gebhart/patrepeval huggingface dataset:
Trans‐splicing of a voltage‐gated sodium channel is regulated by nerve growth factor (1999)

Mammalian sensory neurons express a voltage-gated sodium channel named SNS. Here we report the identification of an SNS transcript (SNS-A) that contains an exact repeat of exons 12, 13 and 14 encoding a partial repeat of domain II. Because the exons 12-14 are present in single copies in genomic DNA, the SNS-A transcript must arise by trans-splicing. Nerve growth factor, which regulates pain thresholds, and the functional expression of voltage-gated sodium channels increases the levels of the SNS-A transcript several-fold both in vivo and in vitro as measured by RNase protection methods, as well as RT-PCR. These data demonstrate a novel regulatory role for the nerve growth factor and are the first example of trans-splicing in the vertebrate nervous system.
External Fiber Fabry-Perot Acoustic Sensor Based on Photonic Crystal Mirror (2006)

We demonstrate an acoustic sensor based on a Fabry-Perot formed by a singlemode fiber and an external photonic-crystal mirror. We observe asymmetric Fabry-Perot resonances that are used to detect pressures as low as 18 µPa/Hz1/2.
Predicting adverse drug reactions through interpretable deep learning framework (2018)

The deep learning model with feature analysis, substructure identification, and statistical assessment provides a promising solution for identifying risky components within molecular structures and can potentially help to improve drug safety evaluation.
High-Power Single-Mode Distributed-Feedback Interband Cascade Lasers for the Midwave-Infrared (2007)

A single-mode output power of 41 mW has been obtained at T=120 K and lambdaap3.44 mum from a narrow-ridge interband cascade laser patterned with a Ge distributed-feedback grating. The sidemode suppression ratio at the maximum power is 23 dB, and the linewidth of 0.1 nm is instrument-limited. An alternate contacting geometry yielded robust single-mode output over a broad range of currents and temperatures, and current tuning of the wavelength by up to 17 nm
Hardening quantum machine learning against adversaries (2018)

Security for machine learning has begun to become a serious issue for present day applications. An important question remaining is whether emerging quantum technologies will help or hinder the security of machine learning. Here we discuss a number of ways that quantum information can be used to help make quantum classifiers more secure or private. In particular, we demonstrate a form of robust principal component analysis that, under some circumstances, can provide an exponential speedup relative to robust methods used at present. To demonstrate this approach we introduce a linear combinations of unitaries Hamiltonian simulation method that we show functions when given an imprecise Hamiltonian oracle, which may be of independent interest. We also introduce a new quantum approach for bagging and boosting that can use quantum superposition over the classifiers or splits of the training set to aggregate over many more models than would be possible classically. Finally, we provide a private form of $k$--means clustering that can be used to prevent an all powerful adversary from learning more than a small fraction of a bit from any user. These examples show the role that quantum technologies can play in the security of ML and vice versa. This illustrates that quantum computing can provide useful advantages to machine learning apart from speedups.
Conversion of Hemicellulose into Furfural Using Solid Acid Catalysts in γ‐Valerolactone (2012)

Hold the water: The hemicellulose fraction of lignocellulose can be converted into furfural in high yields (80 %) using solid acid catalysts (H-mordenite) in a monophasic system with γ-valerolactone (GVL) as the solvent. Furfural degradation reactions are decreased significantly when the water concentration in GVL is minimized, thus resulting in high furfural yields.
Compact Carrier Injection Based Mach-Zehnder Modulator in Silicon (2007)

CMOS-compatible, PIN diode Mach-Zehnder modulators have been fabricated. The devices operate at 10 GHz with a modulation depth of 25% at an input power of 100 mW. Compensated frequency response is flat to 5 GHz.
Nuclear GAPDH cascade mediates stress-dependent pathological cardiac growth (2019)

