gebhart/patrepeval huggingface dataset:
Potent, Metabolically Stable Benzopyrimido-pyrrolo-oxazine-dione (BPO) CFTR Inhibitors for Polycystic Kidney Disease (2011)

We previously reported the discovery of pyrimido-pyrrolo-quinoxalinedione (PPQ) inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and showed their efficacy in an organ culture model of polycystic kidney disease (PKD) (J. Med. Chem. 2009, 52, 6447-6455). Here, we report related benzopyrimido-pyrrolo-oxazinedione (BPO) CFTR inhibitors. To establish structure-activity relationships and select lead compound(s) with improved potency, metabolic stability, and aqueous solubility compared to the most potent prior compound 8 (PPQ-102, IC(50) ∼ 90 nM), we synthesized 16 PPQ analogues and 11 BPO analogues. The analogues were efficiently synthesized in 5-6 steps and 11-61% overall yield. Modification of 8 by bromine substitution at the 5-position of the furan ring, replacement of the secondary amine with an ether bridge, and carboxylation, gave 6-(5-bromofuran-2-yl)-7,9-dimethyl-8,10-dioxo-11-phenyl-7,8,9,10-tetrahydro-6H-benzo[b]pyrimido [4',5':3,4]pyrrolo [1,2-d][1,4]oxazine-2-carboxylic acid 42 (BPO-27), which fully inhibited CFTR with IC(50) ∼ 8 nM and, compared to 8, had >10-fold greater metabolic stability and much greater polarity/aqueous solubility. In an embryonic kidney culture model of PKD, 42 prevented cyst growth with IC(50) ∼ 100 nM. Benzopyrimido-pyrrolo-oxazinediones such as 42 are potential development candidates for antisecretory therapy of PKD.
Cardiac Myosin Binding Protein C Gene Is Specifically Expressed in Heart During Murine and Human Development (1998)

Cardiac myosin binding protein C (MyBP-C) is a substantial component of the sarcomere, with both structural and regulatory roles. The gene encoding cardiac MyBP-C in humans is located on chromosome 11p11.2, and mutations that are most predicted to produce truncated proteins have been identified in this gene in unrelated families with familial hypertrophic cardiomyopathy (FHC). To understand better the pathophysiology of FHC and with a view to the development of animal models for this disease, we have investigated by in situ hybridization the pattern of expression of the cardiac MyBP-C gene during human and mouse development using species-specific oligonucleotide probes. From 4 weeks of human development, a strong labeling of cardiac MyBP-C mRNAs was unambiguously detected in all heart compartments, and no signal could be visualized in somites. In murine embryos, from embryonic day 9.5 until birth, a strong signal was detected exclusively in the heart. Our results showed that during both human and murine development, in contrast to chicken development, the cardiac MyBP-C gene is abundantly and specifically expressed in the heart.
The Pregnane X Receptor Regulates Gene Expression in a Ligand- and Promoter- Selective Fashion (2005)

Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of phase I and phase II drug-metabolizing enzymes, as well as members of the drug transporter family, including multiple drug resistance (MDR) 1, which has a major role in multidrug resistance. Previously, we have demonstrated that steroid/xenobiotics metabolism by tumor tissue through the PXR-cytochrome P-450 3A (CYP3A) pathway might play an important role in endometrial cancer. In this study, we examined which endocrine-disrupting chemicals (EDCs) and anticancer agents might be ligands for PXR and whether these chemicals enhanced PXR-mediated transcription through two different PXR-responsive elements (PXREs), CYP3A4 and MDR1, in endometrial cancer cell lines. Some steroids/EDCs strongly activated PXR-mediated transcription through the CYP3A4-responsive element compared with the MDR1-responsive element, whereas these steroids/EDCs also enhanced the CYP3A4 expression compared with the MDR1 expression. In contrast, the anticancer agents, cisplatin and paclitaxel, strongly activated PXR-mediated transcription through the MDR1-responsive element compared with the CYP3A4-responsive element, whereas these drugs also enhanced the MDR1 expression compared with the CYP3A4 expression. We also analyzed how these ligands regulated PXR-mediated transcription through two different PXREs. In the presence of PXR ligands, there was no difference in the DNA binding affinity of the PXR/retinoid X receptor heterodimer to each PXRE, but there were different interactions of the coactivator to each PXR/PXRE complex. These data suggested that PXR ligands enhanced PXR-mediated transcription in a ligand- and promoter-dependent fashion, which in turn differentially regulated the expression of individual PXR targets, especially CYP3A4 and MDR1.
The Synthesis of Deuterionucleosides (2000)

