gebhart/patrepeval huggingface dataset:
P2–410: Innate immunity stimulation via TLR9 in a non‐human primate model of sporadic cerebral amyloid angiopathy (2013)

Immunomodulation has shown great promise as an Alzheimer's disease (AD) therapy but major limitations must be overcome, such as the need for effectively reducing cerebral amyloid angiopathy (CAA), without associated hemorrhages. CAA is a common feature in AD and cognitively normal elderly individuals. Our initial findings indicate that stimulation of innate immunity with CpG ODN appears to be an effective means of reducing vascular amyloid without inducing toxicity in AD mouse models. We are currently testing our approach in a well characterized non-human primate model of sporadic CAA, squirrel monkey (Saimiri Boliviensis), which share numerous biological similarities with humans. Varying doses of the class B CpG ODN preparation containing the primate specific immunostimulatory sequence were administered in young monkeys by a subcutaneous route (s.c.). The most effective and non-toxic dosage described in young animals was selected for our long term studies in the older animals (with expected CAA deposits). During the treatment, primates were closely monitored for signs of toxicity. The peripheral cytokine responses were determined in PBMC supernatants and plasma from control and treated monkeys at selected time points. In addition, the performances on cognitive tests are being compared between our aged and young squirrel monkeys. We have shown that a TLR9 agonist prevented short-term memory deficits in Tg-SwDI mice, a model with extensive CAA. CpG ODN treatment led to a reduction of CAA in the absence of microhemorrhages and increased inflammation. Transgenic models are ideal for initial screening of a potential therapy but prior to clinical trials it is imperative to perform studies in non-human primates, which are a more biologically proximate model to humans. Short duration safety and efficacy assessment studies were first performed in young monkeys. Characterization of immune responses and evaluation of cognitive function and working memory in our monkeys is currently in progress. Assessment of the therapeutic potential of CpG ODN in aged squirrel monkeys, at a point where CAA is already present, is on-going. Overall, the studies described here provide a basis for potential future clinical trials of TLR9 stimulation with CpG ODNs to ameliorate AD related pathology in humans.
Search for Lepton-Universality Violation in B+→K+ℓ+ℓ− Decays (2019)

A measurement of the ratio of branching fractions of the decays B^{+}→K^{+}μ^{+}μ^{-} and B^{+}→K^{+}e^{+}e^{-} is presented. The proton-proton collision data used correspond to an integrated luminosity of 5.0 fb^{-1} recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range 1.1<q^{2}<6.0 GeV^{2}/c^{4} the ratio of branching fractions is measured to be R_{K}=0.846_{-0.054}^{+0.060}_{-0.014}^{+0.016}, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of R_{K} to date and is compatible with the standard model at the level of 2.5 standard deviations.
Photonic crystal microcavity engineering and high-density bio-patterning for chip-integrated microarray applications (2012)

While Q ~ 1million has been demonstrated in freely suspended photonic crystal (PC) membranes, the reduced refractive index contrast when PC microcavities are immersed in phosphate buffered saline (PBS), a typical ambient for biomolecules, reduces Q by more than 2 orders of magnitude. We experimentally demonstrate photonic crystal microcavity based resonant sensors coupled to photonic crystal waveguides in silicon on insulator for chemical and bio-sensing. Linear L-type microcavities are considered. In contrast to cavities with small modes volumes but low quality factors for bio-sensing, we show that increasing the length of the microcavity enhances the quality factor of the resonance by an order of magnitude and also increases the resonance wavelength shift while still retaining compact device characteristics. Q~26,760 and sensitivity down to 7.5ng/ml and ~9pg/mm<sup>2</sup> in bio-sensing was experimentally demonstrated in SOI devices for goat anti-rabbit IgG antibodies with K<sub>d</sub>~10<sup>-6</sup>M. The increase in cavity length follows from fundamental engineering limitations in ink-jet printing or microfluidic channels when unique receptor biomolecules are coated on separate adjacent sensors in a microarray.
Induction heating cells with cauls over mandrels methods of using thereof (2023)

Disclosed herein are induction heating cells and methods of using these cells for processing. An induction heating cell may be used for processing (e.g., consolidating and/or curing a composite layup having a non-planar portion. The induction heating cell comprises a caul, configured to position over and conform to this non-planar portion. Furthermore, the cell comprises a mandrel, configured to position over the caul and force the caul again the surface of the feature. The CTE of the caul may be closer to the CTE of the composite layup than to the CTE of the mandrel. As such, the caul isolates the composite layup from the dimensional changes of the mandrel, driven by temperature fluctuations. At the same time, the caul may conform to the surface of the mandrel, which can be used to define the shape and transfer pressure to the non-planar portion.
120-GHz long-wavelength low-capacitance photodetector with an air-bridged coplanar metal waveguide (1995)

