gebhart/patrepeval huggingface dataset:
M4 mAChR-Mediated Modulation of Glutamatergic Transmission at Corticostriatal Synapses (2014)

The striatum is the main input station of the basal ganglia and is extensively involved in the modulation of motivated behavior. The information conveyed to this subcortical structure through glutamatergic projections from the cerebral cortex and thalamus is processed by the activity of several striatal neuromodulatory systems including the cholinergic system. Acetylcholine potently modulates glutamate signaling in the striatum via activation of muscarinic receptors (mAChRs). It is, however, unclear which mAChR subtype is responsible for this modulatory effect. Here, by using electrophysiological, optogenetic, and immunoelectron microscopic approaches in conjunction with a novel, highly selective M4 positive allosteric modulator VU0152100 (ML108) and M4 knockout mice, we show that M4 is a major mAChR subtype mediating the cholinergic inhibition of corticostriatal glutamatergic input on both striatonigral and striatopallidal medium spiny neurons (MSNs). This effect is due to activation of presynaptic M4 receptors, which, in turn, leads to a decrease in glutamate release from corticostriatal terminals. The findings of the present study raise the interesting possibility that M4 mAChR could be a novel therapeutic target for the treatment of neurological and neuropsychiatric disorders involving hyper-glutamatergic transmission at corticostriatal synapses.
Ideas (2011)

Once we know the specifications for our target product, we need some ideas to meet these specifications. In fact, all we really need is one good one. Finding this idea is sometimes discussed by reference to the children's fairy tale, “The Frog Prince.” You will remember the story: a somewhat vain princess who is walking in the woods promises her hand in marriage to a frog in return for some simple service. The frog performs the service and then shows up to claim his bride. The distraught princess submits ungraciously and then is astonished to discover that, after she kisses him, the frog turns into the prince of her dreams. Freudian psychoanalysts have enjoyed interpreting this story.
VisReduce: Fast and responsive incremental information visualization of large datasets (2013)

Performance and responsiveness of visual analytics sytems for exploratory data analysis of large datasets has been a long standing problem. We propose a method for incrementally computing visualizations in a distributed fashion by combining a modified MapReduce-style algorithm with a compressed columnar data store, resulting in significant improvements in performance and responsiveness for constructing commonly encountered information visualizations, e.g. bar charts, scatterplots, heat maps, cartograms and parallel coordinate plots. We compare our method with one that queries three other readily available database and data warehouse systems — PostgreSQL, Cloudera Impala and the MapReduce-based Apache Hive — in order to build visualizations. We show that our end-to-end approach allows for greater speed and guaranteed end-user responsiveness, even in the face of large, long-running queries.
Activation of the Fatty Acid α-Dioxygenase Pathway during Bacterial Infection of Tobacco Leaves (2003)

A pathogen-induced oxygenase showing homology to prostaglandin endoperoxide synthases-1 and -2 was recently characterized by in vitro experiments as a fatty acid alpha-dioxygenase catalyzing formation of unstable 2(R)-hydroperoxy fatty acids. To study the activity of this enzyme under in vivo conditions and to elucidate the fate of enzymatically produced 2-hydroperoxides, leaves of tobacco were analyzed for the presence of alpha-dioxygenase-generated compounds as well as for lipoxygenase (LOX) products and free fatty acids. Low basal levels of 2-hydroxylinolenic acid (0.4 nmol/g leaves fresh weight) and 8,11,14-heptadecatrienoic acid (0.1 nmol/g) could be demonstrated. These levels increased strongly upon infection with the bacterium Pseudomonas syringae pv syringae (548 and 47 nmol/g, respectively). Transgenic tobacco plants overexpressing alpha-dioxygenase were developed, and incompatible infection of such plants led to a dramatic elevation of 2-hydroxylinolenic acid (1778 nmol/g) and 8,11,14-heptadecatrienoic acid (86 nmol/g), whereas the levels of LOX products were strongly decreased. Further analysis of oxylipins in infected leaves revealed the presence of a number of 2-hydroxy fatty acids differing with respect to chain length and degree of unsaturation as well as two new doubly oxygenated oxylipins identified as 2(R),9(S)-dihydroxy-10(E),12(Z),15(Z)-octadecatrienoic acid and 2(R),9(S)-dihydroxy-10(E),12(Z)-octadecadienoic acid. alpha-Dioxygenase-generated 2-hydroxylinolenic acid, and to a lesser extent lipoxygenase-generated 9-hydroxyoctadecatrienoic acid, exerted a tissue-protective effect in bacterially infected tobacco leaves.
Hardware-efficient PRBGs based on 1-D piecewise linear chaotic maps (2005)

