gebhart/patrepeval huggingface dataset:
NFIA regulates granule recruitment and exocytosis in the adult pancreas (2019)

Summary After food ingestion, pancreatic cells secrete zymogen and hormone-containing granules to precisely control digestion and blood glucose levels. Identifying regulators of this process is paramount to combatting multiple pancreatic diseases. Here we show that pancreatic deletion of the transcription factor nuclear factor IA (NFIA) leads to hyperglycemia, hypoinsulinemia, and hypolipidemia. Surprisingly, insulin and digestive enzymes are produced in the absence of NFIA, however, they are not secreted properly and instead accumulate inside pancreatic cells. In NFIA-deficient mice we saw a reduction of insulin granules in the ready releasable pool and the first-phase insulin response was impaired. We found that NFIA binds to and activates Rab39b, a Rab GTPase critical for exocytosis. Re-expression of Rab39b in NFIA knockout islets restored glucose-stimulated insulin secretion. In sum, the NFIA-Rab39b axis regulates pancreatic physiology through granule recruitment and docking , linking NFIA to a new process with potential effects in diabetes, pancreatitis, and lipid disorders.
The origin of strain-specific differences in the specificity repertoires of murine cytolytic T lymphocytes. (1986)

Previous studies, in which fine specificity analysis of CTL clones specific for the H-2Kb alloantigen was used to identify and distinguish the receptor of each clone, demonstrated that the composition of the CTL repertoire is influenced by at least two polymorphic genetic regions, the MHC and the IgH. By using double parent radiation chimeras of the type A + B----(A X B)F1, in which A and B differ at the MHC, it was found that the specificity repertoires of A and B, which normally differ in conventional mice of these strains, were very similar when CTLp were obtained from double parent chimeras. Therefore, the influence of MHC on repertoire was attributable to the environment in which the T cell developed rather than to an intracellular event. In the current study, this same strategy was used to determine whether IgH exerts its influence on the CTL repertoire at the environmental level as well. Double parent chimeras where constructed by using stem cells of BALB/c and B10.BR origin. Not only do these cells differ at the MHC, they also differ polymorphically at a large number of genetic regions including IgH and possibly T alpha structural genes. The results indicated that despite these genetic differences, the specificity repertoires of CTLp representative of the two different genotypes in the chimeras were very similar. Therefore, T cell repertoire differences that arise due to IgH polymorphism are determined by the developing environment. Additionally, these results suggest further that any genetic polymorphism which may exist within the T alpha gene complexes of these strains does not result in differences that can be detected within the CTL response to the Kb alloantigen.
Hypomethylation of DNA in ethionine-fed rats (1984)

Ethionine, the hepatocarcinogenic antimetabolite of methionine, was fed to rats in carcinogenic doses for 1-10 weeks. Levels of 5-methyldeoxycytidine (5-MC) in nuclear DNA and total cellular levels of S-adenosylmethionine (AdoMet) and S-adenosylethionine (AdoEt) were determined at 1, 5 and 10 weeks in livers of control and ethionine-treated animals. The percentage of deoxycytidine residues modified to 5-MC in hepatic DNA of ethionine-fed animals was the same as that in the control animals at 1 week but was 3.6% and 7.6% lower than that observed in control animals at 5 and 10 weeks, respectively. Significant levels of AdoEt, a DNA methylase inhibitor, as well as decreases in the levels of AdoMet were also observed in the livers of ethionine-fed animals. In a second study, the levels of 5-MC, AdoMet and AdoEt were determined in the pancreas, kidneys, testes and thymus of control rats and rats fed ethionine for 10 weeks. Only the testes, an organ known to be susceptible to the toxic effects of ethionine, showed a significant (p less than 0.02) decrease in 5-MC in response to ethionine feeding. AdoEt was present in all tissues studied, except thymus, but at lower levels than those observed in the liver. These results demonstrate that ethionine administration alone under conditions which cause tumors is sufficient for the production of hypomethylated DNA in the target organ and one extrahepatic tissue studied. Hypomethylation of hepatic DNA would appear to result from the accumulation of AdoEt coupled with the decreased levels of AdoMet.
Somatic mutations and affinity maturation are impaired by excessive numbers of T follicular helper cells and restored by Treg cells or memory T cells (2015)