We demonstrate a long-wavelength detector structure using an undercut mesa and an air-bridged coplanar metal waveguide to significantly reduce both the diode RC constant and the parasitic capacitance. Record electrical bandwidths of 120 GHz are demonstrated for long-wavelength photodetectors.
Germline DNA repair mutations in metastatic castration-resistant prostate cancer: Therapy response and applicability of circulating tumor DNA. (2017)

140 Background: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to Androgen Receptor (AR) targeted therapy. The aim of this study was to determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies, and secondly to establish whether biallelic DNA-repair gene loss is detectable in matched circulating tumor DNA (ctDNA). Methods: We recruited 319 mCRPC patients and performed targeted germline sequencing of 22 DNA repair genes. In affected patients, matched plasma ctDNA was also sequenced. Prostate-specific antigen response and progression were assessed in relation to initial androgen deprivation therapy (ADT) and subsequent therapy for mCRPC using Kaplan-Meier analysis. Results: 24/319 (7.5%) patients had deleterious germline mutations, with BRCA2 (n = 16), PALB2 (n = 2) and CDK12 (n = 2) being the most frequent. Patients (n = 22) with mutations in genes linked to homologous recombination were heterogeneous at initial presentation but after starting ADT progressed to mCRPC with a median time of 12.3 months (95% CI 5.1-18.4). The median time to progression on first and second line AR-targeted therapy in the mCRPC setting was 3.2 months (95% CI 1.9-4.4) and 1.0 month (95% CI 0.8-1.1), respectively. For patients receiving chemotherapy as their initial therapy for mCRPC (n = 8) the median PFS was 7.5 months (95% CI 6.5-8.2). 10/11 evaluable patients with germline BRCA2 mutations had somatic deletion of the intact allele in ctDNA. Conclusions: mCRPC patients with germline DNA repair defects exhibit transient responses to AR-targeted therapy. Biallelic gene loss was robustly detected in ctDNA suggesting that this patient subset could be prioritized for therapies exploiting defective DNA repair using a liquid biopsy.
Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart (2009)

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis.
<title>Comparison of optomechanical and focal plane array methods for enhanced temporal resolution</title> (1992)

Temporal aliasing is a problem common to all video imaging systems. Infrared video systems are particularly susceptible because of the relatively low (30 Hz) RS-170 frame rate. We have developed two systems which compensate for the effects of aliasing, and allow above-frame- rate events to be imaged. An optomechanically based system utilizes an unmodified commercial imager (Inframetrics IR 600) and allows images of repetitive thermal events at frequencies up to 4 kHz to be acquired. It acquires data selectively using a line-by-line scheme which compares the motion of the camera's horizontal scanning mirror to a reference signal correlated to the event of interest. The resulting images have an effective integration time of 125 microseconds. The focal plane array system is based on a 160 X 244 PtSi detector operating at the standard 30 Hz frame rate. Frame integration time is variable to a minimum of 100 microseconds. Data can be acquired synchronously with respect to an external reference signal derived from the target. The systems will be compared, and relative merits of each will be discussed.
Physics-Informed Transfer Learning for Voltage Stability Margin Prediction (2023)

Assessing set-membership and evaluating distances to the related set boundary are problems of widespread interest, and can often be computationally challenging. Seeking efficient learning models for such tasks, this paper deals with voltage stability margin prediction for power systems. Supervised training of such models is conventionally hard due to high-dimensional feature space, and a cumbersome label-generation process. Nevertheless, one may find related easy auxiliary tasks, such as voltage stability verification, that can aid in training for the hard task. This paper develops a novel approach for such settings by leveraging transfer learning. A Gaussian process-based learning model is efficiently trained using learning- and physics-based auxiliary tasks. Numerical tests demonstrate markedly improved performance that is harnessed alongside the benefit of uncertainty quantification to suit the needs of the considered application.
Abstract 637: Utilization of Retrograde Right Bundle Branch Block to Differentiate Atrio Ventricular Nodal from Accessory Pathway Conduction (2008)

