gebhart/patrepeval huggingface dataset:
Synthesis of Amino[2.2]paracyclophanes—Beneficial Monomers for Bioactive Coating of Medical Implant Materials (2001)

The 13C NMR data given in the Communication by R. Langer et al. in Issue 4, 2001, pp. 726–728 for dinitro[2.2]paracyclophane 2 b were for a mixture of isomers. Data for the pseudo-para isomer as well as revised data for the nitro[2.2]paracyclophane 2 a and the amino[2.2]paracycophane 3 a are given here. 2 a: δ=34.36, 34.69, 34.91, 35.93, 129.45, 129.86, 132.31, 133.07, 133.12, 136.37, 137.27, 137.73, 139.26, 139.68, 142.02, 149.17. 2 b: δ=34.17, 34.60, 129.13, 133.87, 136.46, 137.36, 142.00, 149.71. 3 a: δ=32.23, 33.03, 34.95, 35.37, 122.36, 122.99, 124.60, 126.82, 131.48, 132.43, 133.23, 135.44, 138.91, 138.97, 141.06, 144.72.
Degraded GPS Signal Measurements With A Stand-Alone High Sensitivity Receiver (2002)

The use of GPS for personal location using cellular telephones or other devices requires signal measurements under both outdoor and indoor situations. The outdoor environment may range from clear to shaded/blocked signal measurements. The indoor environment may range for single floor wooden constructions to high-rise buildings and underground facilities.

In this paper, a high sensitivity receiver that operates in unaided stand-alone mode is tested under a range of shaded signal environments, ranging from residential outdoor areas to urban canyons to residential houses. The measurement analysis is performed in both the observation and position domains. The results show that the receiver tested can yield measurements with C/N0 degradations in excess of 20dB-Hz, as compared to lineof-sight measurements. Position results are a function of the geometry of the remaining satellites, which in turn is a
function of the environment.
Collaborative efforts to develop adverse outcome pathways: Oxidative DNA damage leading to chromosomal aberrations and mutations (2019)

International audience
Abstract 4970: TNG462 is a potential best-in-class MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted solid tumors (2023)

Abstract MTAP deletions occur in 10-15% of all human cancers, which provides one of the largest precision oncology patient populations. MTA-cooperative PRMT5 inhibitors leverage the well-characterized synthetic lethal relationship between PRMT5 inhibition and MTAP deletion. TNG908 is a clinical stage MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted solid tumors. TNG462 is an investigational stage MTA-cooperative PRMT5 inhibitor with significantly enhanced potency, selectivity, and extended target coverage designed to be a best-in-class treatment for patients with MTAP-deleted cancer. In vitro, TNG462 is 45X selective for MTAP-deleted cancer cell lines over isogenic MTAP WT cell lines and has marked selectivity for MTAP-deleted cancer cell lines independent of lineage in a large, diverse cell line panel. Oral administration of TNG462 drives dose-dependent antitumor activity including durable tumor regressions and complete responses in cell line- and patient-derived xenograft models representative of clinically relevant histologies. Preclinical data suggest a low risk for drug-drug interactions, supporting clinical combination strategies. With enhanced potency and selectivity for MTAP-deleted cancer cells and improved pharmacokinetic properties to extend target coverage, TNG462 has the potential for broader and deeper clinical activity in MTAP-deleted solid tumors than the MTA-cooperative PRMT5 currently being evaluated in clinical trials. Citation Format: Kimberly J. Briggs, Alice Tsai, Minjie Zhang, Matthew R. Tonini, Brian Haines, Alan Huang, Kevin M. Cottrell. TNG462 is a potential best-in-class MTA-cooperative PRMT5 inhibitor for the treatment of MTAP-deleted solid tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4970.
Chiral Separations by HPLC on Immobilized Polysaccharide Chiral Stationary Phases (2012)

