gebhart/patrepeval huggingface dataset:
Chemistry of Styrene (Water)nClusters,n= 1−5:  Spectroscopy and Structure of the Neutral Clusters, Deprotonation of Styrene Dimer Cation, and Implication to the Inhibition of Cationic Polymerization (2005)

The styrene-water binary clusters SW(n), with n = 1-5 have been studied by the (one-color) resonant two-photon ionization technique using the resonance of styrene. The structures and energetics of the neutral clusters are investigated using a search technique that employs Monte Carlo procedure. The strong tendency for water molecules to form cyclic hydrogen-bonded structures is clearly observed in the SW(n) structures starting from n =3. The results indicate that the spectral shifts correlate with the interaction energies between styrene and the water subcluster (W(n)) within the SW(n) clusters. Evidence is presented that points to (1) the formation of a covalent bonded styrene radical cation dimer following the 193 nm MPI of styrene neutral clusters, (2) proton transfer from the styrene dimer cation to the water or methanol subcluster, resulting in the formation of protonated water or methanol clusters and a styrene dimer radical, and (3) extensive solvation of the styrene dimer radical within the protonated solvent molecules. The proton-transfer reactions may explain the strong inhibition effects exerted by small concentrations of water or methanol on the cationic polymerization of styrene. These results provide a molecular level view of the inhibition mechanism exerted by protic solvents on the cationic polymerization of styrene.
Programming sites of meiotic crossovers using Spo11 fusion proteins (2017)

Meiotic recombination shapes the genetic diversity transmitted upon sexual reproduction. However, its non-random distribution along the chromosomes constrains the landscape of potential genetic combinations. For a variety of purposes, it is desirable to expand the natural repertoire by changing the distribution of crossovers in a wide range of eukaryotes. Toward this end, we report the local stimulation of meiotic recombination at a number of chromosomal sites by tethering the natural Spo11 protein to various DNA-binding modules: full-length DNA binding proteins, zinc fingers (ZFs), transcription activator-like effector (TALE) modules, and the CRISPR-Cas9 system. In the yeast Saccharomyces cerevisiae, each strategy is able to stimulate crossover frequencies in naturally recombination-cold regions. The binding and cleavage efficiency of the targeting Spo11 fusions (TSF) are variable, being dependent on the chromosomal regions and potential competition with endogenous factors. TSF-mediated genome interrogation distinguishes naturally recombination-cold regions that are flexible and can be warmed-up (gene promoters and coding sequences), from those that remain refractory (gene terminators and centromeres). These results describe new generic experimental strategies to increase the genetic diversity of gametes, which should prove useful in plant breeding and other applications.
A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals (2015)

CatalyCEST MRI can detect enzyme activity by monitoring the change in chemical exchange with water after a contrast agent is cleaved by an enzyme. Often these molecules use paramagnetic metals and are delivered with an additional non-responsive reference molecule. To improve this approach for molecular imaging, a single diamagnetic agent with enzyme-responsive and enzyme-unresponsive CEST signals was synthesized and characterized. The CEST signal from the aryl amide disappeared after cleavage of a dipeptidyl ligand with cathepsin B, while a salicylic acid moiety was largely unresponsive to enzyme activity. The ratiometric comparison of the two CEST signals from the same agent allowed for concentration independent measurements of enzyme activity. The chemical exchange rate of the salicylic acid moiety was unchanged after enzyme catalysis, which further validated that this moiety was enzyme-unresponsive. The temperature dependence of the chemical exchange rate of the salicylic acid moiety was non-Arrhenius, suggesting a two-step chemical exchange mechanism for salicylic acid. The good detection sensitivity at low saturation power facilitates clinical translation, along with the potentially low toxicity of a non-metallic MRI contrast agent. The modular design of the agent constitutes a platform technology that expands the variety of agents that may be employed by catalyCEST MRI for molecular imaging.
Herpesvirus trigger accelerates neuroinflammation in a nonhuman primate model of multiple sclerosis (2018)

