gebhart/patrepeval huggingface dataset:
Identification of a Small Molecule That Overcomes HdmX-Mediated Suppression of p53 (2016)

Inactivation of the p53 tumor suppressor by mutation or overexpression of negative regulators occurs frequently in cancer. As p53 plays a key role in regulating proliferation or apoptosis in response to DNA-damaging chemotherapies, strategies aimed at reactivating p53 are increasingly being sought. Strategies to reactivate wild-type p53 include the use of small molecules capable of releasing wild-type p53 from key, cellular negative regulators, such as Hdm2 and HdmX. Derivatives of the Hdm2 antagonist Nutlin-3 are in clinical trials. However, Nutlin-3 specifically disrupts Hdm2-p53, leaving tumors harboring high levels of HdmX resistant to Nutlin-3 treatment. Here, we identify CTX1, a novel small molecule that overcomes HdmX-mediated p53 repression. CTX1 binds directly to HdmX to prevent p53-HdmX complex formation, resulting in the rapid induction of p53 in a DNA damage-independent manner. Treatment of a panel of cancer cells with CTX1 induced apoptosis or suppressed proliferation and, importantly, CTX1 demonstrates promising activity as a single agent in a mouse model of circulating primary human leukemia. CTX1 is a small molecule HdmX inhibitor that demonstrates promise as a cancer therapeutic candidate. Mol Cancer Ther; 15(4); 574-82. ©2016 AACR.
Supercritical Fluid Separation for Selective Quaternary Ammonium Salt Promoted Esterification of Terephthalic Acid (1999)

We report the selective removal of a desired reaction intermediate with a supercritical fluid in a new synthesis route to poly(ethylene terephthalate), avoiding ethylene glycol. We have successfully catalyzed the esterification of terephthalic acid with ethylene oxide in a supercritical fluid with a series of quaternary ammonium salts to form mono(2-hydroxyethyl terephthalate). This desired monoester was removed from the involatile bed of terephthalic acid and catalyst by continuous extraction with supercritical fluid before subsequent reaction to the diester could take place.
Radical Carbonylation with [<sup>11</sup>C]Carbon Monoxide Promoted by Oxygen-Centered Radicals:  Experimental and DFT Studies of the Mechanism (2007)

Photoinitiated carbonylation of alkyl iodides with [11C]carbon monoxide (11C t1/2=20.4 min) is enhanced by ketones that have lowest-lying excited triplet state of npi* character. For example, adding 5 mol % of acetophenone increases radiochemical yields from 3 to 59% in brief 6-min long reactions. Similar or higher yields were achieved by adding di-tert-butyl peroxide. Since radicaloid npi* exited-state ketones and tert-butoxyl radicals have similar reactivity, the photosensitization proceeds most likely via a H-atom transfer mechanism rather than via energy transfer. We propose a mechanism that can account for the enhancement as well as for the formation of observed byproducts. The energy profile obtained by DFT calculations support the feasibility of the mechanism, and observed experimental differences in reactivity could be well rationalized by the calculated data. NBO calculations were performed to further analyze the obtained energetics. Various [carbonyl-11C]esters and some [carbonyl-11C]amides were synthesized in good radiochemical yields from primary and secondary alkyl iodides illustrating the utility of dialkyl peroxides to accelerate the carbonylations. These findings have potential in elaborating new synthetic protocols for the production of 11C-labeled tracers for positron emission tomography.
Highly-Linear Magnet-Free Microelectromechanical Circulators (2019)

This paper reports the first demonstration of a magnet-free, high performance microelectromechanical system (MEMS) based circulator. An innovative circuit based on the commutation of MEMS resonators with high quality (Q) factor using RF switches is designed and implemented. Thanks to the high Q factor, a much smaller modulation frequency can be achieved compared to the previous demonstrations, reducing the power consumption and enabling the use of high power-handling switches. Furthermore, the MEMS resonators greatly reduce the required inductance value, guaranteeing much smaller form factor compared to the previous LC demonstrations. The demonstrated circulator shows broad BW (15 dB-IX BW = 34.7 MHz for an operational frequency around 2.5 GHz), low IL (4 dB), high IX (30 dB), high linearity (P1dB = 28 dBm; IIP3 = 40 dBm) and at the same time low power consumption, addressing several of the current limitations hindering the full development of magnet-free circulators.
Flexbeam helicopter rotor with improved snubber-vibration damper between the torque tube and the flexible spar member (1992)