The synthesis of deuterionucleosides for site-specific incorporation into oligo-DNA or -RAA is herein reviewed for NMR or biological studies. The review covers the following aspects: (i) deuteration of the aglycone; (ii) single-site chemical deuteration of the sugar residues; (iii) multiple-site chemical deuteration of the sugar residues; (iv) enzymatic synthesis of deuterated nucleosides or nucleotides; and (v) synthesis of labelled nucleosides with multiple isotopes
Solid-State Replication of Relief Structures in Semicrystalline Polymers (2000)

The use of semicrystalline polymers for surface structuring allows multiple embossing and structuring of oriented polymer films, in contrast to amorphous polymers. The Figure shows an oriented perfluorinated polymer film (FEP), on which a lamellar grating has been superimposed by solid-state embossing. Polarized optical microscopy reveals the combined optical effects of surface structure and molecular orientation.
Cancer prevention from the perspective of global cancer burden patterns (2017)

Cancer is the second leading cause of death worldwide behind cardiovascular disease (1). According to the Global Burden of Disease (GBD) 2015 Study, which was conducted as part of a comprehensive regional and global research program assessing the mortality and disability caused by major diseases, injuries, and risk factors and involving over 500 researchers representing over 300 institutions and 50 countries, cancer mortality decreased between 2005 and 2015 despite the global incidence rates of cancer increasing during this period (1).
Driving Current through Single Organic Molecules (2002)

We investigate electronic transport through two types of conjugated molecules. Mechanically controlled break junctions are used to couple thiol end groups of single molecules to two gold electrodes. Current-voltage characteristics ( IVs) of the metal-molecule-metal system are observed. These IVs reproduce the spatial symmetry of the molecules with respect to the direction of current flow. We hereby unambiguously detect an intrinsic property of the molecule and are able to distinguish the influence of both the molecule and the contact to the metal electrodes on the transport properties of the compound system.
Using prospero to support integrated location-independent computing (1993)

As computers become pervasive, users will access processing, storage, and communication resources from locations that have not been practical in the past. Such users will demand support for location-independent computing. While the basic system components used might change as the user moves from place to place, the appearance of the system should remain constant. In this paper we discuss the role of, and requirements for, directory services in support of integrated, location-independent computing. We focus on two specific problems: the server selection problem and the user location problem. We present solutions to these problems based on the Prospero Directory Service. The solutions demonstrate several unique features of Prospero that make it particularly suited for support of location-independent computing.
Solid-state field decoupler for off-column detection in capillary electrophoresis (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid-state field decoupler for off-column detection in capillary electrophoresisWim T. Kok and Yuksel. SahinCite this: Anal. Chem. 1993, 65, 18, 2497–2501Publication Date (Print):September 15, 1993Publication History Published online1 May 2002Published inissue 15 September 1993https://pubs.acs.org/doi/10.1021/ac00066a017https://doi.org/10.1021/ac00066a017research-articleACS PublicationsRequest reuse permissionsArticle Views189Altmetric-Citations53LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Incidence and Survival of Pancreatic Head and Body and Tail Cancers (2010)

This study indicates that the incidence of pancreatic head cancer has remained stable, whereas the incidence of pancreatic body/tail cancers is rising. Despite higher survival rates among patients with pancreatic head cancer compared with those with pancreatic body/tail cancers in several variables, patients with local-stage pancreatic body/tail cancers had higher survival rates compared with local-stage pancreatic head cancer.
Hepatitis Delta Virus Antigen Is Methylated at Arginine Residues, and Methylation Regulates Subcellular Localization and RNA Replication (2004)

