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https://www.readbyqxmd.com/read/28226892/a-bifrequent-passive-sensor-system-for-measurement-of-the-pulse-wave-velocity-in-a-stent
#1
Jonathan Schachtele, Jonathan Schachtele, Jonathan Schachtele
In-stent restenosis (ISR) is a frequent complication after stent implantation. Recently, a passive sensor system for integration into a stent has been presented, which is designed to detect an ISR early by measuring the local pulse wave velocity (PWV). This system is based on two pressure sensitive transponders, the resonance frequency of which hits the frequency of a magnetic field generated by an externally applied transceiver coil during a pulse cycle. This method is limited in applicability by the largest PWV it can measure...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225272/a-diastereoselective-multicomponent-reaction-for-construction-of-alkynylamide-substituted-%C3%AE-%C3%AE-diamino-acid-derivatives-to-hunt-hits
#2
Ruirui Lei, Yong Wu, Suzhen Dong, Kaili Jia, Shunying Liu, Wenhao Hu
Highly diasetereoselective Mannich-type multi-component reaction was developed to rapidly construct alkynylamide-substituted α,β-diamino acid derivatives from simple starting materials under mild conditions in moderate to good yields for hit hunting. Most of the resulting products 4 exhibited good anticancer activity in HCT116, BEL7402 and SMMC7721 cells.
February 22, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28225269/indazole-based-covalent-inhibitors-to-target-drug-resistant-epidermal-growth-factor-receptor
#3
Stefano Tomassi, Jonas Lategahn, Julian Engel, Marina Keul, Hannah Lea Tumbrink, Julia Ketzer, Thomas Mühlenberg, Matthias Baumann, Carsten Schultz-Fademrecht, Sebastian Bauer, Daniel Rauh
The specific targeting of oncogenic mutant epidermal growth factor receptor (EGFR) is a breakthrough in targeted cancer therapy and marks a drastic change in the treatment of non-small cell lung cancer (NSCLC). The recurrent emergence of resistance to these targeted drugs requires the development of novel chemical entities that efficiently inhibit drug-resistant EGFR. Herein, we report the optimization process for a hit compound that has emerged from a phenotypic screen resulting in indazole-based compounds...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28224786/cisplatin-crosslinked-multifunctional-nanodrugplexes-for-combination-therapy
#4
Weiqi Zhang, Ching-Hsuan Tung
Combination therapy efficiently tackles cancer by hitting multiple action mechanisms. However, drugs administered, simultaneously or sequentially, may not reach the targeted sites with the desired dose and ratio. The outcomes of combination therapy could be improved with a polymeric nanoparticle, which can simultaneously transport an optimal combination of drugs. We have demonstrated a simple one-pot strategy to formulate nanomedicines based on platinum coordination and the non-covalent interactions of the drugs...
February 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28223964/mouse-models-of-human-gwas-hits-for-obesity-and-diabetes-in-the-post-genomic-era-time-for-reevaluation
#5
Samantha Laber, Roger D Cox
No abstract text is available yet for this article.
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28223231/the-impact-of-in-silico-screening-in-the-discovery-of-novel-and-safer-drug-candidates
#6
REVIEW
Didier Rognan
Drug discovery is a multidisciplinary and multivariate optimization endeavor. As such, in silico screening tools have gained considerable importance to archive, analyze and exploit the vast and ever-increasing amount of experimental data generated throughout the process. The current review will focus on the computer-aided prediction of the numerous properties that need to be controlled during the discovery of a preliminary hit and its promotion to a viable clinical candidate. It does not pretend to the almost impossible task of an exhaustive report but will highlight a few key points that need to be collectively addressed both by chemists and biologists to fuel the drug discovery pipeline with innovative and safe drug candidates...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222777/identification-of-somatic-and-germ-line-dicer1-mutations-in-pleuropulmonary-blastoma-cystic-nephroma-and-rhabdomyosarcoma-tumors-within-a-dicer1-syndrome-pedigree
#7
Lorena Fernández-Martínez, José Antonio Villegas, Íñigo Santamaría, Ana S Pitiot, Marta G Alvarado, Soledad Fernández, Héctor Torres, Ángeles Paredes, Pilar Blay, Milagros Balbín
BACKGROUND: DICER1 syndrome is a pediatric cancer predisposition condition causing a variety of tumor types in children and young adults. In this report we studied a family with two relatives presenting a variety of neoplastic conditions at childhood. METHODS: Germ-line mutation screening of the complete coding region of the DICER1 gene in genomic DNA from the proband was performed. The presence of somatic DICER1 mutation and further alterations in driver genes was investigated in genomic DNA obtained from available tumor samples...
