gebhart/patrepeval huggingface dataset:
Metipranolol promotes structure and function of retinal photoreceptors in the rd10 mouse model of human retinitis pigmentosa (2018)

Metipranolol is a β-adrenergic receptor antagonist that is given orally for the treatment of hypertension and also applied topically to the cornea for treating glaucoma. It also inhibits nitrosative stress which has previously been shown to be the cause of cone photoreceptor death in retinitis pigmentosa. In this study, we tested the hypothesis that metipranolol protects photoreceptor structure and function in the mouse model rd10. At P35, compared with vehicle-treated rd10 mice in which rod degeneration was nearly complete, rd10 mice given daily subcutaneous injections of 40 mg/kg of metipranolol had reduction in markers of nitrosative stress, fewer TUNEL-positive cells, increased outer nuclear layer thickness, and substantially more staining for rhodopsin. This was accompanied by significantly higher mean scotopic and photopic electroretinogram b-wave amplitudes indicating improved photoreceptor function. At P50, metipranolol-treated rd10 mice had decreased 3-nitrotyrosine staining in the retina, increased immunostaining for cone arrestin, a marker for cone photoreceptors, and significantly higher scotopic and photopic b-wave amplitudes at the highest stimulus intensity compared with vehicle-treated mice. At P65, cone density was significantly higher in metipranolol-treated versus vehicle-injected rd10 mice. Metipranolol applied as eye drops promoted cone photoreceptor function in retinas of rd10 mice greater than subcutaneously injected metipranolol. The reduced nitrosative damage and rescue of functional loss of photoreceptors in rd10 mice suggests that metipranolol, a drug with established ocular safety and tolerability, may have potential for treating patients with retinitis pigmentosa.
Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs (2016)

Both historical clinical and recent preclinical data suggest that the M<sub>1</sub> muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M<sub>1</sub> activation. Efforts then shifted to focus on selective activation of M<sub>1</sub> via either allosteric agonists or positive allosteric modulators (PAMs). While M<sub>1</sub> PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M<sub>1</sub> ago-PAMs. Our data demonstrate that closely related M<sub>1</sub> PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M<sub>1</sub> PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M<sub>1</sub> responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M<sub>1</sub> PAMs.
Microfabrication of PDMS structures based on wave optics using EUV radiations from laser-produced plasma (Conference Presentation) (2018)

Polydimethylsiloxane (PDMS) is a material used for bio-chips and micro total analysis systems / lab-on-chips. For further development, it is inevitable to develop a technique to fabricate precise structures on micrometer scale at high aspect ratio. In the previous works, we reported a technique for high-quality micromachining of PDMS sheets, by means of ablating the PDMS sheets using EUV radiations around 10 nm from laser-produced plasma. In the present work, we have investigated fabricated structures based on wave optics, for fabricating designed strutures at submicrometer precision at high aspect ratio up to 10. We experimentally found that a deep hole with a diamter of 100 nm is formed at the center of flat ablated region after EUV irradiation of a PDMS sheet through a circular aperture with a diamter of two micrometers in a contact mask. In the case of EUV irradiation through square apertures, the deep hole was not found on a PDMS sheet, while narrow dip is formed at the edge of the ablated region. We numerically calculated propagations of EUV plane wave light in PDMS sheets. After traveling one micrometer from a circular aperture, an intense peak appears at the center of the beam, which is caused by diffraction. For the square apertures, the enhancement does not occur, while intense profile near the edge is formed due to the Fresnel diffraction. Interestingly, at 100 micormeters from the aperture, the Frenel peaks are superposed at the center, resulting in a narrow and intense beam.
An interface stabilized perovskite solar cell with high stabilized efficiency and low voltage loss (2019)

Newly developed passivation strategy results in unprecedented perovskite optoelectronic device performances.
A novel S,N-double rearrangement; X-ray crystal structure of 5-carbamoyl-4-methylthio-2-phenyl-1,3-thiazin-6-one and its 2,3-dihydro-derivative (1981)

Condensation of 2-cyano-3-mercapto-3-(methyl-thio)acrylamide (1) with benzoic acid in the presence of polyphosphate ester gave 5-carbomoyl-4-methylthio-2-phenyl-1,3-thiazin-6-one (5); the structures of (5) and its 2,3-dihydro-derivative (6) were determined by single-crystal X-ray diffraction.
Cervical cancer in Croatia: state of the art and possibilities for prevention. (2007)

