gebhart/patrepeval huggingface dataset:
Improved Methods for the Synthesis of Aza-Crown Macrocycles and Cryptands (1993)

New strategies for the preparation of aza-crown macrocycles and cryptands from readily available, cheap starting materials are described. One- or few-step processes for forming aza-crowns, peraza-crowns and cryptands with high overall yields have been developed. The methods could also be useful for the synthesis of interesting new classes of macrobicycles and higher order ligating agents. 1. Introduction 1.1. Preface 1.2. Applications of the Aza-Crown Macrocycles and Cryptands 1.3. Usual Methods for the Preparation of the Aza-Crown Macrocycles and Cryptands 2. An Unexpected Ring Closure Reaction to Form Diaza-Crown Macrocycles 3. The Building Block Method to Form Aza-Crown Macrocycles 4. The "Crab-Like" Method to Form Aza-Crown Macrocycles 5. Cryptands via a One-Step Bicyclization Reaction 6. Reflections
Traction-Control-Oriented State Estimation for Motorcycles (2013)

This brief addresses two estimation problems relevant to traction control for motorcycles: longitudinal vehicle velocity estimation and wheelie (i.e., front wheel lifting off the ground during acceleration) detection. Two methods to estimate the vehicle body velocity are discussed and compared: a complementary filter and a Kalman filter. The Kalman filter reduces the noise affecting the estimate of the longitudinal vehicle velocity by an order of magnitude without introducing any phase lag. Furthermore, a wheelie detection algorithm is developed. The approach is based on the fault detection paradigm and detects wheelies in 70 ms. Both methods are computationally efficient and industrially viable. Track tests on an instrumented sport motorcycle are employed to illustrate and validate the methods.
Seamless internet 3G and opportunistic WLAN vehicular connectivity (2011)

Most of the cellular network operators are nowadays striving to solve the problem caused by the increasing demand of mobile data users. In the near future, vehicles will be equipped not only with cellular connectivity, but also with dedicated short-range wireless devices, used to connect via single or multiple hops to fixed road side units attached to the infrastructure network to gain Internet access. Taking this hybrid-connectivity scenario, we propose S eamless I nternet 3G and Opportunistic WL AN V ehicular I nternet Co nnectivity (SILVIO), a solution for providing Internet connectivity in multi-hop vehicular ad hoc networks. Vehicles use the cellular network to assure always-on connectivity, while they opportunistically select to offload some non-critical flows to the multi-hop wireless local area network (WLAN). The advantages of this approach are twofold: the users can benefit from a higher bandwidth, while the operators can alleviate their overloaded cellular networks. SILVIO makes use of existing standard mobility mechanisms integrated, enhanced and extended to provide a seamless connectivity experience without introducing much complexity nor signalling overhead. One of the main contributions of this article is the proposal and analysis of different handover strategies between 3G and multi-hop WLAN networks for the vehicular scenario. A trace-driven simulator was developed to evaluate the performance improvements provided by SILVIO. Real traffic traces from the city of Madrid were used to feed the simulator which considers large vehicles as obstacles, as well. The obtained results show that using SILVIO the cellular network can be offloaded by a factor up to 80%.
Quantitative predictions of photo-emission dynamics in metal halide perovskites via machine learning (2020)

Metal halide perovskite (MHP) optoelectronics may become a viable alternative to standard Si-based technologies, but the current lack of long-term stability precludes their commercial adoption. Exposure to standard operational stressors (light, temperature, bias, oxygen, and water) often instigate optical and electronic dynamics, calling for a systematic investigation into MHP photophysical processes and the development of quantitative models for their prediction. We resolve the moisture-driven light emission dynamics for both methylammonium lead tribromide and triiodide thin films as a function of relative humidity (rH). With the humidity and photoluminescence time series, we train recurrent neural networks and establish their ability to quantitatively predict the path of future light emission with &lt;11% error over 12 hours. Together, our in situ rH-PL measurements and machine learning forecasting models provide a framework for the rational design of future stable perovskite devices and, thus, a faster transition towards commercial applications.
Profilin Is Required for Sustaining Efficient Intra- and Intercellular Spreading of Shigella flexneri (2000)

