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Regulation of antitumor immunity by inflammation-induced epigenetic alterations

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Cellular & Molecular Immunology 2022年第1期19卷 59-66页

作者： michael Karin Shabnam Shalapour Department of Pharmacology School of MedicineUniversity of California San DiegoLa JollaCAUSA Laboratory of Gene Regulation and Signal Transduction Department of PharmacologySchool of MedicineUniversity of California San DiegoLa JollaCAUSA Department of Cancer Biology University of Texas MD Anderson Cancer CenterHoustonTXUSA

Chronic inflammation promotes tumor development,progression,and metastatic dissemination and causes treatment *** accumulation of genetic alterations and loss of normal cellular regulatory processes are not only associated with cancer growth and progression but also result in the expression of tumor-specific and tumor-associated antigens that may activate antitumor *** antagonism between inflammation and immunity and the ability of cancer cells to avoid immune detection affect the course of cancer development and treatment *** inflammation,particularly acute inflammation,supports T-cell priming,activation,and infiltration into infected tissues,chronic inflammation is mostly ***,the main mechanisms that dictate the outcome of the inflammation-immunity interplay are not well *** data suggest that inflammation triggers epigenetic alterations in cancer cells and components of the tumor *** alterations can affect and modulate numerous aspects of cancer development,including tumor growth,the metabolic state,metastatic spread,immune escape,and immunosuppressive or immunosupportive leukocyte *** this review,we discuss the role of inflammation in initiating epigenetic alterations in immune cells,cancer-associated fibroblasts,and cancer cells and suggest how and when epigenetic interventions can be combined with immunotherapies to improve therapeutic outcomes.

关键词： Inflammation Epigenetics Antitumor immunity Immunotherapy

The Neglected Role of Risk Mitigation Perception in the Risk Governance of Underground Technologies——The Example of Induced Seismicity

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International Journal of Disaster Risk Science 2020年第5期11卷 630-639页

作者： Lisa Haemmerli michael Stauffacher D-USYS Transdisciplinarity Lab Department of Environmental Systems Science(D-USYS)ETH Zurich(Swiss Federal Institute of Technology/Eidgenossische Technische Hochschule)8092 ZurichSwitzerland

Subsurface technologies,such as geothermal energy and carbon capture and storage,are options to help limit global *** tech no logies involve the risk of induced *** successful implementation of these technologies depends on the public perception of these *** governance frameworks propose assessing the level of public concern and designing adapted risk mitigation *** propose that concerns should not only be investigated with respect to the perceived risks but also with respect to the potential mitigation *** explore this by analyzing the perception of risk mitigation measures for different subsurface *** an online survey(N=808)in Switzerland we analyzed four technologies(in-between subject design)and four mitigation measures(within subject design).We found that risk mitigation measures are perceived differently,within and across ***,public concerns about risk mitigation really *** suggest that future research should focus on how risk mitigation measures can be applied and communicated to realize the full potential of risk governance frameworks.

关键词： Carbon capture and storage Enhanced geothermal systems Induced seismicity Risk mitigation perception Shale gas Switzerland

Spectral Methods for Resolving Spike Dynamics in the Geirer-Meinhardt Model

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Communications in Computational Physics 2008年第3期3卷 659-678页

作者： michael McCourt Nicholas Dovidio michael Gilbert Department of Applied Mathematics Illinois Institute of TechnologyChicagoIL 60616USA Department of Mathematics Davidson CollegeNorth CarolinaUSA Department of Mathematics and Physics Colorado State University-PuebloColoradoUSA.

The Gierer-Meinhardt reaction-diffusion model is analyzed using a spectralcollocation method. This reaction-diffusion system is governed by activator and inhibitorconcentrations. Initially, the system is considered in one dimension and thenin two dimensions;numerical results are presented for both cases. The algorithmiccomplexity and accuracy are compared to those of a moving finite element ***, observations are made concerning when to use the proposed spectral methodas opposed to the established moving mesh method.

关键词： Spike dynamics Gierer-Meinhardt model spectral collocation.