In Croatia, there are about 355 incident cases and about 100 deaths from cervical cancer every year. The aim of this study is to present the trends of cervical cancer incidence and mortality and to propose preventive strategies for cervical cancer in Croatia. Age-standardised and age-specific cervical cancer incidence rates were calculated for the period 1985-2004. For cervical cancer mortality data, the WHO Mortality Database was used. After an early decrease of cervical cancer incidence and mortality following the introduction of opportunistic screening in Croatia, no further decrease has been observed since the 1990s. An increase in incidence over the last 20 years was observed in the age-groups 40-44 and 45-49 years. To reduce cervical cancer rates, an organised cervical cancer screening programme is essential. In addition, HPV vaccination should be introduced in the school vaccination programme to achieve further reductions in cervical cancer incidence in the future.
Therapeutic suppression of proteolipid protein rescues Pelizaeus-Merzbacher Disease in mice (2018)

Mutations in proteolipid protein 1 ( PLP1 ) result in failure of myelination and severe neurological dysfunction in the X-linked pediatric leukodystrophy Pelizaeus-Merzbacher disease (PMD). The majority of PLP1 variants, including supernumerary copies and various point mutations, lead to early mortality. However, PLP1 -null patients and mice display comparatively mild phenotypes, suggesting that reduction of aberrant PLP1 expression might provide a therapeutic strategy across PMD genotypes. Here we show, CRISPR-Cas9 mediated germline knockdown of Plp1 in the severe jimpy ( Plp1 jp ) point mutation mouse model of PMD rescued myelinating oligodendrocytes, nerve conduction velocity, motor function, and lifespan to wild-type levels, thereby validating PLP1 suppression as a therapeutic approach. To evaluate the therapeutic potential of Plp1 suppression in postnatal PMD mice, we tested antisense oligonucleotides (ASOs) that stably decrease mouse Plp1 mRNA and protein in vivo . Administration of a single intraventricular dose of Plp1 -targeted ASOs to postnatal jimpy mice increased myelination, improved motor behavior, and extended lifespan through an 8-month endpoint. Collectively, these results support the development of PLP1 suppression as a disease-modifying therapy for most PMD patients. More broadly, we demonstrate that RNA therapeutics can be delivered to oligodendrocytes in vivo to modulate neurological function and lifespan, opening a new treatment modality for myelin disorders.
无线电传播简介:专用术语,室内传播和路径损耗计算及实例 (2002)

通过对传播路径损耗的估算来预测无线通信系统在其工作环境下的性能;解释了自由空间传播损耗的计算;电磁波在介质中的发射和反射系数的理论计算是预测反射和发射系数的工具.下面的一些实例和模型是在2.4GHz工作频率时给出的.
Cyclic Peptides as Non-carboxyl-terminal Ligands of Syntrophin PDZ Domains (2021)

Syntrophins, a family of intracellular peripheral membrane proteins of the dystrophin-associated protein complex (DAPC), each contain a single PDZ domain. Syntrophin PDZ domains bind C-terminal peptide sequences with the consensus R/K-E-S/T-X-V-COOH, an interaction that mediates association of skeletal muscle sodium channels with the DAPC. Here, we have isolated cyclic peptide ligands for syntrophin PDZ domains from a library of combinatorial peptides displayed at the N terminus of protein III of bacteriophage M13. Affinity selection from a library of X10C peptides yielded ligands with the consensus X-(R/K)-E-T-C-L/M-A-G-X-Psi-C, where Psi represents any hydrophobic amino acid. These peptides contain residues (underlined) similar to the C-terminal consensus sequence for binding to syntrophin PDZ domains and bind to the same site on syntrophin PDZ domains as C-terminal peptides, but do not bind to other closely related PDZ domains. PDZ binding is dependent on the formation of an intramolecular disulfide bond in the peptides, since treatment with dithiothreitol, or substitution of either of the two cysteines with alanines, eliminated this activity. Furthermore, amino acid replacements revealed that most residues in the phage-selected peptides are required for binding. Our results define a new mode of binding to PDZ domains and suggest that proteins containing similar conformationally constrained sequences may be ligands for PDZ domains.
Natural Isotopic Abundance (2016)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.
Axisymmetric and Asymmetric Naphthalene-Bisthienothiophene Based Nonfullerene Acceptors: On Constitutional Isomerization and Photovoltaic Performance (2020)