Abstract Here we report that stress-induced nuclear translocation of GAPDH mediates heart hypertrophy via Brahma-Related-Gene-1 (BRG1)-associated chromatin remodelling. In response to pressure overload elicited by transverse aortic constriction, we observed nuclear translocation of GAPDH in the mouse heart. We also demonstrated a robust nuclear localization of GAPDH in cardiomyocytes from patients with dilated hypertrophic cardiomyopathy, whereas negligible GAPDH in the nucleus in control subjects. This is the first demonstration of disease-associated nuclear GAPDH directly in living patients. Using immunohistochemical methods and a pharmacological way that selectively blocks GAPDH nuclear translocation (RR compound), we proved the causal involvement of GAPDH cysteine-150 modification in this translocation in Gq-induced cell model for heart hypertrophy. Accordingly, both pharmacological and genetic interventions proved that the same mechanism played a causal role for heart hypertrophy and dysfunction in vivo . We discovered that, upon nuclear translocation, GAPDH augmented the protein interaction of BRG1 and histone deacetylase 2 (HDAC2), which further facilitated the Myh7/Myh6 isoform ratio from the mature to immature status, an essential mechanism for heart hypertrophy. Beyond medical implications, we provide a novel mechanism of stress-induced reversion of a cellular phenotype from adult to fetal state, which is mediated by a “moonlighting” function of GAPDH.
Metabolic engineering of Saccharomyces cerevisiae for bioconversion of d-xylose to d-xylonate (2012)

An NAD(+)-dependent D-xylose dehydrogenase, XylB, from Caulobacter crescentus was expressed in Saccharomyces cerevisiae, resulting in production of 17 ± 2 g D-xylonate l(-1) at 0.23 gl(-1)h(-1) from 23 g D-xylose l(-1) (with glucose and ethanol as co-substrates). D-Xylonate titre and production rate were increased and xylitol production decreased, compared to strains expressing genes encoding T. reesei or pig liver NADP(+)-dependent D-xylose dehydrogenases. D-Xylonate accumulated intracellularly to ∼70 mgg(-1); xylitol to ∼18 mgg(-1). The aldose reductase encoding gene GRE3 was deleted to reduce xylitol production. Cells expressing D-xylonolactone lactonase xylC from C. crescentus with xylB initially produced more extracellular D-xylonate than cells lacking xylC at both pH 5.5 and pH 3, and sustained higher production at pH 3. Cell vitality and viability decreased during D-xylonate production at pH 3.0. An industrial S. cerevisiae strain expressing xylB efficiently produced 43 g D-xylonate l(-1) from 49 g D-xylose l(-1).
Consistent Weighted Sampling (2007)

We describe an efficient procedure for sampling representatives from a weighted set such that the probability that for any weightings S and T, the probability that the two choose the same sample is the Jacard similarity: P x min(S(x), T (x)) P r[sample(S) = sample(T)] = P max(S(x), T (x)) The sampling process takes expected time linear in the number of non-zero weights, independent of the weights themselves. We discuss and develop the implementation of our sampling schemes, reducing the requisite computation substantially, and reducing the randomness required to only four bits in expectation.
Abstract B150: ASN007, a novel oral ERK inhibitor, shows robust antitumor activity in RAS mutant cancer models (2018)

Abstract The extracellular-signal-regulated kinases, ERK1 and ERK2 (ERK1/2), are key players in the RAS/RAF/MEK signaling pathway. This pathway is frequently hyper-activated in a wide range of cancers through mutations in upstream targets such as BRAF, RAS, and receptor tyrosine kinases. Inhibition of ERK1/2 offers a promising therapeutic strategy for these cancers, particularly the ones driven by RAS mutations. In order to inhibit this critical node of the RAS/RAF/MEK pathway, we discovered and characterized ASN007, a novel compound that shows potent inhibition of ERK1/2 kinases in a biochemical assay with low single-digit nM IC50 values. ASN007 showed a slow dissociation rate (long target residence time) as compared to several other known ERK inhibitors. In mechanistic cell-based assays, ASN007 inhibited the phosphorylation of ERK1/2 substrates such as RSK1, FRA1, and Elk1 in various cell lines. ASN007 showed single-digit nanomolar antiproliferative activity that was selective for MAPK-pathway dependent cancer cell lines. Indeed, ASN007 showed much more potent activity against a broader panel of KRAS, NRAS, and HRAS mutant cell lines compared to other ERK1/2 inhibitors such as BVD-523 and GDC-0994. In a daily oral dosing regimen, ASN007 demonstrated strong inhibition of tumor growth in multiple BRAF and KRAS mutant xenograft models in mice and was well tolerated at efficacious doses. Of note, ASN007 also showed strong efficacy using various intermittent dosing regimens. ASN007 has a good pharmacokinetic profile in preclinical species and does not exhibit significant inhibition of CYP enzymes or hERG channel. IND-enabling studies are ongoing in preparation for a phase 1 clinical trial to evaluate oral ASN007 in patients with BRAF and K- , H- , and N-RAS mutant cancers Citation Format: Sanjeeva P. Reddy, Dhanalakshmi Sivanandhan, Purushottam Dewang, Niranjan Rao, Roger A. Smith, Scott K. Thompson. ASN007, a novel oral ERK inhibitor, shows robust antitumor activity in RAS mutant cancer models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B150.
Rhesus macaque θ-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-κB and MAPK pathways (2015)

