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Navasona Krishnan, Konstantis F Konidaris, Gilles Gasser, Nicholas K Tonks
The protein tyrosine phosphatase PTP1B is a negative regulator of insulin and leptin signaling, and a highly validated therapeutic target for diabetes and obesity. Conventional approaches to drug development have produced potent and specific PTP1B inhibitors, but these inhibitors lack oral bioavailability, which limits their potential for drug development. Here we report that DPM-1001, an analogue of the specific PTP1B inhibitor trodusquemine (MSI-1436), is a potent, specific and orally bioavailable inhibitor of PTP1B...
December 7, 2017: Journal of Biological Chemistry
Shrawan Baghel, Helen Cathcart, Niall J O'Reilly
In this study, the dissolution behaviour of dipyridamole (DPM) and cinnarizine (CNZ) spray-dried amorphous solid dispersions (ASDs) using polyvinyl pyrrolidone (PVP) and polyacrylic acid (PAA) as a carrier matrix were evaluated and compared. The drug concentrations achieved from the dissolution of PVP and PAA solid dispersions were significantly greater than the equilibrium solubility of crystalline DPM and CNZ in phosphate buffer pH 6.8 (PBS 6.8). The maximum drug concentration achieved by dissolution of PVP and PAA solid dispersions did not exceed the theoretically calculated apparent solubility of amorphous DPM and CNZ...
November 25, 2017: International Journal of Pharmaceutics
Louise Kiru, Tae Jin Kim, Bin Shen, Frederick T Chin, Guillem Pratx
PURPOSE: Cell-based therapies are showing great promise for a variety of diseases, but remain hindered by the limited information available regarding the biological fate, migration routes and differentiation patterns of infused cells in trials. Previous studies have demonstrated the feasibility of using positron emission tomography (PET) to track single cells utilising an approach known as positron emission particle tracking (PEPT). The radiolabel hexadecyl-4-[(18)F]fluorobenzoate ([(18)F]HFB) was identified as a promising candidate for PEPT, due to its efficient and long-lasting labelling capabilities...
November 15, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Zhaoran Hao, Fanyuan Meng, Pu Wang, Yafei Wang, Hua Tan, Yong Pei, Shijian Su, Yu Liu
Two novel mono- and binuclear cyclometalated platinum(ii) complexes of (BuPyrDPy)Pt(dpm) and (BuPyrDPy)[Pt(dpm)]2 incorporating a pyrenyl-dipyridine-based cyclometalated ligand were synthesized and characterized, respectively. Single-crystal X-ray diffraction of the two materials revealed each complex's coordination mode; their photophysical, electrochemical as well as electroluminescent properties were also investigated. Both complexes exhibited good solubility and excellent thermal stability. (BuPyrDPy)[Pt(dpm)]2 presented dual phosphorescence emissive character at room-temperature and showed an increased quantum efficiency compared to that of (BuPyrDPy)Pt(dpm)...
November 28, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
S Yalcin, S Ozkan, M C Acar, O Meral
1. Two experiments were conducted to determine the effect of slaughter weight on the incidence and intensity of deep pectoral myopathy (DPM) of M. pectoralis minor (p. minor muscle) in commercial conditions in Turkey and to evaluate the impact of DPM on meat quality traits of pectoralis major (p. major) muscle in broilers. 2. In Experiment 1, a total of 116 250 carcasses from 59 Ross-308 broiler flocks, classified according to slaughter weight as 2.0-2.2, 2.2-2.4, 2.4-2.6 and >2.6 kg, were evaluated for occurrence of DPM...
November 8, 2017: British Poultry Science
Balwinder Kaur, Cristiane Andreia Erdmann, Mathias Daniëls, Wim Dehaen, Zbigniew Rafiński, Hanna Radecka, Jerzy Radecki
In the present work, gold electrodes were modified using a redox-active layer based on dipyrromethene complexes with Cu(II) or Co(II) and a dipodal anion receptor functionalized with dipyrromethene. These modified gold electrodes were then applied for the electrochemical detection of anions (Cl(-), SO4(2-), and Br(-)) in a highly diluted water solution (in the picomolar range). The results showed that both systems, incorporating Cu(II) as well as Co(II) redox centers, exhibited highest sensitivity toward Cl(-)...
November 15, 2017: Analytical Chemistry
Jingxu Guo, Peter Erskine, Alun R Coker, Steve P Wood, Jonathan B Cooper
The enzyme porphobilinogen deaminase (PBGD) is one of the key enzymes in tetrapyrrole biosynthesis. It catalyses the formation of a linear tetrapyrrole from four molecules of the substrate porphobilinogen (PBG). It has a dipyrromethane cofactor (DPM) in the active site which is covalently linked to a conserved cysteine residue through a thioether bridge. The substrate molecules are linked to the cofactor in a stepwise head-to-tail manner during the reaction, which is catalysed by a conserved aspartate residue: Asp82 in the B...
