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Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

World Journal of Gastroenterology 2018年第48期24卷 5418-5432页

作者： sandra wagner Christina S Mullins Michael Linnebacher Section of Molecular Oncology and Immunotherapy General SurgeryUniversity Medical Center

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

关键词： Cancer vaccines Colorectal neoplasm Immunotherapy Neoplasm antigen tumor-associated antigens tumor-specific antigens Neoantigen(s)

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Enhanced migration of tissue inhibitor of metalloproteinase overexpressing hepatoma cells is attributed to gelatinases: Relevance to intracellular signaling pathways

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World Journal of Gastroenterology 2005年第8期11卷 1096-1104页

作者： Elke Roeb Anja-Katrin Bosserhoff Sabine Hamacher Bettina Jansen Judith Dahmen sandra wagner Siegfried Matern Department of Internal Medicine Ⅲ Institute of Pathology

AIM: To study the effect of gelatinases (especially MMP-9) on migration of tissue inhibitor of metalloproteinase (TIMP-1) overexpressing hepatoma cells. METHODS: Wild type HepG2 cells, cells stably transfected with TIMP-1 and TIMP-1 antagonist (MMP-9-H401A, a catalytically inactive matrix metalloproteinase (MMP) which still binds and neutralizes TIMP-1) were incubated in Boyden chambers either with or without Galardin (a synthetic inhibitor of MMP-1, -2, -3, -8, -9) or a specific inhibitor of gelatinases. RESULTS: Compared to wild type HepG2 cells, the cells overexpressing TIMP-1 showed 115% migration (P<0.05) and the cells overexpressing MMP-9-H401A showed 62% migration (P<0.01). Galardin reduced cell migration dose dependently in all cases. The gelatinase inhibitor reduced migration in TIMP-1 overexpressing cells predominantly. Furthermore, we examined intracellular signal transduction pathways of TIMP-1-dependent HepG2 cells. TIMP-1 deactivates cell signaling pathways of MMP-2 and MMP-9 involving p38 mitogen-activated protein kinase. Specific blockade of the ERK pathway suppresses gelatinase expression either in the presence or absence of TIMP-1. CONCLUSION: Overexpressing functional TIMP-1-enhanced migration of HepG2-TIMP-l cells depends on enhanced MMP-activity, especially MMP-9.

关键词： HepG2 MMP-2 MMP-9 p38MAPK Galardin Genistein

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Assessment of food supplementation and surveillance as techniques to reduce damage caused by black capuchin monkeys Sapajus nigritus to forest plantations

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Current Zoology 2014年第5期60卷 581-590页

作者： sandra Bos MIKICH Laboratory of Ecology (Laborat6rio de Ecologia) Embrapa Florestas Caixa Postal 319 CEP 83411-000 Colombo PR Brazil Black Capuchin Monkey Program (Programa Macaco-prego) National Fund for the Control of Forest Pests (Fundo Nacional de Controle de Pragas Florestais) Dieter Liebsch Environmental Consulting (Dieter Liebsch Consultoria Ambiental) Curitiba PR Brazil dieterliebsch@yahoo.com.br

Black capuchin monkeys Sapajus nigritus are among several mammalian species that damage forest plantations, pri- marily plantations of pine trees （Pinus spp.） in South Brazil. Management practices to reduce these damages include supplemen- tary food offerings and plantation surveillance. To assess the efficiency of these techniques, four treatments were evaluated： feeding （F, with supplementary bananas and maize）, surveillance （S, in situ, wherein men patrolled the plantations, deterring the monkeys）, feeding ＋ surveillance （FS） and control （no procedures）（C）. The efficiency assessment of each treatment involved the number of recorded primate sightings in the treatments with the presence of guards （S and FS） and a damage inventory of the outskirts of the experimental points immediately before and after the experiment. These data were complemented by a simulta- neous study of the availability of fruit, the primary item in the diet of this primate species, in the remnant native forest in the study area. Most sightings of S. nigritus occurred early in the morning, and in general, sightings were inversely proportional to the availability of native fruits. This trend was most evident in treatment FS, most likely due to the presence of food. Treatments F and FS exhibited higher percentages of damage, indicating that these are inefficient management techniques. Treatment S exhi- bited the lowest damage rate, but at a high cost, making this technique difficult to apply over large expanses. The development of other management techniques, such as environmental enrichment and the use of deterrents, is recommended to minimize the damage caused by capuchins in forest plantations [Current Zoology 60 （5）： 581-590, 2014].