θ-Defensins are pleiotropic, macrocyclic peptides that are expressed uniquely in Old World monkeys. The peptides are potent, broad-spectrum microbicides that also modulate inflammatory responses in vitro and in animal models of viral infection and polymicrobial sepsis. θ-Defensins suppress proinflammatory cytokine secretion by leukocytes stimulated with diverse Toll-like receptor (TLR) ligands. Studies were performed to delineate anti-inflammatory mechanisms of rhesus θ-defensin 1 (RTD-1), the most abundant θ-defensin isoform in macaque granulocytes. RTD-1 reduced the secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-8 in lipopolysaccharide (LPS)-stimulated human blood monocytes and THP-1 macrophages, and this was accompanied by inhibition of nuclear factor κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) pathways. Peptide inhibition of NF-κB activation occurred following stimulation of extracellular (TLRs 1/2 and 4) and intracellular (TLR9) receptors. Although RTD-1 did not inhibit MAPK in unstimulated cells, it induced phosphorylation of Akt in otherwise untreated monocytes and THP-1 cells. In the latter, this occurred within 10 min of RTD-1 treatment and produced a sustained elevation of phosphorylated Akt (pAkt) for at least 4 h. pAkt is a negative regulator of MAPK and NF-κB activation. RTD-1 inhibited IκBα degradation and p38 MAPK phosphorylation, and stimulated Akt phosphorylation in LPS-treated human primary monocytes and THP-1 macrophages. Specific inhibition of phosphatidylinositol 3-kinase (PI3K) blocked RTD-1-stimulated Akt phosphorylation and reversed the suppression of NF-κB activation by the peptide. These studies indicate that the anti-inflammatory properties of θ-defensins are mediated by activation of the PI3K/Akt pathway and suppression of proinflammatory signals in immune-stimulated cells.
Prostate-specific human kallikrein (hK2) as a novel marker for prostate cancer (1996)

Monospecific antibodies for hK2 have been developed for detecting hK2 protein. Our studies indicate that hK2 may be a useful marker for prostate cancer.
Impact of Secondary Structure of Toll-Like Receptor 9 Agonists on Interferon Alpha Induction (2008)

Oligodeoxynucleotides containing a CpG motif and double- or multistranded structure-forming sequences act as agonists of Toll-like receptor 9 (TLR9) and induce high levels of interferon alpha (IFN-alpha) in addition to other Th1-type cytokines. In the present study, we evaluated three highly effective IFN-alpha-inducing agonists of TLR9 to determine the type of duplex structures formed and the agonist's ability to induce immune responses, including IFN-alpha induction, in human cell-based assays and in vivo in mice and nonhuman primates. Thermal melting studies showed that two of the agonists evaluated had a single melting transition with similar hyperchromicity in both heating and cooling cycles, suggesting the formation of intermolecular duplexes. A third agonist showed a biphasic melting transition in the heating cycle and a monophasic melting transition with lower hyperchromicity during the cooling cycle, suggesting the formation of both intra- and intermolecular duplexes. All three agonists induced the production of Th1-type cytokines and chemokines, including high levels of IFN-alpha, in human peripheral blood mononuclear cell and plasmacytoid dendritic cell cultures. Subcutaneous administration of the two intermolecular duplex-forming agonists, but not the intramolecular duplex-forming agonist, induced cytokine secretion in mice. In nonhuman primates, the two agonists that formed intermolecular duplexes induced IFN-alpha and IP-10 secretion. On the contrary, the agonist that formed an intramolecular duplex induced only low levels of cytokines in nonhuman primates, suggesting that this type of structure formation is less immunostimulatory in vivo than the other structure. Taken together, the present results suggest that oligonucleotide-based agonists of TLR9 that form intermolecular duplexes induce potent immune responses in vivo.
T2*‐weighted magnetic resonance imaging with hyperoxia in acute ischemic stroke (2010)