We previously reported that Cd3e-deficient mice adoptively transferred with CD4(+) T cells generate high numbers of T follicular helper (Tfh) cells, which go on to induce a strong B-cell and germinal center (GC) reaction. Here, we show that in this system, GC B cells display an altered distribution between the dark and light zones, and express low levels of activation-induced cytidine deaminase. Furthermore, GC B cells from Cd3e(-/-) mice accumulate fewer somatic mutations as compared with GC B cells from wild-type mice, and exhibit impaired affinity maturation and reduced differentiation into long-lived plasma cells. Reconstitution of Cd3e(-/-) mice with regulatory T (Treg) cells restored Tfh-cell numbers, GC B-cell numbers and B-cell distribution within dark and light zones, and the rate of antibody somatic mutations. Tfh-cell numbers and GC B-cell numbers and dynamics were also restored by pre-reconstitution of Cd3e(-/-) mice with Cxcr5(-/-) Treg cells or non-regulatory, memory CD4(+) T cells. Taken together, these findings underline the importance of a quantitatively regulated Tfh-cell response for an efficient and long-lasting serological response.
A large-stroke flexure fast tool servo with new displacement amplifier (2017)

As the rapid progress of science and technology, the free-form surface optical component has played an important role in spaceflight, aviation, national defense, and other areas of the technology. While the technology of fast tool servo (FTS) is the most promising method for the machining of free-form surface optical component. However, the shortcomings of short-stroke of fast tool servo device have constrained the development of free-form surface optical component. To address this problem, a new large-stroke flexible FTS device is proposed in this paper. A series of mechanism modeling and optimal designs are carried out via compliance matrix theory, pseudo-rigid body theory, and Particle Swarm Optimization (PSO) algorithm, respectively. The mechanism performance of the large-stroke FTS device is verified by the Finite Element Analysis (FEA) method. For this study, a piezoelectric (PZT) actuator P-840.60 that can travel to 90 µm under open-loop control is employed, the results of experiment indicate that the maximum of output displacement can achieve 258.3µm, and the bandwidth can achieve around 316.84 Hz. Both theoretical analysis and the test results of prototype uniformly verify that the presented FTS device can meet the demand of the actual microstructure processing.
A Practical Multichannel Dereverberation Algorithm using Multichannel Dypsa and Spatiotemporal Averaging (2007)

Speech signals for hands-free telecommunication applications are received by one or more microphones placed at some distance from the talker. In an office environment, for example, unwanted signals such as reverberation and background noise from computers and other talkers will degrade the quality of the received signal. These unwanted components have an adverse effect upon speech processing algorithms and impair intelligibility. This paper demonstrates the use of the Multichannel DYPSA algorithm to identify glottal closure instants (GCIs) from noisy, reverberant speech. Using the estimated GCIs, a spatiotemporal averaging technique is applied to attenuate the unwanted components. Experiments with a microphone array demonstrate the dereverberation and noise suppression of the spatiotemporal averaging method, showing up to a 5 dB improvement in segmental SNR and 0.33 in normalized Bark spectral distortion score.
Liquid crystal TV-based white light optical tracking novelty filter (1989)

A compact white light optical tracking novelty filter is demonstrated. Based on the use of two inexpensive liquid crystal televisions, a filtered and collimated white light source, digital delay, and video recorder, this portable white light device performs two major image comparison operations, a real time image subtraction and novelty tracking operations. Some preliminary experimental results are presented.
A Data-Based Nested LUT Model for RF Power Amplifiers Exhibiting Memory Effects (2007)

In this letter, a new model is proposed for radio frequency power amplifiers exhibiting memory effects. The model is based on nested look-up tables that compute the estimated amplifier output signal, based on the current input sample and the preceding ones. The model is validated experimentally, using input and output waveforms of a high-power LDMOS based amplifier driven by a multicarrier WCDMA signal. It is shown that the performance of the proposed model is comparable to that of the conventional memory polynomial model. However, the nested look-up table based model significantly reduces the complexity of the identification of the model's parameters, as well as the computational complexity in calculating the estimated output signal.
LLN Fragment Forwarding and Recovery (2018)