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Novel Oligonucleotides Containing Two 3′-Ends Complementary to Target mRNA Show Optimal Gene-Silencing Activity (2011)

Oligonucleotides are being employed for gene-silencing activity by a variety of mechanisms, including antisense, ribozyme, and siRNA. In the present studies, we designed novel oligonucleotides complementary to targeted mRNAs and studied the effect of 3'-end exposure and oligonucleotide length on gene-silencing activity. We synthesized both oligoribonucleotides (RNAs) and oligodeoxynucleotides (DNAs) with phosphorothioate backbones, consisting of two identical segments complementary to the targeted mRNA attached through their 5'-ends, thereby containing two accessible 3'-ends; these compounds are referred to as gene-silencing oligonucleotides (GSOs). RNA and/or DNA GSOs targeted to MyD88, VEGF, and TLR9 mRNAs had more potent gene-silencing activity than did antisense phosphorothioate oligonucleotides (PS-oligos) in cell-based assays and in vivo. Of the different lengths of GSOs evaluated, 19-mer long RNA and DNA GSOs had the best gene-silencing activity both in vitro and in vivo. These results suggest that GSOs are novel agents for gene silencing that can be delivered systemically with broader applicability.
Analysis of the Photoneutron Yield and Thermal Neutron Flux in an Unreflected Electron Accelerator-Driven Neutron Source (2005)

There are several potential uses for a high-flux thermal neutron source in both industrial and clinical applications. The viable commercial implementation of these applications requires a low-cost, high-flux thermal neutron generator suitable for installation in industrial and clinical environments. This paper describes the Monte Carlo for N-Particle modeling results of a high-flux thermal neutron source driven with an electron accelerator. An electron linear accelerator (linac), fitted with a standard X-ray converter, can produce high neutron yields in materials with low photonuclear threshold energies, such as D and 9Be. Results indicate that a 10-MeV, 10-kW electron linac can produce on the order of 1012 n/s in a heavy water photoneutron target. The thermal neutron flux in an unreflected heavy water target is calculated to be on the order of 1010 n·cm–2·s. The sensitivity of these answers to heavy water purity is also investigated, specifically the dilution of heavy water with light water. It is shown that the peak thermal neutron flux is not adversely effected by dilution up to a light water weight fraction of 35%.
Interaction Between the Vitamin D Receptor Gene and Collagen Type Iα1 Gene in Susceptibility for Fracture (2001)

Osteoporosis is a common disease with a strong genetic component. Polymorphisms in the vitamin D receptor (VDR) gene have been implicated in osteoporosis but explain only a small part of the genetic effect on bone mineral density (BMD) while their effect on fractures is still uncertain. Recently, a G to T polymorphism in an Sp1 site in the collagen type Ialpha1 (COLIA1) gene was found to be associated with reduced BMD and with increased fracture risk. To analyze the combined influence of polymorphisms in the VDR gene and the COLIA1 gene in determining the susceptibility to osteoporotic fracture, we studied 1004 postmenopausal women. The "baT" VDR haplotype, constructed from three adjacent restriction fragment length polymorphisms, was found to be overrepresented among fracture cases (p = 0.009). This corresponded to an odds ratio (OR) of 1.8 (95% CI, 1.0-3.3) for heterozygous carriers and 2.6 (95% CI, 1.4-5.0) for homozygous carriers of the risk haplotype. The effect was similar for vertebral and nonvertebral fractures and, most importantly, independent of BMD. We observed significant interaction (p = 0.03) between VDR and COLIA1 genotype effects. Fracture risk was not VDR genotype-dependent in the COLIA1 "reference" group (genotype GG) while in the COLIA1 "risk" group (genotypes GT and TT) the risk of fracture was 2.1 (95% CI, 1.0-4.4) for heterozygous and 4.4 (95% CI, 2.0-9.4) for homozygous carriers of the VDR risk haplotype. We conclude that both the VDR and the COLIA1 polymorphisms are genetic markers for osteoporotic fracture in women, independent of BMD. Our data indicate that interlocus interaction is likely to be an important component of osteoporotic fracture risk.
Synthesis of 9-cis-retinoic acid and C-20-[3H3C]-9-cis-retinoic acid with high specific activity (1997)

