gebhart/patrepeval huggingface dataset:
1,4-Dioxane ring as a promising template of novel 5-HT1A full agonists (2008)

Among the large number of serotoninergic receptors the 5-HT1A subtype has grown into a considerable research due to its involvement in psychiatric disorders. 5-HT1A Agonists may be useful antidepressant [1] and neuroprotective agents [2]. Since the limited clinical efficacy of partial agonists, such as buspirone, the first 5-HT1A agent launched in the market, seems to be related to their low level of intrinsic activity [3], the discovery of 5-HT1A full agonists proves to be determinant.\nIn the present study the α1-adrenoreceptor (α1-AR) antagonist WB 4101 was chosen as lead molecule because it is well known that this and related compounds are effective ligands also for 5-HT1A serotoninergic receptor and a high degree of homology exists between these two receptor \nfamilies [4]. The quite planar 1,4-benzodioxane template of WB 4101 was replaced by the less conformationally constrained 1,4-dioxane ring substituted in its positions 5 or 6 with one or two pendant phenyl rings (compounds 1-12). The use of 1,4-dioxane was encouraged by a recent study of ours in which this nucleus demonstrated its bioversatility proving to be a suitable scaffold for efficacious and selective muscarinic agonists [5]. All compounds were tested at 5-HT1A receptors expressed in HeLa cells, and human cloned α1-AR subtypes, expressed in Chinese Hamster Ovary (CHO) cells. Compounds 2b, 5b, and 10-12 selected on the basis of their highest 5-HT1A affinity values (8.4-9.2), were examined in the [35S]GTPγS at the human cloned 5-HT1A receptors. The most \ninteresting compound was 12 behaving as a potent full agonist with pD2 value (8.28; % max 106.3) significantly higher than that of 5-hydroxytryptamine. It also showed a good selectivity for 5-HT1A towards the α1A-, α1B- and α1D-AR subtypes (binding assays: 251.2, 251.2 and 50.1; functional assays: 37.2, 109.6, and 11.5, respectively). Therefore, it represents a new lead for developing potent full 5-HT1A agonists significantly selective over α1-ARs. \n[1] Blier, P.; Bergeron, R.; de Montigny, C. Neuropsychopharmacology 1997, 16, 333-338.\n[2] Torup, L.; Møller, A.; Sager, T. N.; Diemer, N. H. Eur. J. Pharmacol. 2000, 395, 137-141.\n[3] Glennon, R. A.; Malgorzata, D. Serotonin 1997, 2, 351-372.\n[4] Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M. J. Med. Chem. 1992, 35, 3448-3462.\n[5] Piergentili, A.; Quaglia, W.; Giannella, M.; Del Bello, F.; Bruni, B.; Buccioni, M.; Carrieri, A.; Ciattini, S. Bioorg Med Chem. 2007, 15, 886-896.
Interaction of LRRK2 with kinase and GTPase signaling cascades (2014)

LRRK2 is a protein that interacts with a plethora of signaling molecules, but the complexity of LRRK2 function presents a challenge for understanding the role of LRRK2 in the pathophysiology of Parkinson's disease (PD). Studies of LRRK2 using over-expression in transgenic mice have been disappointing, however, studies using invertebrate systems have yielded a much clearer picture, with clear effects of LRRK2 expression, knockdown or deletion in Caenorhabditis elegans and Drosophila on modulation of survival of dopaminergic neurons. Recent studies have begun to focus attention on particular signaling cascades that are a target of LRRK2 function. LRRK2 interacts with members of the mitogen activated protein kinase (MAPK) pathway and might regulate the pathway action by acting as a scaffold that directs the location of MAPK pathway activity, without strongly affecting the amount of MAPK pathway activity. Binding to GTPases, GTPase-activating proteins and GTPase exchange factors are another strong theme in LRRK2 biology, with LRRK2 binding to rac1, cdc42, rab5, rab7L1, endoA, RGS2, ArfGAP1, and ArhGEF7. All of these molecules appear to feed into a function output for LRRK2 that modulates cytoskeletal outgrowth and vesicular dynamics, including autophagy. These functions likely impact modulation of α-synuclein aggregation and associated toxicity eliciting the disease processes that we term PD.
Mesenchymal stem cell-derived extracellular vesicles: a glimmer of hope in treating Alzheimer’s disease (2017)

