a face) is implemented by adjusting feature weights of spatial integration. This linear but flexible integration process over space and time bridges past studies on simple perceptual decisions to complex object recognition behavior.<b>SIGNIFICANCE STATEMENT</b> Although simple perceptual decision-making such as discrimination of random dot motion has been successfully explained as accumulation of sensory evidence, we lack rigorous experimental paradigms to study the mechanisms underlying complex perceptual decision-making such as discrimination of naturalistic faces. We develop a stochastic multifeature face categorization task as a systematic approach to quantify the properties and potential limitations of the decision-making processes during object recognition. We show that human face categorization could be modeled as a linear integration of sensory evidence over space and time. Our framework to study object recognition as a spatiotemporal integration process is broadly applicable to other object categories and bridges past studies of object recognition and perceptual decision-making.
Entity ranking for descriptive queries (2014)

We investigate the problem of entity ranking towards descriptive queries, that aims to match entities referred in user queries to entities of a large knowledge base (KB). Entity ranking faces the primary challenge of the sparseness of entity related data, such as various ways of referring to an entity. The lack of sufficient variations of entity referring expressions in KB makes it difficult to find entities referred in user queries, especially when the queries are descriptive. We tackle this problem by enriching KB entries using web documents and query click logs. First, we propose a novel method of injecting textual information from web documents to the KB on a large scale. Since the number of web documents can be large, we propose to use keyword extraction and summarization techniques for compactly representing entity-related information. Second, we mine web search query logs to link entities to existing queries. Experiments show significant improvements after the KB enrichment, compared with two competitive baselines. We also achieve further improvements by combining the data from these two resources.
ChemInform Abstract: Palladium‐Catalyzed Carbonylative Cross‐Coupling with Imines: A Multicomponent Synthesis of Imidazolones. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Novel Synthesis Routes for Polyhydroxyalkanoic Acids with Unique Properties (2005)

Polyhydroxyalkanoates (PHAs) are naturally occurring, biodegradable and biocompatible polyesters and have attracted considerable interest as a renewable resource based thermoplastic. In this study, we express a PHA polymerase capable of polymerizing medium chain length (R)-3-hydroxy precursor molecules in the cytosol of yeast. We demonstrate that these engineered yeasts are capable of synthesizing PHAs comprised of 6-13 carbon monomers. These monomer units are typically produced via the β-oxidation pathway in specialized organelles known as peroxisomes. Therefore, the presented results indicate that the β-oxidation pathway is not solely restricted to peroxisomes but also appears to be functional in the yeast cytosol. This finding provides a basis for novel metabolic engineering strategies that could make the PHA synthesis process more economical and could yield polymers with unique material properties.
Inhibition of glial cell proinflammatory activities by peroxisome proliferator‐activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro (2002)

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the nuclear hormone superfamily originally characterized as a regulator of adipocyte differentiation and lipid metabolism. In addition, PPAR-gamma has important immunomodulatory functions. If the effect of PPAR-gamma's activation in T-cell-mediated demyelination has been recently demonstrated, nothing is known about the role of PPAR-gamma in antibody-induced demyelination in the absence of T-cell interactions and monocyte/macrophage activation. Therefore, we investigated PPAR-gamma's involvement by using an in vitro model of inflammatory demyelination in three-dimensional aggregating rat brain cell cultures. We found that PPAR-gamma was not constitutively expressed in these cultures but was strongly up-regulated following demyelination mediated by antibodies directed against myelin oligodendrocyte glycoprotein (MOG) in the presence of complement. Pioglitazone, a selective PPAR-gamma agonist, partially protected aggregates from anti-MOG demyelination. Heat shock responses and the expression of the proinflammatory cytokine tumor necrosis factor-alpha were diminished by pioglitazone treatment. Therefore, pioglitazone protection seems to be linked to an inhibition of glial cell proinflammatory activities following anti-MOG induced demyelination. We show that PPAR-gamma agonists act not only on T cells but also on antibody-mediated demyelination. This may represent a significant benefit in treating multiple sclerosis patients.
Image-space control variates for rendering (2016)

We explore the theory of integration with control variates in the context of rendering. Our goal is to optimally combine multiple estimators using their covariances. We focus on two applications, re-rendering and gradient-domain rendering, where we exploit coherence between temporally and spatially adjacent pixels. We propose an image-space (iterative) reconstruction scheme that employs control variates to reduce variance. We show that recent works on scene editing and gradient-domain rendering can be directly formulated as control-variate estimators, despite using seemingly different approaches. In particular, we demonstrate the conceptual equivalence of screened Poisson image reconstruction and our iterative reconstruction scheme. Our composite estimators offer practical and simple solutions that improve upon the current state of the art for the two investigated applications.
Characterization by GISAXS and Electrochemical Impedance Spectroscopy of porous oxide films (2018)

Porous oxide films were deposited by reactive sputtering. Some films received UV cures and/or a Si cap. The FTIR analyses show that the deposited films were very hydrophilic. Standard ellipsometric porosimetry was not able to determine porosity nor pore size. With GISAXS, the porosity of different films was determined (approximately 13%) and the pore format (mostly spherical pores with a radius of approximately 5 nm). Electrochemical Impedance Spectroscopy completed the pore analysis, indicating mostly open porosity. These techniques were sufficiently sensitive to show that the Si cap closed the pores somewhat while the UV cure increased the porosity.
Blind channel identification for OFDM-based SIMO systems (2008)

We introduce blind channel identification and equalization for orthogonal frequency division multiplexing (OFDM) system using a guard interval (GI). To perform channel identification, Subspace-based methods are proposed. To achieve enhanced performance and robustness to channel frequency nulls, receiver diversity and OFDM is combined. The performance of the proposed system is illustrated by computer simulations.