Pathogens, particularly human herpesviruses (HHVs), are implicated as triggers of disease onset/progression in multiple sclerosis (MS) and other neuroinflammatory disorders. However, the time between viral acquisition in childhood and disease onset in adulthood complicates the study of this association. Using nonhuman primates, we demonstrate that intranasal inoculations with HHV-6A and HHV-6B accelerate an MS-like neuroinflammatory disease, experimental autoimmune encephalomyelitis (EAE). Although animals inoculated intranasally with HHV-6 (virus/EAE marmosets) were asymptomatic, they exhibited significantly accelerated clinical EAE compared with control animals. Expansion of a proinflammatory CD8 subset correlated with post-EAE survival in virus/EAE marmosets, suggesting that a peripheral (viral?) antigen-driven expansion may have occurred post-EAE induction. HHV-6 viral antigen in virus/EAE marmosets was markedly elevated and concentrated in brain lesions, similar to previously reported localizations of HHV-6 in MS brain lesions. Collectively, we demonstrate that asymptomatic intranasal viral acquisition accelerates subsequent neuroinflammation in a nonhuman primate model of MS.
Observation of radiationless processes in a molecular beam (1976)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Robert K. Sander, Benoit Soep, Richard N. Zare; Observation of radiationless processes in a molecular beam. J. Chem. Phys. 1 February 1976; 64 (3): 1242–1243. https://doi.org/10.1063/1.432272 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioThe Journal of Chemical Physics Search Advanced Search |Citation Search
I.McIC: a single-chip MPEG-2 video encoder for storage (1997)

I.McIC is a single-chip MPEG-2 video encoder for consumer storage applications. It supports both intra- and inter-coding mode to achieve bit rates from 5-15 Mb/s. It contains a recursive motion estimator, a programmable buffer/bit-rate controller, and a temporal noise-reduction stage. The resulting IC has 4.5/spl times/10/sup 6/ transistors and measures 192 mm/sup 2/ in a 0.5-/spl mu/m process. I.McIC was designed using mainly high-level synthesis tools. High-throughput fixed MPEG functions are performed by dedicated hardware. The remainder is performed in software by an embedded application-specific instruction-set processor with downloadable microcode to suit the IC for different applications of video coding.
Pyrrolizidine alkaloid biosynthesis; incorporation of 13C-labelled putrescines into retronecine (1981)

[1,4-13C2]- and [2,3-13C2]-Putrescine are incorporated into retronecine (2) in Senecio isatideus plants, giving labelling patterns consistent with the formation of a C4–N–C4 intermediate in retronecine biosynthesis.
An Inexact Energy System Optimization Model including Environmental Constraints for Beijing, China (2009)

Planning of energy systems is confronted with dual pressures from economic development and environmental protection, and associated with various uncertainties. In this paper, an inexact energy system optimization model (IESOM) was developed, through integrating interval-parameter and mixed integer programming (IMILP) within an energy systems management framework. IESOM would minimize the total cost subject to environmental and economic constraints, and optimizes the development of the energy producing and conversion under given fuel prices, and useful energy demand,over a pre-defined time horizon. IESOM was applied to a case study of Beijing’s energy system. The results indicate that IESOM would establish an economically logical energy supply system, supporting Beijing’s rapid economic grow and get the best environmental benefits through relatively low economic costs.
3D computational and experimental radiation transport assessments of Pu-Be sources and graded moderators for parcel screening (2006)