In this paper, two families of digital maps derived from the sawtooth map and from the tent map are analyzed in terms of suitability for pseudo-random bit generation. In particular, several solutions are investigated taking into account the numerical errors due to the approximation strategy used (truncation/rounding off). To evaluate the performance of the obtained pseudo-random sources a number of statistical parameters and tests that properly measure the characteristics of output bit sequences are considered. Results show that, under specific design conditions, the discretized sawtooth and tent maps are suitable for generating long-period bit sequences with an adequate randomness quality.
ERNIE performance with TSA portals Initial Results (2018)

This project extends the “Enhanced Radiological Nuclear Inspection and Evaluation” (ERNIE) system developed with CBP and DNDO to improve performance of PVT-based Radiation Portal Monitors (RPMs). ERNIE was designed to be used with any RPM system. The first implementation was with the SAIC (Leidos) RPM-8 systems. In this project, we are demonstrating how effective the ERNIE approach can be when applied to the VM250 TSA portals used in NSDD programs. Part of the challenge in adapting ERNIE to handle VM250 portals is the lack of gamma spectral information. We report here on the first results showing how the ERNIE analysis can improve analysis of measurements with the VM250 RPMs.
Human .alpha.-fetoprotein primary structure: a mass spectrometric study (1991)

The amino acid sequence of human alpha-fetoprotein, a 67-kDa protein present in mammalian embryonic serum, was verified by fast atom bombardment mass spectrometric (FAB/MS) analyses of three different enzymatic digests of the protein. Human alpha-fetoprotein obtained from a large-scale cell culture was digested with trypsin and V-8 protease either separately on two different samples or combined on the same one. The V-8 protease digest of the protein was partially fractionated by HPLC; the other samples were directly analyzed by FAB/MS without previous purification steps. About 90% of the alpha-fetoprotein amino acid sequence was verified by mass spectrometric analysis; this also confirmed that the cell-derived protein is identical with the hepatoma-derived protein. FAB analysis revealed that the N terminus of the mature protein is arginine rather than threonine, with the threonine occupying the second position. Therefore, the processing site of the alpha-fetoprotein signal peptide during maturation of the protein occurs at the N-terminal side of the arginine residue formerly indicated as residue-1. Thus mature alpha-fetoprotein contains 591 amino acids rather than 590.
Nucleoproteins of Negative Strand RNA Viruses; RNA Binding, Oligomerisation and Binding to Polymerase Co-Factor (2010)

Commentary on Tawar, R.G.; Duquerroy, S.; Vonrhein, C.; Varela, P.F.; Damier-Piolle, L.; Castagné, N.; MacLellan, K.; Bedouelle, H.; Bricogne, G.; Bhella, D.; Eléouët, J.-F.; Rey, F.A. Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus. Science2009, 326, 1279-1283.
Learning from Multiple Datasets with Heterogeneous and Partial Labels for Universal Lesion Detection in CT (2020)

Large-scale datasets with high-quality labels are desired for training accurate deep learning models. However, due to the annotation cost, datasets in medical imaging are often either partially-labeled or small. For example, DeepLesion is such a large-scale CT image dataset with lesions of various types, but it also has many unlabeled lesions (missing annotations). When training a lesion detector on a partially-labeled dataset, the missing annotations will generate incorrect negative signals and degrade the performance. Besides DeepLesion, there are several small single-type datasets, such as LUNA for lung nodules and LiTS for liver tumors. These datasets have heterogeneous label scopes, i.e., different lesion types are labeled in different datasets with other types ignored. In this work, we aim to develop a universal lesion detection algorithm to detect a variety of lesions. The problem of heterogeneous and partial labels is tackled. First, we build a simple yet effective lesion detection framework named Lesion ENSemble (LENS). LENS can efficiently learn from multiple heterogeneous lesion datasets in a multi-task fashion and leverage their synergy by proposal fusion. Next, we propose strategies to mine missing annotations from partially-labeled datasets by exploiting clinical prior knowledge and cross-dataset knowledge transfer. Finally, we train our framework on four public lesion datasets and evaluate it on 800 manually-labeled sub-volumes in DeepLesion. Our method brings a relative improvement of 49% compared to the current state-of-the-art approach in the metric of average sensitivity. We have publicly released our manual 3D annotations of DeepLesion in https://github.com/viggin/DeepLesion_manual_test_set.
Characterization of an androgen-responsive, ornithine decarboxylase-related protein in mouse kidney (2017)