Considering that an LLN frame can have a MAC payload below 100 bytes,
an IPv6 packet might be fragmented into more than 10 fragments at the
6LoWPAN layer. In a 6LoWPAN mesh-under network, the fragments can be
forwarded individually across the mesh, whereas a route-over mesh
network, a fragmented 6LoWPAN packet must be reassembled at every hop,
which causes latency and congestion. This draft introduces a simple
protocol to forward individual fragments across a route-over mesh
network, and, regardless of the type of mesh, recover the loss of
individual fragments across the mesh and protect the network against
bloat with a minimal flow control.
Pyocycanin, a Contributory Factor in Haem Acquisition and Virulence Enhancement of Porphyromonas gingivalis in the Lung (2015)

Several recent studies show that the lungs infected with Pseudomonas aeruginosa are often co-colonised by oral bacteria including black-pigmenting anaerobic (BPA) Porphyromonas species. The BPAs have an absolute haem requirement and their presence in the infected lung indicates that sufficient haem, a virulence up-regulator in BPAs, must be present to support growth. Haemoglobin from micro-bleeds occurring during infection is the most likely source of haem in the lung. Porphyromonas gingivalis displays a novel haem acquisition paradigm whereby haemoglobin must be firstly oxidised to methaemoglobin, facilitating haem release, either by gingipain proteolysis or capture via the haem-binding haemophore HmuY. P. aeruginosa produces the blue phenazine redox compound, pyocyanin. Since phenazines can oxidise haemoglobin, it follows that pyocyanin may also facilitate haem acquisition by promoting methaemoglobin production. Here we show that pyocyanin at concentrations found in the CF lung during P. aeruginosa infections rapidly oxidises oxyhaemoglobin in a dose-dependent manner. We demonstrate that methaemoglobin formed by pyocyanin is also susceptible to proteolysis by P. gingivalis Kgp gingipain and neutrophil elastase, thus releasing haem. Importantly, co-incubation of oxyhaemoglobin with pyocyanin facilitates haem pickup from the resulting methemoglobin by the P. gingivalis HmuY haemophore. Mice intra-tracheally challenged with viable P. gingivalis cells plus pyocyanin displayed increased mortality compared to those administered P. gingivalis alone. Pyocyanin significantly elevated both methaemoglobin and total haem levels in homogenates of mouse lungs and increased the level of arginine-specific gingipain activity from mice inoculated with viable P. gingivalis cells plus pyocyanin compared with mice inoculated with P. gingivalis only. These findings indicate that pyocyanin, by promoting haem availability through methaemoglobin formation and stimulating of gingipain production, may contribute to virulence of P. gingivalis and disease severity when co-infecting with P. aeruginosa in the lung.
Optical diffusion imaging using nonlinear multigrid optimization (2002)

Summary form only given. The measurement situation we consider involves multiple source and detector locations around the perimeter of a highly scattering domain. A frequency domain measurement involves modulating each light source with a CW signal and performing a coherent detection at this modulation frequency. The multiple scatter and absorption within the domain results in a spatially-dependant magnitude and phase of the light intensity (the measurement data). In particular, we have proposed an iterative coordinate descent optimisation, an ICD/Born method which provides high quality reconstructions and is computationally efficient when compared to the conventional iterative Born approximation methods. However, the computational complexity of ICD/Born is still prohibitive for large three dimensional problems perhaps more importantly, local optimisation methods such as ICD/Born can become trapped in local minimum.
Evidence of universality in the dynamical response of micromechanical diamond resonators at millikelvin temperatures (2009)

