gebhart/patrepeval huggingface dataset:
Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models (2020)

We report the relaxation of methacholine-constricted airways with nebulized MIDD0301, a positive allosteric γ-aminobutyric acid type A receptor (GABA<sub>A</sub>R) modulator. The therapeutic efficacy of nebulized MIDD0301 in reducing airway resistance was investigated in spontaneous breathing mice using a whole-body plethysmograph and in unconscious mice using a forced oscillation technique. Prophylactic nebulized MIDD0301 reduced subsequent methacholine-induced bronchoconstriction in ovalbumin and house dust mite allergic asthma models and in normal mice. Nebulized MIDD0301 exhibited comparable or better therapeutic potency compared to nebulized albuterol and oral montelukast. Prophylactic nebulized MIDD0301 was also effective in reducing bronchoconstriction, comparable to nebulized albuterol or fluticasone, in a steroid resistant asthma mouse model induced by intratracheal installation of lipopolysaccharide and interferon-gamma. Oral dexamethasone was ineffective in this model. Nebulized MIDD0301 was also effective in reversing bronchospasm when dosed after methacholine challenge comparable to albuterol. Pharmacokinetic studies showed that about 0.06% of nebulized MIDD0301 entered the mouse lung when using a whole body plethysmograph and therapeutic levels were sustained in the lung for at least 25 min. Consistent with previous reports on orally dosed MIDD0301, high doses of nebulized MIDD0301 resulted in minimal brain exposure and thus no observable adverse sensorimotor or respiratory depression effects occurred. In addition, no adverse cardiovascular effects were observed following 100 mg/kg i.p. dosing. These results further demonstrate that charged imidazodiazepine MIDD0301 can selectively target lung GABA<sub>A</sub>R without adverse motor, cardiovascular, or respiratory effects and inhaled dosing is effective in reducing bronchoconstriction in allergen and infectious lung inflammation.
Wideband diversity in multipath channels with nonuniform power dispersion profiles (2006)

The focus of this paper is to derive the symbol error probability (SEP) of a Rake receiver with a limited number of fingers that track the strongest multipath components in a frequency-selective Rayleigh fading channel. We develop an analytical framework that allows the computation of the SEP for nonuniform power dispersion profiles (PDPs) and spreading bandwidth. By transforming the physical Rake receiver with correlated ordered paths into the domain of a 'virtual Rake" receiver with conditionally independent virtual paths, analytical expressions for the SEP are derived in terms of the spreading bandwidth, the channel profile, and the number of combined paths. We show how our analytical results can be used to predict the performance of various Rake architectures in environments with nonuniform PDPs using for example, the channel models defined for the next generation wireless standards. Furthermore, we validate our methodology by comparison to data obtained from channel measurements, showing good agreement with our analytically derived results.
Quantification of Atrial Tachyarrhythmia Burden with an Implantable Pacemaker Before and After Pulmonary Vein Isolation (2004)

Long-term efficacy of pulmonary vein (PV) ostial isolation for paroxysmal atrial fibrillation is difficult to assess. We evaluated the net duration of atrial tachyarrhythmia episodes (burden), atrial tachyarrhythmia episode frequency, and quality-of-life (QOL) before and after PV isolation in patients with an existing pacemaker featuring extensive diagnostic capabilities. Due to frequent recurrences of paroxysmal atrial fibrillation, PV isolation was performed 21 +/- 10 months following pacemaker implantation on 12 patients (57 +/- 5 years) with normal left ventricular function. Atrial tachyarrhythmia burden (ATB) and episode frequency were monitored daily by the device both pre- and postablation. QOL questionnaires were collected at ablation and 1, 3, and 6 months thereafter. Patients were followed for 20 +/- 9 and 11 +/- 9 months pre- and postablation, respectively. Membrane-active antiarrhythmic medications were discontinued after ablation in 8 of 12 patients. PV isolation resulted in a significant reduction of ATB from a median of 3.2 hours/day (preablation) to 0.2 hours/day (postablation, P < 0.01, Wilcoxon signed-rank test). The median tachyarrhythmia frequency was 6.4 episodes/day (preablation) and 0.3 episodes/day (postablation, P = 0.09). QOL measures significantly improved over the data collection intervals (P < 0.05). Tachyarrhythmia burden was positively associated with Symptom Checklist frequency and severity (P < 0.01). Significant long-term reductions in total ATB (symptomatic and asymptomatic) were observed. Furthermore, reductions in ATB were associated with improvements in QOL measures. Extensive monitoring capabilities in implantable devices help provide complete disclosure on the effect of PV isolation in paroxysmal atrial fibrillation patients.
Multilayer liquid metal stretchable inductors (2014)