We have investigated and characterized a novel ornithine decarboxylase (ODC) related protein (ODCrp) also annotated as gm853. ODCrp shows 41% amino acid sequence identity with ODC and 38% with ODC antizyme inhibitor 1 (AZIN1). The <i>Odcrp</i> gene is selectively expressed in the epithelium of proximal tubuli of mouse kidney with higher expression in males than in females. Like <i>Odc</i> in mouse kidney, <i>Odcrp</i> is also androgen responsive with androgen receptor (AR)-binding loci within its regulatory region. ODCrp forms homodimers but does not heterodimerize with ODC. Although ODCrp contains 20 amino acid residues known to be necessary for the catalytic activity of ODC, no decarboxylase activity could be found with ornithine, lysine or arginine as substrates. ODCrp does not function as an AZIN, as it neither binds ODC antizyme 1 (OAZ1) nor prevents OAZ-mediated inactivation and degradation of ODC. ODCrp itself is degraded via ubiquination and mutation of Cys<sup>363</sup> (corresponding to Cys<sup>360</sup> of ODC) appears to destabilize the protein. Evidence for a function of ODCrp was found in ODC assays on lysates from transfected Cos-7 cells where ODCrp repressed the activity of endogenous ODC while Cys<sup>363</sup>Ala mutated ODCrp increased the enzymatic activity of endogenous ODC.
High-performance LDPC codes for CDMA applications (2003)

Recently, V. Sorokine et al. (see IEEE Trans. Commun., vol.48, no.10, p.1660-8, 2000; vol.48, no.11, p.1818-28, 2000) have introduced a class of low-density parity-check (LDPC) codes which, when applied on an IS-95 CDMA system, show, at BER=10/sup -3/, a five-fold and two-fold increase in capacity compared to the traditional uncoded scheme and to state-of-the-art low-rate orthogonal convolutional codes, respectively. However, these codes suffer from an error-floor at lower BERs which are needed for high-quality services, such as data. To enhance the capacity of CDMA systems, not only for moderate BER values but also for lower BER values, we modify the construction of these codes slightly, to improve their performance at lower BERs. We use a simple and fast iterative algorithm instead of an exhaustive search for this purpose. Our results show a three-fold increase in capacity at BER=10/sup -5/ compared to the low-rate orthogonal convolutional codes and 1.5 times increase compared to a typical code of the Sorokine et al. ensemble.
Compressible Fabry-Perot refractometer (1987)

The use of a long, thermally stable Fabry-Perot etalon as a refractometer is considered in detail in this study of the refractive index of air. The etalon consists of two flat plates of fused silica 60 mm in diameter, with a cylindrical spacer made of Zerodur (a polycrystalline glass ceramic of extremely low thermal expansion) 200 mm long. The interferogram of light from a frequency-stabilized He-Ne laser is imaged with large-diameter mirror optics. The principal result is a demonstration of the effects of changes in atmospheric pressure on the etalon. The measured refractive-index values deviate by 2 parts in 10(7) from calculated values. Possible causes of error are considered in detail.
Single Particle Characterization of Ultrafine and Accumulation Mode Particles from Heavy Duty Diesel Vehicles Using Aerosol Time-of-Flight Mass Spectrometry (2006)

