Quantitative modeling of the dynamics and intracellular trafficking of far-red light-activatable prodrugs: implications in stimuli-responsive drug delivery system.

Science.gov (United States)

Li, Mengjie; Thapa, Pritam; Rajaputra, Pallavi; Bio, Moses; Peer, Cody J; Figg, William D; You, Youngjae; Woo, Sukyung

2017-12-01

The combination of photodynamic therapy (PDT) with anti-tumor agents is a complimentary strategy to treat local cancers. We developed a unique photosensitizer (PS)-conjugated paclitaxel (PTX) prodrug in which a PS is excited by near-infrared wavelength light to site-specifically release PTX while generating singlet oxygen (SO) to effectively kill cancer cells with both PTX and SO. The aim of the present study was to identify the determinants influencing the combined efficacy of this light-activatable prodrug, especially the bystander killing effects from released PTX. Using PS-conjugated PTX as a model system, we developed a quantitative mathematical model describing the intracellular trafficking. Dynamics of the prodrug and the model predictions were verified with experimental data using human cancer cells in vitro. The sensitivity analysis suggested that parameters related to extracellular concentration of released PTX, prodrug uptake, target engagement, and target abundance are critical in determining the combined killing efficacy of the prodrug. We found that released PTX cytotoxicity was most sensitive to the retention time of the drug in extracellular space. Modulating drug internalization and conjugating the agents targeted to abundant receptors may provide a new strategy for maximizing the killing capacity of the far-red light-activatable prodrug system. These results provide guidance for the design of the PDT combination study in vivo and have implications for other stimuli-responsive drug delivery systems.

Thrombin-activatable fibrinolysis inhibitor is degraded by Salmonella enterica and Yersinia pestis.

Science.gov (United States)

Valls Serón, M; Haiko, J; DE Groot, P G; Korhonen, T K; Meijers, J C M

2010-10-01

 Pathogenic bacteria modulate the host coagulation system to evade immune responses or to facilitate dissemination through extravascular tissues. In particular, the important bacterial pathogens Salmonella enterica and Yersinia pestis intervene with the plasminogen/fibrinolytic system. Thrombin-activatable fibrinolysis inhibitor (TAFI) has anti-fibrinolytic properties as the active enzyme (TAFIa) removes C-terminal lysine residues from fibrin, thereby attenuating accelerated plasmin formation.  Here, we demonstrate inactivation and cleavage of TAFI by homologous surface proteases, the omptins Pla of Y. pestis and PgtE of S. enterica. We show that omptin-expressing bacteria decrease TAFI activatability by thrombin-thrombomodulin and that the anti-fibrinolytic potential of TAFIa was reduced by recombinant Escherichia coli expressing Pla or PgtE. The functional impairment resulted from C-terminal cleavage of TAFI by the omptins.  Our results indicate that TAFI is degraded directly by the omptins PgtE of S. enterica and Pla of Y. pestis. This may contribute to the ability of PgtE and Pla to damage tissue barriers, such as fibrin, and thereby to enhance spread of S. enterica and Y. pestis during infection. © 2010 International Society on Thrombosis and Haemostasis.

Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

International Nuclear Information System (INIS)

Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B.; Rubin, D.H.

1988-01-01

Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 [VP3]; 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time of 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated 51 Cr, [ 14 C]choline, and [ 3 H]inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration

Infectious rotavirus enters cells by direct cell membrane penetration, not by endocytosis

Energy Technology Data Exchange (ETDEWEB)

Kaljot, K.T.; Shaw, R.D.; Greenberg, H.B. (Stanford Univ. School of Medicine, CA (USA) Palo Alto Veterans Administration Medical Center, CA (USA)); Rubin, D.H. (Univ. of Pennsylvania, Philadelphia (USA))

1988-04-01

Rotaviruses are icosahedral viruses with a segmented, double-stranded RNA genome. They are the major cause of severe infantile infectious diarrhea. Rotavirus growth in tissue culture is markedly enhanced by pretreatment of virus with trypsin. Trypsin activation is associated with cleavage of the viral hemagglutinin (viral protein 3 (VP3); 88 kilodaltons) into two fragments (60 and 28 kilodaltons). The mechanism by which proteolytic cleavage leads to enhanced growth is unknown. To determine whether trypsin treatment affected rotavirus internalization, the authors studied the kinetics of entry of infectious rhesus rotavirus (RRV) into MA104 cells. Trypsin-activated RRV was internalized with a half-time of 3 to 5 min, while nonactivated virus disappeared from the cell surface with a half-time of 30 to 50 min. In contrast to trypsin-activated RRV, loss of nonactivated RRV from the cell surface did not result in the appearance of infection, as measured by plaque formation. Purified trypsin-activated RRV added to cell monolayers at pH 7.4 mediated {sup 51}Cr, ({sup 14}C)choline, and ({sup 3}H)inositol released from prelabeled MA104 cells. This release could be specifically blocked by neutralizing antibodies to VP3. These results suggest that MA104 cell infection follows the rapid entry of trypsin-activated RRV by direct cell membrane penetration. Cell membrane penetration of infectious RRV is initiated by trypsin cleavage of VP3. Neutralizing antibodies can inhibit this direct membrane penetration.

Cell-penetrating antimicrobial peptides - prospectives for targeting intracellular infections

DEFF Research Database (Denmark)

Bahnsen, Jesper S; Franzyk, Henrik; Sayers, Edward J

2015-01-01

PURPOSE: To investigate the suitability of three antimicrobial peptides (AMPs) as cell-penetrating antimicrobial peptides. METHODS: Cellular uptake of three AMPs (PK-12-KKP, SA-3 and TPk) and a cell-penetrating peptide (penetratin), all 5(6)-carboxytetramethylrhodamine-labeled, were tested in He......La WT cells and analyzed by flow cytometry and confocal microscopy. Furthermore, the effects of the peptides on eukaryotic cell viability as well as their antimicrobial effect were tested. In addition, the disrupting ability of the peptides in the presence of bilayer membranes of different composition...... the cellular viability to an unacceptable degree. TPk showed acceptable uptake efficiency, high antimicrobial activity and relatively low toxicity, and it is the best potential lead peptide for further development....

Smart activatable and traceable dual-prodrug for image-guided combination photodynamic and chemo-therapy.

Science.gov (United States)

Hu, Fang; Yuan, Youyong; Mao, Duo; Wu, Wenbo; Liu, Bin

2017-11-01

Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.

Science.gov (United States)

Shimizu, Yoichi; Temma, Takashi; Hara, Isao; Makino, Akira; Kondo, Naoya; Ozeki, Ei-Ichi; Ono, Masahiro; Saji, Hideo

2014-08-01

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, λem : 858 nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 ± 0.3 [MT1-hIC7L] vs 3.1 ± 0.2 [hIC7L] 48 h after administration, P fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Antimicrobial and cell-penetrating properties of penetratin analogs

DEFF Research Database (Denmark)

Bahnsen, Jesper Søborg; Franzyk, Henrik; Sandberg-Schaal, Anne

2013-01-01

Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) show great potential as drug delivery vectors and new antibiotic drug entities, respectively. The current study deals with the properties of a variety of peptide analogs derived from the well-known CPP penetratin as well as octaar......Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) show great potential as drug delivery vectors and new antibiotic drug entities, respectively. The current study deals with the properties of a variety of peptide analogs derived from the well-known CPP penetratin as well...... as octaarginine and different Tat sequences. The effects of peptide length, guanidinium content, and sequence of non-cationic residues were assessed in mammalian and bacterial cells. The arginine (Arg) content in the penetratin analogs was found to influence eukaryotic cell uptake efficiency, antimicrobial...... was similar, the eukaryotic cellular uptake of the shuffled analogs was noticeably lower than for native penetratin. Moreover, a point substitution of Met to Leu in native penetratin had no influence on eukaryotic cellular uptake and antimicrobial effect, and only a minor effect on cytotoxicity, in contrast...

Cascading of molecular logic gates for advanced functions: a self-reporting, activatable photosensitizer.

Science.gov (United States)

Erbas-Cakmak, Sundus; Akkaya, Engin U

2013-10-18

Logical progress: Independent molecular logic gates have been designed and characterized. Then, the individual molecular logic gates were coerced to work together within a micelle. Information relay between the two logic gates was achieved through the intermediacy of singlet oxygen. Working together, these concatenated logic gates result in a self-reporting and activatable photosensitizer. GSH=glutathione. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B

NARCIS (Netherlands)

Seron, Mercedes Valls; Plug, Tom; Marquart, J. Arnoud; Marx, Pauline F.; Herwald, Heiko; de Groot, Philip G.; Meijers, Joost C. M.

2011-01-01

Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins ScIA and ScIB at the surface of S. pyogenes. Activation of TAFI at this surface redirects inflammation from a transient to chronic

A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells.

Directory of Open Access Journals (Sweden)

Ki Jung Lim

Full Text Available Cell-penetrating peptides (CPPs have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2 was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57. The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv directed toward a mutated K-ras (G12V. BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.

A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells.

Science.gov (United States)

Lim, Ki Jung; Sung, Bong Hyun; Shin, Ju Ri; Lee, Young Woong; Kim, Da Jung; Yang, Kyung Seok; Kim, Sun Chang

2013-01-01

Cell-penetrating peptides (CPPs) have proven very effective as intracellular delivery vehicles for various therapeutics. However, there are some concerns about non-specific penetration and cytotoxicity of CPPs for effective cancer treatments. Herein, based on the cell-penetrating motif of an anticancer peptide, buforin IIb, we designed several CPP derivatives with cancer cell specificity. Among the derivatives, a 17-amino acid peptide (BR2) was found to have cancer-specificity without toxicity to normal cells. After specifically targeting cancer cells through interaction with gangliosides, BR2 entered cells via lipid-mediated macropinocytosis. Moreover, BR2 showed higher membrane translocation efficiency than the well-known CPP Tat (49-57). The capability of BR2 as a cancer-specific drug carrier was demonstrated by fusion of BR2 to a single-chain variable fragment (scFv) directed toward a mutated K-ras (G12V). BR2-fused scFv induced a higher degree of apoptosis than Tat-fused scFv in K-ras mutated HCT116 cells. These results suggest that the novel cell-penetrating peptide BR2 has great potential as a useful drug delivery carrier with cancer cell specificity.

An eco-friendly in situ activatable antibiotic via cucurbit[8]uril-mediated supramolecular crosslinking of branched polyethylenimine.

Science.gov (United States)

Li, Shengke; Jiang, Nan; Zhao, Wenxuan; Ding, Yuan-Fu; Zheng, Ying; Wang, Lian-Hui; Zheng, Jun; Wang, Ruibing

2017-05-30

We report an unprecedented, eco-friendly, in situ activatable model antibiotic, phenylalanyl-polyethylenimine (PhePEI), to potentially diminish antibiotic pollution of the environment and associated antibiotic resistance. The inactive PhePEI can be reversibly activated upon supramolecular crosslinking by cucurbit[8]uril, conferring potent antibacterial activity.

A cell-penetrating peptide analogue, P7, exerts antimicrobial activity against Escherichia coli ATCC25922 via penetrating cell membrane and targeting intracellular DNA.

Science.gov (United States)

Li, Lirong; Shi, Yonghui; Cheng, Xiangrong; Xia, Shufang; Cheserek, Maureen Jepkorir; Le, Guowei

2015-01-01

The antibacterial activities and mechanism of a new P7 were investigated in this study. P7 showed antimicrobial activities against five harmful microorganisms which contaminate and spoil food (MIC=4-32 μM). Flow cytometry and scanning electron microscopy analyses demonstrated that P7 induced pore-formation on the cell surface and led to morphological changes but did not lyse cell. Confocal fluorescence microscopic observations and flow cytometry analysis expressed that P7 could penetrate the Escherichia coli cell membrane and accumulate in the cytoplasm. Moreover, P7 possessed a strong DNA binding affinity. Further cell cycle analysis and change in gene expression analysis suggested that P7 induced a decreased expression in the genes involved in DNA replication. Up-regulated expression genes encoding DNA damage repair. This study suggests that P7 could be applied as a candidate for the development of new food preservatives as it exerts its antibacterial activities by penetrating cell membranes and targets intracellular DNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Factor XI dependent and independent activation of thrombin activatable fibrinolysis inhibitor (TAFI) in plasma associated with clot formation

NARCIS (Netherlands)

Bouma, B. N.; Mosnier, L. O.; Meijers, J. C.; Griffin, J. H.

1999-01-01

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) also known as plasma procarboxypeptidase B is activated by relatively high concentrations of thrombin in a reaction stimulated by thrombomodulin. In plasma an intact factor XI-dependent feed back loop via the intrinsic pathway is necessary to

A functional single nucleotide polymorphism in the thrombin-activatable fibrinolysis inhibitor (TAFI) gene associates with outcome of meningococcal disease

NARCIS (Netherlands)

Kremer Hovinga, J. A.; Franco, R. F.; Zago, M. A.; ten Cate, Hugo; Westendorp, R. G. J.; Reitsma, P. H.

2004-01-01

In meningococcal sepsis, disseminated intravascular coagulation with deposition of fibrin and formation of microthrombi occurs in various organs and enhanced inhibition of fibrinolysis is associated with adverse outcome. Recently, TAFI (thrombin-activatable fibrinolysis inhibitor) was identified as

Secondary structure of cell-penetrating peptides during interaction with fungal cells.

Science.gov (United States)

Gong, Zifan; Ikonomova, Svetlana P; Karlsson, Amy J

2018-03-01

Cell-penetrating peptides (CPPs) are peptides that cross cell membranes, either alone or while carrying molecular cargo. Although their interactions with mammalian cells have been widely studied, much less is known about their interactions with fungal cells, particularly at the biophysical level. We analyzed the interactions of seven CPPs (penetratin, Pep-1, MPG, pVEC, TP-10, MAP, and cecropin B) with the fungal pathogen Candida albicans using experiments and molecular simulations. Circular dichroism (CD) of the peptides revealed a structural transition from a random coil or weak helix to an α-helix occurs for all peptides when the solvent is changed from aqueous to hydrophobic. However, CD performed in the presence of C. albicans cells showed that proximity to the cell membrane is not necessarily sufficient to induce this structural transition, as penetratin, Pep-1, and MPG did not display a structural shift in the presence of cells. Monte Carlo simulations were performed to further probe the molecular-level interaction with the cell membrane, and these simulations suggested that pVEC, TP-10, MAP, and cecropin B strongly penetrate into the hydrophobic domain of the membrane lipid bilayer, inducing a transition to an α-helical conformation. In contrast, penetratin, Pep-1 and MPG remained in the hydrophilic region without a shift in conformation. The experimental data and MC simulations combine to explain how peptide structure affects their interaction with cells and their mechanism of translocation into cells (direct translocation vs. endocytosis). Our work also highlights the utility of combining biophysical experiments, biological experiments, and molecular modeling to understand biological phenomena. © 2017 The Protein Society.

Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins[S

Science.gov (United States)

Subra, Caroline; Grand, David; Laulagnier, Karine; Stella, Alexandre; Lambeau, Gérard; Paillasse, Michael; De Medina, Philippe; Monsarrat, Bernard; Perret, Bertrand; Silvente-Poirot, Sandrine; Poirot, Marc; Record, Michel

2010-01-01

Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contained the whole set of phospholipases (A2, C, and D) together with interacting proteins such as aldolase A and Hsp 70. They also contained the phospholipase D (PLD) / phosphatidate phosphatase 1 (PAP1) pathway leading to the formation of diglycerides. RBL-2H3 exosomes also carried members of the three phospholipase A2 classes: the calcium-dependent cPLA2-IVA, the calcium-independent iPLA2-VIA, and the secreted sPLA2-IIA and V. Remarkably, almost all members of the Ras GTPase superfamily were present, and incubation of exosomes with GTPγS triggered activation of phospholipase A2 (PLA2)and PLD2. A large panel of free fatty acids, including arachidonic acid (AA) and derivatives such as prostaglandin E2 (PGE2) and 15-deoxy-Δ12,14-prostaglandinJ2 (15-d PGJ2), were detected. We observed that the exosomes were internalized by resting and activated RBL cells and that they accumulated in an endosomal compartment. Endosomal concentrations were in the micromolar range for prostaglandins; i.e., concentrations able to trigger prostaglandin-dependent biological responses. Therefore exosomes are carriers of GTP-activatable phospholipases and lipid mediators from cell to cell. PMID:20424270

[Potential of cell penetrating peptides for cell drug delivery].

Science.gov (United States)

Poillot, Cathy; De Waard, Michel

2011-05-01

The interest of the scientific community for cell penetrating peptides (CPP) has been growing exponentially for these last years, and the list of novel CPP is increasing. These peptides are powerful tools for the delivery of cargoes to their site of action. Indeed, several drugs that cannot translocate through the cell plasma membrane have been successfully delivered into cells when grafted to a CPP. Various cargoes have been linked to CPP, such as oligonucleotides, pharmacologically active drugs, contrast agents for imaging, or nanoparticles as platforms for multigrafting purposes… This review illustrates the fabulous potential of CPP and the diversity of their use, but their most interesting application appears their future clinical use for the treatment of various pathological conditions. © 2011 médecine/sciences - Inserm / SRMS.

Antibacterial Effects of a Cell-Penetrating Peptide Isolated from Kefir.

Science.gov (United States)

Miao, Jianyin; Guo, Haoxian; Chen, Feilong; Zhao, Lichao; He, Liping; Ou, Yangwen; Huang, Manman; Zhang, Yi; Guo, Baoyan; Cao, Yong; Huang, Qingrong

2016-04-27

Kefir is a traditional fermented milk beverage used throughout the world for centuries. A cell-penetrating peptide, F3, was isolated from kefir by Sephadex G-50 gel filtration, DEAE-52 ion exchange, and reverse-phase high-performance liquid chromatography. F3 was determined to be a low molecular weight peptide containing one leucine and one tyrosine with two phosphate radicals. This peptide displayed antimicrobial activity across a broad spectrum of organisms including several Gram-positive and Gram-negative bacteria as well as fungi, with minimal inhibitory concentration (MIC) values ranging from 125 to 500 μg/mL. Cellular penetration and accumulation of F3 were determined by confocal laser scanning microscopy. The peptide was able to penetrate the cellular membrane of Escherichia coli and Staphylococcus aureus. Changes in cell morphology were observed by scanning electron microscopy (SEM). The results indicate that peptide F3 may be a good candidate for use as an effective biological preservative in agriculture and the food industry.

Bioportide: an emergent concept of bioactive cell-penetrating peptides

Czech Academy of Sciences Publication Activity Database

Howl, J.; Matou-Nasri, S.; West, D. C.; Farquhar, M.; Slaninová, Jiřina; Ostenson, C. G.; Zorko, M.; Ostlund, P.; Kumar, S.; Langel, U.; McKeating, J.; Jones, S.

2012-01-01

Roč. 69, č. 17 (2012), s. 2951-2966 ISSN 1420-682X Institutional research plan: CEZ:AV0Z40550506 Keywords : angiogenesis * bioportide * cell-penetrating peptide * second messenger * insulin secretion Subject RIV: CE - Biochemistry Impact factor: 5.615, year: 2012

Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

Directory of Open Access Journals (Sweden)

Caghan Kizil

Full Text Available Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI, RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides

Directory of Open Access Journals (Sweden)

Tingting Lin

2016-07-01

Full Text Available Brain delivery of macromolecular therapeutics (e.g., proteins remains an unsolved problem because of the formidable blood–brain barrier (BBB. Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs, new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available pathways (e.g., epithelial tight junctions, uptake by olfactory neurons, transport into brain tissues, and intra-brain diffusion, a low molecular weight protamine (LMWP cell-penetrating peptide was utilized to facilitate nose-to-brain transport. Cell-penetrating peptides (CPP have been widely used to mediate macromolecular delivery through many kinds of biobarriers. Our results show that conjugates of LMWP–proteins are able to effectively penetrate into the brain after intranasal administration. The CPP-based intranasal method highlights a promising solution for protein therapy of brain diseases.

Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides

Institute of Scientific and Technical Information of China (English)

Tingting Lin; Ergang Liu; Huining He; Meong Cheol Shin; Cheol Moon; Victor C.Yang; Yongzhuo Huang

2016-01-01

Brain delivery of macromolecular therapeutics(e.g., proteins) remains an unsolved problem because of the formidable blood–brain barrier(BBB). Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs,new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available pathways(e.g., epithelial tight junctions, uptake by olfactory neurons, transport into brain tissues, and intra-brain diffusion), a low molecular weight protamine(LMWP) cell-penetrating peptide was utilized to facilitate nose-to-brain transport. Cell-penetrating peptides(CPP)have been widely used to mediate macromolecular delivery through many kinds of biobarriers. Our results show that conjugates of LMWP–proteins are able to effectively penetrate into the brain after intranasal administration.The CPP-based intranasal method highlights a promising solution for protein therapy of brain diseases.

Paramagnetic particles carried by cell-penetrating peptide tracking of bone marrow mesenchymal stem cells, a research in vitro

International Nuclear Information System (INIS)

Liu Min; Guo Youmin; Wu Qifei; Yang Junle; Wang Peng; Wang Sicen; Guo Xiaojuan; Qiang Yongqian; Duan Xiaoyi

2006-01-01

The ability to track the distribution and differentiation of stem cells by high-resolution imaging techniques would have significant clinical and research implications. In this study, a model cell-penetrating peptide was used to carry gadolinium particles for magnetic resonance imaging of the mesenchymal stem cells. The mesenchymal stem cells were isolated from rat bone marrow by Percoll and identified by osteogenic differentiation in vitro. The cell-penetrating peptides labeled with fluorescein-5-isothiocyanate and gadolinium were synthesized by a solid-phase peptide synthesis method and the relaxivity of cell-penetrating peptide-gadolinium paramagnetic conjugate on 400 MHz nuclear magnetic resonance was 5.7311 ± 0.0122 mmol -1 s -1 , higher than that of diethylenetriamine pentaacetic acid gadolinium (p < 0.05). Fluorescein imaging confirmed that this new peptide could internalize into the cytoplasm and nucleus. Gadolinium was efficiently internalized into mesenchymal stem cells by the peptide in a time- or concentration-dependent fashion, resulting in intercellular T1 relaxation enhancement, which was obviously detected by 1.5 T magnetic resonance imaging. Cytotoxicity assay and flow cytometric analysis showed the intercellular contrast medium incorporation did not affect cell viability and membrane potential gradient. The research in vitro suggests that the newly constructed peptides could be a vector for tracking mesenchymal stem cells

Sensitive and selective tumor imaging with novel and highly activatable fluorescence probes

International Nuclear Information System (INIS)

Urano, Yasuteru

2008-01-01

Selective and sensitive tumor imaging in vivo is one of the most requested methodologies in medical sciences. Although several imaging modalities have been developed including positron emission tomography (PET) and magnetic resonance (MR) imaging for the detection of tumors, none of these modalities can activate the signals upon being accumulated or uptaken to tumor sites. Among these modalities, only optical fluorescence imaging has a marked advantage, that is, their signals can be dramatically increased upon detecting some biological features. In this short review, I will introduce some recent strategies for activatable optical fluorescence imaging of tumors, and discuss their advantages over other modalities. (author)

Force-activatable biosensor enables single platelet force mapping directly by fluorescence imaging.

Science.gov (United States)

Wang, Yongliang; LeVine, Dana N; Gannon, Margaret; Zhao, Yuanchang; Sarkar, Anwesha; Hoch, Bailey; Wang, Xuefeng

2018-02-15

Integrin-transmitted cellular forces are critical for platelet adhesion, activation, aggregation and contraction during hemostasis and thrombosis. Measuring and mapping single platelet forces are desired in both research and clinical applications. Conventional force-to-strain based cell traction force microscopies have low resolution which is not ideal for cellular force mapping in small platelets. To enable platelet force mapping with submicron resolution, we developed a force-activatable biosensor named integrative tension sensor (ITS) which directly converts molecular tensions to fluorescent signals, therefore enabling cellular force mapping directly by fluorescence imaging. With ITS, we mapped cellular forces in single platelets at 0.4µm resolution. We found that platelet force distribution has strong polarization which is sensitive to treatment with the anti-platelet drug tirofiban, suggesting that the ITS force map can report anti-platelet drug efficacy. The ITS also calibrated integrin molecular tensions in platelets and revealed two distinct tension levels: 12-54 piconewton (nominal values) tensions generated during platelet adhesion and tensions above 54 piconewton generated during platelet contraction. Overall, the ITS is a powerful biosensor for the study of platelet mechanobiology, and holds great potential in antithrombotic drug development and assessing platelet activity in health and disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma.

Science.gov (United States)

Zhang, Xue; Lin, Congcong; Lu, Aiping; Lin, Ge; Chen, Huoji; Liu, Qiang; Yang, Zhijun; Zhang, Hongqi

2017-11-01

A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.

Improving cell penetration of helical peptides stabilized by N-terminal crosslinked aspartic acids.

Science.gov (United States)

Zhao, Hui; Jiang, Yanhong; Tian, Yuan; Yang, Dan; Qin, Xuan; Li, Zigang

2017-01-04

Cell penetration and nucleus translocation efficiency are important for the cellular activities of peptide therapeutics. For helical peptides stabilized by N-terminal crosslinked aspartic acid, correlations between their penetration efficiency/nucleus translocation and physicochemical properties were studied. An increase in hydrophobicity and isoelectric point will promote cellular uptake and nucleus translocation of stabilized helices.

Thrombin-activatable fibrinolysis inhibitor activity in healthy and diseased dogs

DEFF Research Database (Denmark)

Jessen, Lisbeth Rem; Wiinberg, Bo; Kjelgaard-Hansen, Mads

2010-01-01

Background: In people, increased thrombin-activatable fibrinolysis inhibitor (TAFI) antigen has been associated with increased risk of thrombosis, and decreased TAFI may contribute to bleeding diathesis. TAFI activity in dogs has been described in experimental models, but not in dogs...... with spontaneous disease. Objective: The aim of this study was to compare TAFI activity in healthy dogs with TAFI activity in dogs with spontaneous disease. Methods: Plasma samples from 20 clinically healthy Beagles and from 35 dogs with various diseases were analyzed using a commercial chromogenic assay...... that measured TAFI activity relative to activity in standardized pooled human plasma. Results: Median TAFI activity for the 20 Beagles was 46.1% (range 32.2-70.8%) compared with 62.6% (29.1-250%) for the 35 diseased dogs, and 14/35 (40%) had TAFI activities >the upper limit for controls. The highest individual...

The uptake of arginine-rich cell-penetrating peptides: putting the puzzle together

NARCIS (Netherlands)

Brock, R.E.

2014-01-01

Over the past 20 years, cell-penetrating peptides (CPPs) have captured the attention of biomedical researchers, biophysicists, and (bio)organic chemists. These molecules efficiently enter cells and mediate entry of (macro)molecules that by themselves do not cross the plasma membrane. Since their

Cell-Penetrating Ability of Peptide Hormones: Key Role of Glycosaminoglycans Clustering

Directory of Open Access Journals (Sweden)

Armelle Tchoumi Neree

2015-11-01

Full Text Available Over the last two decades, the potential usage of cell-penetrating peptides (CPPs for the intracellular delivery of various molecules has prompted the identification of novel peptidic identities. However, cytotoxic effects and unpredicted immunological responses have often limited the use of various CPP sequences in the clinic. To overcome these issues, the usage of endogenous peptides appears as an appropriate alternative approach. The hormone pituitary adenylate-cyclase-activating polypeptide (PACAP38 has been recently identified as a novel and very efficient CPP. This 38-residue polycationic peptide is a member of the secretin/glucagon/growth hormone-releasing hormone (GHRH superfamily, with which PACAP38 shares high structural and conformational homologies. In this study, we evaluated the cell-penetrating ability of cationic peptide hormones in the context of the expression of cell surface glycosaminoglycans (GAGs. Our results indicated that among all peptides evaluated, PACAP38 was unique for its potent efficiency of cellular uptake. Interestingly, the abilities of the peptides to reach the intracellular space did not correlate with their binding affinities to sulfated GAGs, but rather to their capacity to clustered heparin in vitro. This study demonstrates that the uptake efficiency of a given cationic CPP does not necessarily correlate with its affinity to sulfated GAGs and that its ability to cluster GAGs should be considered for the identification of novel peptidic sequences with potent cellular penetrating properties.