The ability of Shigella to mediate actin-based motility within the host cell is a prominent pathogenic feature of bacillary dysentery. The ability is dependent on the interaction of VirG with neural Wiskott-Aldrich syndrome protein (N-WASP), which in turn mediates recruitment of Arp2/3 complex and several actin-related proteins. In the present study, we show that profilin I is essential to the rapid movement of Shigella in epithelial cells, for which the capacity of profilin to interact with G-actin and N-WASP is critical. In COS-7 cells overexpressing either mutated profilin H119E, which failed to bind G-actin, or H133S, which is unable to interact with poly-l-proline, Shigella motility was significantly inhibited. Similarly, depletion of profilin from Xenopus egg extracts resulted in a decrease in bacterial motility that was completely rescued by adding back profilin I but not H119E or H133S. In COS-7 cells overexpressing a N-WASP mutant lacking the proline-rich domain (Deltap) unable to interact with profilin, the actin tail formation of intracellular Shigella was inhibited. In N-WASP-depleted extracts, addition of Deltap but not full-length N-WASP was unable to restore the bacterial motility. Furthermore, in a plaque formation assay with Madin-Darby canine kidney cell monolayers infected by Shigella, Madin-Darby canine kidney cells stably expressing H119E, H133S, or Deltap reduced the bacterial cell-to-cell spreading. These results indicate that profilin I associated with N-WASP is an essential host factor for sustaining efficient intra- and intercellular spreading of Shigella.
P5422Long-term performance of vagus nerve stimulation lead: low rate of complications and failures (2019)

Abstract Background Autonomic Regulation Therapy (ART) is a novel therapy for heart failure (HF) that has been shown in a pilot study to be associated with improvement in left ventricular function, 6-minute walk distance, NYHA class, and quality of life. ART is provided using chronic stimulation through a self-sizing lead that is placed on the cervical vagus nerve without any need for response-mapping. The lead is functionally identical in its design and manufacture to a commercially available lead that has been implanted since February 2009 for the treatment of refractory epilepsy and treatment-resistant depression. Purpose A survival analysis was performed to evaluate long-term lead performance. Methods Lead survival was calculated for those patients whose survival status was obtainable from public records. All devices registered as implanted in the United States for any indication were included for the analysis. All available data on device explants, device replacements, returned product analyses, and customer complaints were collected and used to identify failures and out-of-specification conditions. Device survival probability was defined as the likelihood of the implanted device remaining implanted and performing as intended. Results As of the time of this analysis, there have been 26467 registered system implantations and a total of 53200 device-years of lead use. Survival status was obtainable for 9700 patients from public records. After 1 year, 99.5% of implanted leads have remained implanted and performing as intended. At 7 years, 95.8% of leads have remained implanted and performing as intended. The most common causes of lead failure have been infection (0.87%), vocal cord dysfunction (0.68%), lead protrusion (0.36%), and lead extrusion (0.27%). At implant 1 year 2 year 3 year 5 year 7 year Cumulative Survival Probability (%) 100 99.5 (99.4–99.6) 99.1 (98.8–99.2) 98.6 (98.4–98.9) 97.4 (96.9–97.7) 95.8 (94.9–96.5) Number of Patients 9700 8500 7200 6000 3300 700 Conclusions Lead performance during chronic vagus nerve stimulation has included over 5ehz746.0379 device-years of use in over 25000 patients. A low rate of long term complications and failures have been reported, and the cumulative survival probability of the lead appears to be high. Acknowledgement/Funding LivaNova PLC
Mechanism of the ultraviolet laser ablation of polymethyl methacrylate at 193 and 248 nm: laser-induced fluorescence analysis, chemical analysis, and doping studies (1986)

The formation of C2 in the ablation of polymethyl methacrylate (PMMA) by 193- and 248-nm laser pulses was studied by laser-induced fluorescence. The formation of C2 is observable at a fluence at 248 nm that is well below the fluence threshold where significant etching takes place. The opposite is true at 193 nm. The velocity distribution of the diatomic form was also measured and found to approach but not exactly fit a Maxwell–Boltzmann equation. Average translational energies as high as 6 eV were recorded even at the fluence threshold for this product. The other products of the laser ablation of PMMA at 193 or 248 nm are methyl methacrylate (MMA) and a solid that is a low-molecular-weight fraction of PMMA. Although the products are the same at both wavelengths, the mix is quite different. At 193 nm, 18% of the ablated polymer is MMA, whereas at 248 nm less than 1% of the polymer appeared as MMA. A semilog plot of the mass of material removed versus the fluence shows three distinct regions. The central portion at each wavelength (80–300 mJ/cm2 at 193 nm; 600–2000 mJ/cm2 at 248 nm), which corresponds to rapid etching, is identified as ablative photodecomposition. At lower fluences, the etching efficiency falls off rapidly, indicating that there is a threshold fluence. At fluences above the range for ablative photodecomposition, the etching levels off, probably because of the secondary absorption of the incoming photons by the products. The mass of material ablated per joule of energy absorbed in the ablated volume was remarkably similar at both wavelengths. It is suggested that ablative photodecomposition involves both a one-photon process that produces MMA and low-molecular-weight polymeric fragments and a many-photon process that gives rise to products such as C2 with high translational energy. In order to establish the role of the many-photon process, samples of PMMA doped with acridine were exposed to laser pulses. The presence of as little as 2% of acridine lowers the threshold for significant etching at 248 nm from 400 to 90 mJ/cm2. The absorption characteristics of the doped polymer at this wavelength show that the acridine molecules absorb &gt;10 photons each, whereas the absorption of the polymer changes little. The drop in the threshold energy for etching should therefore be attributed to the many-photon decomposition of the acridine and the consequent ablation of the polymer as a whole.
AAV‐mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune response (2020)