Immobilized polysaccharide chiral stationary phases (CSPs) are a new development in chiral chromatography with increasing importance for the resolution of racemic compounds. These CSPs can be used with solvents traditionally applied for the classical coated polysaccharide CSPs as well as solvents that were "forbidden" for the coated phases such as tetrahydrofuran, chloroform, dichloromethane, acetone, 1,4-dioxane, ethylacetate, and certain ethers. However, these forbidden solvents may be required for the determination of the chiral recognition mechanism. Therefore, the immobilized CSPs are effective for the evaluation of chiral recognition mechanisms. Furthermore, immobilized chiral columns are also useful for monitoring the progress of stereospecific synthetic reactions which are normally performed in such solvents. The present chapter describes the detailed experimental protocol of a chiral resolution on immobilized polysaccharides CSPs by HPLC.
Implementation of Computer Aided System for Automated Bone Fracture Detection using Digital Geometry (2022)

A computer-aided detection and diagnosis (CADD) system must include automated fracture identification, which can lead to improve the treatment of orthopedics. This article provides a unified approach for detecting and evaluating orthopedic fractures in digital X-ray images of different types of long bones. Initially, the test images are applied to the gaussian filtering, which performs the image pre-processing, noise removal, artifact removal and also performs the image enhancements. Then, the preprocessed images are applied to the watershed segmentation approach. Then, the digital geometry-based line extraction operation is performed on the segmented images, which draws the lines on the fracture location. Finally, back propagated artificial neural network (BP-ANN) is applied on the fractured region, which identifies the test image status as fractured or not. The simulation results shows that the proposed method resulted in better performance as compared to the conventional approaches.
2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver (2019)

Alternative splicing is a co-transcriptional mechanism that generates protein diversity by including or excluding exons in different combinations, thereby expanding the diversity of protein isoforms of a single gene. Abnormalities in this process can result in deleterious effects to human health, and several xenobiotics are known to interfere with splicing regulation through multiple mechanisms. These changes could lead to human diseases such as cancer, neurological disorders, autoimmune diseases, and developmental disorders. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant generated as a byproduct of various industrial activities. Exposure to this dioxin has been linked to a wide range of pathologies through the alteration of multiple cellular processes. However, the effects of TCDD exposure on alternative splicing have not yet been studied. Here, we investigated whether a single po. dose of 5 μg/kg or 500 μg/kg TCDD influence hepatic alternative splicing in adult male C57BL/6Kou mouse. We identified several genes whose alternative splicing of precursor messenger RNAs was modified following TCDD exposure. In particular, we demonstrated that alternative splicing of Cyp1a1, Ahrr, and Actn1 was significantly altered after TCDD treatment. These findings show that the exposure to TCDD has an impact on alternative-splicing, and suggest a new avenue for understanding TCDD-mediated toxicity and pathogenesis.
Pulsed-field gel electrophoresis for sub-specific differentiation ofSerpulina pilosicoli(formerly âAnguillina coliâ) (1996)

Pulsed-field gel electrophoresis (PFGE) was developed for subspecific differentiation of Serpulina pilosicoli, and was applied to 52 isolates recovered from cases of intestinal spirochaetosis (IS) in pigs, dogs, human beings and various avian species. The technique was highly sensitive, differentiating the isolates into 40 groupings. Only six groups contained more than one isolate; in five of these groups isolates with the same banding pattern were either from pigs in the same herds (four groups), or from humans in the same community: the sixth group contained two identical Australian porcine isolates from unrelated herds in different states. Overall S. pilosicoli isolates were genetically diverse, but in some cases isolates cultured from the same or different animal species were closely related. This suggested the likelihood of cross-species transmission, including zoonotic spread. PFGE was a powerful tool for epidemiological studies of S. pilosicoli and also allowed examination of genetic relationships between isolates.
Palladium‐Catalyzed Fluorination of Cyclic Vinyl Triflates: Effect of TESCF3 as an Additive (2016)

A method for the palladium-catalyzed fluorination of cyclic vinyl triflates has been developed. As with several previous palladium-catalyzed fluorination reactions using fluoride salts, controlling the regioselectivity presented a challenge in developing a practical synthetic procedure. The addition of triethyl(trifluoromethyl)silane (TESCF<sub>3</sub> ) was found to effectively address this problem and resulted in drastically improved regioselectivities in this palladium-catalyzed fluorination reaction. This discovery, along with the use of a new biarylphosphine ligand, allowed for the development of an efficient and highly regioselective protocol for the fluorination of vinyl triflates. This method is compatible with a range of sensitive functional groups and provides access to five-, six-, and seven-membered cyclic vinyl fluorides.
Leveraging structural and 2D-QSAR to investigate the role of functional group substitutions, conserved surface residues and desolvation in triggering the small molecule-induced dimerization of hPD-L1 (2022)