Two pairs of constitutional isomers of fused-octacyclic nonfullerene acceptors (NFAs) based on a naphthalene-bisthienothiophene core with or without fluorination at the ending groups have been developed. Compared with the axisymmetric NFAs N66-IC and N66-2FIC with two six-member-ring bridges, their asymmetric constitutional isomers N65-IC and N65-2FIC both with one six-member-ring bridge and one five-member-ring bridge exhibit remarkable red-shifted absorption, higher crystallinity, and slightly down-shifted LUMO energy levels. Organic solar cells based on PBDB-T-2F:N65-2FIC achieved a promising power conversion efficiency of 10.19%, which is three times higher than that of its counterpart PBDB-T-2F:N66-2FIC cell (3.46%). While being blended with PBDB-T as the donor material, the asymmetric acceptor analogue N65-IC based solar cell pronounces a PCE of 9.03%, being significantly improved from that of 5.45% for the PBDB-T:N66-IC based cell, which is in consistency with the results from those cells from their both fluorinated donor and acceptor counterparts. Design rules on either both fluorinated, both nonfluorinated, or cross-combined donor/acceptors for device fabrication has been explored. In addition, PBDB-T-2F:N65-2FIC possesses very promising device stability with 85% of its initial PCE after an exposure time of 1500 h under one sun illumination, which is meaningful for their future commercial devices.
Abstract 1622: High salt Intake Superimposed On Left Ventricular Hypertrophy Activates Brain Enac And Leads To Sympathetic Hyperactivation And Ventricular Dysfunction (2008)

Background: High-salt intake often predisposes patients with left ventricular hypertrophy (LVH) to congestive heart failure. We hypothesized that high-salt intake superimposed on LVH activates brain epithelial Na channels (ENaC) and leads to sympathetic hyperactivation and LV dysfunction. Methods and Results: We used ICR mice and applied aortic banding (AB) to create LVH. Sham-operated mice served as control. Four weeks after AB, 24-h urinary norepinephrine excretion (U-NE) tended to increase rather than that in control (481±46 vs 354±42, n=10, p=0.09). AB hypertrophied LV wall thickness (WT) (2.2±0.6 vs 1.8±0.6 mm, n=8, p&lt;0.05) without changing fractional shortening (%FS). We then fed the AB mice a high salt (8%) (AB-H) or regular salt (AB-R) diet for additional 4 weeks. AB-H depressed LV function (%FS: 27±2 vs 37±1%, n=8, p&lt;0.05) and hypertrophied LVWT more than those in AB-R (WT: 2.8±0.5 vs 2.5±0.3 mm, n=8, p&lt;0.05). U-NE was higher in AB-H than in AB-R (758±86 vs 459±35 ng/day, n=10, p&lt;0.05). To examine the role of brain ENaC, we intracerebroventriculary (ICV) infused ENaC blocker (benzamil, 0.11μg/hr by osmotic pump) in AB-H for 4weeks. ENaC blocker decreased U-NE (567±35 vs 758±86 ng/day, n=10, p&lt;0.05) and improved depressed LV function (%FS: 39±1 vs 28±3 %, n=10, p&lt;0.05). To confirm the role of central Na in sympathetic hyperactivation and LV dysfunction, we administered, in AB with regular salt diet, high-Na (0.2 M) cerebrospinal fluid ICV (Na-ICV) (0.25μl/hr) for 2 weeks. Na-ICV significantly increased U-NE and deteriorates LV function (U-NE:987±103 ng/day, %FS: 31±1 %n=6) Conclusions: These results suggested that high-salt intake in the presence of LVH activates brain ENaC and leads to sympathetic hyperactivation and LV dysfunction.
The effect of inorganic and organic nucleating agents on the electrical breakdown strength of polyethylene (2018)

ABSTRACT Altering the morphology of polyethylene affects physical and electrical properties with reduced spherulite size correlating with higher electrical breakdown strength. Nucleating agents in polyethylene influence the final crystal morphology by increasing the number of spherulites and reducing spherulite size. Few studies are available that relate the nucleating activity to improved electrical breakdown strength. Although nanosilica is known to improve electrical breakdown strength of polyethylene in addition to serving as a nucleating agent, previous studies have not fully addressed the relationship between the improved breakdown strength and nucleating activity. In this article, direct current electrical breakdown strength and nucleation effects on morphology are assessed on a single set of controlled polyethylene compositions containing two types of surface treated nanosilica particles. The results are compared to composites with two types of organic nucleating agents 1,3:2,4‐ bis (3,4‐dimethylbenzylidene) sorbitol or calcium 1,2‐cyclohexanedicarboxylate (CDA). CDA was the most effective organic nucleating agent and the hexamethyldisilizane treated nanosilica was the most effective inorganic nucleating agent in reducing spherulite sizes in low density polyethylene (LDPE). Reduced spherulite sizes in nucleated samples correlated with increased breakdown strength and lower conduction current compared to the neat LDPE. The LDPE sample with CDA also had the highest increase in crystallization temperature indicating stronger nucleating agent performance than the nanosilica and 1,3:2,4‐ bis (3,4‐dimethylbenzylidene) sorbitol composite samples. The addition of these inorganic and organic nucleating agents all resulted in improvements in electrical breakdown strength. The results show that nucleation deserves more attention as a potential cause for improved breakdown strength observed with silica and organic nucleating agents. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135 , 46325.
Production of C4 and C5 alcohols from biomass-derived materials (2016)