Use of radioactive and neutron-activatable tracers to determine effective hydrogeologic parameters

International Nuclear Information System (INIS)

Yu, C.; Jester, W.A.; Jarrett, A.R.

1985-01-01

The migration of nuclides in a geologic medium is controlled by the hydrogeologic parameters of the medium such as the dispersion coefficient, pore water velocity, retardation factor, degradation rate, mass transfer coefficient, water content, and fraction of dead-end pores. The breakthrough curve (BTC), which is the graphical relationship between the tracer concentration and the elapsed time since introduction, is an integrated picture of the hydrogeologic parameters that produced the BTC. Both radioactive and neutron-activatable tracers have been used to generate BTCs. The BTC of a 92 Br radioactive tracer generated under saturated conditions in a nonhomogeneous (fractured) soil column is shown. From BTCs, the effective hydrogeologic parameters can be identified if appropriate techniques are applied

Internalisation of cell-penetrating peptides into tobacco protoplasts.

Science.gov (United States)

Mäe, Maarja; Myrberg, Helena; Jiang, Yang; Paves, Heiti; Valkna, Andres; Langel, Ulo

2005-05-20

Cells are protected from the surrounding environment by plasma membrane which is impenetrable for most hydrophilic molecules. In the last 10 years cell-penetrating peptides (CPPs) have been discovered and developed. CPPs enter mammalian cells and carry cargo molecules over the plasma membrane with a molecular weight several times their own. Known transformation methods for plant cells have relatively low efficiency and require improvement. The possibility to use CPPs as potential delivery vectors for internalisation in plant cells has been studied in the present work. We analyse and compare the uptake of the fluorescein-labeled CPPs, transportan, TP10, penetratin and pVEC in Bowes human melanoma cells and Nicotiana tabacum cultivar (cv.) SR-1 protoplasts (plant cells without cell wall). We study the internalisation efficiency of CPPs with fluorescence microscopy, spectrofluorometry and fluorescence-activated cell sorter (FACS). All methods indicate, for the first time, that these CPPs can internalise into N. tabacum cv. SR-1 protoplasts. Transportan has the highest uptake efficacy among the studied peptides, both in mammalian cells and plant protoplast. The internalisation of CPPs by plant protoplasts may open up a new effective method for transfection in plants.

Sensing lymphoma cells based on a cell-penetrating/apoptosis-inducing/electron-transfer peptide probe

International Nuclear Information System (INIS)

Sugawara, Kazuharu; Shinohara, Hiroki; Kadoya, Toshihiko; Kuramitz, Hideki

2016-01-01

To electrochemically sense lymphoma cells (U937), we fabricated a multifunctional peptide probe that consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. Electron-transfer peptides derive from cysteine residue combined with the C-terminals of four tyrosine residues (Y_4). A peptide whereby Y_4C is bound to the C-terminals of protegrin 1 (RGGRLCYCRRRFCVCVGR-NH_2) is known to be an apoptosis-inducing agent against U937 cells, and is referred to as a peptide-1 probe. An oxidation response of the peptide-1 probe has been observed due to a phenolic hydroxyl group, and this response is decreased by the uptake of the peptide probe into the cells. To improve the cell membrane permeability against U937 cells, the RGGR at the N-terminals of the peptide-1 probe was replaced by RRRR (peptide-2 probe). In contrast, RNRCKGTDVQAWY_4C (peptide-3 probe), which recognizes ovalbumin, was constructed as a control. Compared with the other probes, the change in the peak current of the peptide-2 probe was the greatest at low concentrations and occurred in a short amount of time. Therefore, the cell membrane permeability of the peptide-2 probe was increased based on the arginine residues and the apoptosis-inducing peptides. The peak current was linear and ranged from 100 to 1000 cells/ml. The relative standard deviation of 600 cells/ml was 5.0% (n = 5). Furthermore, the membrane permeability of the peptide probes was confirmed using fluorescent dye. - Highlights: • We constructed a multifunctional peptide probe for the electrochemical sensing of lymphoma cells. • The peptide probe consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. • The electrode response of the peptide probe changes due to selective uptake into the cells.

Sensing lymphoma cells based on a cell-penetrating/apoptosis-inducing/electron-transfer peptide probe

Energy Technology Data Exchange (ETDEWEB)

Sugawara, Kazuharu, E-mail: kzsuga@maebashi-it.ac.jp [Maebashi Institute of Technology, Gunma 371-0816 (Japan); Shinohara, Hiroki; Kadoya, Toshihiko [Maebashi Institute of Technology, Gunma 371-0816 (Japan); Kuramitz, Hideki [Department of Environmental Biology and Chemistry, Graduate School of Science and Engineering for Research, University of Toyama, Toyama 930-8555 (Japan)

2016-06-14

To electrochemically sense lymphoma cells (U937), we fabricated a multifunctional peptide probe that consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. Electron-transfer peptides derive from cysteine residue combined with the C-terminals of four tyrosine residues (Y{sub 4}). A peptide whereby Y{sub 4}C is bound to the C-terminals of protegrin 1 (RGGRLCYCRRRFCVCVGR-NH{sub 2}) is known to be an apoptosis-inducing agent against U937 cells, and is referred to as a peptide-1 probe. An oxidation response of the peptide-1 probe has been observed due to a phenolic hydroxyl group, and this response is decreased by the uptake of the peptide probe into the cells. To improve the cell membrane permeability against U937 cells, the RGGR at the N-terminals of the peptide-1 probe was replaced by RRRR (peptide-2 probe). In contrast, RNRCKGTDVQAWY{sub 4}C (peptide-3 probe), which recognizes ovalbumin, was constructed as a control. Compared with the other probes, the change in the peak current of the peptide-2 probe was the greatest at low concentrations and occurred in a short amount of time. Therefore, the cell membrane permeability of the peptide-2 probe was increased based on the arginine residues and the apoptosis-inducing peptides. The peak current was linear and ranged from 100 to 1000 cells/ml. The relative standard deviation of 600 cells/ml was 5.0% (n = 5). Furthermore, the membrane permeability of the peptide probes was confirmed using fluorescent dye. - Highlights: • We constructed a multifunctional peptide probe for the electrochemical sensing of lymphoma cells. • The peptide probe consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. • The electrode response of the peptide probe changes due to selective uptake into the cells.

In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides.

Science.gov (United States)

Bolhassani, Azam; Jafarzade, Behnaz Sadat; Mardani, Golnaz

2017-01-01

The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full-length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose-dependent approach. A major disadvantage of PTD-fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non-covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP-based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Alternative Mechanisms for the Interaction of the Cell-Penetrating Peptides Penetratin and the TAT Peptide with Lipid Bilayers

NARCIS (Netherlands)

Yesylevskyy, Semen; Marrink, Siewert-Jan; Mark, Alan E.

2009-01-01

Cell-penetrating peptides (CPPs) have recently attracted much interest due to their apparent ability to penetrate cell membranes in an energy-independent manner. Here molecular-dynamics simulation techniques were used to study the interaction of two CPPs: penetratin and the TAT peptide with

Metabolic cleavage of cell-penetrating peptides in contact with epithelial models

DEFF Research Database (Denmark)

Tréhin, Rachel; Nielsen, Hanne Mørck; Jahnke, Heinz-Georg

2004-01-01

We assessed the metabolic degradation kinetics and cleavage patterns of some selected CPP (cell-penetrating peptides) after incubation with confluent epithelial models. Synthesis of N-terminal CF [5(6)-carboxyfluorescein]-labelled CPP, namely hCT (human calcitonin)-derived sequences, Tat(47-57) a...

Live Cell Genomics: RNA Exon-Specific RNA-Binding Protein Isolation.

Science.gov (United States)

Bell, Thomas J; Eberwine, James

2015-01-01

RNA-binding proteins (RBPs) are essential regulatory proteins that control all modes of RNA processing and regulation. New experimental approaches to isolate these indispensable proteins under in vivo conditions are needed to advance the field of RBP biology. Historically, in vitro biochemical approaches to isolate RBP complexes have been useful and productive, but biological relevance of the identified RBP complexes can be imprecise or erroneous. Here we review an inventive experimental to isolate RBPs under the in vivo conditions. The method is called peptide nucleic acid (PNA)-assisted identification of RBP (PAIR) technology and it uses cell-penetrating peptides (CPPs) to deliver photo-activatible RBP-capture molecule to the cytoplasm of the live cells. The PAIR methodology provides two significant advantages over the most commonly used approaches: (1) it overcomes the in vitro limitation of standard biochemical approaches and (2) the PAIR RBP-capture molecule is highly selective and adaptable which allows investigators to isolate exon-specific RBP complexes. Most importantly, the in vivo capture conditions and selectivity of the RBP-capture molecule yield biologically accurate and relevant RBP data.

Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria -transformed leukocytes

KAUST Repository

Haidar, Malak; de Laté , Perle Latré ; Kennedy, Eileen J.; Langsley, Gordon

2017-01-01

One powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way

Chimeric ZHHH neuroglobin acts as a cell membrane-penetrating inducer of neurite outgrowth.

Science.gov (United States)

Takahashi, Nozomu; Onozuka, Wataru; Watanabe, Seiji; Wakasugi, Keisuke

2017-09-01

Neuroglobin (Ngb) is a heme protein expressed in the vertebrate brain. We previously engineered a chimeric Ngb protein, in which module M1 of human Ngb is replaced by that of zebrafish Ngb, and showed that the chimeric ZHHH Ngb has a cell membrane-penetrating activity similar to that of zebrafish Ngb and also rescues cells from death caused by hypoxia/reoxygenation as does human Ngb. Recently, it was reported that overexpression of mammalian Ngb in neuronal cells induces neurite outgrowth. In this study, we performed neurite outgrowth assays of chimeric Ngb using rat pheochromocytoma PC12 cells. Addition of chimeric Ngb, but not human or zebrafish Ngb, exogenously to the cell medium induces neurite outgrowth. On the other hand, the K7A/K9Q chimeric Ngb double mutant, which cannot translocate into cells, did not induce neurite outgrowth, suggesting that the cell membrane-penetrating activity of the chimeric Ngb is crucial for its neurite outgrowth-promoting activity. We also prepared several site-directed chimeric Ngb mutants and demonstrated that residues crucial for neurite outgrowth-inducing activity of the chimeric Ngb are not exactly the same as those for its neuroprotective activity.

Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity.

Science.gov (United States)

Astrada, Soledad; Fernández Massó, Julio Raúl; Vallespí, Maribel G; Bollati-Fogolín, Mariela

2018-03-30

CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced. Here, we present the results obtained from a comparative analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms involved in three human tumor-derived cell lines from different origins: mammary gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell surface markers relevant for internalization processes such as phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization, were also evaluated. We found that both endocytosis and transduction are involved in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552 incorporation efficiency and contribution of each mechanism is cell-line dependent. Finally, sensitivity was directly correlated with high internalization capacity in those cell lines where endocytosis had a major contribution on CIGB-552 internalization.

Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria -transformed leukocytes

KAUST Repository

Haidar, Malak

2017-09-08

One powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets. Theileria-transformed leukocytes display high PKA activity, but PKAis an enzyme that plays key roles in multiple cellular processes; consequently genetic ablation of kinase activity gives rise to a myriad of confounding phenotypes. By contrast, ablation of a specific kinase-substrate interaction has the potential to give more refined information and we illustrate this here by describing how surgically ablating PKA interactions with BAD gives precise information on the type of glycolysis performed by Theileria-transformed leukocytes. In addition, we provide two other examples of how ablating specific protein-protein interactions in Theileria-infected leukocytes leads to precise phenotypes and argue that constrained penetrating peptides have great therapeutic potential to combat infectious diseases in general.

Thrombin activatable fibrinolysis inhibitor (TAFI in cord blood.

Directory of Open Access Journals (Sweden)

Krzysztof Góralczyk

2007-03-01

Full Text Available Thrombin activatable fibrinolysis inhibitor (TAFI is a plasma zymogene (procarboxypeptidase B which can decrease fibrinolysis and thus act as a haemostatic factor. TAFI is now extensively studied in many complications as well as in physiological and complicated pregnancy. The question we posed in the present study was whether TAFI antigen is present in cord blood plasma. The study group consisted of 38 parturient women, 26 primiparous and 12 multiparous with normal course of pregnancy and delivery. The cord blood was sampled from the cord vein, and the mother's blood from the antecubital vein. 3.2% sodium citrate was used as an anticoagulant. TAFIa/ai antigen was measured by ELISA method. TAFIa/ai antigen was identified in all samples of cord blood plasma. Its level was 91.50 ng/ml (range: 71.76 - 160.77 ng/ml vs. 55.46 ng/ml (range: 39.77 - 68.54 ng/ml in the mother's blood, which means that the level of TAFIa/ai antigen was significantly higher in fetal blood than in maternal blood (p<0.00001. TAFIa/ai antigen is an integral component of cord blood plasma. The concentration of TAFIa/ai antigen is about two times higher in fetal blood than in maternal blood.

Visualization of the Nucleolus in Living Cells with Cell-Penetrating Fluorescent Peptides.

Science.gov (United States)

Martin, Robert M; Herce, Henry D; Ludwig, Anne K; Cardoso, M Cristina

2016-01-01

The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of ribosomal RNA synthesis and assembly of ribosomes. The nucleolus plays also a major role in nuclear organization as the largest compartment within the nucleus. The prominent structure of the nucleolus can be detected using contrast light microscopy providing an approximate localization of the nucleolus, but this approach does not allow to determine accurately the three-dimensional structure of the nucleolus in cells and tissues. Immunofluorescence staining with antibodies specific to nucleolar proteins albeit very useful is time consuming, normally antibodies recognize their epitopes only within a small range of species and is applicable only in fixed cells. Here, we present a simple method to selectively and accurately label this ubiquitous subnuclear compartment in living cells of a large range of species using a fluorescently labeled cell-penetrating peptide.