Determining whether retrograde ventriculoatrial (VA) conduction is through the AV node (AVN) or an accessory pathway (AP) is critical for successful ablation of supraventricular tachycardia (SVT). With introduction of ventricular extrastimuli (VEST), retrograde right bundle branch block (retro RBBB) may occur and result in abrupt VH interval prolongation. We hypothesized when retrograde conduction is via an AP, VA interval change is less than VH interval change, whereas with retrograde AVN conduction, VA interval change is equal to or greater than VH interval change. We retrospectively reviewed the electrophysiology (EP) studies of patients undergoing ablation for AVNRT (n=55) or AVRT (n=50). The intracardiac electrograms were reviewed for induction of retro RBBB and change in VH and VA intervals during VEST. Parahisian pacing, decremental pacing, arrhythmia diagnosis and ablation outcomes were reviewed. All results were found to be reproducible between two independent observers with inter and intra observer reliability scores of 1.00 for identification of retro RBBB and greater than 0.85 for measurement of VH and VA intervals. Of 105 patients, 84 (80%) had evidence of induced retro RBBB during VEST. The average VH interval increase with induction of retro RBBB was 53.7 ms for patients with retrograde AP conduction and 54.4 ms for patients with AVN conduction (p=ns). The average VA interval increase with induction of retro RBBB was 13.6 ms with AP conduction and 70.1 ms with AVN conduction (P &lt; 0.001). All patients with a greater VH than VA interval change had a final diagnosis of AVRT and those with a VH change less than VA change had AVNRT, yielding sensitivity and specificity of 100%. Using a cutoff of 50 ms for change in VA interval with onset of retro RBBB to diagnose AVNRT accurately identified AVNRT in 100% and AVRT in 95%. Induction of retro RBBB during VEST is common during EP studies for SVT. The relative change in the VH and VA intervals during retro RBBB accurately differentiates retrograde AVN from retrograde AP conduction with strong predictive accuracy. The use of retro RBBB based intervals is a useful technique facilitating the diagnosis of SVT in the EP laboratory, even in the absence of inducible tachycardia.
Nano Additives and Plateau Burning Rates of Ammonium-Perchlorate-Based Composite Solid Propellants (2009)

Plateau propellants exhibit burning rate curves that do not follow the typical linear relationship between burning rate and pressure when plotted on a log-log scale, and because of this deviation, their burning behavior is classified as anomalous burning. This paper contains a literature review chronicling the last half-century of research to better understand the mechanisms that govern anomalous burning and to shed light on current research into plateau and related propellants. In addition to the review, a series of experiments investigating the use of nanoscale TiO2-based additives in ammonium-perchlorate hydroxyl-terminated polybutadiene composite propellants was performed. The baseline propellant consisted of either 70 or 80% monomodal ammonium Perchlorate (223 μm) and 30 or 20% binder composed of isophorone-diisocyanate-cured hydroxyl-terminated polybutadiene with Tepanol. Propellants were tested using a strand bomb between 3.45 and 17.24 MPa (34.0-170.1 atm). Analysis of the burning rate data shows that the crystal phase and synthesis method of the TiO2 additive are influential to plateau tailoring and to the apparent effectiveness of the additive in altering the burning rate of the composite propellant. Some of the discrepancy in the literature regarding the effectiveness of TiO2 as a tailoring additive may be due to differences in how the additive was produced. Doping the TiO2 with small amounts of metallic elements (Al, Fe, or Gd) showed additional effects on the burning rate that depend on the doping material and the amount of the dopant. This work provides the first published propellant mixtures and burning rate results for composite propellants employing metaldoped nanoparticle additives. Copyright © 2009 by the authors. Published by the American Institute of Aeronautics and Astronautics, Inc.,.
Structural analysis of the recombinant therapeutic product rFVIII and its PEGylated variants using 2‐D DIGE (2011)

This article was originally published in Electrophoresis 2011, 32 , 1292–1301, DOI 10.1002/elps.201000627
Expression, crystallization, and preliminary X-ray analysis of a sialic acid-binding fragment of sialoadhesin in the presence and absence of ligand (1997)

Sialoadhesin is a macrophage-restricted cell surface receptor, consisting of 17 immunoglobulin domains, which mediates cell adhesion via the recognition of specific sialylated glycoconjugates. A functional fragment of sialoadhesin, comprising the N-terminal immunoglobulin domain, has been expressed in Chinese hamster ovary cells as both native (SnD1) and selenomethionyl (Se-SnD1) stop protein. The successful production of 86% selenomethionine-incorporated protein represents a rare example of production of selenium-labeled protein in mammalian cells. SnD1 and Se-SnD1 have been crystallized in the absence of ligand, and SnD1 has also been crystallized in the presence of its ligand 2,3 sialyllactose. The ligand-free crystals of SnD1 and Se-SnD1 were isomorphous, of space group P3(1)21 or P3(2)21, with unit cell dimensions a = b 38.9 A,c = 152.6 A, alpha = beta = 90 degrees, gamma = 120 degrees, and diffracted to a maximum resolution of 2.6 A. Cocrystals containing 2,3 sialyllactose diffracted to 1.85 A at a synchrotron source and belong to space group P2(1)2(1)2(1), with unit cell dimensions a = 40.9 A, b = 97.6 A,c = 101.6 A, alpha = beta = gamma = 90 degrees.
Molecular and genetic regulation of pig pancreatic islet cell development (2019)