The aerodynamic size and chemical composition of individual ultrafine and accumulation mode particle emissions (Da = 50-300 nm) were characterized to determine mass spectral signatures for heavy duty diesel vehicle (HDDV) emissions that can be used for atmospheric source apportionment. As part of this study, six in-use HDDVs were operated on a chassis dynamometer using the heavy heavy-duty diesel truck (HHDDT) five-cycle driving schedule under different simulated weight loads. The exhaust emissions were passed through a dilution/residence system to simulate atmospheric dilution conditions, after which an ultrafine aerosol time-of-flight mass spectrometer (UF-ATOFMS) was used to sample and characterize the HDDV exhaust particles in real-time. This represents the first study where refractory species including elemental carbon and metals are characterized directly in HDDV emissions using on-line mass spectrometry. The top three particle classes observed with the UF-ATOFMS comprise 91% of the total particles sampled and show signatures indicative of a combination of elemental carbon (EC) and engine lubricating oil. In addition to the vehicle make/year, the effects of driving cycle and simulated weight load on exhaust particle size and composition were investigated.
Long-Acting Parenteral Nanoformulated Antiretroviral Therapy: Interest and Attitudes of HIV-Infected Patients (2013)

The majority of respondents indicated that they definitely or probably would try parenteral nanoformulated antiretroviral therapy.
Intratumoral administration of endostatin plasmid inhibits vascular growth and perfusion in MCa-4 murine mammary carcinomas. (2001)

Endostatin, a fragment of the COOH-terminal domain of mouse collagen XVIII is a recently demonstrated endogenous inhibitor of tumor angiogenesis and endothelial cell growth. Antiangiogenic therapy with endostatin in animals requires multiple and prolonged administration of the protein. Gene therapy could provide an alternative approach to continuous local delivery of this antiangiogenic factor in vivo. Established MCa-4 murine mammary carcinomas, grown in immunodeficient mice, were treated with intratumoral injection of endostatin plasmid at 7-day intervals. At the time of sacrifice, 14 days after the first injection, endostatin-treated tumor weights were 51% of controls (P < 0.01). Tumor growth inhibition was accompanied by a marked reduction in total vascular density. Specifically, computerized image analysis showed a 18-21% increase in the median distances between tumor cells and both the nearest anatomical (CD31-stained) vessel [48.1 +/- 3.8 versus 38.3 +/- 1.6 microm (P < 0.05)] and the nearest tumor-specific (CD105-stained) vessel [48.5 +/- 1.5 versus 39.8 +/- 1.5 microm (P < 0.01)]. An increased apoptotic index of tumor cells in endostatin-treated tumors [3.2 +/- 0.5% versus 1.9 +/- 0.3% (P < 0.05)] was observed in conjunction with a significant decrease in tumor perfused vessels (DiOC7 staining), and an increase in tumor cell hypoxia (EF5 staining). Hypoxia resulting from endostatin therapy most likely caused a compensatory increase of in situ vascular endothelial growth factor (VEGF) and VEGF receptor mRNA expression. Increased immunoreactivity of endostatin staining in endostatin-treated tumors was also associated with an increased thrombospondin-1 staining [1.12 +/- 0.16 versus 2.44 +/- 0.35]. Our data suggest that intratumoral delivery of the endostatin gene efficiently suppresses murine mammary carcinoma growth and support the potential utility of the endostatin gene for cancer therapy.
Data from PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8<sup>+</sup> T-Cell–Driven Antitumor Immunity (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti–PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models. Global transcriptional profiling and flow cytometry analysis were used to delineate mechanisms underpinning the observed synergy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; PD-1/PD-L1 blockade and agonist anti-CD27 mAb synergize for increased CD8&lt;sup&gt;+&lt;/sup&gt; T-cell expansion and effector function, exemplified by enhanced IFNγ, TNFα, granzyme B, and T-bet. Transcriptome analysis of CD8&lt;sup&gt;+&lt;/sup&gt; T cells revealed that combination therapy triggered a convergent program largely driven by IL2 and Myc. However, division of labor was also apparent such that anti–PD-1/L1 activates a cytotoxicity–gene expression program whereas anti-CD27 preferentially augments proliferation. In tumor models, either dependent on endogenous CD8&lt;sup&gt;+&lt;/sup&gt; T cells or adoptive transfer of transgenic T cells, anti-CD27 mAb synergized with PD-1/L1 blockade for antitumor immunity. Finally, we show that a clinically relevant anti-human CD27 mAb, varlilumab, similarly synergizes with PD-L1 blockade for protection against lymphoma in human–CD27 transgenic mice.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our findings suggest that suboptimal T-cell invigoration in cancer patients undergoing treatment with PD-1 checkpoint blockers will be improved by dual PD-1 blockade and CD27 agonism and provide mechanistic insight into how these approaches cooperate for CD8&lt;sup&gt;+&lt;/sup&gt; T-cell activation. &lt;i&gt;Clin Cancer Res; 24(10); 2383–94. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Reasoning about Cases with Diagrams (1996)