Liquid metals are ideally suited for creating low resistance traces able to undergo large mechanical strains. In this work, multilayer fluidic channels in soft silicone are used to create two inductor topologies, a solenoid and a double planar coil, based on the liquid metal galinstan. Electromechanical models were developed for the inductance upon stretching for each inductor, finding that the double planar coil has lower strain sensitivity in each direction than the solenoid. A three turn double planar coil and six turn solenoid, with unstretched inductances of approximately 250 nH and 55 nH respectively, were fabricated and tested using custom tensile and compressive strain testing setups and compared with the analytical model. The double planar coil was found to increase in inductance when stretched in either in-plane axes, with a measured rise of approximately 40% for 100% strain. The solenoid decreased in inductance by 24% for 100% strain along the core direction, and increased by 50% for the same strain along the core width.
A poesia de Liberto Cruz: arte e comunicação (2016)

En este artículo intentamos mostrar cómo la obra del escritor portugués Liberto Cruz establece un compromiso entre el poema como texto libre de cualquier imposición ideológica y el poema como acción social y política; entre la experiencia interna y personal del autor, y su compromiso con la historia del país; entre la autosuficiencia del poema y sus vínculos con el mundo en general; entre comunicación y elevación; entre la expansión del trabajo de imagen y semántica, y la comunicación de sentimientos, emociones e ideas; y entre el "yo" textual y el "yo" biográfico.
Heterogeneity in PHGDH protein expression potentiates cancer cell dissemination and metastasis (2021)

Abstract Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs. Genetic, transcriptional and translational intra-tumor heterogeneity contributes to this dynamic process. Beyond this, metabolic intra-tumor heterogeneity has also been observed, yet its role for cancer progression remains largely elusive. Here, we discovered that intra-tumor heterogeneity in phosphoglycerate dehydrogenase (PHGDH) protein expression drives breast cancer cell dissemination and metastasis formation. Specifically, we observed intra-tumor heterogeneous PHGDH expression in primary breast tumors, with low PHGDH expression being indicative of metastasis in patients. In mice, Phgdh protein, but not mRNA, expression is low in circulating tumor cells and early metastatic lesions, leading to increased dissemination and metastasis formation. Mechanistically, low PHGDH protein expression induces an imbalance in glycolysis that can activate sialic acid synthesis. Consequently, cancer cells undergo a partial EMT and show increased p38 as well as SRC phosphorylation, which activate cellular programs of dissemination. In turn, inhibition of sialic acid synthesis through knock-out of cytidine monophosphate N-acetylneuraminic acid synthetase (CMAS) counteracts the increased cancer cell dissemination and metastasis induced by low PHGDH expression. In conclusion, we find that heterogeneity in PHGDH protein expression promotes cancer cell dissemination and metastasis formation.
We are all lurkers (2010)