One of the pathological hallmarks of Alzheimer's disease (AD) is the presence of extracellular plaques resulting from the accumulation of beta-amyloid peptide (Aβ). To date, a definitive cure for this disease is still lacking as the currently approved drugs used are mainly symptomatic treatments. The revolutionary discovery of extracellular vesicles (EVs) has shed new light on the development of disease-modifying treatments for AD, owing to their potential in delivering the therapeutic agents to the brain. The feasibility of harnessing EVs for clinical applications is highly dependent on the donor cell, which determines the intrinsic properties of EVs. The merit of mesenchymal stem cells (MSCs) as therapeutic delivery vehicles, and the proven therapeutic effects of the EVs derived from these cells, make researchers esteem MSCs as ideal producers of EVs. Therefore, MSC-derived EVs (MSC-EVs) emerge to be an appealing therapeutic delivery approach for the treatment of AD. Here, we discuss perspectives on the therapeutic strategies using MSC-EVs to treat AD and the associated challenges in clinical application.
Direct Hematological Toxicity and Illegitimate Chromosomal Recombination Caused by the Systemic Activation of CreERT2, (2009)

The CreER(T2) for conditional gene inactivation has become increasingly used in reverse mouse genetics, which enables temporal regulation of Cre activity using a mutant estrogen binding domain (ER(T2)) to keep Cre inactive until the administration of tamoxifen. In this study, we present the severe toxicity of ubiquitously expressed CreER(T2) in adult mice and embryos. The toxicity of Cre recombinase or CreER(T2) in vitro or in vivo organisms are still less sufficiently recognized considering the common use of Cre/loxP system, though the toxicity might compromise the phenotypic analysis of the gene of interest. We analyzed two independent lines in which CreER(T2) is knocked-in into the Rosa26 locus (R26CreER(T2) mice), and both lines showed thymus atrophy, severe anemia, and illegitimate chromosomal rearrangement in hematopoietic cells after the administration of tamoxifen, and demonstrated complete recovery of hematological toxicity in adult mice. In the hematopoietic tissues in R26CreER(T2) mice, reduced proliferation and increased apoptosis was observed after the administration of tamoxifen. Flow cytometric analysis revealed that CreER(T2) toxicity affected several hematopoietic lineages, and that immature cells in these lineages tend to be more sensitive to the toxicity. In vitro culturing of hematopoietic cells from these mice further demonstrated the direct toxicity of CreER(T2) on growth and differentiation of hematopoietic cells. We further demonstrated the cleavage of the putative cryptic/pseudo loxP site in the genome after the activation of CreER(T2) in vivo. We discussed how to avoid the misinterpretation of the experimental results from potential toxic effects due to the activated CreER(T2).
Probing extra-framework cations in alkali- and alkaline-earth-metal Linde type A zeolites by Fourier transform far-infrared spectroscopy (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProbing extra-framework cations in alkali- and alkaline-earth-metal Linde type A zeolites by Fourier transform far-infrared spectroscopyMark D. Baker, John Godber, Kate Helwig, and Geoffrey A. OzinCite this: J. Phys. Chem. 1988, 92, 21, 6017–6024Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/j100332a036https://doi.org/10.1021/j100332a036research-articleACS PublicationsRequest reuse permissionsArticle Views183Altmetric-Citations20LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Partial Retro−Inverso, Retro, and Inverso Modifications of Hydrazide Linked Bifunctional Peptides for Opioid and Cholecystokinin (CCK) Receptors (2006)