Conformational analysis of Infectious bursal disease virus (IBDV derived cell penetrating peptide (CPP analogs

Directory of Open Access Journals (Sweden)

Vinay G. Joshi

2013-12-01

Full Text Available Aim: This study was designed to develop peptide analogs of Infectious Bursal Disease (IBD virus VP5 protein segment having cell penetrating ability to improve their interaction with cargo molecule (Nucleic acid without affecting the backbone conformation. Materials and Methods: IBDV VP5 protein segment designated as RATH peptide were synthesized using solid phase peptide synthesis and their solution conformation was elucidated using CD spectroscopy in polar (water and apolar (TFE solvents. Cell penetrating ability of RATH-CONH2 was observed using FITC labeled peptide internalization in to HeLa cells under fluorescent microscopy. The efficacy of RATH analog interactions with nucleic acids was evaluated using FITC labeled oligonucleotides by fluorescence spectroscopy and plasmid constructs in gel retardation assay. Results: CD spectra of RATH analogs in water and apolar trifluroethanol (TFE helped to compare their secondary structures which were almost similar with dominant beta conformations suggesting successful induction of positive charge in the analogs without affecting back bone conformation of CPP designed. Cell penetrating ability of RATH CONH2 in HeLa cell was more than 90%. The fluorescence spectroscopy and plasmid constructs in gel retardation assay demonstrated successful interaction of amide analogs with nucleic acid. Conclusion: Intentional changes made in IBDV derived peptide RATH COOH to RATH CONH2 did not showed major changes in backbone conformation and such modifications may help to improve the cationic charge in most CPPs to interact with nucleic acid. [Vet World 2013; 6(6.000: 307-312

Self-association of a highly charged arginine-rich cell-penetrating peptide

Czech Academy of Sciences Publication Activity Database

Tesei, G.; Vazdar, M.; Jensen, M. R.; Cragnell, C.; Mason, Philip E.; Heyda, J.; Skepö, M.; Jungwirth, Pavel; Lund, M.

2017-01-01

Roč. 114, č. 43 (2017), s. 11428-11433 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA16-01074S Institutional support: RVO:61388963 Keywords : cell-penetrating peptide * self-association * MD simulations * SAXS * NMR Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 9.661, year: 2016

Preconcentration method using an activatable yield tracer for neutron activation analysis

International Nuclear Information System (INIS)

Tsukada, Masamichi; Yamamoto, Daijiro; Endo, Kazutoyo; Nakahara, Hiromichi

1991-01-01

Previously, the use of an enriched stable isotope as an activatable yield tracer in preconcentration steps has been tested by use of commercially available enriched 116 Cd and 156 Dy for biological standard reference materials. In the present work, this method has been further applied to the determination of lanthanoid contents in various kinds of samples: one coal fly-ash, three Japanese standard rocks, and eight standard soils. Samples were decomposed by alkali fusion in the preconcentration step. Thirteen elements were determined for coal fly-ash and soil samples, and 14 elements for rocks. The data obtained for coal fly-ash and standard rocks are compared with the data reported in literature. The data for soil samples have been newly determined in the present work. The ordinary instrumental neutron activation analysis and radiochemical neutron activation analysis were also performed to confirm the accuracy and usefulness of the present method. (author) 10 refs.; 4 tabs

Analysis of in vitro toxicity of five cell-penetrating peptides by metabolic profiling

International Nuclear Information System (INIS)

Kilk, Kalle; Mahlapuu, Riina; Soomets, Ursel; Langel, Ulo

2009-01-01

Cell-penetrating peptides (CPPs) are promising candidates for safe and efficient delivery vectors for a wide range of cargoes. However, any compound that is internalized into cells may affect the cell homeostasis. The plethora of possible biological responses makes large scale 'omics' studies appealing approaches for hunting any unsuspected side-effects and evaluate the toxicity of drug candidates. Here we have compared the alterations in cytosolic metabolome of CHO cells caused by five representatives of the most common CPPs: transportan (TP), penetratin (pAntp), HIV Tat derived peptide (pTat), nonaarginine (R 9 ) and model amphipathic peptide (MAP). Analysis was done by liquid chromatography-mass spectrometry techniques, principal component analysis and heatmap displays. Results showed that the intracellular metabolome was the most affected by TP followed by pTat and MAP. Only minor changes could be associated with pAntp or R 9 treatment. The cells could recover from a treatment with 5 μM TP, but no recovery was observed at higher concentration. Both metabolomic and control experiments showed that TP affected cellular redox potential, depleted energy and the pools of purines and pyrimidines. In conclusion, we have performed a metabolomic analysis comparing the safety of cell-penetrating peptides and demonstrate the toxicity of one of them.

Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells.

Science.gov (United States)

Kaitsuka, Taku; Tomizawa, Kazuhito

2015-11-06

Protein transduction using cell-penetrating peptides (CPPs) is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS) cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

Cell-Penetrating Peptide as a Means of Directing the Differentiation of Induced-Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Taku Kaitsuka

2015-11-01

Full Text Available Protein transduction using cell-penetrating peptides (CPPs is useful for the delivery of large protein molecules, including some transcription factors. This method is safer than gene transfection methods with a viral vector because there is no risk of genomic integration of the exogenous DNA. Recently, this method was reported as a means for the induction of induced pluripotent stem (iPS cells, directing the differentiation into specific cell types and supporting gene editing/correction. Furthermore, we developed a direct differentiation method to obtain a pancreatic lineage from mouse and human pluripotent stem cells via the protein transduction of three transcription factors, Pdx1, NeuroD, and MafA. Here, we discuss the possibility of using CPPs as a means of directing the differentiation of iPS cells and other stem cell technologies.

Parametric analysis of neutron streaming through major penetrations in the 0.914 m TFTR test cell floor

International Nuclear Information System (INIS)

Ku, L.P.; Liew, S.L.; Kolibal, J.G.

1985-09-01

Neutron streaming through penetrations in the 0.914 m TFTR test cell floor has two distinct features: (1) the oblique angle of incidence; and (2) the high order of anisotropy in the angular distribution for incident neutrons with energies > 10 keV. The effects of these features on the neutron streaming into the TFTR basement were studied parametrically for isolated penetrations. Variations with respect to the source energies, angular distributions, and sizes of the penetrations were made. The results form a data base from which the spatial distribution of the neutron flux in the basement due to multiple penetrations may be evaluated

Controlling Factors of Cell Design on Large-format Li-ion Battery Safety During Nail Penetration

Directory of Open Access Journals (Sweden)

Qing eWang

2015-08-01

Full Text Available In this paper we investigate the controlling design parameters of large-format Li-ion batteries on safety while undergoing nail penetration. We have identified three critical design parameters that control the safety during the nail penetration process: nail diameter, single sheet foil area, and cell capacity.Using commercial AutoLion software, we have investigated two typical design problems related to the selection of cell thickness and aspect ratio, namely: (1 the safety ramifications of increasing cell capacity via greater cell thickness for a fixed footprint, and (2 the effect of aspect ratio, or single sheet foil size, on safety at a given capacity. For a fixed footprint, our results indicate that the safety of the cell can be predicted by (Qcell Dnail^-0.5. For a given cell capacity, our results indicate that typically a larger single sheet foil area leads to a greater likelihood for thermal runaway due to its effect of making the heating more local in nature; however, for small cells (~ 5Ah and large nails (~ 20mm, the greater aspect ratio can lead to a safer cell, as the greater surface area strongly cools the global heating of the cell.

Controlling Factors of Cell Design on Large-Format Li-Ion Battery Safety during Nail Penetration

Energy Technology Data Exchange (ETDEWEB)

Wang, Qing; Shaffer, Christian Edward, E-mail: ceshaffer@ecpowergroup.com; Sinha, Puneet K. [EC Power, State College, PA (United States)

2015-08-21

In this paper, we investigate the controlling design parameters of large-format Li-ion batteries on safety while undergoing nail penetration. We have identified three critical design parameters that control the safety during the nail penetration process: nail diameter (D{sub nail}), single sheet foil area (A{sub foil}), and cell capacity (Q{sub cell}).Using commercial AutoLion™ software, we have investigated two typical design problems related to the selection of cell thickness and aspect ratio, namely, (1) the safety ramifications of increasing cell capacity via greater cell thickness for a fixed footprint and (2) the effect of aspect ratio, or single sheet foil size, on safety at a given capacity. For a fixed footprint, our results indicate that the safety of the cell can be predicted by (Q{sub cell} D{sub nail}{sup -0.5}). For a given cell capacity, our results indicate that typically a larger single sheet foil area leads to a greater likelihood for thermal runaway due to its effect of making the heating more local in nature; however, for small cells (~5 Ah) and large nails (~20 mm), the greater aspect ratio can lead to a safer cell, as the greater surface area strongly cools the global heating of the cell.

Enhanced Cellular Uptake of Albumin-Based Lyophilisomes when Functionalized with Cell-Penetrating Peptide TAT in HeLa Cells

NARCIS (Netherlands)

van Bracht, Etienne; Versteegden, Luuk R. M.; Stolle, Sarah; Verdurmen, Wouter P. R.; Woestenenk, Rob; Raave, Rene; Hafmans, Theo; Oosterwijk, Egbert; Brock, Roland; van Kuppevelt, Toin H.; Daamen, Willeke F.

2014-01-01

Lyophilisomes are a novel class of biodegradable proteinaceous nano/micrometer capsules with potential use as drug delivery carrier. Cell-penetrating peptides (CPPs) including the TAT peptide have been successfully implemented for intracellular delivery of a broad variety of cargos including various

Translocation of cell penetrating peptides and calcium-induced membrane fusion share same mechanism

Czech Academy of Sciences Publication Activity Database

Magarkar, Aniket; Allolio, Christoph; Jurkiewicz, Piotr; Baxová, Katarína; Šachl, Radek; Horinek, D.; Heinz, V.; Rachel, R.; Ziegler, C.; Jungwirth, Pavel

2017-01-01

Roč. 46, Suppl 1 (2017), S386 ISSN 0175-7571. [IUPAB congress /19./ and EBSA congress /11./. 16.07.2017-20.07.2017, Edinburgh] Institutional support: RVO:61388963 ; RVO:61388955 Keywords : membrane interactions * membrane fusion * cell penetration Subject RIV: BO - Biophysics

Intracellular delivery of cell-penetrating peptide-transcriptional factor fusion protein and its role in selective osteogenesis

Science.gov (United States)

Suh, Jin Sook; Lee, Jue Yeon; Choi, Yoon Jung; You, Hyung Keun; Hong, Seong-Doo; Chung, Chong Pyoung; Park, Yoon Jeong

2014-01-01

Protein-transduction technology has been attempted to deliver macromolecular materials, including protein, nucleic acids, and polymeric drugs, for either diagnosis or therapeutic purposes. Herein, fusion protein composed of an arginine-rich cell-penetrating peptide, termed low-molecular-weight protamine (LMWP), and a transcriptional coactivator with a PDZ-binding motif (TAZ) protein was prepared and applied in combination with biomaterials to increase bone-forming capacity. TAZ has been recently identified as a specific osteogenic stimulating transcriptional coactivator in human mesenchymal stem cell (hMSC) differentiation, while simultaneously blocking adipogenic differentiation. However, TAZ by itself cannot penetrate the cells, and thus needs a transfection tool for translocalization. The LMWP-TAZ fusion proteins were efficiently translocalized into the cytosol of hMSCs. The hMSCs treated with cell-penetrating LMWP-TAZ exhibited increased expression of osteoblastic genes and protein, producing significantly higher quantities of mineralized matrix compared to free TAZ. In contrast, adipogenic differentiation of the hMSCs was blocked by treatment of LMWP-TAZ fusion protein, as reflected by reduced marker-protein expression, adipocyte fatty acid-binding protein 2, and peroxisome proliferator-activated receptor-γ messenger ribonucleic acid levels. LMWP-TAZ was applied in alginate gel for the purpose of localization and controlled release. The LMWP-TAZ fusion protein-loaded alginate gel matrix significantly increased bone formation in rabbit calvarial defects compared with alginate gel matrix mixed with free TAZ protein. The protein transduction of TAZ fused with cell-penetrating LMWP peptide was able selectively to stimulate osteogenesis in vitro and in vivo. Taken together, this fusion protein-transduction technology for osteogenic protein can thus be applied in combination with biomaterials for tissue regeneration and controlled release for tissue

Tumor penetrating peptides

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Tambet eTeesalu

2013-08-01

Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

Polymeric pH nanosensor with extended measurement range bearing octaarginine as cell penetrating peptide

DEFF Research Database (Denmark)

Ke, Peng; Sun, Honghao; Liu, Mingxing

2016-01-01

A synthetic peptide octaarginine which mimics human immunodeficiency virus-1, Tat protein is used as cell penetrating moiety for new pH nanosensors which demonstrate enhanced cellular uptake and expanded measurement range from pH 3.9 to pH 7.3 by simultaneously incorporating two complemental pH-s......H-sensitive fluorophores in a same nanoparticle. The authors believe that this triple fluorescent pH sensor provides a new tool to pH measurements that can have application in cellular uptake mechanism study and new nanomedicine design.......A synthetic peptide octaarginine which mimics human immunodeficiency virus-1, Tat protein is used as cell penetrating moiety for new pH nanosensors which demonstrate enhanced cellular uptake and expanded measurement range from pH 3.9 to pH 7.3 by simultaneously incorporating two complemental p...

Manipulation of Cell Cycle and Chromatin Configuration by Means of Cell-Penetrating Geminin.

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Yoshinori Ohno

Full Text Available Geminin regulates chromatin remodeling and DNA replication licensing which play an important role in regulating cellular proliferation and differentiation. Transcription of the Geminin gene is regulated via an E2F-responsive region, while the protein is being closely regulated by the ubiquitin-proteasome system. Our objective was to directly transduce Geminin protein into cells. Recombinant cell-penetrating Geminin (CP-Geminin was generated by fusing Geminin with a membrane translocating motif from FGF4 and was efficiently incorporated into NIH 3T3 cells and mouse embryonic fibroblasts. The withdrawal study indicated that incorporated CP-Geminin was quickly reduced after removal from medium. We confirmed CP-Geminin was imported into the nucleus after incorporation and also that the incorporated CP-Geminin directly interacted with Cdt1 or Brahma/Brg1 as the same manner as Geminin. We further demonstrated that incorporated CP-Geminin suppressed S-phase progression of the cell cycle and reduced nuclease accessibility in the chromatin, probably through suppression of chromatin remodeling, indicating that CP-Geminin constitutes a novel tool for controlling chromatin configuration and the cell cycle. Since Geminin has been shown to be involved in regulation of stem cells and cancer cells, CP-Geminin is expected to be useful for elucidating the role of Geminin in stem cells and cancer cells, and for manipulating their activity.