Most knowledge repositories focus on the role of knowledge-creators. In this paper, by contrast, we examined the work of Lurkers in an enterprise file-sharing service, and we compared their lurking behaviors to the lurking behaviors of users who uploaded files (Uploaders), and users who contributed metadata about files (Contributors). For comparability, we restricted our analyses to the consuming behaviors that are common to the three roles (Uploaders, Contributors, and Lurkers). Independent principal components analysis showed highly similar seven-factor solutions of lurking activities across all three roles, although the relative emphases of those factors varied across roles. Uploaders tended to view and download more groups of files, showed less emphasis on searching for files, and tended to work directly with the file-sharing application, unmediated by external applications. Contributors showed the opposite pattern: more emphasis on searching and responding to recommendations from other users, often via a form of remote access. Lurkers' lurking behaviors were less intense, and showed little difference in emphases among the lurker factors. We use these results, and the published research literature, to motivate a research agenda for lurkers in social media.
Discovery and Development of the First Antibody–Antibiotic Conjugate Linker-Drug (2019)

With growing resistance to conventional antibiotics in microbial populations and few new treatment options available, we have embarked on utilizing an innovative molecular paradigm to address the challenge of infectious diseases. Building on a Genentech-engineered monoclonal antibody (mAb) designed to bind specifically to the cell wall of Staphylococcus aureus, we have discovered a novel and precise antibiotic that can be conjugated to the mAb via controlled linker technology. This powerful mAb-linker-drug molecular construct has been shown to combat S. aureus in vivo with promise as a new treatment option for microbial infections. Chemical development of the highly complex small molecule linker-drug, utilizing sophisticated continuous processing technology, has allowed the program to enter the clinic and establish a benefit to patients.
Numerical Study of Turbulence Models in the Computation of Blood Flow in Cannulas (2008)

In recent years, CFD has become an increasingly used tool in the design of blood-based devices. However, the estimation of red blood cells damage (hemolysis) remains a very important challenge due to the complex rheology of blood and the turbulence present in most pumping devices. The objective of this study was to identify an appropriate turbulence model suitable for predicting hemolysis in Hemodialysis cannula. Several modern turbulence models were evaluated in comparison to Direct Numerical Simulation (DNS), which was used as the gold standard. The fluid dynamics in the cannula was modeled as a coaxial jet in which Reynolds’ number approached 2800. Based on comparison of velocity and stress time-averaged profiles, the Shear Stress Transport (SST) model with Gamma-Theta transition was identified as an optimal compromise between accuracy and computational cost.
A real-time error correction system for spindle errors (2002)

A methodology for machining of near-perfect bores on mild steel workpieces using an error correction system attached to a conventional, preloaded ball bearing machine tool spindle is described. The approach detects machine tool errors in real-time by using a laser-based sensor, models the errors as a background computation and uses the model to compensate, in real-time, for the deterministic errors. The hardware developed to implement the methodology scans the workpiece surface after matching with a spindle-mounted probe. If the model-based machine tool errors are subtracted from the scanned signal, and the remaining error is modeled, then an in-situ bore measurement is effectively made. This approach avoids the axis locating problem intrinsic with use of a separate measuring machine. The machine tool errors are modeled as deviations from all ideal cylinder in space. With respect to the machine tool coordinates, the model parameters include axis orientation, diameter, and cylindricity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Phosphodiester content measured in human liver by in vivo 31P MR spectroscopy at 7 tesla (2017)

We report human in vivo hepatic T<sub>1</sub> s for phosphatidylcholine, NAD<sup>+</sup> , and UDPG for the first time at 7T. Our protocol allows high signal-to-noise, repeatable measurement of metabolite concentrations in human liver. The splitting of PDE into its constituent peaks at 7T may allow more insight into changes in metabolism. Magn Reson Med 78:2095-2105, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Photosensing and quorum sensing are integrated to control Pseudomonas aeruginosa collective behaviors (2019)