关键词： Cebus Damage control Wildlife management Pinus Food provisioning

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Geostatistical seismic inversion and 3D modelling of metric flow units,porosity and permeability in Brazilian presalt reservoir

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Petroleum Science 2024年第3期21卷 1699-1718页

作者： Rodrigo Penna wagner Moreira Lupinacci Exploratory Interpretation and Reservoir Characterization Group(GIECAR) Department of Geology and GeophysicsUniversidade Federal FluminenseNiteroiRJ24210-346Brazil Petrobras Rio de JaneiroRJ20031-912Brazil

Flow units(FU)rock typing is a common technique for characterizing reservoir flow behavior,producing reliable porosity and permeability estimation even in complex geological ***,the lateral extrapolation of FU away from the well into the whole reservoir grid is commonly a difficult task and using the seismic data as constraints is rarely a subject of *** paper proposes a workflow to generate numerous possible 3D volumes of flow units,porosity and permeability below the seismic resolution limit,respecting the available seismic data at larger *** methodology is used in the Mero Field,a Brazilian presalt carbonate reservoir located in the Santos Basin,who presents a complex and heterogenic geological setting with different sedimentological processes and diagenetic *** generated metric flow units using the conventional core analysis and transposed to the well log ***,given a Markov chain Monte Carlo algorithm,the seismic data and the well log statistics,we simulated acoustic impedance,decametric flow units(DFU),metric flow units(MFU),porosity and permeability volumes in the metric *** aim is to estimate a minimum amount of MFU able to calculate realistic scenarios porosity and permeability scenarios,without losing the seismic lateral *** other words,every porosity and permeability volume simulated produces a synthetic seismic that match the real seismic of the area,even in the metric *** achieved 3D results represent a high-resolution fluid flow reservoir modelling considering the lateral control of the seismic during the process and can be directly incorporated in the dynamic characterization workflow.

关键词： Flowunits Geostatistical inversion Presalt reservoir 3D reservoir modelling Petrophysical modelling

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Pork Meat Quality of Preto Alentejano and Commercial Largewhite Landrace Cross

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Journal of Integrative Agriculture 2013年第11期12卷 1961-1971页

作者： Alfredo Teixeira sandra Rodrigues Veterinary and Animal Reserch Centre (CECAV) Agrarian School of Polytechnic Institute of BraganaCampus Sta Apolónia Apt.1172Bragan a 5301-855Portugal Mountain Research Centre(CIMO) Agrarian School of Polytechnic Institute of BraganaCampus Sta Apolónia Apt.1172Bragan a 5301-855Portugal

This work aimed to evaluate the physical-chemical characteristics of pork from a local breed （Portuguese black pork called Preto Alentejano） and a commercial breed. Sixteen animals were used, 4 females and 4 males from each breed. Animals had 80-100 kg of live weight. The longissimus muscle between the 5th thoracic vertebra and the 10th lumbar vertebra was used in the analysis. Samples were analysed for protein, fat, pigments, ashes, dry mater, water-holding capacity, and texture. Results of fat and pigments contents indicate signiifcant （P〈0.05 and P〈0.01） differences for all treatments. For protein, ashes, dry mater, water-holding capacity and texture, no signiifcant differences were found for sex. In the analysis of fatty acids composition, ten were detected, being the main ones C16：0, C18：0, C16：1, C18：1, C18：2. There was a predominance of monounsaturated fatty acids （MUFA）, followed by saturated （SFA） and polyunsaturated （PUFA）. Differences were signiifcant for sex （P〈0.01） and breed （P〈0.01）. Preto Alentejano breed and females presented the higher percentages of SFA （P〈0.01） and MUFA （P〈0.001） fatty acids. Differences between breeds might be due to breed production system and feed differences.

关键词： breed sex pork meat quality

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Hyper-chaos encryption using convolutional masking and model free unmasking

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Chinese Physics B 2014年第5期23卷 161-166页

作者：齐国元 sandra Bazebo Matondo Department of Electrical Engineerin Tshwane University of Technology Pretoria

In this paper, during the masking process the encrypted message is convolved and embedded into a Qi hyper-chaotic system characterizing a high disorder degree. The masking scheme was tested using both Qi hyper-chaos and Lorenz chaos and indicated that Qi hyper-chaos based masking can resist attacks of the filtering and power spectrum analysis, while the Lorenz based scheme fails for high amplitude data. To unmask the message at the receiving end, two methods are proposed. In the first method, a model-free synchronizer, i.e. a multivariable higher-order differential feedback controller between the transmitter and receiver is employed to de-convolve the message embedded in the receiving signal. In the second method, no synchronization is required since the message is de-convolved using the information of the estimated derivative.