February 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28222763/the-discovery-of-novel-lpmo-families-with-a-new-hidden-markov-model
#8
Gerben P Voshol, Erik Vijgenboom, Peter J Punt
BACKGROUND: Renewable biopolymers, such as cellulose, starch and chitin are highly resistance to enzymatic degradation. Therefore, there is a need to upgrade current degradation processes by including novel enzymes. Lytic polysaccharide mono-oxygenases (LPMOs) can disrupt recalcitrant biopolymers, thereby enhancing hydrolysis by conventional enzymes. However, novel LPMO families are difficult to identify using existing methods. Therefore, we developed a novel profile Hidden Markov model (HMM) and used it to mine genomes of ascomycetous fungi for novel LPMOs...
February 21, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28221352/dynamic-undocking-and-the-quasi-bound-state-as-tools-for-drug-discovery
#9
Sergio Ruiz-Carmona, Peter Schmidtke, F Javier Luque, Lisa Baker, Natalia Matassova, Ben Davis, Stephen Roughley, James Murray, Rod Hubbard, Xavier Barril
There is a pressing need for new technologies that improve the efficacy and efficiency of drug discovery. Structure-based methods have contributed towards this goal but they focus on predicting the binding affinity of protein-ligand complexes, which is notoriously difficult. We adopt an alternative approach that evaluates structural, rather than thermodynamic, stability. As bioactive molecules present a static binding mode, we devised dynamic undocking (DUck), a fast computational method to calculate the work necessary to reach a quasi-bound state at which the ligand has just broken the most important native contact with the receptor...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28221002/computational-biology-and-chemistry-in-mti-emphasis-on-the-prediction-of-some-admet-properties
#10
REVIEW
Maria A Miteva, Bruno O Villoutreix
Our research and teaching group called MTi (Molécules Thérapeutiques in silico) has developed numerous applications available online, thanks to the RPBS platform (Ressource Parisienne en Bioinformatique Structurale), in the field of chemoinformatics, structural bioinformatics and drug design. Since its opening in 2009, over 200 articles/reviews have been reported and involve virtual screening studies, prediction of druggability, analysis of protein-protein interaction inhibitors, development of databases, data mining and knowledge discovery, as well as combined in silico-in vitro work to search for new hits and chemical probes acting on original targets in several therapeutic areas...
February 21, 2017: Molecular Informatics
https://www.readbyqxmd.com/read/28220866/the-correlation-and-risk-factors-between-carotid-intima-media-thickening-and-alcoholic-liver-disease-coupled-with-helicobacter-pylori-infection
#11
Qu Bao-Ge, Wang Hui, Jia Yi-Guo, Su Ji-Liang, Wang Zhong-Dong, Wang Ya-Fei, Han Xing-Hai, Liu Yuan-Xun, Pan Jin-Dun, Ren Guang-Ying
The aim of this study was to explore the associations and differences in influencing factors between alcoholic liver disease (ALD) coupled with Helicobacter pylori infection and atherosclerosis and to determine whether there is a "double hit phenomenon" in atherosclerosis patients with ALD and H. pylori infections. Included cases (n = 160) were categorized into 4 groups: 41 cases of ALD coupled with H. pylori infections (group A), 35 cases of H. pylori infections without ALD (group B), 37 cases of ALD without H...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220535/interaction-of-approved-drugs-with-synaptic-vesicle-protein-2a
#12
Azeem Danish, Vigneshwaran Namasivayam, Anke C Schiedel, Christa E Müller
Levetiracetam (LEV) and its recently approved derivative brivaracetam are anti-epileptic drugs with a unique mechanism of action. The synaptic vesicle protein 2A (SV2A) was previously identified as their main target. In the current study, we tested a collection of 500 approved drugs for interaction with the human SV2A protein expressed in Chinese hamster ovary cells. Competition binding studies were performed using cell lysates with high SV2A expression and [(3) H]brivaracetam as a radioligand. A hit rate of 3% was obtained, defined as compounds that inhibited radioligand binding by more than 90% at a screening concentration of 20 μM...
February 21, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28219086/first-report-of-awake-craniotomy-of-a-famous-musician-suprasellar-tumor-surgery-of-pianist-clara-haskil-in-1942
#13
Elena Romana Gasenzer, Ayhan Kanat, Edmund A M Neugebauer
Clara Haskil (January 7, 1895-December 7, 1960) was one of the most famous female pianists of the 20th century. In her life and work she set new standards in piano playing. However, her career was beset by poor health and the adversities of two world wars. In her lifetime Haskil had three major disorders: juvenile scoliosis requiring treatment in her adolescence, a tumor of the sellar region requiring surgery at age 47 years, and a traumatic brain injury causing her death at the age of 65. Her medical history illustrates the development of surgical methods and rehabilitation in medicine before and after World War II...