Bacteria convert changes in sensory inputs into alterations in gene expression, behavior, and lifestyles. A common lifestyle choice that bacteria make is whether to exhibit individual behavior and exist in the free-living planktonic state or to engage in collective behavior and form sessile communities called biofilms. Transitions between individual and collective behaviors are controlled by the chemical cell-to-cell communication process called quorum sensing. Here, we show that quorum sensing represses Pseudomonas aeruginosa biofilm formation and virulence by activating expression of genes encoding the KinB-AlgB two-component system (TCS). Phospho-AlgB represses biofilm and virulence genes, while KinB dephosphorylates and thereby inactivates AlgB. We discover that the photoreceptor BphP is the kinase that, in response to light, phosphorylates and activates AlgB. Indeed, exposing P. aeruginosa to light represses biofilm formation and virulence gene expression. To our knowledge, P. aeruginosa was not previously known to detect and respond to light. The KinB-AlgB-BphP module is present in all pseudomonads, and we demonstrate that AlgB is the partner response regulator for BphP in diverse bacterial phyla. We propose that in the KinB-AlgB-BphP system, AlgB functions as the node at which varied sensory information is integrated. This network architecture provides a mechanism enabling bacteria to integrate at least two different sensory inputs, quorum sensing (via RhlR-driven activation of algB) and light (via BphP-AlgB), into the control of collective behaviors. This study sets the stage for light-mediated control of P. aeruginosa infectivity.
Data Lifecycle and Tagging for Internet of Things Applications (2016)

The number of sensors and the amount of data those sensors are collecting is increasing exponentially in the form of sensor networks collectively known as the Internet of Things (IoT). Using this large volume of IoT data in context-aware systems requires new preprocessing methods. This paper introduces an IoT data lifecycle, a proposed definition of an IoT-specific context tag, and required for an automated preprocessing method called data tagging before suggesting some uses of this IoT context tag and outlining possible directions for future research.
Prototype of an intertwined secondary-metabolite supercluster (2013)

The hallmark trait of fungal secondary-metabolite gene clusters is well established, consisting of contiguous enzymatic and often regulatory gene(s) devoted to the production of a metabolite of a specific chemical class. Unexpectedly, we have found a deviation from this motif in a subtelomeric region of Aspergillus fumigatus. This region, under the control of the master regulator of secondary metabolism, LaeA, contains, in its entirety, the genetic machinery for three natural products (fumitremorgin, fumagillin, and pseurotin), where genes for fumagillin and pseurotin are physically intertwined in a single supercluster. Deletions of 29 adjoining genes revealed that fumagillin and pseurotin are coregulated by the supercluster-embedded regulatory gene with biosynthetic genes belonging to one of the two metabolic pathways in a noncontiguous manner. Comparative genomics indicates the fumagillin/pseurotin supercluster is maintained in a rapidly evolving region of diverse fungal genomes. This blended design confounds predictions from established secondary-metabolite cluster search algorithms and provides an expanded view of natural product evolution.
A Phase I/Ib Study of Folate Immune (EC90 Vaccine Administered With GPI-0100 Adjuvant Followed by EC17) With Interferon-α and Interleukin-2 in Patients With Renal Cell Carcinoma (2014)

Folate immune (EC90 vaccine with GPI-0100 adjuvant followed by EC17) is a novel folate-targeted hapten immunotherapy designed to exploit the overexpression of folate receptors on renal cell carcinoma (RCC) cells. In this open-label, phase I/II clinical study, we report the safety, pharmacokinetics, and antitumor activity of folate immune with concurrent interleukin-2 (IL-2) and interferon-α (IFN-α) in patients with recurrent or metastatic RCC. Twenty-four patients were enrolled. Following 2 phase I cohorts of 6 patients each, we extended the study to 12 additional patients: 18 received weekly vaccination of 1.2 mg of EC90 with 3.0 mg of GPI-0100 adjuvant for 4 weeks. Beginning on cycle 1, day 8, 0.3 mg/kg of EC17 was administered once daily, 5 days per week (Monday-Friday) for 4 consecutive weeks. Beginning on cycle 1, day 15, IL-2 and IFN-α were administered at doses of 12 and 3.0 MIU, respectively, after the EC17 dose, 3 times per week (Monday, Wednesday, and Friday) for 3 weeks. In cycle 2, IL-2 and IFN-α, doses of 7.0 and 3.0 MIU, respectively, were administered 3 days per week (Monday, Wednesday, and Friday) for 4 consecutive weeks. No dose-limiting toxicities were observed. Most adverse events reported were grade 1 or 2, with only twelve grade ≥3 toxicities reported. Sixteen patients had progressive disease, 7 patients were observed to have stable disease, and 1 patient achieved a partial response lasting 71 days. Overall, folate immune plus low-dose IFN-α and IL-2 was safe and well tolerated with some observed clinical activity.
Passive remote detection of atmospheric pollutants using Fourier transform infrared (FTIR) spectroscopy (1994)