EndoN treatment allows neuroblasts to leave the rostral migratory stream and migrate towards a lesion within the prefrontal cortex of rats

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Neural Regeneration Research 2020年第9期15卷 1740-1747页

作者： Jannis Gundelach michael Koch Department of Neuropharmacology Center for Cognitive Sciences University of Bremen

The binding properties of neural cell adhesion molecule are modulated by a polysialic acid moiety. This plays an important role in the migration of adult born neuroblasts from their area of origin, the subventricular zone, towards the olfactory bulb. Polysialisation increases the migration speed of the cells and helps to prevent the neuroblasts from leaving their migration route, the rostral migratory stream. Here, we evaluated the potential of intraventricular application of endoneuraminidase-N, an enzyme that specifically cleaves polysialic acid from neural cell adhesion molecule, in a rat model for structural prefrontal cortex damage. As expected, endoneuraminidase-N caused the rostral migratory stream to become wider, with a less uniform cellular orientation. Furthermore, endoneuraminidase-N treatment caused the neuroblasts to leave the rostral migratory stream and migrate towards the lesioned tissue. Despite the neuroblasts not being differentiated into neurons after a survival time of three weeks, this technique provides a solid animal model for future work on the migration and differentiation of relocated neuroblasts and might provide a basis for a future endogenous stem cell-based therapy for structural brain damage. The experiments were approved by the local animal care committee(522-27-11/02-00, 115;Senatorin für Wissenschaft, Gesundheit und Verbraucherschutz, Bremen, Germany) on February 10, 2016.

关键词： endogenous stem cells endoneuraminidase neural cell adhesion molecule neuroblast migration olfactory bulb polisialic acid structural brain damage subventricular zone

Precision time protocol attack strategies and their resistance to existing security extensions

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Cybersecurity 2021年第1期4卷 160-176页

作者： Waleed Alghamdi michael Schukat School of Computer Science National University of Ireland Galway Ireland

The IEEE 1588 precision time protocol(PTP)is very important for many industrial sectors and applications that require time synchronization accuracy between computers down to microsecond and even nanosecond ***,PTP and its underlying network infrastructure are vulnerable to cyber-attacks,which can stealthily reduce the time synchronization accuracy to unacceptable and even damage-causing levels for individual clocks or an entire network,leading to financial loss or even physical *** security protocol extensions only partially address this *** paper provides a comprehensive analysis of strategies for advanced persistent threats to PTP infrastructure,possible attacker locations,and the impact on clock and network synchronization in the presence of security protocol extensions,infrastructure redundancy,and protocol *** distinguishes between attack strategies and attacker types as described in RFC7384,but further distinguishes between the spoofing and time source attack,the simple internal attack,and the advanced internal *** experiments were conducted to demonstrate the impact of PTP *** analysis shows that a sophisticated attacker has a range of methodologies to compromise a PTP ***,all PTP infrastructure components can host an attacker,making the comprehensive protection of a PTP network against a malware infiltration,as for example exercised by Stuxnet,a very tedious task.

关键词： APT Cyber-attacks IEEE 1588 PTP Security Time synchronization protocols

Regulation of expression of drug-metabolizing enzymes by oncogenic signaling pathways in liver tumors: a review

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Acta Pharmaceutica Sinica B 2020年第1期10卷 113-122页

作者： Albert Braeuning michael Schwarz German Federal Institute for Risk Assessment Dept.Food SafetyBerlin 10589Germany Eberhard Karls University of Tu¨bingen Inst.of Pharmacology and ToxicologyDept.of ToxicologyTu¨bingen 72074Germany