The synthesis of 9-cis-retinoic acid starting from 2,2,6-trimethylcyclohexanone is described. The same methodology was extended for the synthesis of deuterium and tritium labeled 9-cis-retinoic acid with high specific activity (73 Ci/mmol). In this methodology, a Grignard reaction was utilized for introducing three tritium atoms simultaneously in the final synthetic steps. © 1997 John Wiley & Sons, Ltd.
Synthesis and organoleptic properties of various 3-methyl-2-oxopentanoates, 2-hydroxy-3-methylpentanoates, and 2-acyloxy-3-methylpentanoates (2005)

As part of a research programme concerned with the discovery of new perfumery ingredients, a series of racemic alkyl 3-methyl-2-oxopentanoates 2–8, ethyl and methyl 2-hydroxy-3-methylpentanoates (13[sol ]14 and 15[sol ]16, respectively), together with methyl and ethyl 2-acyloxy-3-methylpentanoates, 17–32, have been prepared and their organoleptic properties evaluated. Ethyl-3-methyl-2-oxopentanoate (3), exhibiting a strong, fresh walnut, fruity odour, is of special interest, and its enantiomers were thus selectively synthesized from (l)-(+)-isoleucine [(+)-9] and (l)-(+)-allo-isoleucine [(+)-10], respectively. Whilst (+)-3 and (−)-3 have a similar odour profile, (+)-3 is more powerful and less pungent than its antipode. The intermediate hydroxy esters (+)-13 and (+)-14 were also found to have a distinct walnut character, as did their respective enantiomers, (−)-13 and (−)-14. Apart from 13[sol ]14 (camphoraceous, earthy, fruity), 15[sol ]16 (walnut, cacao, carob bean) and 25[sol ]26 (fruity, camomile, carob bean), the organoleptic properties of the other compounds were found to be less interesting, exhibiting a variety of weak fruity, camomile, bean and medicinal notes. Copyright © 2005 John Wiley & Sons, Ltd.
Molecular Characterization of Cryptosporidium Isolates from Humans and other Animals Using Random Amplified Polymorphic DNA Analysis (1995)

Genetic variation in 25 Cryptosporidium isolates was analyzed using the random amplified polymorphic DNA (RAPD) technique. Simple reproducible polymorphisms were generated (using five primers) from Cryptosporidium DNA that was free of contaminating bacterial DNA. The results generated by four of the five primers were statistically correlated (P < 0.001). The combined data from three primers were used to construct a phenogram using Jaccard's distance. Four groupings could be distinguished. Two C. serpentis isolates from snakes formed a distinct group of their own, whereas C. parvum isolates were divided into two main groups: one containing most human isolates and the other containing mostly domestic animals plus two remaining human isolates. Due to the sensitivity of the RAPD technique, isolates can now be analyzed genetically, directly from fecal samples without further biological amplification. This represents a significant advance on current techniques.
Vitrified sperm banks: the new aseptic technique for human spermatozoa allows cryopreservation at −86 °C (2012)

The vitrification technique is simple, quick, cost-effective and has showed a significantly stronger cryoprotective effect in contrast to conventional freezing. The method is based on the rapid cooling of the cell by direct immersion in liquid nitrogen (LN (2) ), thereby avoiding the formation of ice crystals, due to the lower risk of water thawing, which impairs cell function. The aim of this study was to evaluate the effect of storage at -86 °C compared to the conventional -196 °C (under LN (2) ) on essential parameters of the functioning of aseptically vitrified human sperm. Sperm motility, integrity of mitochondrial membrane potential and the rate of DNA fragmentation were determined. The comparison of -86 °C and -196 °C demonstrated no statistical difference in sperm progressive motility (73% vs. 77%), integrity of mitochondrial membrane potential (71% vs. 74%) or DNA fragmentation (3.1% vs. 2.9%). In conclusion, aseptically vitrified sperm can be preserved at -86 °C; eliminating the use of LN (2) simplifies and significantly reduces the costs associated with storage in sperm banks by decreasing the time and space needed for storage, the effort in finding stored samples, and by improving safety for the operator. However, for prolonged storage further studies are needed.
Optical microsphere resonators: optimal coupling to high-Q whispering-gallery modes (1999)

A general model is presented for coupling of high-Q whispering-gallery modes in optical microsphere resonators with coupler devices that possess a discrete and continuous spectrum of propagating modes. By contrast to conventional high-Q optical cavities, in microspheres the independence of high intrinsic quality-factor and controllable parameters of coupling via an evanescent field offer a variety of regimes similar to those that are already available in rf devices. The theory is applied to data reported earlier on different types of couplers to microsphere resonators and is complemented by the experimental demonstration of enhanced coupling efficiency (∼80%) and variable loading regimes with Q>108 fused-silica microspheres.
Electron bunch length diagnostic with coherent Smith-Purcell radiation (2002)