Abstract Reliance on rodents for understanding pancreatic genetics, development and islet function could limit progress in developing interventions for human diseases like diabetes mellitus. Similarities of pancreas morphology and function suggest that porcine and human pancreas developmental biology may have useful homologies. However, little is known about pig pancreas development. To fill this knowledge gap, we investigated fetal and neonatal pig pancreas at multiple, crucial developmental stages using modern experimental approaches. Purification of islet β-, α- and δ-cells followed by transcriptome analysis (RNA-Seq) and immunohistology identified cell- and stage-specific regulation, and revealed that pig and human islet cells share characteristic features not observed in mice. Morphometric analysis also revealed endocrine cell allocation and architectural similarities between pig and human islets. Our analysis unveiled scores of signaling pathways linked to native islet β-cell functional maturation, including evidence of fetal α-cell GLP-1 production and signaling to β-cells. Thus, the findings and resources detailed here show how pig pancreatic islet studies complement other systems for understanding the developmental programs that generate functional islet cells, and that are relevant to human pancreatic diseases. Summary Statement This study reveals transcriptional, signaling and cellular programs governing pig pancreatic islet development, including striking similarities to human islet ontogeny, providing a novel resource for advancing human islet replacement strategies.
Consolidating the Precision of Interferometric GNSS-R Ocean Altimetry Using Airborne Experimental Data (2014)

This paper revises the precision of altimetric measurements made with signals of the Global Navigation Satellite Systems (GNSS) reflected (GNSS-R) off the sea surface. In particular, we investigate the performance of two different GNSS-R techniques, referred to here as the clean-replica and interferometric approaches. The former has been used in GNSS-R campaigns since the late 1990s, while the latter has only been tested once, in 2010, from an 18-m-high bridge in static conditions and estuary waters. In 2011, we conducted an airborne experiment over the Baltic Sea at 3-km altitude to test the interferometric concept in dynamic and rougher conditions. The campaign also flew a clean-replica GNSS-R instrument with the purpose of comparing both approaches. We have analyzed with detail the data sets to extract and validate models of the noise present in both techniques. After predicting the noise models and verifying these with aircraft data, we used them to obtain the precision of altimetric measurements and to extrapolate the performance analysis to spaceborne scenarios. The main conclusions are that the suggested noise model agrees with measured data and that the GNSS-R interferometric technique is at least two times better in precision than a technique based on using a clean replica of the publicly available GPS code. This represents a factor of at least four times finer along-track resolution. A precision of 22 cm in 65-km along-track averaging should be achievable using near-nadir interferometric GNSS-R observations from a low earth orbiter.
An Improved Overlay and Mapping Algorithm Supporting Rapid Triggering for FPGA Debug (2017)

Embedded system designers can benefit from FPGA accelerators to achieve higher performance and efficiency. However, there are challenges that do not exist in software development; using software simulators to validate large and complex hardware designs can be extremely slow and impractical. Debugging designs implemented on an FPGA enables running the design at speed for long runs and more exhaustive test cases. However, limited observability is the primary challenge in hardware debug. To enhance hardware observability, trace-buffers and a trigger circuitry are inserted into the design. During the device operation, a history of signals of interest is recorded into the trace-buffers for off-line debug and validation. Recompiling the design every time the designer wishes to modify the trigger condition results in long debug turn-around times and reduced productivity. In this work, we present a pre-synthesized overlay fabric and algorithm to enable rapid triggering; during debug turn-around, TriggerPlus , a greedy algorithm, is used to implement a trigger circuit on the overlay. TriggerPlus is fast and simple, yet still capable of mapping the trigger circuit to the overlay fabric. We evaluate our techniques using VPR, showing that using our overlay and mapping algorithm together is at least an order of magnitude faster than the previous work resulting in a significant reduction in debug turn-around times.
A DTN routing scheme for quasi-deterministic networks with application to LEO satellites topology (2012)

International audience
Dynamics of active defects on the anisotropic surface of an ellipsoidal droplet (2023)

Cells are fundamental building blocks of living organisms displaying an array of shapes, morphologies, and textures that encode specific functions and physical behaviors. Elucidating the rules of this code remains a challenge. In this work, we create biomimetic structural building blocks by coating ellipsoidal droplets of a smectic liquid crystal with a protein-based active cytoskeletal gel, thus obtaining core-shell structures. By exploiting the patterned texture and anisotropic shape of the smectic core, we were able to mold the complex nematodynamics of the interfacial active material and identify new time-dependent states where topological defects periodically oscillate between rotational and translational regimes. Our nemato-hydrodynamic simulations of active nematics demonstrate that, beyond topology and activity, the dynamics of the active material are profoundly influenced by the local curvature and smectic texture of the droplet, as well as by external hydrodynamic forces. These results illustrate how the incorporation of these constraints into active nematic shells orchestrates remarkable spatio-temporal motifs, offering critical new insights into biological processes and providing compelling prospects for designing bio-inspired micro-machines.