November 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
Marco Lorenzi, Maurizio Filippone, Giovanni B Frisoni, Daniel C Alexander, Sebastien Ourselin
Disease progression modeling (DPM) of Alzheimer's disease (AD) aims at revealing long term pathological trajectories from short term clinical data. Along with the ability of providing a data-driven description of the natural evolution of the pathology, DPM has the potential of representing a valuable clinical instrument for automatic diagnosis, by explicitly describing the biomarker transition from normal to pathological stages along the disease time axis. In this work we reformulated DPM within a probabilistic setting to quantify the diagnostic uncertainty of individual disease severity in an hypothetical clinical scenario, with respect to missing measurements, biomarkers, and follow-up information...
October 24, 2017: NeuroImage
Kamil Janowski, Maria Goliszek, Joanna Cielecka-Kuszyk, Irena Jankowska, Joanna Pawłowska
Congenital hepatic fibrosis (CHF) is a rare, autosomal recessive disorder, clinically characterized by hepatic fibrosis and portal hypertension. CHF results from ductal plate malformation (DPM) of the intrahepatic bile ducts. Four clinical forms can be observed: portal hypertensive, cholangitic, mixed and latent. CHF is one of the "fibropolycystic diseases" which also include several conditions with a variety of intrahepatic bile duct dilatation and associated periportal fibrosis such as Caroli disease, autosomal recessive and dominant polycystic kidney disease (ARPKD or ADPKD), Ivemark, Jeune, Joubert, Bardet-Biedl, Meckel-Gruber and Arima syndromes...
September 2017: Clinical and Experimental Hepatology
Annette M Klein, Sarah Bergmann, Lars O White
In their study, Wichstrøm et al. (2017) have proposed a novel groundbreaking approach for developmental psychopathology that undoubtedly will inspire other research. Applying the dynamic panel model (DPM), the authors were able to show that within-disorder (homotypic) and between-disorder (heterotypic) continuities of psychiatric symptoms are mostly due to unmeasured time-invariant factors while only few effects of earlier symptoms on later symptoms remained significant after accounting for these factors...
November 2017: Journal of Child Psychology and Psychiatry, and Allied Disciplines
Kazuaki Yamasaki, Atsushi Yamashita, Yan Zhao, Yoichi Shimizu, Ryuichi Nishii, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yujiro Asada, Yuji Kuge
INTRODUCTION: Detection of vulnerable plaques is critically important for the selection of appropriate treatment and/or the prevention of atherosclerosis and ensuing cardiovascular diseases. In order to clarify the utility of [(11)C]acetate for atherosclerosis imaging, we determined the uptake and metabolism of acetate by in vitro studies using rabbit atherosclerotic arteries and [(14)C]acetate. METHODS: Rabbits were fed with a conventional (n=5) or a 0.5% cholesterol diet (n=6)...
August 24, 2017: Nuclear Medicine and Biology
Aleksandra Vulović, Tijana Šušteršič, Sandra Cvijić, Svetlana Ibrić, Nenad Filipović
One of the critical components of the respiratory drug delivery is the manner in which the inhaled aerosol is deposited in respiratory tract compartments. Depending on formulation properties, device characteristics and breathing pattern, only a certain fraction of the dose will reach the target site in the lungs, while the rest of the drug will deposit in the inhalation device or in the mouth-throat region. The aim of this study was to link the Computational fluid dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in order to predict aerolisolization of different dry powder formulations, and estimate concomitant in vivo deposition and absorption of amiloride hydrochloride...
October 17, 2017: European Journal of Pharmaceutical Sciences
Eric J Esswein, Marissa Alexander-Scott, John Snawder, Michael Breitenstein
Diesel engines serve many purposes in modern oil and gas extraction activities. Diesel particulate matter (DPM) emitted from diesel engines is a complex aerosol that may cause adverse health effects depending on exposure dose and duration. This study reports on personal breathing zone (PBZ) and area measurements for DPM (expressed as elemental carbon) during oil and gas extraction operations including drilling, completions (which includes hydraulic fracturing) and servicing work. Researchers at the National Institute for Occupational Safety and Health (NIOSH) collected 104 full-shift air samples (49 PBZ and 55 area) in Colorado, North Dakota, Texas, and New Mexico during a four year period from 2008-2012 The arithmetic mean (AM) of the full shift TWA PBZ samples was 10 µg/m(3); measurements ranged from 0...