We have designed a new technique for measuring subpicosecond electron bunch lengths using coherent Smith-Purcell radiation. This new diagnostic technique involves passing the electron beam in close proximity of a grating with period comparable to the electron bunch length. The emitted Smith-Purcell radiation will have a coherent component whose angular position and distribution are directly related to the electron bunch length and longitudinal profile, respectively. This new diagnostic technique is inherently simple, inexpensive and non-intercepting. We show that the new technique is also scaleable to femtosecond regime.
Sidestream dark-field imaging versus orthogonal polarization spectroscopic imaging: a comparative study (2008)

Sidestream dark-field (SDF) imaging, a stroboscopic LED ring-based imaging modality for clinical observation of the microcirculation, was validated by quantitative and qualitative comparison with orthogonal polarization spectral (OPS) imaging.
Engineered Antigen-Specific Human Regulatory T Cells Suppress Both FVIII-Specific T- and B-Cell Responses (2014)

Abstract Expansion of human regulatory T cells (Tregs) for clinical applications offers great promise for the treatment of undesirable immune responses in autoimmunity, transplantation, allergy and anti-drug antibody responses, including inhibitor responses in hemophilia A patients. However, polyclonal Tregs are “nonspecific” and therefore their therapeutic application could potentially cause global immunosuppression. To avoid this undesirable outcome, the generation of antigen-specific Tregs would represent a significant advance. In this study, we demonstrate the production and properties of engineered antigen-specific Tregs created by transduction of a recombinant T-cell receptor into expanded human FoxP3+ Tregs. The DNA sequence of this T cell receptor was obtained from a FVIII-specific T cell clone that had been expanded from blood donated by a hemophilia A subject. The resulting engineered FVIII-specific Tregs efficiently suppressed both proliferation and cytokine production of FVIII-specific CD4 T effector cells. Moreover, studies with an HLA-transgenic, FVIII-deficient mouse model demonstrated that antibody production from FVIII-primed spleen cells in vitro was profoundly inhibited in the presence of these FVIII-specific Tregs, suggesting that this novel approach has translational potential for the prevention and/or reversal of inhibitor responses in hemophilia A patients. Furthermore, these FVIII-specific Tregs successfully cross-suppressed unrelated, bystander T effector cells (specific for a myelin peptide) only in the presence of FVIII and the unrelated, stimulatory myelin peptide. These data strongly imply that such FVIII-specific Tregs would be effective at suppressing multiple effector cells, e.g., CD4 T effector cells specific for other FVIII epitopes besides that recognized by the Tregs expressing the engineered TCR, in the local milieu when FVIII is present. Thus, we propose that FVIII-specific Tregs have potential as a therapeutic tool to induce tolerance to FVIII, by preventing or reversing inhibitor formation in hemophilia A patients. Supported by NIH RO1-HL061883 (DWS), funding from Bayer and CSL Behring (KPP) and intramural support from NIAID (EMS). We thank the Puget Sound Blood Center for enrolling hemophilia A patients and we thank all blood donors. Disclosures Kim: Henry Jackson Foundation: YCK and DWS have a provisional patent filing via the Henry Jackson Foundation on Design and use of specific regulatory T cells to induce immune tolerance Patents & Royalties. Scott:Henry Jackson Foundation: YCK and DWS have a provisional patent filing via the Henry Jackson Foundation on Design and use of specific regulatory T cells to induce immune tolerance Patents & Royalties.
Low Delay Complexity Constrained Encoding (2016)

Complex software appliances typically consist of multiple software processes running concurrently to exploit the available computational resources in the hardware. However, the computational complexity of these software processes is often variable and the processes can interfere with each other. This can be an issue for real-time applications with a fixed deadline like low delay video encoding. In the context of High Efficiency Video Coding (HEVC), a limited number of publications have focused on controlling the complexity of an HEVC video encoder. In this paper, we propose a technique to control complexity by deciding between 2Nx2N merge mode and full encoding, at different Coding Unit (CU) depths. Our results demonstrate fast convergence to a given complexity threshold after a maximum of 10 frames, and a limited loss in rate-distortion performance (on average 2.84% Bjontegaard delta rate for 60% complexity reduction).
Ligand design for human nicotinic acetylcholine receptors using in situ freeze‐frame click chemistry (2010)