We report kelvin- to millikelvin-temperature measurements of dissipation and frequency shift in megahertz-range resonators fabricated from ultrananocrystalline diamond. Frequency shift $\ensuremath{\delta}f/{f}_{0}$ and dissipation ${Q}^{\ensuremath{-}1}$ demonstrate temperature dependence in the millikelvin range similar to that predicted by the glass model of tunneling two-level systems. The logarithmic temperature dependence of $\ensuremath{\delta}f/{f}_{0}$ is in good agreement with such models, which include phonon relaxation and phonon resonant absorption. Dissipation shows a weak power law, ${Q}^{\ensuremath{-}1}\ensuremath{\propto}{T}^{1/3}$, followed by saturation at low temperature. A comparison of both the scaled frequency shift and dissipation in equivalent micromechanical structures made of single-crystal silicon and gallium arsenide indicates universality in the dynamical response.
ChemInform Abstract: Reversible Inhibitors of the Gastric (H+/K+)‐ATPase. Part 1. 1‐Aryl‐4‐methylpyrrolo(3,2‐c)quinolines as Conformationally Restrained Analogues of 4‐(Arylamino)quinolines. (1990)

Abstract The diaminoquinoline (IV), prepared from the chloronitroquinoline (I) and the aniline (II) and subsequent reduction, is cyclized by reaction with formic acid (V), NaNO 2 (VII), or CS 2 (IX) to give the five‐membered heterocycles (VI), (VIII), and (X).
A second-order semi-digital clock recovery circuit based on injection locking (2003)

A 3.125Gb/s clock recovery circuit in 0.18/spl mu/m CMOS comprises a multiplying delay-locked loop (MDLL), an injection-locked slave oscillator and a phase control unit. Injection locking reduces MDLL clock distortion and varies the delay of the recovered clock, while a frequency loop in the phase control unit ameliorates the trade off between phase wander and frequency tolerance. Experimental results show high frequency jitter tolerance is improved by 0.08UI.
Abstract B121: An oncogene-linked prodrug strategy in lung cancer (2019)

Abstract KEAP1-mutant non-small cell lung cancer is a high prevalence indication that responds poorly to conventional chemotherapy owing to constitutive activation of NRF2 and its associated drug metabolism target genes. Using an approach to identify compounds that selectively kill cancer cell lines in a biomarker-driven manner, we identify BRD-K19050021 (K1905), a compound displaying strong toxicity in cells expressing CYP4F11 - a cytochrome p450 family member and NRF2 transcriptional target. Using genome-wide pooled CRISPR screens, we show that CYP4F11 activity is necessary and sufficient for response to K1905, and in acquired resistance models developed from multiple cell lines, we show a minor subpopulation of cells mechanistically converge on suppressed CYP4F11 expression to bypass K1905 response. CYP4F11 converts K1905 from a prodrug into a covalent active metabolite that alkylates several cellular targets, triggering all three canonical arms of the unfolded protein response pathway and culminating in cell death. We propose that CYP4F11 and similar metabolic enzyme activities promoted by oncogenic drivers represent a unique opportunity to restrict prodrug activation within tumors, provided that normal tissue expression of such prodrug-converting enzymes do not diminish therapeutic index. Citation Format: Aaron Boudreau, Jennifer Roth, James Rong, Niclas Olsson, Chris Mader, Jordan Byran, Jordan Rossen, Li Wang, Kevin Larpenteur, Amy Goodale, Colin Trepicchio, Samantha Bender, Aviad Tsherniak, Aravind Subramanian, Mustafa Kocak, Federica Piccioni, Josh Bittker, Cong Zhu, Frank Li, Nick Eriksson, Daphne Koller, Fiona McAllister, Todd Golub, Jeff Settleman, Ari Firestone, David Stokoe. An oncogene-linked prodrug strategy in lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B121. doi:10.1158/1535-7163.TARG-19-B121
RSR: Reduced-State Routing in the Internet (2004)

November 2004. In today's Internet core, routers store forwarding state proportional to the number of edge networks. As the Internet grows and core line rates increase, routers require memories that are increasingly fast and large--and are correspondingly increasingly expensive and difficult to engineer. In this paper, we present Reduced-State Routing (RSR), in which core routers require state only concerning the network topology within a two-hop radius, and thus of a size independent of the total number of Internet edge networks. RSR achieves this feat by routing geographically using two sets of node addresses: virtual coordinates, that are assigned to reflect the link costs within an autonomous system; and geographic coordinates, that correspond to nodes' physical locations. RSR routes greedily on virtual coordinates, and falls back to face routing on geographic coordinates when greedy progress is impossible on virtual coordinates. Unlike previous geographic routing schemes, RSR works on Internet-like graphs (rather than only on wireless-like graphs), and supports policy routing. By simulating RSR on real tier-1 ISP topologies, we demonstrate that RSR achieves low path stretch, comparable to that caused by policy routing in today's Internet.
The Cell Tracking Challenge: 10 years of objective benchmarking (2023)

