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minocycline fails to improve neurologic and histologic outcome after ventricular fibrillation cardiac arrest in rats

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World Journal of Critical Care medicine 2019年第7期8卷 106-119页

作者： Andreas Janata Ingrid Am magnet Kristin L Schreiber Caleb D Wilson Jason P Stezoski Keri Janesko-Feldman patrick m kochanek Tomas Drabek Safar Center for Resuscitation Research University of Pittsburgh School of MedicinePittsburghPA 15224United States Department of Critical Care medicine University of Pittsburgh School of MedicinePittsburghPA 15213United States Emergency Department KA RudolfstiftungVienna 1030Austria Department of Emergency medicine Vienna General HospitalMedical University of ViennaVienna 1090Austria Department of Anesthesiology and Perioperative medicine University of Pittsburgh School of MedicinePittsburghPA 15213United States Department of Anesthesiology Perioperative and Pain MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115United States Wyoming Otolaryngology Wyoming Medical CenterCasperWY 82604United States

BACKGROUND Prolonged cardiac arrest(CA)produces extensive neuronal death and microglial proliferation and activation resulting in neuro-cognitive *** other potential mechanisms,microglia have been implicated as triggers of neuronal death after hypoxic-ischemic *** is neuroprotective in some brain ischemia models,either by blunting the microglial response or by a direct effect on *** To improve survival,attenuate neurologic deficits,neuroinflammation,and histological damage after ventricular fibrillation(VF)CA in *** Adult male isoflurane-anesthetized rats were subjected to 6 min VF CA followed by 2 min resuscitation including chest compression,epinephrine,bicarbonate,and *** return of spontaneous circulation(ROSC),rats were randomized to two groups:(1)minocycline 90 mg/kg intraperitoneally(i.p.)at 15 min ROSC,followed by 22.5 mg/kg *** 12 h for 72 h;and(2)Controls,receiving the same volume of vehicle(phosphate-buffered saline).The rats were kept normothermic during the postoperative *** injury was assessed daily using Overall Performance Category(OPC;1=normal,5=dead)and Neurologic Deficit Score(NDS;0%=normal,100%=dead).Rats were sacrificed at 72 *** degeneration(Fluoro-Jade C staining)and microglia proliferation(anti-Iba-1 staining)were quantified in four selectively vulnerable brain regions(hippocampus,striatum,cerebellum,cortex)by three independent reviewers masked to the group *** In the minocycline group,8 out of 14 rats survived to 72 h compared to 8 out of 19 rats in the control group(P=0.46).The degree of neurologic deficit at 72 h[median,(interquartile range)]was not different between survivors in minocycline vs controls:OPC 1.5(1-2.75)vs 2(1.25-3),P=0.442;NDS 12(2-20)vs 17(7-51),P=0.328)or between all studied *** number of degenerating neurons(minocycline vs controls,mean±SEm:Hippocampus 58±8 vs 76±8;striatum 121±43 vs 153±32;cerebellum 20±7 vs 22

关键词： Heart arrest/pathology Cardiopulmonary resuscitation Survival rate Neurons/drug effects microglia/drug effects minocycline/pharmacology

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Local and range-wide distribution of song types suggest Ovenbirds(Seiurus aurocapilla)have song neighborhoods but not macro-dialects

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Avian Research 2023年第2期14卷 191-199页

作者： patrick m.Jagielski Jennifer R.Foote Department of Biology Algoma UniversitySault Ste.MarieONCanada

The song systems of oscine passerines(songbirds)are complex and *** songs are used for both mate attraction and territory defense and are therefore important signals for survival and reproduction,comprehensive knowledge of within and among species song structure and distribution is informative for understanding the evolution of song repertoires and vocal *** this study,we explored variation in the song structure of the Ovenbird(Seiurus aurocapilla),a widespread warbler(Family Parulidae)found in North American *** analyzed recordings from the 2021 breeding season to assess song type variation at a local(n=158 birds;Sault ***,ON)and breeding range scale(n=512 birds;eBird).We characterized the local song types and tested whether Ovenbirds share song types with their neighbors more often than expected by *** then characterized song types of Ovenbirds across the breeding range to determine whether any geographic pattern of song clustering exists(i.e.,macro-dialects).We found 10 distinct song types and some evidence for song type clustering at the local study site(i.e.,song neighborhoods).We found 7 of those 10 song types throughout the breeding range and identified an additional 24 types that were not recorded in our local *** found no evidence for song dialects across the Ovenbird breeding *** study contributes to our understanding of Ovenbird song while simultaneously adding to our understanding of geographic structuring of warbler *** work contributes to delineating a more comprehensive understanding of factors affecting dialect development for this diverse group of songbirds.