Nicotinic acetylcholine receptors (nAChRs) are ionotropic receptors activated by acetylcholine in synapses of the CNS, neuromuscular junctions, and autonomic ganglia. The α4β2 and α7 nAChR subtypes are therapeutic targets for smoking cessation and treatment of schizophrenia. We developed a structure‐guided design strategy utilizing the Aplysia californica and Lymnaea stagnalis acetylcholine binding proteins (AChBPs) as homologous structural surrogates for the nicotinic receptor extracellular domain. We show that in situ click chemistry can be performed at subunit interfaces to generate selective nAChR agonists and antagonists. Lead compounds can then be refined through catalytic synthesis of close triazole congeners on a submilligram scale to assay AChBP template affinity and pharmacological activity on α4β2 and α7 nAChRs. Responses to other receptors that are potential complementary or “off targets” for the compounds were measured including α1 nAChR, 5‐HT 3A and M1 muscarinic receptors. Crystallography of AChBP with the compounds was implemented to identify determinants involved in agonist or antagonist responses. The results of the functional and binding responses suggest that in situ freeze‐frame click chemistry can be a powerful tool in the future for developing specific ligands of various receptors. (Support from R37‐GM18360, UO1‐DA019372, NSF GK12 0742551)
BIRCH (1996)

Finding useful patterns in large datasets has attracted considerable interest recently, and one of the most widely studied problems in this area is the identification of clusters, or densely populated regions, in a multi-dimensional dataset. Prior work does not adequately address the problem of large datasets and minimization of I/O costs.This paper presents a data clustering method named BIRCH (Balanced Iterative Reducing and Clustering using Hierarchies), and demonstrates that it is especially suitable for very large databases. BIRCH incrementally and dynamically clusters incoming multi-dimensional metric data points to try to produce the best quality clustering with the available resources (i.e., available memory and time constraints). BIRCH can typically find a good clustering with a single scan of the data, and improve the quality further with a few additional scans. BIRCH is also the first clustering algorithm proposed in the database area to handle "noise" (data points that are not part of the underlying pattern) effectively.We evaluate BIRCH's time/space efficiency, data input order sensitivity, and clustering quality through several experiments. We also present a performance comparisons of BIRCH versus CLARANS, a clustering method proposed recently for large datasets, and show that BIRCH is consistently superior.
An introduction to PON technologies [Topics in Optical Communications] (2007)

Passive optical networks are the most important class of fiber access systems in the world today. This article first reviews the reasons why the PON as a general architecture is so important. We then outline in some depth the technologies used to implement this architecture, including the G-PON and E-PON systems being deployed today, and the advanced PON systems that provide the evolution path to ever higher bandwidths
Two-frequency wiggler for better control of free-electron-laser dynamics (1991)

We study the physics of a free-electron laser based on a ``two-frequency'' undulator (TFU) which induces large nonlinear effects, especially on the spectral dynamics. These effects are analyzed in an extended formalism where the spontaneous emission, the low-gain regime, and the strong-field saturation regime are studied. Numerical simulations show that an optimized TFU generates a laser field having both a large extraction efficiency and a narrow spectrum.
Measurement sequences for magic state distillation (2021)

Magic state distillation uses special codes to suppress errors in input states, which are often tailored to a Clifford-twirled error model. We present detailed measurement sequences for magic state distillation protocols which can suppress arbitrary errors on any part of a protocol, assuming the independence of errors across qubits. Provided with input magic states, our protocol operates on a two-dimensional square grid by measurements of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>Z</mml:mi><mml:mi>Z</mml:mi></mml:math> on horizontal pairs of qubits, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>X</mml:mi><mml:mi>X</mml:mi></mml:math> on vertical pairs, and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>Z</mml:mi><mml:mo>,</mml:mo><mml:mi>X</mml:mi></mml:math> on single qubits.
Palladium‐Catalyzed <i>N</i>‐Demethylation/<i>N</i>‐Acylation of Some Morphine and Tropane Alkaloids (2008)

Abstract Hydrocodone was converted to various N ‐acyl derivatives via a one‐pot N ‐demethylation/ N ‐acylation protocol catalyzed by palladium(II). The procedure has also been successfully applied to several N ‐methyltropane alkaloids. A plausible mechanism is suggested.