Probing the effect of polymer molecular weight on penetration into the wood cell wall using polyethylenimine (PEI) as a model compound.

Science.gov (United States)

Dorvel, Brian; Boopalachandran, Praveenkumar; Chen, Ida; Bowling, Andrew; Williams, Kerry; King, Steve

2018-05-01

Decking is one of the largest applications for the treated wood market. The most challenging property to obtain for treated wood is dimensional stability, which can be achieved, in part, by cell wall bulking, cell wall polymer crosslinking and removal of hygroscopic components in the cell wall. A commonly accepted key requirement is for the actives to infuse through the cell wall, which has a microporosity of ∼5-13 nm. Equally as challenging is being able to measure and quantify the cell wall penetration. Branched polyethylenimine (PEI) was studied as a model polymer for penetration due to its water solubility, polarity, variable molecular weight ranges, and ability to form a chelation complex with preservative metals to treat lumbers. Two different molecular weight polyethylenimines (PEI), one with a weight average molecular weight (Mw) equal to 800 Da and the other 750 000 Da, were investigated for penetration by microscopy and spectroscopy techniques. Analytical methods were developed to both create smooth interfaces and for relative quantitation and visualisation of PEI penetration into the wood. The results showed both PEI with Mw of 800 Da and PEI with Mw of 750 000 Da coated the lumens in high density. However, only the PEI with Mw of 800 appeared to penetrate the cell walls in sufficient levels. Literature has shown the hydrodynamic radii of PEI 750 000 is near 29 nm, whereas a smaller PEI at 25 K showed 4.5 nm. Most importantly the results, based on methods developed, show how molecular weight and tertiary structure of the polymer can affect its penetration, with the microporosity of the wood being the main barrier. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Invasin of Yersinia pseudotuberculosis activates human peripheral B cells.

OpenAIRE

Lundgren, E; Carballeira, N; Vazquez, R; Dubinina, E; Bränden, H; Persson, H; Wolf-Watz, H

1996-01-01

The Yersinia pseudotuberculosis cell surface-located protein invasin was found to promote binding between the pathogen and resting peripheral B cells via beta 1 integrin receptors (CD29). B cells responded by expressing several activation markers and by growing, In contrast, T cells did not react, although these cells express CD29. An isogenic invA mutant failed to activate B cells. The mutation could be complemented by providing the invA+ gene in trans. Purified invasin alone did not activat...

Design of ultrasonically-activatable nanoparticles using low boiling point perfluorocarbons.

Science.gov (United States)

Sheeran, Paul S; Luois, Samantha H; Mullin, Lee B; Matsunaga, Terry O; Dayton, Paul A

2012-04-01

Recently, an interest has developed in designing biomaterials for medical ultrasonics that can provide the acoustic activity of microbubbles, but with improved stability in vivo and a smaller size distribution for extravascular interrogation. One proposed alternative is the phase-change contrast agent. Phase-change contrast agents (PCCAs) consist of perfluorocarbons (PFCs) that are initially in liquid form, but can then be vaporized with acoustic energy. Crucial parameters for PCCAs include their sensitivity to acoustic energy, their size distribution, and their stability, and this manuscript provides insight into the custom design of PCCAs for balancing these parameters. Specifically, the relationship between size, thermal stability and sensitivity to ultrasound as a function of PFC boiling point and ambient temperature is illustrated. Emulsion stability and sensitivity can be 'tuned' by mixing PFCs in the gaseous state prior to condensation. Novel observations illustrate that stable droplets can be generated from PFCs with extremely low boiling points, such as octafluoropropane (b.p. -36.7 °C), which can be vaporized with acoustic parameters lower than previously observed. Results demonstrate the potential for low boiling point PFCs as a useful new class of compounds for activatable agents, which can be tailored to the desired application. Copyright © 2012 Elsevier Ltd. All rights reserved.

Potent inhibition of late stages of hepadnavirus replication by a modified cell penetrating peptide

DEFF Research Database (Denmark)

Abdul, Fabien; Ndeboko, Bénédicte; Buronfosse, Thierry

2012-01-01

Cationic cell-penetrating peptides (CPPs) and their lipid domain-conjugates (CatLip) are agents for the delivery of (uncharged) biologically active molecules into the cell. Using infection and transfection assays we surprisingly discovered that CatLip peptides were able to inhibit replication...... by confocal laser scanning microscopy indicating severe structural changes of preS/S. Sucrose gradient analysis of supernatants from Deca-(Arg)8-treated cells showed unaffected naked viral nucleocapsids release, which was concomitant with a complete arrest of virion and surface protein-containing subviral...

A+-Helix of Protein C Inhibitor (PCI) Is a Cell-penetrating Peptide That Mediates Cell Membrane Permeation of PCI*

Science.gov (United States)

Yang, Hanjiang; Wahlmüller, Felix Christof; Sarg, Bettina; Furtmüller, Margareta; Geiger, Margarethe

2015-01-01

Protein C inhibitor (PCI) is a serpin with broad protease reactivity. It binds glycosaminoglycans and certain phospholipids that can modulate its inhibitory activity. PCI can penetrate through cellular membranes via binding to phosphatidylethanolamine. The exact mechanism of PCI internalization and the intracellular role of the serpin are not well understood. Here we showed that testisin, a glycosylphosphatidylinositol-anchored serine protease, cleaved human PCI and mouse PCI (mPCI) at their reactive sites as well as at sites close to their N terminus. This cleavage was observed not only with testisin in solution but also with cell membrane-anchored testisin on U937 cells. The cleavage close to the N terminus released peptides rich in basic amino acids. Synthetic peptides corresponding to the released peptides of human PCI (His1–Arg11) and mPCI (Arg1–Ala18) functioned as cell-penetrating peptides. Because intact mPCI but not testisin-cleaved mPCI was internalized by Jurkat T cells, a truncated mPCI mimicking testisin-cleaved mPCI was created. The truncated mPCI lacking 18 amino acids at the N terminus was not taken up by Jurkat T cells. Therefore our model suggests that testisin or other proteases could regulate the internalization of PCI by removing its N terminus. This may represent one of the mechanisms regulating the intracellular functions of PCI. PMID:25488662

Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate.

Science.gov (United States)

Wang, Julie T-W; Giuntini, Francesca; Eggleston, Ian M; Bown, Stephen G; MacRobert, Alexander J

2012-01-30

Photochemical internalisation (PCI) is a site-specific technique for improving cellular delivery of macromolecular drugs. In this study, a cell penetrating peptide, containing the core HIV-1 Tat 48-57 sequence, conjugated with a porphyrin photosensitiser has been shown to be effective for PCI. Herein we report an investigation of the photophysical and photobiological properties of a water soluble bioconjugate of the cationic Tat peptide with a hydrophobic tetraphenylporphyrin derivative. The cellular uptake and localisation of the amphiphilic bioconjugate was examined in the HN5 human head and neck squamous cell carcinoma cell line. Efficient cellular uptake and localisation in endo/lysosomal vesicles was found using fluorescence detection, and light-induced, rupture of the vesicles resulting in a more diffuse intracellular fluorescence distribution was observed. Conjugation of the Tat sequence with a hydrophobic porphyrin thus enables cellular delivery of an amphiphilic photosensitiser which can then localise in endo/lysosomal membranes, as required for effective PCI treatment. PCI efficacy was tested in combination with a protein toxin, saporin, and a significant reduction in cell viability was measured versus saporin or photosensitiser treatment alone. This study demonstrates that the cell penetrating peptide-photosensitiser bioconjugation strategy is a promising and versatile approach for enhancing the therapeutic potential of bioactive agents through photochemical internalisation. Copyright © 2011 Elsevier B.V. All rights reserved.

Translocation of cell-penetrating peptides into Candida fungal pathogens.

Science.gov (United States)

Gong, Zifan; Karlsson, Amy J

2017-09-01

Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

The uptake of arginine-rich cell-penetrating peptides: putting the puzzle together.

Science.gov (United States)

Brock, Roland

2014-05-21

Over the past 20 years, cell-penetrating peptides (CPPs) have captured the attention of biomedical researchers, biophysicists, and (bio)organic chemists. These molecules efficiently enter cells and mediate entry of (macro)molecules that by themselves do not cross the plasma membrane. Since their discovery, models on the mechanism by which uptake occurs have seen major revisions. Starting from direct penetration across the plasma membrane, it later became apparent that for large molecular weight cargos in particular, endocytosis plays a role in uptake and furthermore that the route of uptake is a function of CPP, cell-type, cargo, and concentration. For the class of arginine-rich CPPs, this dependence on conditions has been elucidated in particular. As I will discuss here for this class of CPPs, a downside of this multitude of possibilities has been a lack of attention for commonalities in the observation of apparently distinct phenomena. At the same time, differences of apparently similar observations were not appreciated sufficiently. In addition, there has been insufficient acknowledgment of observations that are incompatible with the proposed models. Nevertheless, a considerable amount of data can be assembled into a quite coherent picture and the data that is left creates the basis for concrete future lines of research to resolve the questions that remain. Moreover, any uptake mechanism has its distinct structure-activity relationship for uptake giving room for the molecular design of molecules to preferentially direct uptake to either of them.

Role of Cell-Penetrating Peptides in Intracellular Delivery of Peptide Nucleic Acids Targeting Hepadnaviral Replication

DEFF Research Database (Denmark)

Ndeboko, Benedicte; Ramamurthy, Narayan; Lemamy, Guy Joseph

2017-01-01

Peptide nucleic acids (PNAs) are potentially attractive antisense agents against hepatitis B virus (HBV), although poor cellular uptake limits their therapeutic application. In the duck HBV (DHBV) model, we evaluated different cell-penetrating peptides (CPPs) for delivery to hepatocytes of a PNA...

Spermatozoa of the shrew, Suncus murinus, undergo the acrosome reaction and then selectively kill cells in penetrating the cumulus oophorus.

Science.gov (United States)

Kaneko, T; Iida, H; Bedford, J M; Mōri, T

2001-08-01

In the musk shrew, Suncus murinus (and other shrews), the cumulus oophorus is ovulated as a discrete, compact, matrix-free ball of cells linked by specialized junctions. In examining how they penetrate the cumulus, Suncus spermatozoa were observed to first bind consistently by the ventral face over the acrosomal region to the exposed smooth surface of a peripheral cumulus cell. This was apparently followed by point fusions between the plasma and outer acrosomal membranes. Thereafter, spermatozoa without acrosomes were observed within cumulus cells that displayed signs of necrosis, as did some radially neighboring cumulus cells linked by zona adherens and gap junctions. Eventually, penetration of spermatozoa as far as the perizonal space around the zona pellucida left linear tracks of locally necrotic cells flanked by normal cumulus cells. Based on these and previous observations, we conclude that the acrosome reaction in Suncus is always induced by cumulus cells, and that reacted spermatozoa penetrate the cumulus by selective invasion and killing of cumulus cells along a linear track. Loss of the acrosome also exposes an apical body/perforatorium that is covered with barbs that appear to assist reacted fertilizing spermatozoa in binding to the zona pellucida. Because fertilized eggs displayed no other spermatozoa within or bound to the zona, an efficient block to polyspermy must prevent such binding of additional spermatozoa.

Analysis of the transient response and durability characteristics of a proton exchange membrane fuel cell with different micro-porous layer penetration thicknesses

International Nuclear Information System (INIS)

Cho, Junhyun; Park, Jaeman; Oh, Hwanyeong; Min, Kyoungdoug; Lee, Eunsook; Jyoung, Jy-Young

2013-01-01

Highlights: • The GDL which has a large MPL penetration showed a better transient response. • The transient response of the PEMFC was affected by the water balance of the GDL. • A large MPL penetration balanced the capillary pressure gradient through the GDL. • The carbon corrosion induced loss of the MPL penetration region. - Abstract: The optimal design of the gas diffusion layer (GDL) of proton exchange membrane fuel cells is crucial because it directly determines the mass transport mechanism of the reactants and products. In this study, the micro-porous layer (MPL) penetration thickness, which affects the pore size profile through the GDL, is varied as the design parameter of the GDL. The cell performance is investigated under various humidity conditions, and the water permeability characteristics are studied. In addition, the accelerated carbon corrosion stress test is conducted to determine the effect of MPL penetration on GDL degradation. GDLs with large MPL penetration thickness show better performance in the high-current–density region due to the enhanced management of water resulting from a balanced capillary pressure gradient. However, the loss of penetrated MPL parts is observed due to the low binding force between the MPL and the GDL substrate

Antibody tumor penetration

Science.gov (United States)

Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

2009-01-01

Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue. PMID:18541331

Lateral Tension-Induced Penetration of Particles into a Liposome

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Kazuki Shigyou

2017-07-01

Full Text Available It is important that we understand the mechanism of the penetration of particles into a living cell to achieve advances in bionanotechnology, such as for treatment, visualization within a cell, and genetic modification. Although there have been many studies on the application of functional particles to cells, the basic mechanism of penetration across a biological membrane is still poorly understood. Here we used a model membrane system to demonstrate that lateral membrane tension drives particle penetration across a lipid bilayer. After the application of osmotic pressure, fully wrapped particles on a liposome surface were found to enter the liposome. We discuss the mechanism of the tension-induced penetration in terms of narrow constriction of the membrane at the neck part. The present findings are expected to provide insight into the application of particles to biological systems.

Cell penetrating peptide-modified poly(lactic-co-glycolic acid) nanoparticles with enhanced cell internalization.

