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Phosphodiesterase 4 inhibitors and drugs of abuse： current knowledge and therapeutic opportunities

Frontiers in Biology 2016年第5期11卷 376-386页

作者： christopher m. Olsen Qing-Song Liu Department of Pharmacology and Toxicology Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee W1 53226 USA Neuroscience Research Center Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee WI 53226 USA

BACKGROUND： Long-term exposure to drugs of abuse causes an upregulation of the cAmP-signaling pathway in the nucleus accumbens and other forebrain regions, this common neuroadaptation is thought to underlie aspects of drug tolerance and dependence. Phosphodiesterase 4 （PDE4） is an enzyme that the selective hydrolyzes intracellular cAmP. It is expressed in several brain regions that regulate the reinforcing effects of drugs of abuse. OBJECTIVE： Here, we review the current knowledge about central nervous system （CNS） distribution of PDE4 isoforms and the effects of systemic and brain-region specific inhibition of PDE4 on behavioral models of drug addiction. mETHODS： A systematic literature search was performed using the Pubmed. RESULTS： Using behavioral sensitization, conditioned place preference and drug self-administration as behavioral models, a large number of studies have shown that local or systemic administration of PDE4 inhibitors reduce drug intake and/or drug seeking for psychostimulants, alcohol, and opioids in rats or mice. CONCLUSIONS： Preclinical studies suggest that PDE4 could be a therapeutic target for several classes of substance use disorder. We conclude by identifying opportunities for the development of subtype-selective PDE4 inhibitors that may reduce addiction liability and minimize the side effects that limit the clinical potential of non-selective PDE4 inhibitors. Several PDE4 inhibitors have been clinically approved for other diseases. There is a promising possibility to repurpose these PDE4 inhibitors for the treatment of drug addiction as they are safe and well-tolerated in patients.

关键词： PDE4 PDE4 inhibitors VTA nucleus accumbens drug addiction

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The strawberry genome:a complicated past and promising future

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Horticulture Research 2019年第1期6卷 518-520页

作者： Kevin m.Folta christopher R.Barbey Horticultural Sciences Department University of FloridaGainesvilleFL 32611USA

Within the juicy red flesh of the commercial strawberry lies a deep history that spans at least three continents and hundreds of thousands of *** genetic heritage of this prized dessert fruit was crafted by nature,with its modern improvement driven by the indigenous mapuche people of South America,a seafaring a French spy,and a plant-loving teenager that gathered fruits to present to a *** many stories that punctuate the history of the modern strawberry relate to its contemporary cultivation as well as origins that span a significant portion of the globe1,2.

关键词： straw hundreds berry

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Secular change in earth processes： Preface

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Geoscience Frontiers 2018年第4期9卷 965-966页

作者： Richard m.Palin christopher J.Spencer Department of Geology and Geological Engineering Colorado School of Mines Golden CO 80401 USA The Institute of Geoscience Research (TIGER) School of Earth and Planetary Sciences Curtin University WA 6102 Australia

*** Uniformitarianism is a traditional approach used in many areas of geoscience that assumes the geologic processes observed today operated similarly throughout all of Earth history（Hutton,1788;Windley,1993）,with such an ideology commonly encapsulated by the maxim＂the present is the key to the past＂.This concept is closely associated with the philosophical principle of Occam’s razor.

关键词： Secular change in earth processes Preface

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Pillar design and coal burst experience in Utah Book Cliffs longwall operations

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International Journal of mining Science and Technology 2021年第1期31卷 33-41页

作者： christopher mark michael Gauna mine Safety and Health Administration Technical Support PittsburghPA 15236USA

Longwall mining has existed in Utah for more than half a *** of this mining occurred at depths of cover that significantly exceed those encountered by most other US longwall *** cover causes high ground stress,which can combine with geology to create a coal burst *** every longwall mine operating within the Utah’s Book Cliffs coalfield has been affected by coal *** design has been a key component in the burst control strategies employed by mines in the Book ***,most longwall mines employed double-use two-entry yield pillar ***-use signifies that the gate system serves first as the headgate,and then later serves as the tailgate for the adjacent *** the 1996 burst fatality at the Aberdeen mine,the inter-panel barrier design was *** this layout,a wide barrier pillar protects each longwall panel from the previously mined panel,and each gate system is used just *** paper documents the deep cover longwall mining conducted with each type of pillar design,together with the associated coal burst *** of the six longwall mining complexes in the Book Cliffs having a coal burst history is described on a panel-by-panel *** analysis shows that where the mining depth exceeded 450 m,each design has been employed for about 38000 total m of longwall panel *** double-use yield pillar design has been used primarily at depths less than 600 m,however,while the inter-panel barrier design has been used mainly at depths exceeding 600 *** its greater depth of use,the inter-panel barrier gate design has been associated with about one-third as much face region burst activity as the double-use yield pillar design.