Partially modified retro-inverso, retro, and inverso isomers of hydrazide linked bifunctional peptides were designed, synthesized, and evaluated for bioactivities at delta/mu opioid receptors and CCK-1/CCK-2 receptors. All modifications of the CCK pharmacophore moiety affected bioactivities for the CCK-1 and CCK-2 receptors (up to 180-fold increase in the binding affinity with higher selectivity) and for the delta and mu opioid receptors. The results indicate that the opioid and CCK pharmacophores in one molecule interact with each other to induce topographical changes for both pharmacophores.
SUCCESSFUL LIVER TRANSPLANTATION AFTER INDUCTION CHEMOTHERAPY IN CHILDREN WITH INOPERABLE, MULTIFOCAL PRIMARY HEPATIC MALIGNANCY (1999)

In children with inoperable primary liver malignancy with no extrahepatic tumor growth, orthotopic liver transplantation has an excellent outcome.
Multi-Session Partitioning for Parallel Timing Optimization (2005)

In this paper a new partitioning algorithm for parallelization of post-placement VLSI procedures is presented. The partitioning technique divides problem tasks into multiple sessions of parallel processes, so that interprocessor communication is entirely removed during each session. Communication is performed only in the end of each session. The algorithm is especially useful for parallelizing processes whose tasks are heavily connected to each other and may result in high communication overhead in parallel processing. Post-placement optimization of electrical violations represents such a task and was implemented in our experiments to validate the partitioning and parallelization techniques. On industry ASIC designs ranging in size from 300K to 1M gates, our partitioning scheme speeds up the execution time of this optimization by up to 2.5x over serial processing by dynamically utilizing 1-6 processors.
Super-realistic environmental sound synthesizer for location-based sound search system (2011)

This paper presents a proposal of a super realistic environmental sound synthesizer for a location-based sound search system. The location-based sound search system enables a user to experience any environmental sound in any desired remote place. This synthesizer is achieved by spatial audio mixing considering real-world conditions such as geographical features and townscapes, as well as dynamic situations such as those of town events and weather. Furthermore, a new velocity vector-based clustering method is proposed to reduce the cost of audio processing on the server side, which achieves a lower number of composing and decomposing clusters that have a direct and strong impact on high-cost audio processing such as spatial audio mixing <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> .
A Coding Theory Perspective on Multiplexed Molecular Profiling of\n Biological Tissues (2021)

High-throughput and quantitative experimental technologies are experiencing\nrapid advances in the biological sciences. One important recent technique is\nmultiplexed fluorescence in situ hybridization (mFISH), which enables the\nidentification and localization of large numbers of individual strands of RNA\nwithin single cells. Core to that technology is a coding problem: with each RNA\nsequence of interest being a codeword, how to design a codebook of probes, and\nhow to decode the resulting noisy measurements? Published work has relied on\nassumptions of uniformly distributed codewords and binary symmetric channels\nfor decoding and to a lesser degree for code construction. Here we establish\nthat both of these assumptions are inappropriate in the context of mFISH\nexperiments and substantial decoding performance gains can be obtained by using\nmore appropriate, less classical, assumptions. We propose a more appropriate\nasymmetric channel model that can be readily parameterized from data and use it\nto develop a maximum a posteriori (MAP) decoders. We show that false discovery\nrate for rare RNAs, which is the key experimental metric, is vastly improved\nwith MAP decoders even when employed with the existing sub-optimal codebook.\nUsing an evolutionary optimization methodology, we further show that by\npermuting the codebook to better align with the prior, which is an\nexperimentally straightforward procedure, significant further improvements are\npossible.\n
Intraosseous Lipoma of the Calcaneus (1997)

We present two patients with pathologically proven intraosseous lipoma of the os calcis. A review of the literature, the radiologic criteria, and the differential diagnosis are provided.
Geothermite Reactions for In Situ Resource Utilization on the Moon and Beyond (2010)