Hepatitis delta virus (HDV) contains a circular RNA which encodes a single protein, hepatitis delta antigen (HDAg). HDAg exists in two forms, a small form (S-HDAg) and a large form (L-HDAg). S-HDAg can transactivate HDV RNA replication. Recent studies have shown that posttranslational modifications, such as phosphorylation and acetylation, of S-HDAg can modulate HDV RNA replication. Here we show that S-HDAg can be methylated by protein arginine methyltransferase (PRMT1) in vitro and in vivo. The major methylation site is at arginine-13 (R13), which is in the RGGR motif of an RNA-binding domain. The methylation of S-HDAg is essential for HDV RNA replication, especially for replication of the antigenomic RNA strand to form the genomic RNA strand. An R13A mutation in S-HDAg inhibited HDV RNA replication. The presence of a methylation inhibitor, S-adenosyl-homocysteine, also inhibited HDV RNA replication. We further found that the methylation of S-HDAg affected its subcellular localization. Methylation-defective HDAg lost the ability to form a speckled structure in the nucleus and also permeated into the cytoplasm. These results thus revealed a novel posttranslational modification of HDAg and indicated its importance for HDV RNA replication. This and other results further showed that, unlike replication of the HDV genomic RNA strand, replication of the antigenomic RNA strand requires multiple types of posttranslational modification, including the phosphorylation and methylation of HDAg.
Modeling of Autocatalytic Hydrolysis of Adefovir Dipivoxil in Solid Formulations (2011)

The stability and hydrolysis kinetics of a phosphate prodrug, adefovir dipivoxil, in solid formulations were studied. The stability relationship between five solid formulations was explored. An autocatalytic mechanism for hydrolysis could be proposed according to the kinetic behavior which fits the Prout-Tompkins model well. For the classical kinetic models could hardly describe and predict the hydrolysis kinetics of adefovir dipivoxil in solid formulations accurately when the temperature is high, a feedforward multilayer perceptron (MLP) neural network was constructed to model the hydrolysis kinetics. The build-in approaches in Weka, such as lazy classifiers and rule-based learners (IBk, KStar, DecisionTable and M5Rules), were used to verify the performance of MLP. The predictability of the models was evaluated by 10-fold cross-validation and an external test set. It reveals that MLP should be of general applicability proposing an alternative efficient way to model and predict autocatalytic hydrolysis kinetics for phosphate prodrugs.
Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study (2001)

This large, prospective study allowed the authors to define better the conditions for the use of GM immunocapture ELISA in surveying patients who are at high risk for IA. The presence of antigen has a good diagnostic value mainly when there is an increase in the titer on two consecutive sera samples. A repeated negative result is a strong argument against the diagnosis of IA; however, an awareness of the possibility of unexplained false negative results is important.
18F-Fluorobenzyl Triphenyl Phosphonium: A Noninvasive Sensor of Brown Adipose Tissue Thermogenesis (2011)

The intense uptake of (18)F-FBnTP into BAT at room temperature and the response to cold stimulation suggest the unique potential advantage of (18)F-FBnTP not only in detecting unstimulated BAT at high contrast but also in quantifying the mitochondrial thermogenic activity. (18)F-FBnTP PET may serve as a useful technique to assess BAT volume and function.
LOH on 10p14‐p15 targets the PFKFB3 gene locus in human glioblastomas (2011)