Science.gov (United States)

Steinbach, Jill M; Seo, Young-Eun; Saltzman, W Mark

2016-01-01

The surface modification of nanoparticles (NPs) can enhance the intracellular delivery of drugs, proteins, and genetic agents. Here we studied the effect of different surface ligands, including cell penetrating peptides (CPPs), on the cell binding and internalization of poly(lactic-co-glycolic) (PLGA) NPs. Relative to unmodified NPs, we observed that surface-modified NPs greatly enhanced cell internalization. Using one CPP, MPG (unabbreviated notation), that achieved the highest degree of internalization at both low and high surface modification densities, we evaluated the effect of two different NP surface chemistries on cell internalization. After 2h, avidin-MPG NPs enhanced cellular internalization by 5 to 26-fold relative to DSPE-MPG NP formulations. Yet, despite a 5-fold increase in MPG density on DSPE compared to Avidin NPs, both formulations resulted in similar internalization levels (48 and 64-fold, respectively) after 24h. Regardless of surface modification, all NPs were internalized through an energy-dependent, clathrin-mediated process, and became dispersed throughout the cell. Overall both Avidin- and DSPE-CPP modified NPs significantly increased internalization and offer promising delivery options for applications in which internalization presents challenges to efficacious delivery. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  Cell Penetrating Peptoids (CPPos: Synthesis of a Small Combinatorial Library by Using IRORI MiniKans

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Dominik K. Kölmel

2012-11-01

Full Text Available Cell penetrating peptoids (CPPos are potent mimics of the corresponding cell penetrating peptides (CPPs. The synthesis of diverse oligomeric libraries that display a variety of backbone scaffolds and side-chain appendages are a very promising source of novel CPPos, which can be used to either target different cellular organelles or even different tissues and organs. In this study we established the submonomer-based solid phase synthesis of a “proof of principle” peptoid library in IRORI MiniKans to expand the amount for phenotypic high throughput screens of CPPos. The library consisting of tetrameric peptoids [oligo(N-alkylglycines] was established on Rink amide resin in a split and mix approach with hydrophilic and hydrophobic peptoid side chains. All CPPos of the presented library were labeled with rhodamine B to allow for the monitoring of cellular uptake by fluorescent confocal microscopy. Eventually, all the purified peptoids were subjected to live cell imaging to screen for CPPos with organelle specificity. While highly charged CPPos enter the cells by endocytosis with subsequent endosomal release, critical levels of lipophilicity allow other CPPos to specifically localize to mitochondria once a certain lipophilicity threshold is reached.

Intracellular delivery of cell-penetrating peptide-transcriptional factor fusion protein and its role in selective osteogenesis

Directory of Open Access Journals (Sweden)

Suh JS

2014-03-01

Full Text Available Jin Sook Suh,1,* Jue Yeon Lee,2,* Yoon Jung Choi,1 Hyung Keun You,3 Seong-Doo Hong,4 Chong Pyoung Chung,2 Yoon Jeong Park1,2 1Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 2Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC, Seoul, 3Department of Periodontology, College of Dentistry, Wonkwang University, Iksan, 4Department of Oral Pathology, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Protein-transduction technology has been attempted to deliver macromolecular materials, including protein, nucleic acids, and polymeric drugs, for either diagnosis or therapeutic purposes. Herein, fusion protein composed of an arginine-rich cell-penetrating peptide, termed low-molecular-weight protamine (LMWP, and a transcriptional coactivator with a PDZ-binding motif (TAZ protein was prepared and applied in combination with biomaterials to increase bone-forming capacity. TAZ has been recently identified as a specific osteogenic stimulating transcriptional coactivator in human mesenchymal stem cell (hMSC differentiation, while simultaneously blocking adipogenic differentiation. However, TAZ by itself cannot penetrate the cells, and thus needs a transfection tool for translocalization. The LMWP-TAZ fusion proteins were efficiently translocalized into the cytosol of hMSCs. The hMSCs treated with cell-penetrating LMWP-TAZ exhibited increased expression of osteoblastic genes and protein, producing significantly higher quantities of mineralized matrix compared to free TAZ. In contrast, adipogenic differentiation of the hMSCs was blocked by treatment of LMWP-TAZ fusion protein, as reflected by reduced marker-protein expression, adipocyte fatty acid-binding protein 2, and peroxisome proliferator-activated receptor-γ messenger ribonucleic acid levels. LMWP-TAZ was applied in

Study on Penetration Characteristics of Tungsten Cylindrical Penetrator

Energy Technology Data Exchange (ETDEWEB)

Jo, Jong Hyun; Lee, Young Shin; Kim, Jae Hoon [Chungnam Nat' l Univ., Daejeon (Korea, Republic of); Bae, Yong Woon [Agency for Defense Development, Daejeon (Korea, Republic of)

2013-09-15

The design of missile require extremely small warheads that must be highly efficient and lethal. The penetration characteristics of each penetrator and the total number of penetrators on the warhead are obvious key factors that influence warhead lethality. The design of the penetrator shape and size are directly related to the space and weight of the warhead. The design of the penetrator L/D was directly related to the space and weight of the warhead. L and D are the length and the diameter of the projectile, respectively. The AUTODYN-3a code was used to study the effect of penetrator penetration. The objective of numerical analysis was to determine the penetration characteristics of penetrator produced by hypervelocity impacts under different initial conditions such as initial velocity, obliquity angle and L/D of penetrator. The residual velocity and residual mass were decreased with increasing initial impact velocity under L/D{<=}4.

Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation.

Science.gov (United States)

Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

2017-03-01

Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving NSCs in the left hemisphere and PBS in the right; group B, receiving NSCs in the right hemisphere and PBS in the left; and group C, receiving equal NSCs in both hemispheres. Murine brains were stained for morphological analysis and subsequent evaluation of infiltrated immune cells. ELISA was performed to detect neurotrophic and immunomodulatory factors in the brain. The findings indicated that brain injury and secondary inflammation in the left hemisphere were more severe than those in the right hemisphere, following NSC transplantation. In contrast to the left hemisphere, more neurotrophic factors but less pro-inflammatory cytokines were detected in the right hemisphere. In addition, increased levels of neurotrophic factors and interleukin (IL)-10 were observed in the NSC transplantation side when compared with the PBS-treated hemispheres, although lower levels of IL-6 and tumor necrosis factor-α were detected. In conclusion, the present study indicated that syringe needle skull penetration vs. drill penetration is an improved method that reduces the risk of brain injury and secondary inflammation following intracerebral NSC transplantation. Furthermore, NSCs have the potential to modulate inflammation secondary to brain injuries.

Relationships between Cargo, Cell Penetrating Peptides and Cell Type for Uptake of Non-Covalent Complexes into Live Cells

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Andrea-Anneliese Keller

2013-02-01

Full Text Available Modulating signaling pathways for research and therapy requires either suppression or expression of selected genes or internalization of proteins such as enzymes, antibodies, nucleotide binding proteins or substrates including nucleoside phosphates and enzyme inhibitors. Peptides, proteins and nucleotides are transported by fusing or conjugating them to cell penetrating peptides or by formation of non-covalent complexes. The latter is often preferred because of easy handling, uptake efficiency and auto-release of cargo into the live cell. In our studies complexes are formed with labeled or readily detectable cargoes for qualitative and quantitative estimation of their internalization. Properties and behavior of adhesion and suspension vertebrate cells as well as the protozoa Leishmania tarentolae are investigated with respect to proteolytic activity, uptake efficiency, intracellular localization and cytotoxicity. Our results show that peptide stability to membrane-bound, secreted or intracellular proteases varies between different CPPs and that the suitability of individual CPPs for a particular cargo in complex formation by non-covalent interactions requires detailed studies. Cells vary in their sensitivity to increasing concentrations of CPPs. Thus, most cells can be efficiently transduced with peptides, proteins and nucleotides with intracellular concentrations in the low micromole range. For each cargo, cell type and CPP the optimal conditions must be determined separately.

Coexistence of a two-states organization for a cell-penetrating peptide in lipid bilayer.

Science.gov (United States)

Plénat, Thomas; Boichot, Sylvie; Dosset, Patrice; Milhiet, Pierre-Emmanuel; Le Grimellec, Christian

2005-12-01

Primary amphipathic cell-penetrating peptides transport cargoes across cell membranes with high efficiency and low lytic activity. These primary amphipathic peptides were previously shown to form aggregates or supramolecular structures in mixed lipid-peptide monolayers, but their behavior in lipid bilayers remains to be characterized. Using atomic force microscopy, we have examined the interactions of P(alpha), a primary amphipathic cell-penetrating peptide which remains alpha-helical whatever the environment, with dipalmitoylphosphatidylcholine (DPPC) bilayers. Addition of P(alpha) at concentrations up to 5 mol % markedly modified the supported bilayers topography. Long and thin filaments lying flat at the membrane surface coexisted with deeply embedded peptides which induced a local thinning of the bilayer. On the other hand, addition of P(alpha) only exerted very limited effects on the corresponding liposome's bilayer physical state, as estimated from differential scanning calorimetry and diphenylhexatriene fluorescence anisotropy experiments. The use of a gel-fluid phase separated supported bilayers made of a dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine mixture confirmed both the existence of long filaments, which at low peptide concentration were preferentially localized in the fluid phase domains and the membrane disorganizing effects of 5 mol % P(alpha). The simultaneous two-states organization of P(alpha), at the membrane surface and deeply embedded in the bilayer, may be involved in the transmembrane carrier function of this primary amphipathic peptide.

p53 Aggregates penetrate cells and induce the co-aggregation of intracellular p53.

Directory of Open Access Journals (Sweden)

Karolyn J Forget

Full Text Available Prion diseases are unique pathologies in which the infectious particles are prions, a protein aggregate. The prion protein has many particular features, such as spontaneous aggregation, conformation transmission to other native PrP proteins and transmission from an individual to another. Protein aggregation is now frequently associated to many human diseases, for example Alzheimer's disease, Parkinson's disease or type 2 diabetes. A few proteins associated to these conformational diseases are part of a new category of proteins, called prionoids: proteins that share some, but not all, of the characteristics associated with prions. The p53 protein, a transcription factor that plays a major role in cancer, has recently been suggested to be a possible prionoid. The protein has been shown to accumulate in multiple cancer cell types, and its aggregation has also been reproduced in vitro by many independent groups. These observations suggest a role for p53 aggregates in cancer development. This study aims to test the «prion-like» features of p53. Our results show in vitro aggregation of the full length and N-terminally truncated protein (p53C, and penetration of these aggregates into cells. According to our findings, the aggregates enter cells using macropinocytosis, a non-specific pathway of entry. Lastly, we also show that once internalized by the cell, p53C aggregates can co-aggregate with endogenous p53 protein. Together, these findings suggest prion-like characteristics for p53 protein, based on the fact that p53 can spontaneously aggregate, these aggregates can penetrate cells and co-aggregate with cellular p53.

Market penetration analysis of fuel cell vehicles in Japan by using the energy system model MARKAL

International Nuclear Information System (INIS)

Endo, Eiichi

2007-01-01

The objective of the present work is to validate the hydrogen energy roadmap of Japan by analyzing the market penetration of fuel cell vehicles (FCVs) and the effects of a carbon tax using an energy system model of Japan based on MARKAL. The results of the analysis show that a hydrogen FCV would not be cost competitive until 2050 without a more severe carbon tax than the government's planned 2400 JPY/t-C carbon tax. However, as the carbon tax rate increases, instead of conventional vehicles including the gasoline hybrid electric vehicle, hydrogen FCVs gain market penetration earlier and more. By assuming a more severe carbon tax rate, such as 10 000 JPY/t-C, the market share of hydrogen FCVs approaches the governmental goal. This suggests that cheaper vehicle cost and hydrogen cost than those targeted in the roadmap should be attained or subsidies to hydrogen FCV and hydrogen refueling station will be necessary for achieving the goal of earlier market penetration. (author)

Probing intra-cellular drug release event using activatable (OFF/ON) CdS:Mn/ZnS quantum dots (Qdots): spectroscopic studies to investigate interaction of Qdots with quencher

Science.gov (United States)

Tharkur, Jeremy; Teblum, Andrew; Basumallick, Srijita; Shah, Rikhav; Cantarero, Karishma; Maity, Niharika; Rifai, Sara; Doshi, Mona; Gesquiere, Andre J.; Santra, Swadeshmukul

2013-02-01

In recent years, activatable Quantum Dots (AQdots) are gaining popularity in a number of chemical and biological sensing applications. A basic design of AQdot probes involves a suitable quencher which is capable of altering optical properties of the Qdots. In our previous studies we have shown that CdS:Mn/ZnS fluorescence can be effectively quenched using small molecule quenchers (such as dopamine, chemotherapeutic drug) as well as iron oxide nanoparticle via electron/energy transfer process. We have also shown that the quenched Qdot fluorescence can be restored when the Qdots are separated from the quencher. Using Qdot based activatable probes, we detected intracellular drug release event. Qdot fluorescence was restored upon interaction with the intracellular glutathione (GSH). In this paper, we report a GSH induced quenching of water-soluble N-Acetyl Cysteine (NAC) surface-conjugated Cds:Mn/ZnS Qdots. Quenching of NAC-Qdots was due to aggregation of Qdots in solution. This aggregation induced fluorescence quenching phenomenon resembles with the self-quenching phenomenon of traditional organic fluorescence dyes at high concentrations. UV-VIS and fluorescence emission spectroscopy data support the interaction and binding of GSH with the NAC-Qdots. Increase in particle size due to GSH induced aggregation of NAC-Qdots was confirmed by the Dynamic Light Scattering (DLS) data.

Extending the fundamental imaging-depth limit of multi-photon microscopy by imaging with photo-activatable fluorophores.

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Chen, Zhixing; Wei, Lu; Zhu, Xinxin; Min, Wei

2012-08-13

It is highly desirable to be able to optically probe biological activities deep inside live organisms. By employing a spatially confined excitation via a nonlinear transition, multiphoton fluorescence microscopy has become indispensable for imaging scattering samples. However, as the incident laser power drops exponentially with imaging depth due to scattering loss, the out-of-focus fluorescence eventually overwhelms the in-focal signal. The resulting loss of imaging contrast defines a fundamental imaging-depth limit, which cannot be overcome by increasing excitation intensity. Herein we propose to significantly extend this depth limit by multiphoton activation and imaging (MPAI) of photo-activatable fluorophores. The imaging contrast is drastically improved due to the created disparity of bright-dark quantum states in space. We demonstrate this new principle by both analytical theory and experiments on tissue phantoms labeled with synthetic caged fluorescein dye or genetically encodable photoactivatable GFP.

Persistent enhancement of bacterial motility increases tumor penetration.