Utilization of in-situ lunar resources will decrease launch mass and thus the expense of missions to the Moon, and will also give a lunar base a degree of self-sufficiency. Geothermite© reactions utilize an in-situ mixture of minerals and a reducing agent as reactants in a thermite-type chemical reaction. The geothermite© reaction investigated within this study used a mixture of JSC-1A series of lunar regolith simulant and aluminum powder as reactants. The JSC-1A series of simulant is an approximation of chemical and mineralogical characteristics of actual lunar regolith. Upon application of heat, an exothermic reaction initiated, and a coherent ceramic-composite material was produced. Experiments have shown that a geothermite© reaction occurred within the regolith-aluminum mixture over a range of reactant proportions. XRD analysis indicated that silicon, corundum (Al2O3), grossite (CaAl4O7), and spinel (MgAl2O4) were common species present in the reaction product. SEM/EDS analysis of samples reacted in a standard atmosphere showed formation of nanoscale whiskers containing aluminum, oxygen, and nitrogen. XRD results indicate that the whiskers are likely to be composed of aluminum oxides and aluminum nitrides. The compressive strength of products formed in a standard atmosphere was observed to vary depending on reactant proportions and particle size of the simulant. The largest mean compressive strength was found to be 18 ± 3.7 MPa. To better simulate conditions on the lunar surface, further experiments were conducted in a vacuum environment. No whisker formation was observed within samples reacted in a vacuum environment. It is hypothesized that the removal of gases by the vacuum environment decreased overall interparticle contact by preventing solid-gas chemical reactions. Neutron radiation transmission measurements were conducted on two samples to determine the preliminary radiation shielding capability of the reaction product.
Wallarray: a project to design glycan microarrays of cell wall polysaccharides for functional genomics (2012)

National audience
Three-dimensional Reconstruction of the Vascular Architecture of the Passive CLARITY-cleared Mouse Ovary (2017)

The ovary is the main organ of the female reproductive system and is essential for the production of female gametes and for controlling the endocrine system, but the complex structural relationships and three-dimensional (3D) vasculature architectures of the ovary are not well described. In order to visualize the 3D connections and architecture of blood vessels in the intact ovary, the first important step is to make the ovary optically clear. In order to avoid tissue shrinkage, we used the hydrogel fixation-based passive CLARITY (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/ Immunostaining/In situ-hybridization-compatible Tissue Hydrogel) protocol method to clear an intact ovary. Immunostaining, advanced multiphoton confocal microscopy, and 3D image-reconstructions were then used for the visualization of ovarian vessels and follicular capillaries. Using this approach, we showed a significant positive correlation (P <0.01) between the length of the follicular capillaries and volume of the follicular wall.
Biochemical and Molecular Regulation of Monoterpene Accumulation in Peppermint (Mentha × piperita) (2002)

SUMMARY Recent advances in the biochemistry and molecular biology of monoterpene metabolism in peppermint suggest that increased accumulation of the menthol-rich essential oil in this species might be achieved by a general enhancement of the rate of biosynthesis and, more specifically, by increasing the expression of the gene encoding (−)-limonene synthase, the first committed step in monoterpene biosynthesis.
The IEC Fusion-Plasma Torch - A Path for Closing the Materials Cycle (2009)

There are two interrelated requirements for achieving a sustainable modern world: 1) the availability of clean energy sources, and 2) the ability to close the materials cycle from use to reuse. Nature has always operated on a closed cycle process powered by solar energy. After the industrial revolution humans increasingly embarked upon an open cycle process extracting resources from the earth, dispersing them, and depositing the wastes into the earth’s life support systems of air, water, and soil. Fusion energy has unique capabilities for addressing the root cause of the resulting energy-environment-economy dilemma that our planet now faces. We propose an industrial evolutionary path for solving the dilemma based on the hydrogen-boron (p-11B) fusion fuel cycle and the application of ultra-high temperature plasmas (fusion plasmas) for materials recycling. This concept is known as the Fusion Torch and would return waste material back to its original 92 elemental states. An Inertial Electrostatic Confinement fusion device is proposed due to its characteristic non-Maxwellian plasma which enables burning p-B11.
Phase I clinical trial with fractionated radioimmunotherapy using 131I-labeled chimeric G250 in metastatic renal cancer. (2004)