Abstract Loss of heterozygosity (LOH) on chromosome arm 10p is very common in high‐grade gliomas and is, among others, concentrated on the region 10p14‐p15. Presence of multiple tumor suppressor genes is assumed, but until now only Krüpple‐like transcription factor 6 ( KLF6 ) has been suggested as possible target of LOH in this region. On the basis of the fact that the splice variant 4 ( UBI2K4 ) of the PFKFB3 gene, located in 10p15.1, inhibits the anchorage‐independent growth of U87 glioblastoma cells, we hypothesized that PFKFB3 is a target gene of LOH in glioblastomas. In this study, we analyzed 40 glioblastomas for LOH in 10p15, including the PFKFB3 and KLF6 loci, by PCR‐based microsatellite analysis. We detected LOH of PFKFB3 in 55% (22/40) of glioblastomas. LOH of KLF6 , mapped 2.5 cM telomerically to the PFKFB3 locus, was not stringently correlated to the PFKFB3 LOH. The allelic deletion of PFKFB3 resulted in a decrease of PFKFB3 mRNA level accompanied by a lower PFKFB3 protein level. The expression of growth‐inhibiting splice variant UBI2K4 was effectively reduced in glioblastomas with PFKFB3 LOH and a positive correlation with overall PFKFFB3 expression was observed. The PFKFB3 LOH as well as the resulting low UBI2K4 expression level was associated with a poor prognosis of glioblastoma patients. We conclude that LOH on 10p14‐p15 in glioblastomas targets PFKFB3 and in particular splice variant UBI2K4 , a putative tumor suppressor protein in glioblastomas. © 2011 Wiley Periodicals, Inc.
Milatuzumab-Conjugated Liposomes as Targeted Dexamethasone Carriers for Therapeutic Delivery in CD74+ B-cell Malignancies (2012)

These studies provide evidence and support for a potential use of CD74-targeted liposomal dexamethasone as a new therapy for B-cell malignancies.
Modelling and equalization of rapidly fading channels (1996)

Basis expansion ideas are employed in order to equalize frequency-selective, rapidly fading channels. For certain multipath fading channels (e.g. the mobile radio channel), the time variations of the coefficients can be modelled as a combination of a small number of complex exponentials, under the assumption of linearly changing path delays. Based on this observation, novel adaptive and decision feedback algorithms are derived which exploit such an explicit modelling of the channel's variations. The problem of estimating the frequencies of the exponentials is also addressed using second- and higher-order cyclic statistics. By integrating ideas from cyclostationary signal analysis, both batch and recursive methods are developed. Finally, some illustrative simulations are presented.
Quality of life issues and measurement in patients with psoriasis (2012)

Abstract: Psoriasis is a chronic immunologic disease characterized by red papules and plaques with a silver colored scale. The impact of psoriasis on patients’ overall quality of life is significant, broad, and deep, including effects on emotional wellbeing, psychological stress, self-esteem, relationship, work, social activities, financial burden, and even physical function. Although there are various measures available for assessing health-related quality of life (HRQoL) in research studies, there is no consensus on which measure is best to use in clinical practice or for research comparing different treatments. Choosing treatments based on patients’ specific individual preferences, goal-orientation, and close, attentive cooperation between patients and their doctors may be an effective strategy that can be applied to improve patients’ quality of life. Keywords: treatment, health related quality of life, HRQoL
Purification, characterization and biological significance of tumor-derived exosomes. (2005)

Exosomes are nanovesicles that are released into the extracellular environment during the fusion of multivesicular bodies with the plasma membrane. Exosomes released from dendritic cells, dexosomes, have several biological functions, for example as immunostimulants. Some tumor cells also secrete exosomes (Tu-exosomes). Although experimental data obtained with the use of dexosomes suggest a biological function of Tu-exosomes, this still remains poorly understood. To examine the function of Tu-exosomes, we established a method for collecting highly purified Tu-exosomes, using paramagnetic beads coated with antibodies against tumor-specific proteins such as HER2/neu. With these antibody-coated beads (Ab-beads), it was possible to collect HER2-expressing Tu-exosomes of high purity. Tu-exosomes were also collected from malignant ascites, which contain exosomes secreted from various types of cells such as tumor cells, lymphoid cells and mesothelial cells. The isolation of Tu-exosomes was confirmed by FACS analysis. With regard to their biological functions, Tu-exosomes cultured with a human breast cancer cell line bound to the cell surface and increased tumor cell proliferation. These data indicate that Tu-exosomes may have physiological functions.
Functionalized Fluorescent Oxide Nanoparticles:  Artificial Toxins for Sodium Channel Targeting and Imaging at the Single-Molecule Level (2004)