Feasibility studies on the use of passive FTIR spectroscopy for the remote detection of atmospheric pollutants have shown that gases may be identified remotely with an optically modified commercial FTIR spectrometer when only a small 7 degree(s)C) temperature difference exists between the gas and a background IR emitter. A correlation technique was used to extract information from noisy (SNR on the order of magnitude 1) emission spectra from which low temperature differential or low concentration gases or mixtures with interferant species were analyzed. Quantitative measurements of gas concentrations were made by first determining the temperature of the remote gas from rotational line intensity distributions. The product of concentration and pathlength was obtained by comparing the remotely detected emission spectra with simulated spectra obtained from computer models at the measured temperature. Laboratory experiments measured the temperature of CO from its emission spectrum to +/- 5% and the concentration also to +/- 5%. Tomographic reconstructions of molecular distributions within a methane flame have recently been obtained.
Supplementary Table 1 from A High-Throughput Immune-Oncology Screen Identifies EGFR Inhibitors as Potent Enhancers of Antigen-Specific Cytotoxic T-lymphocyte Tumor Cell Killing (2023)

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Encoding of the amplitude modulation of pulsatile electrical stimulation in the feline cochlear nucleus by neurons in the inferior colliculus; effects of stimulus pulse rate (2013)

The findings have implications for improved sound processors for present and future ABIs. The performance of ABIs may benefit from using pulse rates greater than those presently used in most ABIs, and by sound processing strategies that enhance the modulation depth of the electrical stimulus while preserving dynamic range.
110-fs, 5.3-µm ZGP Parametric Amplifier Driven by a ps Ho:YAG Chirped Pulse Amplifier (2016)

110-fs, 5.3-µm parametric amplifier driven by a ps 2.1-µm Ho:YAG chirped-pulse amplifier is demonstrated. It offers an all-in-one solution for seeding, pumping, and CEP-stabilization of few-cycle pulses in ZnGeP2 and similar mid-IR crystals.
Picosecond ultrasonic microscopy of semiconductor nanostructures (2011)

We describe a new picosecond ultrasonics method for the study of nanostructures. A sound pulse is generated when an ultra-short laser pulse is absorbed in a transducer structure. The sound then propagates across a thin layer of water and is reflected from the surface of the sample being examined. A resonant optical cavity is used to improve the efficiency of optoacoustic detection and generation of the sound. We report on experiments in which sound is reflected from patterned nanostructures. In these experiments, we are able to study the propagation of sound down channels of width as small as 35 nm.
Distributed stochastic optimization with gradient tracking over strongly-connected networks (2019)

In this paper, we study distributed stochastic optimization to minimize a sum of smooth and strongly-convex local cost functions over a network of agents, communicating over a strongly-connected graph. Assuming that each agent has access to a stochastic first-order oracle (SFO), we propose a novel distributed method, called S-AB, where each agent uses an auxiliary variable to asymptotically track the gradient of the global cost in expectation. The S-AB algorithm employs row- and column-stochastic weights simultaneously to ensure both consensus and optimality. Since doubly-stochastic weights are not used, S-AB is applicable to arbitrary strongly-connected graphs. We show that under a sufficiently small constant step-size, S-AB converges linearly (in expected mean-square sense) to a neighborhood of the global minimizer. We present numerical simulations based on real-world data sets to illustrate the theoretical results.