Measurements of whole-body and serum clearance of cG250 antibody can be used to accurately predict the clearance of subsequent administrations, thus enabling rational treatment planning. An additional practical benefit of real-time pharmacokinetic monitoring is that therapy can be altered dynamically to reduce toxic side effects. However, there was no evidence for fractionation-induced sparing of the hematopoietic system in this study.
Efficacy of 5-Aminolevulinic Acid in Photodynamic Detection and Photodynamic Therapy in Veterinary Medicine (2019)

5-Aminolevulinic acid (5-ALA), a commonly used photosensitizer in photodynamic detection (PDD) and therapy (PDT), is converted in situ to the established photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. To extend 5-ALA-PDT application, we evaluated the PpIX fluorescence induced by exogenous 5-ALA in various veterinary tumors and treated canine and feline tumors. 5-ALA-PDD sensitivity and specificity in the whole sample group for dogs and cats combined were 89.5 and 50%, respectively. Notably, some small tumors disappeared upon 5-ALA-PDT. Although single PDT application was not curative, repeated PDT+/-chemotherapy achieved long-term tumor control. We analyzed the relationship between intracellular PpIX concentration and 5-ALA-PDT in vitro cytotoxicity using various primary tumor cells and determined the correlation between intracellular PpIX concentration and 5-ALA transporter and metabolic enzyme mRNA expression levels. 5-ALA-PDT cytotoxicity in vitro correlated with intracellular PpIX concentration in carcinomas. Ferrochelatase mRNA expression levels strongly negatively correlated with PpIX accumulation, representing the first report of a correlation between mRNA expression related to PpIX accumulation and PpIX concentration in canine tumor cells. Our findings suggested that the results of 5-ALA-PDD might be predictive for 5-ALA-PDT therapeutic effects for carcinomas, with 5-ALA-PDT plus chemotherapy potentially increasing the probability of tumor control in veterinary medicine.
It's a Non-Dialysis Day… Do You Know How Your Patient Is Doing? A Case for Research into Interdialytic Activity (2015)

Hemodialysis (HD) patients are less active than their healthy counterparts; this is associated with higher mortality. Healthcare workers observe their patients only during HD, which accounts for about 7% of the week. Knowing more about what occurs in between sessions, particularly with respect to physical activity, may improve patient care and prognosis. Yet without a standard method to measure interdialytic activity, it is difficult to compare the effect of interventions. However, it is unclear how interdialytic activity can be accurately measured. Since activity associated with quality of life is multi-dimensional, objective and subjective tools should be used in conjunction. While commercially available tracking devices can be seamlessly incorporated into everyday life and can increase awareness of user's activity, their validation is needed in the HD population. Fertile topics for research should include the relationship between objective and subjective measures in HD patients, and the investigation of physical activity in non-ambulatory HD patients.
Tunable Quantum Beat of Single Photons Enabled by Nonlinear Nanophotonics (2019)

We demonstrate the tunable quantum beat of single photons through the co-development of core nonlinear nanophotonic technologies for frequency-domain manipulation of quantum states in a common physical platform. Spontaneous four-wave mixing in a nonlinear resonator is used to produce non-degenerate, quantum-correlated photon pairs. One photon from each pair is then frequency shifted, without degradation of photon statistics, using four-wave mixing Bragg scattering in a second nonlinear resonator. Fine tuning of the applied frequency shift enables tunable quantum interference of the two photons as they are impinged on a beamsplitter, with an oscillating signature that depends on their frequency difference. Our work showcases the potential of nonlinear nanophotonic devices as a valuable resource for photonic quantum information science.