February 20, 2017: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/28218724/remote-sensing-of-urban-microclimate-change-in-l-aquila-city-italy-after-post-earthquake-depopulation-in-an-open-source-gis-environment
#14
Valerio Baiocchi, Fabio Zottele, Donatella Dominici
This work reports a first attempt to use Landsat satellite imagery to identify possible urban microclimate changes in a city center after a seismic event that affected L'Aquila City (Abruzzo Region, Italy), on 6 April 2009. After the main seismic event, the collapse of part of the buildings, and the damaging of most of them, with the consequence of an almost total depopulation of the historic city center, may have caused alterations to the microclimate. This work develops an inexpensive work flow-using Landsat Enhanced Thematic Mapper Plus (ETM+) scenes-to construct the evolution of urban land use after the catastrophic main seismic event that hit L'Aquila...
February 19, 2017: Sensors
https://www.readbyqxmd.com/read/28218620/endothelial-antigen-assembly-leads-to-thrombotic-complications-in-heparin-induced-thrombocytopenia
#15
Vincent Hayes, Ian Johnston, Gowthami M Arepally, Steven E McKenzie, Douglas B Cines, Lubica Rauova, Mortimer Poncz
Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies against complexes between human platelet factor 4 (hPF4) and heparin. A better understanding of the events that initiate the prothrombotic state may improve approaches to antithrombotic management. Here, we visualized thrombus formation in an in vivo murine model and an endothelialized microfluidic system that simulate the pathogenesis of HIT. hPF4 released from platelets predominantly bound to peri-injury endothelium and formed HIT antigenic complexes that were dissociated by heparin...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28218421/frameshift-mutational-target-gene-analysis-identifies-similarities-and-differences-in-constitutional-mismatch-repair-deficiency-and-lynch-syndrome
#16
Claudia Maletzki, Maja Huehns, Ingrid Bauer, Tim Ripperger, Maureen M Mork, Eduardo Vilar, Sabine Klöcking, Heike Zettl, Friedrich Prall, Michael Linnebacher
Mismatch-repair deficient (MMR-D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood-form of constitutional mismatch repair-deficiency (CMMR-D); caused by bi-allelic MMR gene mutations. A hallmark of LS-associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR-D patients are thought to display a somatic mutation pattern differing from LS...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28218273/discovery-of-the-first-dual-inhibitor-of-the-5-lipoxygenase-activating-protein-and-soluble-epoxide-hydrolase-using-pharmacophore-based-virtual-screening
#17
Veronika Temml, Ulrike Garscha, Erik Romp, Gregor Schubert, Jana Gerstmeier, Zsofia Kutil, Barbara Matuszczak, Birgit Waltenberger, Hermann Stuppner, Oliver Werz, Daniela Schuster
Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer of AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. The soluble epoxide hydrolase (sEH) converts AA-derived anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatetraenoic acids (di-HETEs). Its inhibition consequently also counteracts inflammation...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217939/pitx2-dependent-gene-regulation-in-atrial-fibrillation-and-rhythm-control
#18
Fahima Syeda, Paulus Kirchhof, Larissa Fabritz
Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. There are several major mechanisms that cause AF in patients, including a genetic predisposition to develop AF. Genome-wide association studies (GWAS) have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription factor PITX2. The effect of these common gene variants on cardiac PITX2 mRNA is currently under study...
February 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28217315/gemcitabine-induced-cardiomyopathy-a-case-of-multiple-hit-cardiotoxicity
#19
Donya Mohebali, Jason Matos, James Ducksoon Chang
Gemcitabine is a commonly used antineoplastic agent used to treat a variety of cancers with rarely reported cardiac side effects. We describe a case of a 67-year-old woman with follicular lymphoma who experienced a rarely reported side effect of gemcitabine: cardiomyopathy. This case highlights a multiple hit mechanism of myocyte damage that may occur following the use of multiple cardio-toxic agents despite their administration in doses not associated with cardiotoxicity.
February 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28216121/pigeons-unlike-humans-do-not-prefer-near-hits-in-a-slot-machine-like-task
#20
Inês Fortes, Jacob P Case, Thomas R Zentall
Slot machines are among the most popular forms of commercial gambling, and the high frequency of losses that come close to winning - near hits - in this game appears to contribute to its popularity. In the present experiment we tested if pigeons, similarly to humans, prefer an alternative that provides near-hit outcomes in a slot-machine-like task. The pigeons received series of three stimuli, one every two seconds: if the three stimuli matched, food was delivered (a win); if they did not match, food was not delivered (a loss)...
February 16, 2017: Behavioural Processes
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