关键词： Qi hyper-chaos masking high-order differentiator chaos-based encryption

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Compaction analysis and optimisation of convex-faced pharmaceutical tablets using numerical techniques

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Particuology 2019年第6期17卷 10-21页

作者： Ahmad Baroutaji sandra Lenihan Keith Bryan School of Engineering Faculty of Science and EngineeringUniversity of WolverhamptonTelfordUK School of Mechanical Electrical and Process EngineeringCork Institute of TechnologyCorkIreland

Capping failure,edge chipping,and non-uniform mechanical properties of convex-faced pharmaceutical tablets are common problems in the pharma *** this paper,the finite element method(FEM)and design of experiment techniques are used to determine the optimal shape of convex-faced(CF)pharmaceutical tablet which has more uniform mechanical properties and less capping and chipping *** effects of different geometrical parameters and friction on the compaction responses of convex-faced pharmaceutical tablets were first identified and *** FEM model of the tabletting process was generated using the implicit code ABAQUS and validated against experimental *** surface methodology was used to establish the relationship between the design variables,represented by the geometrical parameters and friction coefficient,and compaction responses of interest including residual die pressure,relative density variation within a tablet,and relative shear stress at the edge of a tablet.A statistical-based optimisation approach was then used to optimise the shape of CF *** obtained results demonstrated how the geometrical parameters and friction coefficient of CF pharmaceutical tablets strongly affect their compaction behaviour and quality.

关键词： Capping failure Edge chipping Tabletting FEM Optimisation Residual radial pressure

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Ultrahigh temporal contrast performance of the PHELIX petawatt facility

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High Power Laser Science and Engineering 2016年第4期4卷 1-8页

作者： V.Bagnoud F.wagner Plasma physics dep. GSI Helmholtzzentrum für Schwerionenforschung GmbH Helmholtz Institute Jena

We report on the temporal contrast performance of the PHELIX facility in view of the requirements imposed by solidtarget interaction experiments. The requirement analysis for the nanosecond and picosecond temporal contrast is derived from empirical data and simple theoretical modeling, while the realization shows that using an ultrafast optical parametric amplifier and plasma mirrors enables meeting this specification.

关键词： amplified spontaneous emission chirped-pulse amplification optical parametric amplification temporal contrast

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Measurements of Laminar Burning Velocities of Alternative Fuels:Application in Transport and Aerospace

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Journal of Thermal Science 2023年第2期32卷 503-512页

作者： RICHTER sandra BRAUN-UNKHOFF Marina NAUMANN Clemens German Aerospace Center(DLR) Institute of Combustion TechnologyDepartment of Chemical Kinetics and AnalyticsStuttgart 70569Germany

The laminar burning velocity belongs to the fundamental combustion properties of fuels being a measure for their heat release,flame length,as well as reactivity and combustion stability,and thus,may impact the design of burners and combustion ***,these experimental data are needed for the validation and optimization within the construction and development of detailed chemical kinetic reaction *** this study,an overview of the different applications of fuel characterization regarding the specific area of interest(road transport,aviation,and aerospace)will be *** on the application,effects of different molecular characteristics on the laminar burning velocity are evaluated:the presence of oxygen atoms and the grade of branching in a specific fuel molecule as well as the difference in the type of a chemical bond,here,single and double *** of alternative fuels being discussed in the present study are:(Ⅰ)oxymethylene ether(OMEn)in the field of road transport;(Ⅱ)a paraffinic Alcohol-to-Jet fuel as sustainable aviation fuel;and(Ⅲ)mixtures of ethane or ethene with nitrous oxide as green propellants for rocket propulsion applications.

关键词： laminar burning velocity alternative sustainable fuels road transport aviation fuels green propellants

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Catastrophic climate change and the collapse of human societies

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National Science Review 2023年第6期10卷 52-54页

作者： Josep Pe?uelas sandra Nogué CREAF Cerdanyola del Vallès CSIC Global Ecology Unit CREAF-CSIC-UAB Universitat Autònoma de Barcelona

The scientific community has focused the agenda of studies of climate change on lower-end warming and simple risk analyses,because more realistic complex assessments of risk are more difficult,the benchmark of the international targets is the Paris Agreement goal of limiting warming to <2℃,and the culture of climate science is to try to avoid alarmism[1].Current fires,prolonged droughts,floods and heat waves,together with the consequent food insecurity,civil unrest and migrations,however,are opening the eyes not only of most scientists but also of most people all over the world to the need for considering,at least,the potential catastrophic effects of the collapse of ecosystems and society due to the current emergency of climate change.

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