The Florida Institute for Nuclear Detection and Security (FINDS) is currently working on the design and evaluation of a prototype neutron detector array that may be used for parcel screening systems and homeland security applications. In order to maximize neutron detector response over a wide spectrum of energies, moderator materials of different compositions and amounts are required, and can be optimized through 3-D discrete ordinates and Monte Carlo model simulations verified through measurement. Pu-Be sources can be used as didactic source materials to augment the design, optimization, and construction of detector arrays with proper characterization via transport analysis. To perform the assessments of the Pu-Be Source Capsule, 3-D radiation transport computations are used, including Monte Carlo (MCNP5) and deterministic (PENTRAN) methodologies. In establishing source geometry, we based our model on available source schematic data. Because both the MCNP5 and PENTRAN codes begin with source neutrons, exothermic (<i>&#945;,n</i>) reactions are modeled using the SCALE5 code from ORNL to define the energy spectrum and the decay of the source. We combined our computational results with experimental data to fully validate our computational schemes, tools and models. Results from our computational models will then be used with experiment to generate a mosaic of the radiation spectrum. Finally, we discuss follow-up studies that highlight response optimization efforts in designing, building, and testing an array of detectors with varying moderators/thicknesses tagged to specific responses predicted using 3-D radiation transport models to augment special nuclear materials detection.
Resonant Activation of a Synthetic Antiferromagnet (2011)

The magnetic decay time of a synthetic antiferromagnet comprised of two closely spaced magnetic dipoles is measured in the presence of microwave excitation. The system is known to be highly stable with respect to switching between its two antiparallel ground states under quasistatic magnetic fields. We show that an order of magnitude lower field can switch the pair, provided the field is applied in resonance with the optical eigenmode of the collective spin dynamics in the system. We furthermore show that thermal agitation can play an essential role in spin-flop switching for resonant excitations of near- or subcritical amplitude.
HIV-1 Conserved Mosaics Delivered by Regimens with Integration-deficient, DC-targeting Lentivirus Induce Robust T Cells (2016)

Background: To be effective against HIV-1, vaccine-induced&#13;\nT cells must selectively target functionally conserved and, at&#13;\nthe same time, protective epitopes present on the majority of&#13;\ncurrently circulating and reactivated HIV-1 strains, and rapidly&#13;\nreach protective frequencies upon exposure to the virus.&#13;\nHeterologous prime-boost regimens using virally vectored&#13;\nvaccines are currently the most promising strategy towards&#13;\nachieving this goal, nevertheless, induction of robust longterm&#13;\nmemory remains challenging. To this end, lentiviral&#13;\nvectors induce high frequencies of memory cells due to their&#13;\nlow-inflammatory nature, while typically inducing only low antivector&#13;\nimmune responses.&#13;\nMethods: We describe construction of novel candidate vaccines&#13;\nZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an&#13;\nintegration-deficient lentiviral vector platform with preferential&#13;\ntransduction of human dendritic cells and express bivalent&#13;\nmosaic of conserved-region T-cell immunogens with a high&#13;\nglobal HIV-1 match.&#13;\nResults: Each of the two mosaics was individually immunogenic&#13;\nand together in heterologous prime-boost regimens with nonreplicating&#13;\nsimian (chimpanzee) adenovirus or non-replicating&#13;\npoxvirus MVA vaccines induced very high frequencies of&#13;\nplurifunctional and broadly cross-reactive T cells in BALB/c and&#13;\noutbred CD1-SWISS mice.&#13;\nConclusions: These data support further development of this&#13;\nvaccine concept.
Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection (2011)

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant viruses that are resistant to conventional antiretroviral agents. Altogether, our results reveal a novel signaling pathway involved in the early steps of HIV-1 infection that may be targeted with new therapeutic approaches.
Allele-Specific PCR with Competitive Probe Blocking for Sensitive and Specific Detection of <i>BRAF</i> V600E in Thyroid Fine-Needle Aspiration Specimens (2011)