October 20, 2017: Journal of Occupational and Environmental Hygiene
Jieyu Wang, Yoshihiro Hayashi, Asumi Yokota, Zefeng Xu, Yue Zhang, Rui Huang, Xiaomei Yan, Hongyun Liu, Liping Ma, Mohammad Azam, James P Bridges, Jose A Cancelas, Theodosia A Kalfa, Xiuli An, Zhijian Xiao, Gang Huang
Activated EPO receptor (EPOR) signaling causes erythrocytosis. The important role of macrophages for the erythroid expansion and differentiation process has been reported, both in baseline and stress erythropoiesis. However, the significance of EPOR signaling for regulation of macrophages contributing to erythropoiesis has not been fully understood. Here we show that EPOR signaling activation quickly expands both erythrocytes and macrophages in vivo in mouse models of primary and secondary erythrocytosis. To mimic the chimeric condition and expansion of the disease clone in the polycythemia vera patients, we combined Cre-inducible Jak2V617F/+ allele with LysM-Cre allele which expresses in mature myeloid cells and some of the HSC/Ps (LysM-Cre;Jak2V617F/+ mice)...
October 19, 2017: Haematologica
Xin Li, Tao Liao, Lung Wa Chung
The photoinduced Zimmerman di-π-methane (DPM) rearrangement of polycyclic molecules to form synthetically useful cyclopropane derivatives was found experimentally to proceed in a triplet excited state. We have applied state-of-the-art quantum mechanical methods, including M06-2X, DLPNO-CCSD(T) and variational transition-state theory with multidimensional tunneling corrections, to an investigation of the reaction rates of the two steps in the triplet DPM rearrangement of dibenzobarrelene, benzobarrelene and barrelene...
November 9, 2017: Journal of the American Chemical Society
Siddharth Chandra, Frederick T L Leong
Martin's (2017) comment on Chandra and Leong (2016) highlighted (a) lack of definitional clarity of the concept of adaptability, (b) conceptual generality of the model, and (c) incomplete citations of the literature on adaptability. In this reply, the authors contend that lack of definitional clarity of adaptability is symptomatic of the multitude of definitions of adaptability by psychologists of diverse persuasions. Conceptual generality of the diversified portfolio model (DPM) stems from the choice of a broad definition of adaptability, which extends beyond the narrower definitions provided by scholars including Martin, as well as the capability of the model to mesh with this broad definition...
October 2017: American Psychologist
Andrew J Martin
Chandra and Leong (2016) propose a new model of adaptability: the diversified portfolio model (DPM) of adaptability. Further thought and research on adaptability is a welcome addition to the limited body of work conducted on this topic to date. However, in their discussion there is a lack of definitional clarity, and there is frequent conflation of adaptability and resilience. It is also the case that the hypothesized adaptability model is general and could apply to many psychological constructs and processes (not just adaptability)...
October 2017: American Psychologist
Ashish Verma, Anup Kumar Ojha, Yash Pal, Parveen Kumari, Peter Schumann, Harald Gruber-Vodicka, Syed G Dastager, Ramesh Kumar Natarajan, S Mayilraj, Srinivasan Krishnamurthi
The species "Bacillus aminovorans" was categorized as species Incertae Sedis meaning taxa with uncertain taxonomic position because of insufficient description of phenotypic properties and lack of understanding of its phylogenetic relationship (Claus and Berkeley [5]). In this study two strains "B. aminovorans" DSM 1314(T) and DSM 4337 were phenotypically and phylogenomically analyzed. The strains are Gram-staining-positive, spore forming rods and unable to utilize/ferment most of the sugars tested except glucose...
August 18, 2017: Systematic and Applied Microbiology
Breanne Y Farris, James M Antonini, Jeffrey S Fedan, Robert R Mercer, Katherine A Roach, Bean T Chen, Diane Schwegler-Berry, Michael L Kashon, Mark W Barger, Jenny R Roberts
The effects of acute pulmonary coexposures to silica and diesel particulate matter (DPM), which may occur in various mining operations, were investigated in vivo. Rats were exposed by intratracheal instillation (IT) to silica (50 or 233 µg), DPM (7.89 or 50 µg) or silica and DPM combined in phosphate-buffered saline (PBS) or to PBS alone (control). At one day, one week, one month, two months and three months postexposure bronchoalveolar lavage and histopathology were performed to assess lung injury, inflammation and immune response...
October 1, 2017: Inhalation Toxicology
Giovanni Filardo, Baron L Hamman, Briget da Graca, Danielle M Sass, Natalie J Machala, Safiyah Ismail, Benjamin D Pollock, Ashley W Collinsworth, Paul A Grayburn
BACKGROUND: Despite many studies comparing on- versus off-pump coronary artery bypass graft (CABG), there is no consensus as to whether one of these techniques offers patients better outcomes. METHODS: We searched PubMed from inception to June 30, 2015, and identified additional studies from bibliographies of meta-analyses and reviews. We identified 42 randomized controlled trials (RCTs) and 31 rigorously adjusted observational studies (controlling for the Society of Thoracic Surgeons-recognized risk factors for mortality) reporting mortality for off-pump versus on-pump CABG at specified time points...
September 1, 2017: Journal of Thoracic and Cardiovascular Surgery
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