This paper investigate how diagrams can be used as indices and queries in a case based functional design environment. Case bases for functional design need diagramming support for two reasons: First, most designers prefer to sketch early design ideas with a pen. They sketch diagrams to explore possible adaptations of old cases to current design tasks. Second, functional design tasks that deal with layout configuration such as arranging pipes and wires for building facilities often benefit from previous successful or failure cases. Therefore, we are developing an interactive tool called the Electronic Cocktail Napkin to enable designers to index, access, and adapt case knowledge for design using diagrams. The Napkin program has links to a case based design aid Archie to support reasoning with diagrams for case retrieval.
The most active Cu facet for low-temperature water gas shift reaction (2017)

Identification of the active site is important in developing rational design strategies for solid catalysts but is seriously blocked by their structural complexity. Here, we use uniform Cu nanocrystals synthesized by a morphology-preserved reduction of corresponding uniform Cu<sub>2</sub>O nanocrystals in order to identify the most active Cu facet for low-temperature water gas shift (WGS) reaction. Cu cubes enclosed with {100} facets are very active in catalyzing the WGS reaction up to 548 K while Cu octahedra enclosed with {111} facets are inactive. The Cu-Cu suboxide (Cu<sub>x</sub>O, x ≥ 10) interface of Cu(100) surface is the active site on which all elementary surface reactions within the catalytic cycle proceed smoothly. However, the formate intermediate was found stable at the Cu-Cu<sub>x</sub>O interface of Cu(111) surface with consequent accumulation and poisoning of the surface at low temperatures. Thereafter, Cu cubes-supported ZnO catalysts are successfully developed with extremely high activity in low-temperature WGS reaction.Nanocrystals display a variety of facets with different catalytic activity. Here the authors identify the most active facet of copper nanocrystals relevant to the low-temperature water gas shift reaction and further design zinc oxide-copper nanocubes with exceptionally high catalytic activity.
Earthworm Casting in Plant Propagation (1985)

Abstract Rooting experiments on layers of Ficus elastica Roxb. ex Hornem., Dieffenbachia amoena Bull., Cordyline terminalis (L.) Kunth, Dracaena deremensis Engl., and on shoots of Ficus elastica, Begonia masoniana Irmsch, Aglaonema costatum N.E. Br., Saintpaulia ionatha H. Wendl. were performed to ascertain the possibility of employing earthworm casting in plant propagation. Rooting of layers was favored when casting alone was supplied whereas, rooting of shoots generally was enhanced when casting mixtures were used.
Lack of ERK activation and cell migration in FGF‐2‐deficient endothelial cells (2002)

The formation of blood capillaries from preexisting vessels (angiogenesis) and vascular remodeling secondary to atherosclerosis or vessel injury are characterized by endothelial cell migration and proliferation. Numerous growth factors control these cell functions. Basic fibroblast growth factor (FGF-2), a potent angiogenesis inducer, stimulates endothelial cell proliferation, migration, and proteinase production in vitro and in vivo. However, mice genetically deficient in FGF-2 have no apparent vascular defects. We have observed that endothelial cell migration in response to mechanical damage in vitro is accompanied by activation of the extracellular signal-regulated kinase (ERK) pathway, which can be blocked by neutralizing anti-FGF-2 antibodies. Endothelial cells from mice that are genetically deficient in FGF-2 neither migrate nor activate ERK in response to mechanical wounding. Addition of exogenous FGF-2 restores a normal cell response, which shows that impaired migration results from the genetic deficiency of this growth factor. Injury-induced ERK activation in endothelial cells occurs only at the edge of the wound. In addition, FGF-2-induced ERK activation mediates endothelial cell migration in response to wounding without a significant effect on proliferation. These data show that FGF-2 is a key regulator of endothelial cell migration during wound repair.