关键词： Dialects eBird Geographic variation Ovenbird Parulidae Seiurus aurocapilla Song type

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A direct solver with O（N） complexity for integral equations on one-dimensional domains

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Frontiers of mathematics in China 2012年第2期7卷 217-247页

作者： Adrianna GILLmAN patrick m. YOUNG Per-Gunnar mARTINSSON Department of Applied mathematics University of Colorado at Boulder BoulderCO 80309-0526 USA

An algorithm for the direct inversion of the linear systems arising from NystrSm discretization of integral equations on one-dimensional domains is described. The method typically has O（N） complexity when applied to boundary integral equations （BIEs） in the plane with non-oscillatory kernels such as those associated with the Laplace and Stokes＇ equations. The scaling coefficient suppressed by the ＂big-O＂ notation depends logarithraically on the requested accuracy. The method can also be applied to BIEs with oscillatory kernels such as those associated with the Helmholtz and time-harmonic maxwell equations; it is efficient at long and intermediate wave-lengths, but will eventually become prohibitively slow as the wave-length decreases. To achieve linear complexity, rank： deficiencies in the off-diagonal blocks of the coefficient matrix are exploited. The technique is conceptually related to the H- and H2-matrix arithmetic of Hackbusch and coworkers, and is closely related to previous work on Hierarchically Semi-Separable matrices.

关键词： Direct solver integral equation fast direct solver boundary value problem boundary integral equation hierarchically semi-separable matrix mSC 65R20,65F05

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Importance of being Nernst: Synaptic activity and functional relevance in stem cell-derived neurons

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World Journal of Stem Cells 2015年第6期7卷 899-921页

作者： Aaron B Bradford patrick m mcNutt Cell/molecular Biology Branch US Army Medical Research Institute of Chemical DefenseAberdeen Proving Grounds-EAMD 21010United States

Functional synaptogenesis and network emergence are signature endpoints of neurogenesis. These behaviors provide higher-order confirmation that biochemical and cellular processes necessary for neurotransmitter release, post-synaptic detection and network propagationof neuronal activity have been properly expressed and coordinated among cells. The development of synaptic neurotransmission can therefore be considered a defining property of neurons. Although dissociated primary neuron cultures readily form functioning synapses and network behaviors in vitro, continuously cultured neurogenic cell lines have historically failed to meet these criteria. Therefore, in vitro-derived neuron models that develop synaptic transmission are critically needed for a wide array of studies, including molecular neuroscience, developmental neurogenesis, disease research and neurotoxicology. Over the last decade, neurons derived from various stem cell lines have shown varying ability to develop into functionally mature neurons. In this review, we will discuss the neurogenic potential of various stem cells populations, addressing strengths and weaknesses of each, with particular attention to the emergence of functional behaviors. We will propose methods to functionally characterize new stem cell-derived neuron(SCN) platforms to improve their reliability as physiological relevant models. Finally, we will review how synaptically active SCNs can be applied to accelerate research in a variety of areas. Ultimately, emphasizing the critical importance of synaptic activity and network responses as a marker of neuronal maturation is anticipated to result in in vitro findings that better translate to efficacious clinical treatments.

关键词： Synapses Neurotransmission In vitrotechniques Induced pluripotent stem cells Neuronalnetworks Neurogenesis Neural stem cells Embryonicstem cells Induced neurons

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Stroma-targeting strategies in pancreatic cancer:Past lessons,challenges and prospects

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World Journal of Gastroenterology 2021年第18期27卷 2105-2121页

作者： Faran Polani patrick m Grierson Kian-Huat Lim Division of Oncology Department of Internal MedicineBarnes-Jewish Hospital and The Alvin J.Siteman Comprehensive Cancer CenterWashington University School of MedicineSaint LouisMO 63110United States

Pancreatic ductal adenocarcinoma(PDAC)is projected to emerge as the second leading cause of cancer-related death after *** treatment resistance is perhaps the most significant factor that underlies the poor prognosis of *** date,combination chemotherapy remains the mainstay of treatment for most PDAC *** to other cancer types,treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and *** from typically harboring genetic alterations that to date remain undruggable and are drivers of treatment resistance,PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting cancer progression and treatment ***,emerging evidence also suggests that indiscriminate targeting and near complete depletion of stroma may promote PDAC aggressiveness and lead to detrimental *** conflicting results undoubtedly warrant the need for a more in-depth understanding of the heterogeneity of tumor stroma in order to develop modulatory strategies in favor of tumor *** advent of novel techniques including single cell RNA sequencing and multiplex immunohistochemistry have further illuminated the complex heterogeneity of tumor cells,stromal fibroblasts,and immune *** new knowledge is instrumental for development of more refined therapeutic strategies that can ultimately defeat this ***,we provide a concise review on lessons learned from past stromatargeting strategies,new challenges revealed from recent preclinical and clinical studies,as well as new prospects in the treatment of PDAC.