Differences in T2*-weighted signal intensity-time curves during oxygen challenge in brain regions with different pathophysiological states after stroke are likely to reflect differences in deoxyhemoglobin concentration, and therefore differences in metabolic activity. Despite its underlying complexities, this technique offers a possible novel mode of metabolic imaging in acute stroke.
Resonant optical propelling of microspheres: A path to selection of almost identical photonic atoms (2012)

Near field optical manipulation of microparticles is usually considered a nonresonant effect determined by the momentum conservation law. In this work we study optical propelling of polystyrene microspheres with diameters from 3 to 20 μm in the evanescent field produced by water immersed tapered microfibers. We show that the velocity of propelling increases with the average diameter of the sphere reaching extraordinary high values ~ 0.4 mm/s at modest guided optical powers (43 mW) for some of the spheres with diameters around 20 μm. We show that the optical forces exerted on such transparent dielectric spheres approach the total absorption limit and far exceed estimates for conventional nonresonant effects. By using transmission spectroscopy we demonstrate efficient coupling of light to high quality (~ 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> ) whispering gallery modes in the spheres with diameters of 15-20 μm in range and argue that these effects can be responsible for resonant enhancement of the propelling velocities. We support our model by statistical analysis of a large number of propelling events for spheres with a broad range of mean diameters. This work opens the path for size sorting of spherical “photonic atoms” with almost identical resonant frequencies which can be used in various microphotonic applications.
Operation of an optically coherent frequency comb outside the metrology lab (2014)

We demonstrate a self-referenced fiber frequency comb that can operate outside the well-controlled optical laboratory. The frequency comb has residual optical linewidths of < 1 Hz, sub-radian residual optical phase noise, and residual pulse-to-pulse timing jitter of 2.4 - 5 fs, when locked to an optical reference. This fully phase-locked frequency comb has been successfully operated in a moving vehicle with 0.5 g peak accelerations and on a shaker table with a sustained 0.5 g rms integrated acceleration, while retaining its optical coherence and 5-fs-level timing jitter. This frequency comb should enable metrological measurements outside the laboratory with the precision and accuracy that are the hallmarks of comb-based systems.
A Deterministic Dynamic Element Matching Approach for Testing High-Resolution ADCs With Low-Accuracy Excitations (2006)

Dynamic element matching (DEM) is capable of providing good average linearity performance in matching critical circuits in the presence of major component mismatch, but the approach has received minimal industrial adoption outside of /spl Sigma/-/spl Delta/ structures because of challenges associated with implementation of a required randomizer and because of the time-local nonstationarity. This paper presents a DEM approach to analog-to-digital converter (ADC) testing in which low-precision DEM digital-to-analog converters (DACs) are used to generate stimulus signals for ADCs under test. It is shown that in a testing environment, this approach provides very high precision test results, and time-local nonstationarity is of no concern. In addition to traditional random DEM techniques, a deterministic DEM (DDEM) strategy that eliminates the need for a randomizer is introduced. The performance of the DDEM method is established mathematically and validated with detailed simulation results. Furthermore, the DDEM method requires far fewer samples to achieve the same level of average linearity than the random DEM approach. It is demonstrated that both the random DEM and DDEM methods can be used to accurately test ADCs with linearity that far exceeds that of the DAC used as a signal generator. This technique of using imprecise excitations and DEM to test much more accurate ADCs offers potential for use in both production test and built-in self-test environments where high linearity test sources are difficult to implement.
Sterilization Characteristics of Tube Inner Surface Using Oxygen Plasma Produced by AC HV Discharge (2008)