Treatment of patients with thyroid nodules is guided by FNA biopsy, which can be scantly cellular, necessitating a sensitive test that can detect low levels of BRAF V600E mutation in a WT background. We report increased detection of BRAF V600E in FNA specimens using allele-specific/blocking probe PCR, which has an analytical sensitivity of 0.01%.
Data from A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with Temozolomide in Acute Myeloid Leukemia (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; In preclinical studies, the PARP inhibitor veliparib enhanced the antileukemic action of temozolomide through potentiation of DNA damage. Accordingly, we conducted a phase 1 study of temozolomide with escalating doses of veliparib in patients with relapsed, refractory acute myeloid leukemia (AML) or AML arising from aggressive myeloid malignancies.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Patients received veliparib [20–200 mg once a day on day 1 and twice daily on days 4–12 in cycle 1 (days 1–8 in cycle ≥2)] and temozolomide [150–200 mg/m&lt;sup&gt;2&lt;/sup&gt; daily on days 3–9 in cycle 1 (days 1–5 in cycle ≥2)] every 28 to 56 days. Veliparib pharmacokinetics and pharmacodynamics [ability to inhibit poly(ADP-ribose) polymer (PAR) formation and induce H2AX phosphorylation] were assessed. Pretreatment levels of MGMT and PARP1 protein, methylation of the &lt;i&gt;MGMT&lt;/i&gt; promoter, and integrity of the Fanconi anemia pathway were also examined.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Forty-eight patients were treated at seven dose levels. Dose-limiting toxicities were oral mucositis and esophagitis lasting &gt;7 days. The MTD was veliparib 150 mg twice daily with temozolomide 200 mg/m&lt;sup&gt;2&lt;/sup&gt; daily. The complete response (CR) rate was 17% (8/48 patients). Veliparib exposure as well as inhibition of PAR polymer formation increased dose proportionately. A veliparib-induced increase in H2AX phosphorylation in CD34&lt;sup&gt;+&lt;/sup&gt; cells was observed in responders. Three of 4 patients with &lt;i&gt;MGMT&lt;/i&gt; promoter methylation achieved CR.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Veliparib plus temozolomide is well tolerated, with activity in advanced AML. Further evaluation of this regimen and of treatment-induced phosphorylation of H2AX and &lt;i&gt;MGMT&lt;/i&gt; methylation as potential response predictors appears warranted. &lt;i&gt;Clin Cancer Res; 23(3); 697–706. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Quasi-Bayesian Dual Instrumental Variable Regression (2021)

Recent years have witnessed an upsurge of interest in employing flexible machine learning models for instrumental variable (IV) regression, but the development of uncertainty quantification methodology is still lacking. In this work we present a novel quasi-Bayesian procedure for IV regression, building upon the recently developed kernelized IV models and the dual/minimax formulation of IV regression. We analyze the frequentist behavior of the proposed method, by establishing minimax optimal contraction rates in $L_2$ and Sobolev norms, and discussing the frequentist validity of credible balls. We further derive a scalable inference algorithm which can be extended to work with wide neural network models. Empirical evaluation shows that our method produces informative uncertainty estimates on complex high-dimensional problems.
The Need for Accurate Osmotic Pressure and Mass Transfer Resistances in Modeling Osmotically Driven Membrane Processes (2021)

The widely used van 't Hoff linear relation for predicting the osmotic pressure of NaCl solutions may result in errors in the evaluation of key system parameters, which depend on osmotic pressure, in pressure-retarded osmosis and forward osmosis. In this paper, the linear van 't Hoff approach is compared to the solutions using OLI Stream Analyzer, which gives the real osmotic pressure values. Various dilutions of NaCl solutions, including the lower solute concentrations typical of river water, are considered. Our results indicate that the disparity in the predicted osmotic pressure of the two considered methods can reach 30%, depending on the solute concentration, while that in the predicted power density can exceed over 50%. New experimental results are obtained for NanoH2O and Porifera membranes, and theoretical equations are also developed. Results show that discrepancies arise when using the van 't Hoff equation, compared to the OLI method. At higher NaCl concentrations (C > 1.5 M), the deviation between the linear approach and the real values increases gradually, likely indicative of a larger error in van 't Hoff predictions. The difference in structural parameter values predicted by the two evaluation methods is also significant; it can exceed the typical 50-70% range, depending on the operating conditions. We find that the external mass transfer coefficients should be considered in the evaluation of the structural parameter in order to avoid overestimating its value. Consequently, measured water flux and predicted structural parameter values from our own and literature measurements are recalculated with the OLI software to account for external mass transfer coefficients.
Active Two-Dimensional Electric Field Imaging at Very Low Frequencies (2017)