Small molecules are rising as a new generation of immune checkpoints' inhibitors, with compounds targeting the human Programmed death-ligand 1 (hPD-L1) protein are pioneering this area of research. Promising examples include the recently disclosed compounds from Bristol-Myers-Squibb (BMS). These molecules bind specifically to hPD-L1 through a unique mode of action. They induce dimerization between two hPD-L1 monomers through the hPD-1 binding interface in each monomer, thereby inhibiting the PD-1/PD-L1 axis. While the recently reported crystal structures of such small molecules bound to hPD-L1 reveal valuable insights regarding their molecular interactions, there is still limited information about the dynamics driving this unusual complex formation. The current study provides an in-depth computational structural analysis to study the interactions of five small molecule compounds in complex with hPD-L1. By employing a combination of molecular dynamic simulations, binding energy calculations and computational solvent mapping techniques, our analyses quantified the dynamic roles of different hydrophilic and lipophilic residues at the surface of hPD-L1 in mediating these interactions. Furthermore, ligand-based analyses, including Free-Wilson 2D-QSAR was conducted to quantify the impact of R-group substitutions at different sites of the phenoxy-methyl biphenyl core. Our results emphasize the importance of a terminal phenyl ring that must be present in any hPD-L1 small molecule inhibitor. This phenyl moiety overlaps with a very unfavorable hydration site, which can explain the ability of such small molecules to trigger hPD-L1 dimerization.
Malfunction Issue of SiC-SIT Based DC Circuit Breaker in 400V DC Power Distribution Systems for Data Centers (2012)

400V DC power distribution systems for data centers require a fast response DC circuit breaker is required. The semiconductor DC circuit breaker is an important key technology in DC power distribution systems. This paper considers the malfunction of Silicon Carbide- Static Induction Transistor (SiC-SIT) based DC circuit breakers in 400V DC power distribution systems for data centers. The malfunction mechanism is explained, and a solution is proposed. Investigations are achieved by MATLAB/Simulink and experimental verification.
Abnormal Microglia and Enhanced Inflammation-Related Gene Transcription in Mice with Conditional Deletion ofCtcfinCamk2a-Cre-Expressing Neurons (2017)

CCCTC-binding factor (CTCF) is an 11 zinc finger DNA-binding domain protein that regulates gene expression by modifying 3D chromatin structure. Human mutations in <i>CTCF</i> cause intellectual disability and autistic features. Knocking out <i>Ctcf</i> in mouse embryonic neurons is lethal by neonatal age, but the effects of CTCF deficiency in postnatal neurons are less well studied. We knocked out <i>Ctcf</i> postnatally in glutamatergic forebrain neurons under the control of <i>Camk2a-Cre. Ctcf</i><sup>loxP/loxP</sup>;<i>Camk2a-Cre</i><sup>+</sup> (<i>Ctcf</i> CKO) mice of both sexes were viable and exhibited profound deficits in spatial learning/memory, impaired motor coordination, and decreased sociability by 4 months of age. <i>Ctcf</i> CKO mice also had reduced dendritic spine density in the hippocampus and cerebral cortex. Microarray analysis of mRNA from <i>Ctcf</i> CKO mouse hippocampus identified increased transcription of inflammation-related genes linked to microglia. Separate microarray analysis of mRNA isolated specifically from <i>Ctcf</i> CKO mouse hippocampal neurons by ribosomal affinity purification identified upregulation of chemokine signaling genes, suggesting crosstalk between neurons and microglia in <i>Ctcf</i> CKO hippocampus. Finally, we found that microglia in <i>Ctcf</i> CKO mouse hippocampus had abnormal morphology by Sholl analysis and increased immunostaining for CD68, a marker of microglial activation. Our findings confirm that <i>Ctcf</i> KO in postnatal neurons causes a neurobehavioral phenotype in mice and provide novel evidence that CTCF depletion leads to overexpression of inflammation-related genes and microglial dysfunction.<b>SIGNIFICANCE STATEMENT</b> CCCTC-binding factor (CTCF) is a DNA-binding protein that organizes nuclear chromatin topology. Mutations in <i>CTCF</i> cause intellectual disability and autistic features in humans. CTCF deficiency in embryonic neurons is lethal in mice, but mice with postnatal CTCF depletion are less well studied. We find that mice lacking <i>Ctcf</i> in <i>Camk2a</i>-expressing neurons (<i>Ctcf</i> CKO mice) have spatial learning/memory deficits, impaired fine motor skills, subtly altered social interactions, and decreased dendritic spine density. We demonstrate that <i>Ctcf</i> CKO mice overexpress inflammation-related genes in the brain and have microglia with abnormal morphology that label positive for CD68, a marker of microglial activation. Our findings suggest that inflammation and dysfunctional neuron-microglia interactions are factors in the pathology of CTCF deficiency.
Effect of Gastric Bypass and Gastric Banding on Proneurotensin Levels in Morbidly Obese Patients (2006)