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Thornlow, Dana N; Brackett, Emily L; Gigas, Jonathan M; Van Dessel, Nele; Forbes, Neil S

2015-11-01

Motile bacteria can overcome the transport limitations that hinder many cancer therapies. Active bacteria can penetrate through tissue to deliver treatment to resistant tumor regions. Bacterial therapy has had limited success, however, because this motility is heterogeneous, and within a population many individuals are non-motile. In human trials, heterogeneity led to poor dispersion and incomplete tumor colonization. To address these problems, a swarm-plate selection method was developed to increase swimming velocity. Video microscopy was used to measure the velocity distribution of selected bacteria and a microfluidic tumor-on-a-chip device was used to measure penetration through tumor cell masses. Selection on swarm plates increased average velocity fourfold, from 4.9 to 18.7 μm/s (P < 0.05) and decreased the number of non-motile individuals from 51% to 3% (P < 0.05). The selected phenotype was both robust and stable. Repeating the selection process consistently increased velocity and eliminated non-motile individuals. When selected strains were cryopreserved and subcultured for 30.1 doublings, the high-motility phenotype was preserved. In the microfluidic device, selected Salmonella penetrated deeper into cell masses than unselected controls. By 10 h after inoculation, control bacteria accumulated in the front 30% of cell masses, closest to the flow channel. In contrast, selected Salmonella accumulated in the back 30% of cell masses, farthest from the channel. Selection increased the average penetration distance from 150 to 400 μm (P < 0.05). This technique provides a simple and rapid method to generate high-motility Salmonella that has increased penetration and potential for greater tumor dispersion and clinical efficacy. © 2015 Wiley Periodicals, Inc.

Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation

OpenAIRE

Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

2017-01-01

Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving...

Molecular imaging of a cell-penetrating peptide labeled fluorescein-5-isothiocyanate and MR contrast agents: gadopentetate dimeglumine

International Nuclear Information System (INIS)

Liu Min; Guo Youmin; Duan Xiaoyi; Guo Xiaojuan; Yang Junle; Xu Min

2006-01-01

Objective: To study the value of a new intracellular contrast agent--cell penetrating peptide labeled Fluorescein-5-isothiocyanate (FITC) and MRI contrast agent, Gadopentetate dimeglumine in molecular imaging. Methods: A new cell penetration peptides (CPPs)sequence LAGRRRRRRRRRK were synthesized in solid phase on the base of arginine (9) and were labelled with FITC (CPP 13 -FITC) and Gd - DTPA (CPP 13 -DTPA-Gd). Hepatic carcinoma cell line-HEPG 2 and mouse bone marrow stem cell was respectively stained by CPP 13 -FITC for different time intervals for observing the uptake and intracellular distribution. HEPG 2 in three l00 mm 2 culture plates was respectively incubated with CPP 13 -DTPA-Gd, Gd- DTPA and Dulbecco minimum essential medium for 30 min and imaged by 1.5 T MRI for studying the intracellular uptake and T 1 WI signal characteristics. Results: The peptide was synthesized by the manual solid-phase method successfully. The calculated molecular weight was 1792.78 and the chemical purity was over 95%. By inverted fluorescence microscope, HEPG 2 and mouse stem cell could transport CPP-FITC in cytoplasm and nuclear in 10 min. By MR imaging, CPP-DTPA-Gd could be uptake by HEPG 2 in 30 min and had a short T 1 short T 2 signal, furthermore. T 1 WI signal intensity ratio between in-tube (Ii) and out-tube (Io) in three groups of three scan slices were shown below: Iil/Io of group 1 (Group 1 was the cell incubated by CPP 13 -DTPA-Gd ) respectively was 2.84, 2.60, 2. 48; Iil/Io of group 2 (Group 2 was the cell incubated by DTPA-Gd) respectively is 1.15, 1.11, 1.12; Iil/Io of group 3 (Group 3 was the controled cell ) respectively was 1.15, 1.11, 1.11. By ANVOA analysis, the signal intensity among group 1, group 2 and group 3 had significant difference(F (1,2) = 201.88 P (1,3) =206.37 P (2,3) =0.529 P=0.507). Conclusion: The new constructed cell penetration peptide on the base of the polyargnine can translocate cell by carting FITC and MRI contrast agent-DTPA-Gd and the

Two functional motifs define the interaction, internalization and toxicity of the cell-penetrating antifungal peptide PAF26 on fungal cells.

Directory of Open Access Journals (Sweden)

Alberto Muñoz

Full Text Available The synthetic, cell penetrating hexapeptide PAF26 (RKKWFW is antifungal at low micromolar concentrations and has been proposed as a model for cationic, cell-penetrating antifungal peptides. Its short amino acid sequence facilitates the analysis of its structure-activity relationships using the fungal models Neurospora crassa and Saccharomyces cerevisiae, and human and plant pathogens Aspergillus fumigatus and Penicillium digitatum, respectively. Previously, PAF26 at low fungicidal concentrations was shown to be endocytically internalized, accumulated in vacuoles and then actively transported into the cytoplasm where it exerts its antifungal activity. In the present study, two PAF26 derivatives, PAF95 (AAAWFW and PAF96 (RKKAAA, were designed to characterize the roles of the N-terminal cationic and the C-terminal hydrophobic motifs in PAF26's mode-of-action. PAF95 and PAF96 exhibited substantially reduced antifungal activity against all the fungi analyzed. PAF96 localized to fungal cell envelopes and was not internalized by the fungi. In contrast, PAF95 was taken up into vacuoles of N. crassa, wherein it accumulated and was trapped without toxic effects. Also, the PAF26 resistant Δarg1 strain of S. cerevisiae exhibited increased PAF26 accumulation in vacuoles. Live-cell imaging of GFP-labelled nuclei in A. fumigatus showed that transport of PAF26 from the vacuole to the cytoplasm was followed by nuclear breakdown and dissolution. This work demonstrates that the amphipathic PAF26 possesses two distinct motifs that allow three stages in its antifungal action to be defined: (i its interaction with the cell envelope; (ii its internalization and transport to vacuoles mediated by the aromatic hydrophobic domain; and (iii its transport from vacuoles to the cytoplasm. Significantly, cationic residues in PAF26 are important not only for the electrostatic attraction and interaction with the fungal cell but also for transport from the vacuole to the

Quantitative & qualitative analysis of endothelial cells of donor cornea before & after penetrating keratoplasty in different pathological conditions

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Aruna K.R. Gupta

2016-01-01

Full Text Available Background & objectives: Endothelial cells of the donor cornea are known to be affected quantitatively and qualitatively in different pathological conditions after penetrating keratoplasty (PK and this has direct effect on the clarity of vision obtained after PK. This study was undertaken to analyze the qualitative and quantitative changes in donor endothelial cells before and after PK in different pathological conditions. Methods: A prospective investigational analysis of 100 consecutive donor corneas used for penetrating keratoplasty between June 2006 and June 2008, was conducted. The patients were evaluated on the first day, at the end of first week, first month, third and six months and one year. Results: A decrease was observed in endothelial cell count in all pathological conditions. After one year of follow up the loss was 33.1 per cent in corneal opacity, 45.9 per cent in acute infective keratitis (AIK, 58.5 per cent in regrafts, 28.5 per cent in pseudophakic bullous keratopathy (PBK, 37 per cent in descemetocele, 27 per cent in keratoconus and 35.5 per cent in aphakic bullous keratopathy (ABK cases. Interpretation & conclusions: The endothelial cell loss was highest in regraft cases which was significant (P<0.05, while the least endothelial cell loss was seen in keratoconus cases. The cell loss was associated with increase in coefficient of variation (CV, i.e. polymegathism and pleomorphism. Inspite of this polymegathism and pleomorphism, the clarity of the graft was maintained.

Harnessing the capacity of cell-penetrating peptides for drug delivery to the central nervous system.

Science.gov (United States)

Kang, Ting; Gao, Xiaoling; Chen, Jun

2014-01-01

The existence of blood-brain barrier (BBB) represents the most formidable challenge for drug delivery to the central nervous system (CNS). Modern breakthrough in biology offers multiple choices for overcoming this barrier but yields modest outcomes for clinical application due to various problems such as safety concerns, insufficient delivery efficiency and poor penetration. Cell penetrating peptides (CPPs) possessing powerful transmembrane capacity have been shown to be effective transport vectors for bioactive molecules and an attractive alternative to traditional active targeting approaches. However, the non-specificity of CPPs has hindered them from targeting a desired site of action. Promisingly, design of novel CPP-mediated nanoparticulate delivery systems with specific targeting property may extricate CPPs from the dilemma. In this review, both the traditional and novel applications of CPPs-based strategies for CNS drug delivery will be discussed.

Identification of a cell-penetrating peptide domain from human beta-defensin 3 and characterization of its anti-inflammatory activity

Directory of Open Access Journals (Sweden)

Lee JY

2015-08-01

Full Text Available Jue Yeon Lee,1,* Jin Sook Suh,2,* Jung Min Kim,1 Jeong Hwa Kim,1 Hyun Jung Park,1 Yoon Jeong Park,1,2 Chong Pyoung Chung1 1Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC, Chungcheongbuk-do, Republic of Korea; 2Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Human beta-defensins (hBDs are crucial factors of intrinsic immunity that function in the immunologic response to a variety of invading enveloped viruses, bacteria, and fungi. hBDs can cause membrane depolarization and cell lysis due to their highly cationic nature. These molecules participate in antimicrobial defenses and the control of adaptive and innate immunity in every mammalian species and are produced by various cell types. The C-terminal 15-mer peptide within hBD3, designated as hBD3-3, was selected for study due to its cell- and skin-penetrating activity, which can induce anti-inflammatory activity in lipopolysaccharide-treated RAW 264.7 macrophages. hBD3-3 penetrated both the outer membrane of the cells and mouse skin within a short treatment period. Two other peptide fragments showed poorer penetration activity compared to hBD3-3. hBD3-3 inhibited the lipopolysaccharide-induced production of inducible nitric oxide synthase, nitric oxide, and secretory cytokines, such as interleukin-6 and tumor necrosis factor in a concentration-dependent manner. Moreover, hBD3-3 reduced the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. Further investigation also revealed that hBD3-3 downregulated nuclear factor kappa B-dependent inflammation by directly suppressing the degradation of phosphorylated-IκBα and by downregulating active nuclear factor kappa B p65. Our findings indicate that hBD3-3 may be conjugated with drugs of interest to ensure their proper translocation to

Selective mono-radioiodination and characterization of a cell-penetrating peptide. L-Tyr-maurocalcine

Energy Technology Data Exchange (ETDEWEB)

Ahmadi, Mitra; Bacot, Sandrine; Perret, Pascale; Riou, Laurent; Ghezzi, Catherine [Universite Joseph Fourier, Grenoble (France); INSERM U1039, Grenoble (France). Radiopharmaceutiques Biocliniques; Poillot, Cathy; Cestele, Sandrine [INSERM U836, Grenoble (France). Grenoble Inst. of Neuroscience; Universite Joseph Fourier, Grenoble (France); Desruet, Marie-Dominique [INSERM U1039, Grenoble (France). Radiopharmaceutiques Biocliniques; Couvet, Morgane; Bourgoin, Sandrine; Seve, Michel [CRI-INSERM U823, Grenoble (France). Inst. of Albert Bonniot; Universite Joseph Fourier, Grenoble (France); Waard, Michel de [INSERM U836, Grenoble (France). Grenoble Inst. of Neuroscience; Universite Joseph Fourier, Grenoble (France); Smartox Biotechnologies, Grenoble (France)

2014-07-01

Mono-and poly-iodinated peptides form frequently during radioiodination procedures. However, the formation of a single species in its mono-iodinated form is essential for quantitative studies such as determination of tissue concentration or image quantification. Therefore, the aim of the present study was to define the optimal experimental conditions in order to exclusively obtain the mono-iodinated form of L-maurocalcine (L-MCa). L-MCa is an animal venom toxin which was shown to act as a cell-penetrating peptide. In order to apply the current direct radioiodination technique using oxidative agents including chloramine T, Iodo-Gen {sup registered} or lactoperoxidase, an analogue of this peptide containing a tyrosine residue (Tyr-L-MCa) was synthesized and was shown to fold/oxidize properly. The enzymatic approach using lactoperoxidase/H{sub 2}O{sub 2} was found to be the best method for radioiodination of Tyr-L-MCa. MALDI-TOF mass spectrometry analyses were then used for identification of the chromatographic eluting components of the reaction mixtures. We observed that the production of different radioiodinated species depended upon the reaction conditions. Our results successfully described the experimental conditions of peptide radioiodination allowing the exclusive production of the mono-iodinated form with high radiochemical purity and without the need for a purification step. Mono-radioiodination of L-Tyr-MCa will be crucial for future quantitative studies, investigating the mechanism of cell penetration and in vivo biodistribution.

Imaging Lysosomal pH Alteration in Stressed Cells with a Sensitive Ratiometric Fluorescence Sensor.

Science.gov (United States)

Xue, Zhongwei; Zhao, Hu; Liu, Jian; Han, Jiahuai; Han, Shoufa

2017-03-24

The organelle-specific pH is crucial for cell homeostasis. Aberrant pH of lysosomes has been manifested in myriad diseases. To probe lysosome responses to cell stress, we herein report the detection of lysosomal pH changes with a dual colored probe (CM-ROX), featuring a coumarin domain with "always-on" blue fluorescence and a rhodamine-lactam domain activatable to lysosomal acidity to give red fluorescence. With sensitive ratiometric signals upon subtle pH changes, CM-ROX enables discernment of lysosomal pH changes in cells undergoing autophagy, cell death, and viral infection.

DNA-histone complexes as ligands amplify cell penetration and nuclear targeting of anti-DNA antibodies via energy-independent mechanisms.