We present a 2-D electric field imaging array and a new active method to image objects that are not direct sources of electric fields. The array is comprised of D-dot sensor pixels, which measure current proportional to the time derivative of the electric field, and are multiplexed through a lock-in amplifier, which achieves a high signal-to-noise ratio. By placing a large and flat active electrode parallel to the imager, a known voltage and frequency can be applied to create a uniform electric field. Objects placed in the field will then distort the field in shape and strength. The distortions can then be imaged, analyzed, and interpreted. The objects imaged in this research include bodies of dielectrics (e.g., water), wires carrying a dc voltage, and floating wires.
Age‐related anabolic resistance after endurance‐type exercise in healthy humans (2010)

Age-related skeletal muscle loss is thought to stem from suboptimal nutrition and resistance to anabolic stimuli. Impaired microcirculatory (nutritive) blood flow may contribute to anabolic resistance by reducing delivery of amino acids to skeletal muscle. In this study, we employed contrast-enhanced ultrasound, microdialysis sampling of skeletal muscle interstitium, and stable isotope methodology, to assess hemodynamic and metabolic responses of older individuals to endurance type (walking) exercise during controlled amino acid provision. We hypothesized that older individuals would exhibit reduced microcirculatory blood flow, interstitial amino acid concentrations, and amino acid transport when compared with younger controls. We report for the first time that aging induces anabolic resistance following endurance exercise, manifested as reduced (by ∼40%) efficiency of muscle protein synthesis. Despite lower (by ∼40-45%) microcirculatory flow in the older than in the younger participants, circulating and interstitial amino acid concentrations and phenylalanine transport into skeletal muscle were all equal or higher in older individuals than in the young, comprehensively refuting our hypothesis that amino acid availability limits postexercise anabolism in older individuals. Our data point to alternative mediators of age-related anabolic resistance and importantly suggest correction of these impairments may reduce requirements for, and increase the efficacy of, dietary protein in older individuals.
Imaging the Sialome during Zebrafish Development with Copper‐Free Click Chemistry (2012)

The sialome comprises sialylated glycoproteins and glycolipids that play essential roles in cell-cell communication. Using azide-modified molecular precursors of sialic acids and copper-free click chemistry, we visualized the spatiotemporal dynamics of the sialome in live zebrafish embryos.
Faculty Opinions recommendation of Genomic Ly49A transgenes: basis of variegated Ly49A gene expression and identification of a critical regulatory element. (2004)

Several gene families are known in which member genes are expressed in variegated patterns in differentiated cell types. Mechanisms responsible for imposition of a variegated pattern of gene expression are unknown. Members of the closely linked Ly49 inhibitory receptor gene family are expressed in a variegated fashion by NK cells. Variegated expression of these genes results in subsets of NK cells that differ in specificity for MHC class I molecules. To address the mechanisms underlying variegation, a 30-kb genomic fragment containing a single Ly49 gene was used to generate a panel of murine transgenic lines. The results demonstrated that, in almost all of the lines, the isolated Ly49A gene was expressed in a variegated pattern, remarkably similar in nearly all respects to the expression pattern of the endogenous Ly49A gene. Furthermore, the developmental timing of gene expression and regulation by host MHC molecules closely mirrored that of the endogenous Ly49A gene. Therefore, Ly49 variegation does not require competition in cis between different Ly49 genes, and the sequences imposing variegation are located proximally to Ly49 genes. Efforts to define regulatory elements of the Ly49A gene led to the identification of a DNase I hypersensitive site 4.5 kb upstream of the Ly49A gene transcription initiation site, which was shown to be essential for transgene expression. Highly related sequence elements were found upstream of other Ly49 genes, suggesting that a similar regulatory element controls each Ly49 gene. PMID: 14707081 Funding information This work was supported by: NIAID NIH HHS, United States Grant ID: R01 AI 39642