Plasma pro-NT/NMN levels show a more pronounced increase after gastric bypass compared with gastric banding, suggesting that specific bariatric surgical procedures result in distinct alterations of gastrointestinal hormone metabolism. The more stable precursor pro-NT/NMN provides a new tool to quantify neurotensin levels in clinical practice.
Mechanistic/mammalian target of rapamycin: Recent pathological aspects and inhibitors (2018)

The mechanistic/mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin, regulates many normal cell processes such as transcription, cell growth, and autophagy. Overstimulation of mTOR by its ligands, amino acids, sugars, and/or growth factors leads to physiological disorders, including cancer and neurodegenerative diseases. In this study, we reviewed the recent advances regarding the mechanism that involves mTOR in cancer, aging, and neurodegenerative diseases. The chemical and biological properties of recently reported small molecules that function as mTOR kinase inhibitors, including adenosine triphosphate-competitive inhibitors and dual mTOR/PI3K inhibitors, have also been reviewed. We focused on the reports published in the literature from 2012 to 2017.
Structure of the p300 Histone Acetyltransferase Bound to Acetyl-Coenzyme A and Its Analogues (2014)

The p300 and CBP transcriptional coactivator paralogs (p300/CBP) regulate a variety of different cellular pathways, in part, by acetylating histones and more than 70 non-histone protein substrates. Mutation, chromosomal translocation, or other aberrant activities of p300/CBP are linked to many different diseases, including cancer. Because of its pleiotropic biological roles and connection to disease, it is important to understand the mechanism of acetyl transfer by p300/CBP, in part so that inhibitors can be more rationally developed. Toward this goal, a structure of p300 bound to a Lys-CoA bisubstrate HAT inhibitor has been previously elucidated, and the enzyme's catalytic mechanism has been investigated. Nonetheless, many questions underlying p300/CBP structure and mechanism remain. Here, we report a structural characterization of different reaction states in the p300 activity cycle. We present the structures of p300 in complex with an acetyl-CoA substrate, a CoA product, and an acetonyl-CoA inhibitor. A comparison of these structures with the previously reported p300/Lys-CoA complex demonstrates that the conformation of the enzyme active site depends on the interaction of the enzyme with the cofactor, and is not apparently influenced by protein substrate lysine binding. The p300/CoA crystals also contain two poly(ethylene glycol) moieties bound proximal to the cofactor binding site, implicating the path of protein substrate association. The structure of the p300/acetonyl-CoA complex explains the inhibitory and tight binding properties of the acetonyl-CoA toward p300. Together, these studies provide new insights into the molecular basis of acetylation by p300 and have implications for the rational development of new small molecule p300 inhibitors.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice (2012)