关键词： Longwall Ground control Coal burst Pillar design Yield pillar

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molecular Analysis of Legume Nodule Development and Autoregulation

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Journal of Integrative Plant Biology 2010年第1期52卷 61-76页

作者： Brett J. ferguson Arief Indrasumunar Satomi Hayashi Yu-Hsiang Lin Dugald E. Reid Peter m. Gresshoff ARC Centre of Excellence for Integrative Legume Research The University of Queensland

Legumes are highly important food, feed and biofuel crops. With few exceptions, they can enter into an intricate symbiotic relationship with specific soil bacteria called rhizobia. This interaction results in the formation of a new root organ called the nodule in which the rhizobia convert atmospheric nitrogen gas into forms of nitrogen that are useable by the plant. The plant tightly controls the number of nodules it forms, via a complex root-to-shoot-to-root signaling loop called autoregulation of nodulation （AON）. This regulatory process involves peptide hormones, receptor kinases and small metabolites. Using modern genetic and genomic techniques, many of the components required for nodule formation and AON have now been isolated. This review addresses these recent findings, presents detailed models of the nodulation and AON processes, and identifies gaps in our understanding of these process that have yet to be fully explained.

关键词： molecular Analysis of Legume Nodule Development and Autoregulation

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CROSS-LINKING OF AROmATIC POLY(THIOETHER)S

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Chinese Journal of Polymer Science 2007年第5期25卷 509-517页

作者： matthew m. Yonkey Dillip K. mohanty christopher Crouse Zhong-biao Zhang Department of Chemistry Central Mich-igan University Mt. Pleasant M1-48858 USA Department of Chemistry Rice-University Houston TX-77251 USA Department of Chemistry Virginia Tech Blacksburg VA-24060 USA

A novel cross-linking process using two high molecular weight aromatic poly（thioether）s, which were synthesized by the reactions of 4,4＇-thiobisbenzenethiol with 4,4＇-difluorobenzophenone and 4,4＇-difluorodiphenylsulfone, respectively, and commercially available lower molecular weight poly（p-phenylene sulfide） was investigated. These reactions were carried out in bulk by the addition of silver tetrafluroborate and α,α＇-dibromo-p-xylene at 190℃ over a period of 45 min. Furthermore, the same procedure could be modified to cross-link compression-molded films of these three polymers. The thermal and solubility behaviors of these polymers before and after cross-linking reactions, are presented.

关键词： Aromatic poly(thioether)s Chemical cross-linking Solubility Thermal stability.

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Polymer-capped gold nanoparticles and ZnO nanorods form binary photocatalyst on cotton fabrics: Catalytic breakdown of dye

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Frontiers of materials Science 2021年第3期15卷 431-447页

作者： Bharat BARUAH christopher KELLEY Grace B.DJOKOTO Kelly m.HARTNETT Department of Chemistry and Biochemistry Kennesaw State UniversityKennesawGA 30144-5591USA Division of Natural Sciences Oglethorpe UniversityAtlantaGA 30319USA

This work reports the immobilization of zinc oxide(ZnO)nanostructures and gold nanoparticles(AuNPs)on cotton fabrics(CFs).The ZnO and AuNPs containing CF composite materials demonstrated excellent photocatalytic activity towards degradation of the model organic dye molecule.A two-step method was used to first create zinc oxide nanorods(ZnONRs)on the CF ***,these ZnONRs were decorated with cationic polymer-capped AuNPs to yield the composite materials.A one-pot synthetic route was developed to synthesize polymer-capped *** water-soluble cationic polymers used here are polyguanidino oxanorbornenes(PGONs)at 20 kDa and polyamino oxanorbornenes(PAONs)at 20 ***-vis was utilized to monitor the composite materials’photocatalytic activity in degrading model organic dye *** the materials were characterized by FTIR,UV-visible DRS,SEm,EDX,and *** composite materials exhibited excellent photocatalytic activity and recyclability in the presence of UV light.

关键词： cationic polymer polymer-capped nanoparticles ZnO nanorods fabric photocatalysis

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Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes

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World Journal of Gastroenterology 2016年第45期22卷 9966-9973页

作者： Neil Rajoriya Dhiraj Tripathi Joanna A Leithead Bridget K Gunson Sophie Lord James W ferguson Gideon m Hirschfield Liver Unit Queen Elizabeth Hospital Centre for Liver Research NIHR Birmingham Liver Biomedical Research Unit University of Birmingham

AIm To establish the impact of portal hypertension(PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease(PCLD) listed for liver transplantation. mETHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters:(1) presence of radiological or endoscopic documented varices from our own centre or the referral centre;(2) splenomegaly(> 11 cm) on radiology inabsence of splenic cysts accounting for increased imaging size;(3) thrombocytopenia(platelets m a single cyst. RESULTS Forty-seven PCLD patients(F: m = 42: 5) were listed for liver transplantation(LT)(single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients(40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age(PH group, 50.6(6.4); non-PH group, 47.1(7.4) years; P = 0.101), median listing mELD(PH group, 12; non-PH group, 11; P = 0.422) median listing UKELD score(PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy(P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay(PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length(PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy(PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity.