The Cell Tracking Challenge is an ongoing benchmarking initiative that has become a reference in cell segmentation and tracking algorithm development. Here, we present a significant number of improvements introduced in the challenge since our 2017 report. These include the creation of a new segmentation-only benchmark, the enrichment of the dataset repository with new datasets that increase its diversity and complexity, and the creation of a silver standard reference corpus based on the most competitive results, which will be of particular interest for data-hungry deep learning-based strategies. Furthermore, we present the up-to-date cell segmentation and tracking leaderboards, an in-depth analysis of the relationship between the performance of the state-of-the-art methods and the properties of the datasets and annotations, and two novel, insightful studies about the generalizability and the reusability of top-performing methods. These studies provide critical practical conclusions for both developers and users of traditional and machine learning-based cell segmentation and tracking algorithms.
Influence of substrate-lens design in terahertz time-domain spectroscopy (2002)

We describe measurements of the angular radiation patterns from lens-coupled terahertz antennas fabricated on photoconductive substrates. These measurements were performed with a novel terahertz (THz) time-domain spectrometer in which the femtosecond optical pulses used to gate the emitter and receiver antennas were delivered by optical fiber. We used this system to perform a comparison between the two substrate-lens designs commonly used in THz time-domain spectrometers. We measured both E-plane and H-plane emission patterns for a 90° bow-tie antenna. By comparing these experimental results with simulations based on Fresnel–Kirchoff diffraction, we find that the choice of substrate-lens design is important in determining not only the directivity of the emitted beam but also the spectral bandwidth. These results emphasize the significance of this crucial component in the design of broadband THz spectrometers.
MMF and Calcineurin Taper in Recurrent Hepatitis C After Liver Transplantation: Impact on Histological Course (2005)

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal. The optimal immunosuppression for these patients is still under discussion. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) treatment in patients with recurrent hepatitis C. Forty patients with histologically proven hepatitis C recurrence after OLT were treated with MMF and calcineurin inhibitor (CNI) taper for 24 months and matched with 40 non-MMF-treated positive liver transplant recipients. Liver biopsies were obtained prior to MMF treatment and after a mean follow-up of 24 months. Histological changes were evaluated utilizing the Metavir score. Comparison of fibrosis/inflammation showed no impairment of histological findings during MMF treatment. In contrast, histological findings of the 40 non-MMF patients showed a significant increase of severity for inflammation/fibrosis. Viral load was similar in both groups. The course of alanin amino transferase (ALT) levels measured during MMF treatment showed a significant decrease. MMF in combination with CNI taper showed a positive effect on fibrosis progression, graft inflammation and ALT levels and may improve the clinical course of HCV after OLT, however, the antiviral properties of MMF are still unconfirmed.
Viscosity Rise during Free Radical Crosslinking Polymerization with Inhibition (1985)

A study of the viscosity rise during free radical crosslinking polymerization is presented. Techniques were developed for monitoring isothermal viscosity rise during fast polymerization reactions. The chemical system used was composed of a dimethacrylate resin in styrene monomer, t-butyl perbenzoate initiator, and hydroquinone as the inhibitor. When reduced viscosity is plotted versus conversion, data at all temperatures collapsed into a single curve. A theoretical equation is suggested for the time required to reach the gel point in free radical crosslinking polymerization with inhibition. This equation showed good agreement with experimental observations.
A TECHNOLOGICAL INTERVENTION FOR PROMOTING EYE CONTACT AMONG BOYS WITH AUTISM SPECTRUM DISORDER: CAN METACOGNITIVE SKILLS MAKE A DIFFERENCE? (2022)

A TECHNOLOGICAL INTERVENTION FOR PROMOTING EYE CONTACT AMONG BOYS WITH AUTISM SPECTRUM DISORDER: CAN METACOGNITIVE SKILLS MAKE A DIFFERENCE?