The acute phase response is an evolutionarily conserved reaction in which physiological stress triggers the liver to remodel the blood proteome. Although thought to be involved in immune defense, the net biological effect of the acute phase response remains unknown. As the acute phase response is stimulated by diverse cytokines that activate either NF-κB or STAT3, we hypothesized that it could be eliminated by hepatocyte-specific interruption of both transcription factors. Here, we report that the elimination in mice of both NF-κB p65 (RelA) and STAT3, but neither alone, abrogated all acute phase responses measured. The failure to respond was consistent across multiple different infectious, inflammatory, and noxious stimuli, including pneumococcal pneumonia. When the effects of infection were analyzed in detail, pneumococcal pneumonia was found to alter the expression of over a thousand transcripts in the liver. This outcome was inhibited by the combined loss of RelA and STAT3. Moreover, this interruption of the acute phase response increased mortality and exacerbated bacterial dissemination during pneumonia, possibly as a result of acute humoral enhancement of macrophage opsonophagocytosis, which was impaired in the mutant mice. Thus, we conclude that RelA and STAT3 are essential for stress-induced transcriptional remodeling in the liver and the subsequent activation of the acute phase response, whose functional role includes compartmentalization of local infection.
Chemical Imaging with Desorption Electrospray Ionization Mass Spectrometry (2010)

Desorption electrospray ionization mass spectrometry (DESI-MS) is a relatively new ambient surface analysis method. This technique requires little or no sample preparation prior to the actual analysis. Along with other application areas, DESI-MS is used to obtain chemical images of different biomolecules in biological tissue sections. In the case of biological tissue analysis, only preparation of the tissue slices is necessary. Furthermore, the method does not require the use of an ionization matrix preventing the redistribution of analytes prior to the analysis. Chemical images are obtained by monitoring the mass spectrometric signals of compounds while moving the sample relative to the DESI sprayer.
Rate of readmission and mortality risks of schizophrenia patients who were discharged against medical advice (2011)

Abstract Purpose To compare the readmission and the mortality rates of schizophrenia patients who were discharged against medical advice (AMA) and patients who were discharged by physician recommendation. Methods The records (1984–2005) of all consecutive admissions ( n = 12,937) of schizophrenia patients ( n = 8,052) were reviewed. Out of this group, 673 (8.3%) refused to remain in the hospital and signed a hospital form for discharge AMA. Their records were analyzed for rates of re-hospitalization and mortality at study closure. The records of AMA patients were compared to those of patients with regular discharge ( n = 1345). Results AMA patients were younger at admission ( P &lt;0.001), comprised more males ( P &lt;0.01), more were single ( P &lt;0.0001), and had a shorter duration of illness than the controls ( P &lt;0.05). A total of 49.9% of AMA events occurred within the first 2weeks of hospitalization. The readmission rate was significantly higher for AMA patients than for the controls ( P &lt;0.001). The mortality rate as a result of suicide ( P &lt;0.0001) and accidents ( P &lt;0.05) was higher for AMA patients compared to controls. Conclusion The schizophrenia patients discharged AMA have a higher readmission rate and a higher mortality rate due to suicide and accidents compared to non-AMA discharged patients. Patients with AMA discharge warrant special community surveillance to improve outcome.
Severe Acute Respiratory Syndrome : From Benchtop to Bedside (2004)

A Global Outbreak: Will the SARS Epidemic Recur? - J J Y Sung The Epidemiology of SARS - T W Wong & W Q Chen Virology of SARS - P K S Chan Clinical Diagnosis - D S C Hui Screening at the Primary Care Setting - T H Rainer Intensive Care - G Joynt SARS in the Elderly Patients - T Kwok SARS in Children - T F Fok Herbal Medicine in the Treatment of SARS - P C Leung Infection Control - P Tong Nosocomial Infections - L Chan Preparing for the Return - J J Y Sung and other articles.
TALE and TALEN genome editing technologies (2021)

TALEN were the first easy-to-use genome editing technology and sparked the genome editing revolution. Their application in multiple species brought targeted mutagenesis to the attention of scientists worldwide. Key breakthrough successes of genome editing have since been achieved using TALEN, among these, the first commercialization of an edited crop and the first human cured from cancer. TALEN have since been largely replaced by the CRISPR technologies which are somewhat easier to build, much easier to multiplex, and have spawned multiple derived techniques. Nevertheless, the flexible and precise positioning of TALEN is unmatched, and thus they have continued to evolve to new functionalities. Here, we assemble essential facts, design guidelines as well as important past and exciting novel developments.