Mutations in genes encoding key players in oncogenic signaling pathways trigger specific downstream gene expression profiles in the respective tumor cell *** regulation of genes related to cell growth,survival,and death has been extensively studied,much less is known on the regulation of drug-metabolizing enzymes(DMEs)by oncogenic ***,a comprehensive review of the available literature is presented summarizing the impact of the most relevant genetic alterations in human and rodent liver tumors on the expression of DMEs with a focus on phasesⅠandⅡof xenobiotic *** few data are available with respect to DME regulation by p53-dependent signaling,telomerase expression or altered chromatin *** contrast,DME regulation by constitutive activation of oncogenic signaling via the RAS/RAF/mitogen-activated protein kinase(MAPK)cascade or via the canonical WNT/β-catenin signaling pathway has been analyzed in greater depth,demonstrating mostly positive-regulatory effects of WNT/β-catenin signaling and negativeregulatory effects of MAPK *** studies have revealed molecular interactions between oncogenic signaling and nuclear xeno-sensing receptors which underlie the observed alterations in DME expression in liver *** of altered DME expression and inducibility in liver tumors with a specific gene expression profile may impact pharmacological treatment options.

关键词： Xenobiotic metabolism Hepatocytes WNT/b-catenin signaling RAS/MAPK signaling Gene mutation Cytochrome P450

Acetylation of Starch Extracted from Rejected Fruits of <i>Musa ×paradisiaca L.</i>to Obtain a Pharmaceutical Disintegrant

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Pharmacology & Pharmacy 2020年第6期11卷 118-126页

作者： Karla Dumancela Eduardo Mayorga Javier Santamaría- aguirre Facultad de Ciencias Químicas Universidad Central del Ecuador Quito Ecuador Instituto de Investigación en Salud Pública y Zoonosis CIZ Universidad Central del Ecuador Quito Ecuador

There are many natural sources to obtain pharmaceutical grade starch, one of which is banana (Musa × paradisiaca L.);nevertheless, the use of native starch has certain disadvantages compared to modified starches, whose disintegrating properties are better. In this study, starch extracted from rejected fruits of Musa × paradisiaca L., was modified by acetylation, under the following optimized experimental conditions: 130 mL acetic anhydride, 3 mL sodium hydroxide 50% p/v for each 15 grams of native starch, at 123℃ during 3 hours. The reaction resulted in a modified green banana starch with twice as much swelling capacity compared to unmodified (native) starch;acetylation was verified by infrared spectroscopy and degree of substitution of acetyl groups by back titration. The dissolution profiles of Ibuprofen tablets made with banana modified starch and commercial disintegrant, have no differences according with their similarity factor, f2. It is concluded that it is feasible to use green banana starch modified through acetylation as a pharmaceutical disintegrant.

关键词： Modified Banana Starch Acetylation Swelling Capacity Disintegrant Dissolution Profile

Book review of Land Use Transitions and Rural Restructuring in China by Hualou Long

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Journal of Geographical Sciences 2020年第8期30卷 1382-1384页

作者： WOODS michael Department of Geography and Earth Sciences Aberystwyth UniversityAberystwyth SY233DBUK

The restructuring of rural China is one of the most important elements of global social and economic change in the early twenty-first *** a traditionally rural country,with deep cultural roots in the‘soil’,China has been transformed into a highly advanced and largely urbanized society within the course of a few *** scale and significance of the transformation is equivalent to the industrialization and urbanization of Europe in the nineteenth and early twentieth centuries,and like the European experience a century earlier,its impacts reverberate around the ***,contemporary China is not Victorian-era Europe and whilst there are parallels,we cannot assume that the trajectories,consequences and responses are the same.

关键词： Rural Transition consequences

A method for automatic tuning of flight simulator motion platforms

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International Journal of Modeling, Simulation, and Scientific Computing 2017年第4期8卷 43-63页

作者： michael Jones German Aerospace Center Braunschweig NiedersachsenGermany

When tuning motion platforms,subjective opinion is usually regarded as sufficient for most applications,as it should provide verification that no false cueing ***,often systems are not configured to fully utilize the available motion for the desired *** paper presents a new method to objectively tune simulation motion *** usage of the available platform motion space is shown through an example of its application to a specific mission *** difference in motion filter settings for two simulator platform geometries is *** displays the suitability of the platforms for completion of the two-axis lateral reposition task.

关键词： Simulation flight motion optimization