关键词： Polycystic liver disease Portal hypertension Liver transplantation

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Polyplex interaction strength as a driver of potency during cancer immunotherapy

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Nano Research 2018年第10期11卷 5642-5656页

作者： Shannon d. Tsai James I. Andorko Xiangbin Zeng Joshua m. Gammon christopher m. dewell Fischell Department of Bioengineering University of Marylond 8278 Paint Branch Drive College Park MD 20742 USA Robert E. Fischell Institute for Biomedicol Devices University of Maryland 8278 Paint Branch Drive College Park MD 20742 USA United States Department of Veterans Affairs Maryland VA Health Care System 10 North Greene Street Baltimore MD 21201 USA Deportment of microbiology and Immunology University of Maryland Medical School 685 West Baltimore Street Baltimore MD 21201 USA marlene and Stewart Greenebaum Cancer Center 22 South Greene Street Baltimore MD 21201 USA

many experimental cancer vaccines are exploring toll-like receptor agonists （TLRas） such as CpG, a DNA motif that agonizes toll-like receptor 9 （TLR9）, to trigger immune responses that are potent and molecularly-specific. The ability to tune the immune response is especially important in the immunosuppressive microenvironments of tumors. Because TLR9 is located intracellularly, CpG must be internalized by immune cells for functionality. Polyplexes can be self- assembled through electrostatics using DNA （anionic） condensed by a positively charged carrier. These structures improve cell delivery and have been widely explored for gene therapy. In contrast, here we use cationic poly （^-amino esters）（PBAEs） to assemble polyplexes from CpG as an adjuvant to target and improve immune stimulation in cells and mouse models. Polyplexes were formed over a range of PBAE：CpG ratios, resulting in a library of complexes with increasingly positive charge and stronger binding as PBAE：CpG ratio increased. Although higher PBAE：CpG ratios exhibited improved CpG uptake, lower ratios of PBAE：CpG--which condensed CpG more weakly, activated DCs and tumorspecific T cells more effectively. In a mouse melanoma model, polyplexes with lower binding affinities improved survival more effectively compared with higher binding affinities. These data demonstrate that altering the polyplex interaction strength impacts accessibility of CpG to TLRs in immune cells. Thus, physiochemical properties, particularly the interplay between charge, uptake, and affinity, play a key role in determining the nature and efficacy of the immune response generated. This insight identifies new design considerations that must be balanced for engineering effective immunotherapies and vaccines.

关键词： cancer immunotherapy nanoparticle vaccine polyplex

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Unanticipated multiple seam stresses from pillar systems behaving as pseudo gob–case histories

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International Journal of mining Science and Technology 2017年第1期27卷 131-137页

作者： Gauna michael mark christopher Pittsburgh Safety and Health Technology Center Mine Safety and Health Administration(MSHA)PittsburghPA 15236USA

Underground coal mining in the U.S. is conducted in numerous regions where previous workings exist above and/or below an actively mined seam. miners know that overlying or underlying fully extracted coal areas, also known as gob regions, can result in abutment stresses that affect the active mining. If there was no full extraction, and the past mining consists entirely of intact pillars, the stresses on the active seam are usually minimal. However, experience has shown that in some situations there has been sufficient yielding in overlying or underlying pillar systems to cause stress transfer to the adjoining larger pillars or barriers, which in turn, transfer significant stresses onto the workings of the active seam. In other words, the overlying or underlying pillar system behaves as a ‘‘pseudo gob." The presence of a pseudo gob is often unexpected, and the consequences can be severe. This paper presents several case histories, summarized briefly below, that illustrate pseudo gob phenomenon:(1) pillar rib degradation at a West Virginia mine at 335 m depth that contributed to a rib roll fatality,(2) pillar rib deterioration at a Western Kentucky mine at 175 m depth that required pillar size adjustment and installation of supplemental bolting,(3) roof deterioration at an eastern Kentucky mine at 400 m depth that stopped mine advance and required redirecting the section development,(4) coal burst on development at an eastern Kentucky mine at 520 m depth that had no nearby pillar recovery, and(5) coal burst on development at a West Virginia mine at the relatively shallow depth of 335 m that also had no nearby pillar recovery. The paper provides guidance so that when an operation encounters a potential pseudo gob stress interaction the hazard can be mitigated based on an understanding of the mechanism encountered.

关键词： Underground mining Coal multiple seam Gob Ground control

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