Liver metastasis is the main cause of colorectal cancer (CRC)-related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long-term daily administrations of recombinant DNase I, we have developed an adeno-associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV-mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV-DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8<sup>+</sup> T cells while keeping CD4<sup>+</sup> T cells similar between AAV-DNase I and AAV-null treatments. Our data suggest that AAV-mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.
<title>Experimental and theoretical analysis of multichannel XMP-based wavelength conversion in optical fibers</title> (2001)

A detailed experimental and theoretical analysis of multi- channel XPM-based wavelength conversion in standard communication fibers. Dispersion impact is taken into account and comparison with FWM based conversion technique is also offered.
Attosecond Extreme Ultraviolet Beams with Time-Varying Orbital Angular Momentum: The Self-Torque of Light (2019)

Light beams with self-torque -a temporal variation of their orbital angular momentum-are described and produced for the first time. This new property of light beams is naturally mapped onto extreme-ultraviolet waveforms via high-harmonic generation. © 2019 The Author(s)
Migration mediated by the oxysterol receptor GPR183 depends on arrestin coupling but not receptor internalization (2023)

The chemotactic G protein-coupled receptor GPR183 and its most potent endogenous oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-OHC) are important for immune cell positioning in secondary lymphoid tissues. This receptor-ligand pair is associated with various diseases, in some cases contributing favorably and in other cases adversely, making GPR183 an attractive target for therapeutic intervention. We investigated the mechanisms underlying GPR183 internalization and the role of internalization in the main biological function of the receptor, chemotaxis. We found that the C terminus of the receptor was important for ligand-induced internalization but less so for constitutive (ligand-independent) internalization. β-arrestin potentiated ligand-induced internalization but was not required for ligand-induced or constitutive internalization. Caveolin and dynamin were the main mediators of both constitutive and ligand-induced receptor internalization in a mechanism independent of G protein activation. Clathrin-mediated endocytosis also contributed to constitutive GPR183 internalization in a β-arrestin-independent manner, suggesting the existence of different pools of surface-localized GPR183. Chemotaxis mediated by GPR183 depended on receptor desensitization by β-arrestins but could be uncoupled from internalization, highlighting an important biological role for the recruitment of β-arrestin to GPR183. The role of distinct pathways in internalization and chemotaxis may aid in the development of GPR183-targeting drugs for specific disease contexts.
Does the granular matter? (2000)

Granular materials, such as sand, gravel, powders, and pharmaceutical pills, are large aggregates of macroscopic, individually solid particles, or "grains." Far from being simple materials with simple properties, they display an astounding range of complex behavior that defies their categorization as solid, liquid, or gas. Just consider how sand can stream through the orifice of an hourglass yet support one's weight on the beach; how it can form patterns strikingly similar to a liquid when vibrated, yet respond to stirring by "unmixing" of large and small grains. Despite much effort, there still is no comprehensive understanding of other forms of matter, like ordinary fluids or solids. In what way, therefore, is granular matter special, and what makes it so difficult to understand? An emerging interdisciplinary approach to answering these questions focuses directly on the material's discontinuous granular nature.
Integrated switch for simultaneous mode-division multiplexing (MDM) and wavelength-division multiplexing (WDM) (2015)

Leveraging the spatial modes of multimode waveguides using mode-division multiplexing (MDM) on an integrated photonic chip allows unprecedented scaling of bandwidth density for on-chip communication. Switching channels between waveguides is critical for future scalable optical networks, but its implementation in multimode waveguides must address how to simultaneously control modes with vastly different optical properties. Here we present a platform for switching signals between multimode waveguides based on individually processing the spatial mode channels using single-mode elements. Using this wavelength-division multiplexing (WDM) compatible platform, we demonstrate a 1x2 multimode switch for a silicon chip which routes four data channels with low (
Regulation of Cytokine and Viral Gene Expression in Monocytes Infected with the Human Immunodeficiency Virus (1991)