Oxygen plasma inside a narrow tube using an AC high-voltage glow discharge at low pressure was produced for the sterilization of the inner surface of a tube. A tube having a length of 500 mm and diameter of 4 mm was sterilized by treatment for 10 min.
Scenario-based comparison of source-tracing and dynamic source routing protocols for ad-hoc networks (2002)

We present source-tracing as a new viable approach to routing in ad-hoc networks where routers communicate the second-to-last hop and distance in preferred paths to destinations. We use two source-tracing algorithms, a table-driven protocol (BEST) in which routers maintain routing information for all destinations, and an on-demand routing protocol (DST) in which routers maintain routing information for only those destinations to whom they need to forward data. Simulation experiments are used to compare these protocols with DSR, which has been shown to incur less control overhead than other on-demand routing protocols. The simulations show that DST requires far less control packets to achieve comparable or better average delays and percentage of packet delivered than DSR, and that BEST achieves comparable results to DSR while maintaining routing information for all destinations.
New Nanostructured Materials for Efficient Photon Upconversion (2014)

Although methods for harvesting subbandgap solar photons have been demonstrated, present approaches still face substantial challenges. We evaluate carrier escape mechanisms in an InAs/GaAs quantum dot (QD) intermediate band photovoltaic (PV) device using photocurrent measurements under subbandgap illumination. We show that subbandgap photons can generate photocurrent through a two-photon absorption process, but that carrier trapping and retrapping limit the overall photocurrent regardless of whether the dominant carrier escape mechanism is optical, tunneling, or thermal. We introduce a new design for an InAs QD-based nanostructured material that can efficiently upconvert two low-energy photons into one high-energy photon. Efficiency is enhanced by intentionally sacrificing a small amount of photon energy to minimize radiative and nonradiative loss. Upconversion PV devices based on this approach separate the absorption of subbandgap photons from the current-harvesting junction, circumventing the carrier-trapping problems.
Abstract A86: Preclinical refinement of a highly-penetrative polymeric nanoparticle drug delivery system for the treatment of glioblastoma multiforme. (2013)

Abstract Survival statistics for glioblastoma multiforme (GBM) have remained static despite years of research. Two challenges must be overcome to extend survival: drug delivery and resistance to current therapies. Recently, we have developed a highly-penetrative polymeric nanoparticle system capable of being safely delivered to brain parenchyma using convection-enhanced delivery (CED). We have previously shown that this system is capable of protecting and releasing in a controlled manner agents with activity against glioma stem cells (GSCs), significantly improving survival in a rat xenograft model of GSC-derived GBM. We describe here our efforts to further refine this potential therapeutic. First, utilizing high-throughput small molecule screening of a library of generic and FDA- and internationally-approved compounds against GSCs of varying morphologies and genetic composition, we describe the discovery of a novel class of compounds with profound anti-proliferative activity against GSCs but with only very limited activity against normal glial cells. Identified compounds are notably small and lipophilic, making them ideal candidates for translation in our highly-penetrative polymeric nanoparticle system. Second, building upon recent advances in magnetic resonance imaging technology, we describe the incorporation of supraparamagnetic iron oxide (SPIO) in our highly-penetrative polymeric nanoparticle system. We show that incorporation of SPIO does not alter size or in vitro properties of these nanoparticles. Further, we show that SPIO-loaded nanoparticles can be safely delivered to brain parenchyma using CED and can stably release their contents in a controlled fashion over a matter of weeks. These results represent important steps toward clinical application of a promising drug delivery technology. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A86. Citation Format: Garth W. Strohbehn, Komli-Kofi Atsina, Toral R. Patel, Joseph M. Piepmeier, Jiangbing Zhou, W. Mark Saltzman. Preclinical refinement of a highly-penetrative polymeric nanoparticle drug delivery system for the treatment of glioblastoma multiforme. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A86.
Compositions useful for transferring therapeutically active polynucleotides into a target cell, and their use in gene.. (1999)

The present invention relates to a composition which is intended for transferring at least one therapeutically active substance into the interior of a target cell, characterized in that it comprises a mixture of at least one therapeutically active..