关键词： Stroma Pancreatic cancer Treatment resistance Cancer-associated fibroblasts Clinical trials

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Crystallization kinetics of Sn_(40)Se_(60) thin films for phase change memory applications

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Journal of Semiconductors 2015年第6期36卷 17-20页

作者： Joshua m.Kundu patrick m.Karimi Walter K.Njoroge Department of Physics Kenyatta University

The crystallization kinetics of Sn4oSe6o thin films has been successfully investigated using sheet resis- tance versus temperature measurements. Thermal evaporation was used to deposit the films on ordinary glass sub- strates. The crystallization temperature for Sn4oSe60 thin film was found to be 156.6 -t- 0.3 ~C. In the as-deposited state, the sheet resistance was found to be 195 mf2/[2, this value declined to 1560 f2/[2] upon annealing. The value of activation energy obtained from the Kissinger plot was 0.62 ＋ 0.07 eV. From the results obtained, SnaoSe60 is a promising alloy for PCm application because of its high electrical contrast, high crystallization temperature, and relatively high activation energy.

关键词： crystallization temperature activation energy electrical contrast phase change memory

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Chronic peripheral inflammation: a possible contributor to neurodegenerative diseases

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Neural Regeneration Research 2021年第9期16卷 1711-1714页

作者： patrick Süβ Addison J.Lana Johannes C.m.Schlachetzki Department of molecular Neurology Friedrich-Alexander-University Erlangen-NürnbergUniversity Hospital ErlangenErlangenGermany Department of Cellular and molecular medicine University of California San DiegoLa JollaCAUSA

The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases. In addition, progressive systemic inflammation is increasingly recognized during aging. Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules. There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances. In this perspective, we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia, the resident immune cells of the brain parenchyma.

关键词： aging Alzheimer's disease inflammation innate immune system microglia neurodegeneration Parkinson's disease

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Revisiting the dissolution of biogenic Si in marine sediments： a key term in the ocean Si budget

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Acta Geochimica 2017年第3期36卷 429-432页

作者： patrick Frings Department of Geoscience Swedish Museum of Natural History 10405 Stockholm Sweden Earth Surface Geochemistry GFZ German Research Centre for Geosciences 14473 Telegrafenberg Potsdam Germany

Of the　~240*10^(12)mol year^(-1)of biogenic silica(bSi)produced by diatoms and other silicifying organisms,only roughly 3%–4%escapes dissolution to be permanently *** the global scale,how,where and why b Si is preserved in sediment is not well *** help address this,I compile 6245 porewater dissolved Si concentrations from 453 sediment cores,to derive the concentration gradient at the sediment–water interface and thus diffusive fluxes out of the *** range from\0.002 to 3.4 mol m^(-2)year^(-1),and are independent of temperature,depth and *** classified by sediment lithology,predominantly siliceous sediments unsurprisingly have higher mean diffusive fluxes than predominantly calcareous or clay-rich *** with the areal extent of these lithologies,the‘best-guess’global sedimentary b Si recycling flux is69 9 10^(12)mol year^(-1).

关键词： Biogenic silica Diatoms Ocean Si cycle Dissolution

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Better together?Comparing physical activity of parents walking outdoors with and without their child

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Sports medicine and Health Science 2023年第3期5卷 190-195页

作者： patrick m.Filanowski Emily Slade Department of Sport Science&management Xavier UniversityCincinnatiOH45207USA Department of Biostatistics University of KentuckyLexingtonKY40506USA

This study compares the physical activity levels and enjoyment of parents(n=50;age=41.8±4.0 years)during outdoor,self-paced walking sessions while walking alone and when walking with their 6-to-12-year-old *** counts,moderate-to-vigorous physical activity(mVPA),vigorous physical activity,and enjoyment were compared using paired *** modeling was used to examine the impact of children's age and adults'and children's body mass index on the disparity in step counts experienced by *** attained high percentages of time spent in mVPA while walking alone(99.8%)and when walking with their child(96.6%).However,more of this time was categorized as vigorous physical activity when walking alone(13.6%vs.3.0%,p=0.006).Adults'step counts decreased by an average of 6.4%while walking with their child compared to walking alone(pmal-weight adults(p=0.042).Although adults obtained higher step counts and vigorous physical activity while walking alone,they enjoyed walking more with their child(pmaking recommendations for parent-child co-participation in physical activity,and parents may wish to supplement their physical activity obtained while walking with their child(ren)with additional activities that result in vigorous physical activity.

关键词： alone walking younger

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The emerging role and targetability of the TCA cycle in cancer metabolism

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Protein & Cell 2018年第2期9卷 216-237页

作者： Nicole m. Anderson patrick mucka Joseph G. Kern Hui Feng Abramson Family Cancer Research Institute University of Pennsylvania Philadelphia PA 19104-6160 USA Perelman School of medicine at the University of Pennsylvania Philadelphia PA 19104 USA Departments of Pharmacology and medicine The Center for Cancer Research Section of Hematology and Medical Oncology Boston University School of Medicine Boston MA 02118 USA Program in Biomedical Sciences Boston University School of Medicine Boston MA 02118 USA

The tricarboxylic acid （TCA） cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance require- ments. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for thera- peutic interventions in various cancer types.

关键词： glutaminolysis the TCA cycle cancer metabolism glycolysis

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