Monocytes treated with interferon-α (IFN-α) at virus challenge show no evidence of human immunodeficiency virus (HIV) infection: no p24 antigen or reverse transcriptase (RT) activity, no viral mRNA and no proviral DNA. Levels of p24 antigen and RT activity in monocytes infected with HIV 1–3 weeks before IFN-α treatment gradually decrease to baseline. HIV-induced cytopathic changes are markedly reduced, as are levels of HIV mRNA: the frequency of productively infected cells is ≤ 1 %. But, levels of proviral DNA in the IFN-α-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-α-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-α in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-α, interleukin-1 β, interleukin-6, IFN-ω or IFN-β are not detected nor the mRNA expressed in HIV-infected or uninfected monocytes. Both uninfected and HIV-infected monocytes produce high levels of these cytokines after treatment with synthetic double-stranded RNA (poly-LC). Uninfected monocytes also produce high levels of IFN-α after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-α activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-α reflects a specific transcriptional block and may be an adaptive mechanism of virus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes.
Visual detection of orientation modulators suggests limitations to scale invariance of second order mechanisms (2010)

Using a second-order visual stimulus in which the orientation of a noise carrier was spatially modulated, we probed the relationship between the frequency of the band-pass filtered carrier and that of the envelope periodic spatial modulator. In a 2-AFC psychophysical detection task, we obtained the threshold tuning functions for both the carrier luminance contrast and the modulation depth for a range of ratios of the two frequency parameters using a foveally presented stimulus in a circular aperture. With a scale invariant neural mechanism, suggested for second-order stimuli, functions of the ratio of carrier and modulator frequencies should show consistent tuning, largely independent of the specific pair of frequency parameters. We found that was not the case. For the carrier contrast threshold, the functions showed a low-pass tuning when the carrier frequency was varied and band-pass tuning when the modulator frequency was varied. For both parametric manipulations, the ratio had a similar range of tested values. When we measured modulation depth thresholds with the stimuli controlled for luminance contrast detectability, the functions showed more modest differences in tuning. To exclude an explanation based on averaging of any optimal tuning spatially across the visual field, we repeated the measurements for a stimulus confined in eccentricity (Annulus, radius 14.6 deg of visual angle). That configuration was more difficult to detect and returned broadly similar tuning functions. These results do not support the idea of a constant coupling between the scales of mechanisms detecting the carrier and modulator that would be required for scale invariance.
ChemInform Abstract: A Convenient Method to Access Long‐Chain and Functionalized Mixed Methylphosphonate Esters and Their Application in the Synthesis of Ionic Liquids. (2012)

Abstract The solvent‐free reaction of ionic liquid (I) with alkyl halides (II) leads to the mixed methylphosphonate esters (III), which are used for the synthesis of novel methylphosphonate ionic liquids such as (V) and (VII).
O1‐06‐03: Preclinical characterization of LY2886721: A BACE1 inhibitor in clinical development for early Alzheimer's disease (2012)

BACE1 is a key protease targeting the amyloid processing pathways in AD. Previously we published on LY2811376, the first small molecule BACE1 inhibitor reported to provide robust CSF Abeta changes in healthy subjects. LY2811376 progressed to clinical trials but was terminated due to non-clinical tox findings. Here we report the preclinical pharmacology of LY2886721, a new BACE1 inhibitor that is in clinical development for early AD. Enzyme assays were conducted with recombinant enzymes using a FRET platform. Cell based assays were conducted with either a HEK293Swe cell line or primary neuronal cultures prepared from PDAPP mice. D ose response and time course studies were conducted in young PDAPP transgenic mice with brain collected at various times after oral gavage and extracts analyzed by ELISA for relevant PD biomarkers including Abeta, C99 and sAPPbeta. Plasma and CSF PK/PD studies were conducted in beagle dogs using a multi-week paradigm which involved establishing vehicle-treated baseline CSF Abeta values for within dog comparison to subsequent CSF samples taken from LY-treated dogs. LY2886721 inhibited recombinant hBACE1 with an IC50 of 20.3 nM. In cellular assays, LY2886721 inhibited Abeta with an IC50 of 18.7 nM and 10.7 nM, HEK293Swe and PDAPP neuronal culture, respectively. Oral administration of LY2886721 to PDAPP mice produced dose-dependent reductions in brain Abeta, C99 and sAPPbeta. Brain Abeta levels were decreased ∼20% -65% relative to vehicle-treated groups three hours after a 3–30 mg/kg dose of LY2886721. Brain C99 and sAPPb levels also were reduced in a dose-dependent manner consistent with BACE1 inhibition in vivo. The pharmacodynamic responses to LY2886721 persisted out to 9 hours post dose in brains of PDAPP mice. Pharmacodynamic studies in beagle dog revealed robust and sustained reductions in plasma Abeta following 1 mg/kg LY2886721 dosing. Central effects of BACE1 inhibition in dog were manifested by a 50% reduction in CSF Abeta at 9 hours after a 0.5 mg/kg dose of LY2886721. LY2886721 is a potent inhibitor of BACE1 which demonstrates robust in vitro and in vivo BACE1 inhibition in pre-clinical models. Phase 2 clinical trials in AD patients are planned for 2012.