Lanthanide ion-doped oxide nanoparticles were functionalized for use as fluorescent biological labels. These nanoparticles are synthesized directly in water, which facilitates their functionalization, and are remarkably photostable without emission intermittency. Nanoparticles functionalized with guanidinium groups act as artificial toxins and specifically target sodium channels. They are individually detectable in live cardiac myocytes, revealing a heterogeneous distribution of sodium channels. Functionalized oxide nanoparticles appear to be a novel tool that is particularly attractive for long-term single-molecule tracking.
Implantable Unpowered Parylene MEMS Intraocular Pressure Sensor (2006)

This paper presents the first implantable, unpowered, parylene-based micro-electro-mechanical-systems (MEMS) pressure sensor for intraocular pressure (IOP) sensing. From <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in situ</i> mechanical deformation of the compliant structures, this sensor registers pressure variations without power consumption/transduction. Micromachined high-aspect-ratio thin-walled tubes in different geometric layouts are exploited to obtain a high-sensitivity pressure response. An integrated packaging method has been successfully developed to realize suture-less implantation of the device. <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">In vitro</i> testing results have demonstrated that the IOP sensor can achieve 0.67 degree/mmHg angular sensitivity with a spiral-tube design, 3.43 μm/mmHg lateral sensitivity with a long-armed-tube design, and 0.38 μm/mmHg longitudinal sensitivity with a serpentine-tube design. This IOP sensor is designed to be implanted in the anterior chamber of the eye and anchored directly on the iris so that, under incident visible light, the pressure response of the implant can be directly observed from outside the eye, which enables faithful and unpowered IOP monitoring in glaucoma patients.
Spatially resolved characterization of HgCdTe materials and devices by scanning laser microscopy (1993)

Spatially resolved characterization of HgCdTe materials and p-n junction diodes using scanning laser microscopy is reviewed. Several techniques that yield spatial maps of electrical inhomogeneities in HgCdTe material and non-uniformities in various performance parameters of p-n junctions fabricated using these materials have been developed. Many of the techniques are non-destructive, or can be made such with minor changes in sample preparation, and are scalable to large full wafers. A high-resolution and non-destructive technique called 'laser beam induced current (LBIC)' has been developed for spatial mapping of electrically active regions in HgCdTe. When applied to unprocessed HgCdTe material, LBIC images represent spatial distributions of electrically active defects including inclusions, strain, damage, precipitates, stacking faults, twin boundaries, dislocation clusters, bandgap and doping variations. Device structures such as p-n junctions are special cases of electrically active regions, therefore the LBIC technique lends itself to a non-destructive study of p-n junction arrays without requiring any direct electrical contact to the individual elements of the array. The remote contacting, especially using pressure contacts, makes the application of the LBIC technique non-destructive, allowing testing at various stages of device processing to identify particular processing procedures that need optimization. LBIC has also been used to spatially map electrical non-uniformities at the HgCdTe surface near its interface with an insulating passivation layer. Besides LBIC imaging, scanning laser microscopy has been used for several other applications. For HgCdTe p-n junctions, applications include photoresponse mapping (uniformity, active area and diffusion length determination, contact bonding effects), spatially resolved light-induced degradation, and avalanche photodiode properties (ionization coefficients, localized breakdown). A key technique currently in development is the non-contact diode R0A determination based on trapping mode photoconductivity. Examples of scanning laser microscopy on HgCdTe materials are infrared transmission mapping (thickness and bandgap variations), photoluminescence mapping, and minority carrier lifetime mapping (distribution of recombination centres).
Tracking hands above large interactive surfaces with a low-cost scanning laser rangefinder (1998)

No abstract available.