The present critical review focuses on the production of C4, C5 diols and monoalcohols from precursors derived from the biomass.
Clinical versus Subclinical Pituitary Apoplexy: Presentation, Surgical Management, and Outcome in 21 Patients (1990)

A retrospective review of 16 consecutive patients with pituitary apoplexy treated over a 10-year period is reported. Eight men and 8 women (mean age, 48 years) underwent transsphenoidal decompression after an average duration of symptoms of 19 days. The diagnosis of pituitary apoplexy was made by the sudden onset of headache (88%), nausea (56%), or meningismus (13%), with or without visual disturbances (75%), in the setting of a sellar tumor on computed tomographic or magnetic resonance imaging scans. Thirteen of 16 patients showed significant improvement of symptoms after surgery (average follow-up, 2.5 years). In addition, 5 patients with clinically silent yet extensive pituitary hemorrhage were treated. Although extensive pituitary hemorrhage often produced fulminant apoplexy, it also presented insidiously over many days with few, if any, clinical signs. Rapid diagnosis, endocrine replacement, and transsphenoidal decompression constituted effective therapy. Magnetic resonance imaging (after at least 12 hours of symptoms) was superior to computed tomography in detecting hemorrhage.
Metric-guided regularisation parameter selection for statistical iterative reconstruction in computed tomography (2019)

As iterative reconstruction in Computed Tomography (CT) is an ill-posed problem, additional prior information has to be used to get a physically meaningful result (close to ground truth if available). However, the amount of influence of the regularisation prior is crucial to the outcome of the reconstruction. Therefore, we propose a scheme for tuning the strength of the prior via a certain image metric. In this work, the parameter is tuned for minimal histogram entropy in selected regions of the reconstruction as histogram entropy is a very basic approach to characterise the information content of data. We performed a sweep over different regularisation parameters showing that the histogram entropy is a suitable metric as it is well behaved over a wide range of parameters. The parameter determination is a feedback loop approach we applied to numerically simulated FORBILD phantom data and verified with an experimental measurement of a micro-CT device. The outcome is evaluated visually and quantitatively by means of root mean squared error (RMSE) and structural similarity (SSIM) for the simulation and visually for the measured sample (no ground truth available). The final reconstructed images exhibit noise-suppressed iterative reconstruction. For both datasets, the optimisation is robust where its initial value is concerned. The parameter tuning approach shows that the proposed metric-driven feedback loop is a promising tool for finding a suitable regularisation parameter in statistical iterative reconstruction.
Respiratory motion correction in PET/MRI using a generalized reconstruction by inversion of coupled systems (GRICS) approach (2012)

International audience
Organocatalytic Synthesis of Quinine-Functionalized Poly(carbonate)s (2012)

The ring-opening polymerization of substituted cyclic carbonates with 1-(3,5-bis-trifluoromethyl-phenyl)-3-cyclohexyl-thiourea (TU)/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) organocatalysts afford highly functionalized oligocarbonates. The fluorescent alkaloid quinine can be readily incorporated into the oligocarbonates either by initiation from quinine or by ring-opening polymerization of a quinine-functionalized cyclic carbonate (MTC-Q). Copolymerization of MTC-Q with a boc-protected guanidinium cyclic carbonate affords, after deprotection, highly water-soluble cationic copolymers functionalized with both quinine and pendant guanidinium groups. When multiple quinine groups are attached to the oligomers, they exhibit minimal fluorescence due to self-quenching. Upon hydrolysis, the fluorescence intensity increases, providing a potential strategy for monitoring the hydrolysis rates in real time.
Robust Structured Light Pattern for Use with a Spatial Light Modulator in 3-D Endoscopy (2013)

This article introduces a novel structured light pattern designed to be compatible with the spatial light modulator (SLM) projection. The proposed pattern is a De Bruijn-based sequence applied to a combination of continuous and dashed lines for the pattern. The sequence is coded in the period and duty cycles of the dashed lines. It provides 16 different lines which limits to two the required number of dashed lines needed for identification. The segmentation has been made easier by alternating continuous and dashed lines. As required by the use of SLMs, the sequence has been adapted by making it symmetric. It has been improved by guaranteeing a hamming distance equal to two for two successive dashed lines. The implementation on a virtual model has shown that a subpixel accuracy has been achieved. This pattern has been developped for 3-D endoscopy.