Science.gov (United States)

Zannikou, Markella; Bellou, Sofia; Eliades, Petros; Hatzioannou, Aikaterini; Mantzaris, Michael D; Carayanniotis, George; Avrameas, Stratis; Lymberi, Peggy

2016-01-01

We have generated three monoclonal cell-penetrating antibodies (CPAbs) from a non-immunized lupus-prone (NZB × NZW)F1 mouse that exhibited high anti-DNA serum titres. These CPAbs are polyreactive because they bind to DNA and other cellular components, and localize mainly in the nucleus of HeLa cells, albeit with a distinct nuclear labelling profile. Herein, we have examined whether DNA-histone complexes (DHC) binding to CPAbs, before cell entry, could modify the cell penetration of CPAbs or their nuclear staining properties. By applying confocal microscopy and image analysis, we found that extracellular binding of purified CPAbs to DHC significantly enhanced their subsequent cell-entry, both in terms of percentages of positively labelled cells and fluorescence intensity (internalized CPAb amount), whereas there was a variable effect on their nuclear staining profile. Internalization of CPAbs, either alone or bound to DHC, remained unaltered after the addition of endocytosis-specific inhibitors at 37° or assay performance at 4°, suggesting the involvement of energy-independent mechanisms in the internalization process. These findings assign to CPAbs a more complex pathogenetic role in systemic lupus erythematosus where both CPAbs and nuclear components are abundant. © 2015 John Wiley & Sons Ltd.

Human cytomegalovirus chemokine receptor US28 induces migration of cells on a CX3CL1-presenting surface

DEFF Research Database (Denmark)

Hjortø, Gertrud M; Kiilerich-Pedersen, Katrine; Selmeczi, David

2013-01-01

Human cytomegalovirus (HCMV)-encoded G protein-coupled-receptor US28 is believed to participate in virus dissemination through modulation of cell migration and immune evasion. US28 binds different CC chemokines and the CX3C chemokine CX3CL1. Membrane-anchored CX3CL1 is expressed by immune-activat...

Cell-Penetrating Peptides as Carriers for Oral Delivery of Biopharmaceuticals

DEFF Research Database (Denmark)

Kristensen, Mie; Nielsen, Hanne Mørck

2016-01-01

Oral delivery of biopharmaceuticals, for example peptides and proteins, constitutes a great challenge in drug delivery due to their low chemical stability and poor permeation across the intestinal mucosa, to a large extent limiting the mode of administration to injections, which is not favouring...... patient compliance. Nevertheless, cell-penetrating peptides (CPPs) have shown promising potential as carriers to overcome the epithelium, and this minireview highlights recent knowledge gained within the field of CPP-mediated transepithelial delivery of therapeutic peptides and proteins from the intestine...... is to be preferred depends on the physicochemical properties of both the specific CPP and the specific cargo. In addition to the physical epithelial barrier, a metabolic barrier must be overcome in order to obtain CPP-mediated delivery of a cargo drug from the intestine, and a number of strategies have been employed...

Electrical detection of cellular penetration during microinjection with carbon nanopipettes

Science.gov (United States)

Anderson, Sean E.; Bau, Haim H.

2014-06-01

The carbon nanopipette (CNP) is comprised of a pulled-glass pipette terminating with a nanoscale (tens to hundreds of nm) diameter carbon pipe. The entire inner glass surface of the CNP is coated with a carbon film, providing an electrically conductive path from the carbon tip to the distal, macroscopic end of the pipette. The CNP can double as a nanoelectrode, enabling electrical measurements through its carbon lining, and as a nanoinjector, facilitating reagent injection through its hollow bore. With the aid of a lock-in amplifier, we measured, in real time and with millisecond resolution, variations in impedance and interfacial capacitance as the CNP penetrated into the cytoplasm and nucleus of adherent human osteosarcoma (U20S) cells during microinjection. The capacitance change associated with nucleus penetration was, on average, 1.5 times greater than the one associated with cell membrane penetration. The experimental data was compared and favorably agreed with theoretical predictions based on a simple electrical network model. As a proof of concept, the cytoplasm and nucleus were transfected with fluorescent tRNA, enabling real-time monitoring of tRNA trafficking across the nuclear membrane. The CNP provides a robust and reliable means to detect cell and nucleus penetration, and trigger injection, thereby enabling the automation of cell injection.

Electrical detection of cellular penetration during microinjection with carbon nanopipettes

International Nuclear Information System (INIS)

Anderson, Sean E; Bau, Haim H

2014-01-01

The carbon nanopipette (CNP) is comprised of a pulled-glass pipette terminating with a nanoscale (tens to hundreds of nm) diameter carbon pipe. The entire inner glass surface of the CNP is coated with a carbon film, providing an electrically conductive path from the carbon tip to the distal, macroscopic end of the pipette. The CNP can double as a nanoelectrode, enabling electrical measurements through its carbon lining, and as a nanoinjector, facilitating reagent injection through its hollow bore. With the aid of a lock-in amplifier, we measured, in real time and with millisecond resolution, variations in impedance and interfacial capacitance as the CNP penetrated into the cytoplasm and nucleus of adherent human osteosarcoma (U20S) cells during microinjection. The capacitance change associated with nucleus penetration was, on average, 1.5 times greater than the one associated with cell membrane penetration. The experimental data was compared and favorably agreed with theoretical predictions based on a simple electrical network model. As a proof of concept, the cytoplasm and nucleus were transfected with fluorescent tRNA, enabling real-time monitoring of tRNA trafficking across the nuclear membrane. The CNP provides a robust and reliable means to detect cell and nucleus penetration, and trigger injection, thereby enabling the automation of cell injection. (papers)

The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo

International Nuclear Information System (INIS)

Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung; Park, Yoon-Jeong; Chung, Chong-Pyoung

2012-01-01

Highlights: ► HBP sequence identified from HB-EGF has cell penetration activity. ► HBP inhibits the NF-κB dependent inflammatory responses. ► HBP directly blocks phosphorylation and degradation of IκBα. ► HBP inhibits nuclear translocation of NF-κB p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-α and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-α and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-κB-dependent inflammatory responses by directly blocking the phosphorylation and degradation of IκBα and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-κB. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.

Analyses on Cost Reduction and CO2 Mitigation by Penetration of Fuel Cells to Residential Houses

Science.gov (United States)

Aki, Hirohisa; Yamamoto, Shigeo; Kondoh, Junji; Murata, Akinobu; Ishii, Itaru; Maeda, Tetsuhiko

This paper presents analyses on the penetration of polymer electrolyte fuel cells (PEFC) into a group of 10 residential houses and its effects of CO2 emission mitigation and consumers’ cost reduction in next 30 years. The price is considered to be reduced as the penetration progress which is expected to begin in near future. An experimental curve is assumed to express the decrease of the price. Installation of energy interchange systems which involve electricity, gas and hydrogen between a house which has a FC and contiguous houses is assumed to utilize both electricity and heat more efficiently, and to avoid start-stop operation of fuel processor (reformer) as much as possible. A multi-objective model which considers CO2 mitigation and consumers’ cost reduction is constructed and provided a Pareto optimum solution. A solution which simultaneously realizes both CO2 mitigation and consumers’ cost reduction appeared in the Pareto optimum solution. Strategies to reduce CO2 emission and consumers’ cost are suggested from the results of the analyses. The analyses also revealed that the energy interchange systems are effective especially in the early stage of the penetration.

Cell-penetrating superoxide dismutase attenuates oxidative stress-induced senescence by regulating the p53-p21Cip1 pathway and restores osteoblastic differentiation in human dental pulp stem cells

Directory of Open Access Journals (Sweden)

Park YJ

2012-09-01

Full Text Available Yoon Jung Choi,1,* Jue Yeon Lee,2,* Chong Pyoung Chung,2 Yoon Jeong Park,1,21Craniomaxillofacial Reconstructive Sciences, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea; 2Research Institute, Nano Intelligent Biomedical Engineering, Seoul, Republic of Korea*These authors contributed equally to this workBackground: Human dental pulp stem cells (DPSCs have potential applications in tissue regeneration because of their convenient cell harvesting procedures and multipotent capacity. However, the tissue regenerative potential of DPSCs is known to be negatively regulated by aging in long-term culture and under oxidative stress. With an aim of reducing cellular senescence and oxidative stress in DPSCs, an intracellular delivery system for superoxide dismutase 1 (SOD1 was developed. We conjugated SOD1 with a cell-penetrating peptide known as low-molecular weight protamine (LMWP, and investigated the effect of LMWP-SOD1 conjugates on hydrogen peroxide-induced cellular senescence and osteoblastic differentiation.Results: LMWP-SOD1 significantly attenuated enlarged and flattened cell morphology and increased senescence-associated β-galactosidase activity. Under the same conditions, LMWP-SOD1 abolished activation of the cell cycle regulator proteins, p53 and p21Cip1, induced by hydrogen peroxide. In addition, LMWP-SOD1 reversed the inhibition of osteoblastic differentiation and downregulation of osteogenic gene markers induced by hydrogen peroxide. However, LMWP-SOD1 could not reverse the decrease in odontogenesis caused by hydrogen peroxide.Conclusion: Overall, cell-penetrating LMWP-SOD1 conjugates are effective for attenuation of cellular senescence and reversal of osteoblastic differentiation of DPSCs caused by oxidative stress inhibition. This result suggests potential application in the field of antiaging and tissue engineering to overcome the limitations of senescent stem cells.Keywords: superoxide

Hydrophobic and electrostatic interactions between cell penetrating peptides and plasmid DNA are important for stable non-covalent complexation and intracellular delivery.

Science.gov (United States)

Upadhya, Archana; Sangave, Preeti C

2016-10-01

Cell penetrating peptides are useful tools for intracellular delivery of nucleic acids. Delivery of plasmid DNA, a large nucleic acid, poses a challenge for peptide mediated transport. The paper investigates and compares efficacy of five novel peptide designs for complexation of plasmid DNA and subsequent delivery into cells. The peptides were designed to contain reported DNA condensing agents and basic cell penetrating sequences, octa-arginine (R 8 ) and CHK 6 HC coupled to cell penetration accelerating peptides such as Bax inhibitory mutant peptide (KLPVM) and a peptide derived from the Kaposi fibroblast growth factor (kFGF) membrane translocating sequence. A tryptophan rich peptide, an analogue of Pep-3, flanked with CH 3 on either ends was also a part of the study. The peptides were analysed for plasmid DNA complexation, protection of peptide-plasmid DNA complexes against DNase I, serum components and competitive ligands by simple agarose gel electrophoresis techniques. Hemolysis of rat red blood corpuscles (RBCs) in the presence of the peptides was used as a measure of peptide cytotoxicity. Plasmid DNA delivery through the designed peptides was evaluated in two cell lines, human cervical cancer cell line (HeLa) and (NIH/3 T3) mouse embryonic fibroblasts via expression of the secreted alkaline phosphatase (SEAP) reporter gene. The importance of hydrophobic sequences in addition to cationic sequences in peptides for non-covalent plasmid DNA complexation and delivery has been illustrated. An alternative to the employment of fatty acid moieties for enhanced gene transfer has been proposed. Comparison of peptides for plasmid DNA complexation and delivery of peptide-plasmid DNA complexes to cells estimated by expression of a reporter gene, SEAP. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Cell-penetrating peptides as tools to enhance non-injectable delivery of biopharmaceuticals

DEFF Research Database (Denmark)

Kristensen, Mie; Nielsen, Hanne Mørck

2016-01-01

Non-injectable delivery of peptide and protein drugs is hampered by their labile nature, hydrophilicity, and large molecular size; thus limiting their permeation across mucosae, which represent major biochemical and physical barriers to drugs administered via e.g. the oral, nasal, and pulmonary...... routes. However, in recent years cell-penetrating peptides (CPP) have emerged as promising tools to enhance mucosal delivery of co-administered or conjugated peptide and protein cargo and more advanced CPP-cargo formulations are emerging. CPPs act as transepithelial delivery vectors, but the mechanism...... understanding, documentation of CPP-mediated delivery in higher animal species than rodent as well as extensive toxicological studies are necessary for CPP-containing non-injectable DDSs to reach the clinic....

Vesicles mimicking normal and cancer cell membranes exhibit differential responses to the cell-penetrating peptide Pep-1.

Science.gov (United States)

Almarwani, Bashiyar; Phambu, Esther Nzuzi; Alexander, Christopher; Nguyen, Ha Aimee T; Phambu, Nsoki; Sunda-Meya, Anderson

2018-06-01

The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the blue shift of its maximal emission wavelength. DSC data show that Pep-1 induces segregation of lipids. At high peptide concentration, IR data indicate that the interaction of Pep-1 is relatively stronger with normal cell membrane than with cancer cell membrane through the phosphate groups, while the interaction is weaker with normal cell membrane than with cancer cell membrane through the carbonyl groups. TGA and DSC data reveal that vesicles of normal cell membrane are thermally more stable than vesicles of cancer cell membrane. This suggests that the additional lipid PS included in cancer cell membrane has a destabilizing effect on the membrane structure. SEM images reveal that Pep-1 form superstructures including spherical particles and fibrils in the presence of both model membranes. PS seems to enhance peptide transport across cellular membranes. The biophysical techniques in this study provide valuable insights into the properties of CPPs in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Electrochemistry of a ferrocene-grafted cell-penetrating peptide

International Nuclear Information System (INIS)

Messina, Pierluca; Hallais, Géraldine; Labbé, Eric; Béranger, Marie; Chassaing, Gérard; Lavielle, Solange; Mansuy, Christelle; Buriez, Olivier

2012-01-01

A cationic cell-penetrating peptide (CPP) labeled with both a ferrocenyl (Fc) moiety and a biotin (B) was successfully synthesized and investigated by electrochemistry. This original CPP derivative noted as Fc-CPP-B could be electrochemically detected, at a micromolar concentration, at a naked gold bead electrode. The presence of a biotin tag in the Fc-CPP-B complex allowed its complexation with avidin, which was itself tethered to a thiolated self-assembled monolayer. Such an avidin-modified gold surface, characterized by atomic force microscopy (AFM), allowed the immobilization of Fc-CPP-B onto the electrode surface, which greatly enhanced its electrochemical detection. Nevertheless, under these conditions the electrogenerated ferrocenium cation could not be reduced during the backward scan, indicating its unexpected reactivity when tethered within the avidin environment. In terms of detection and redox probe regeneration the best results were obtained at a glassy carbon electrode modified with a cation-exchange polymer. Ion-exchange voltammetry, performed under these conditions, allowed the pre-concentration of the peptide at the electrode surface thanks to the net positive charge of the CPP derivative. Interestingly, the anionic character of the polymer contributed to retain the electrogenerated cation Fc + in the film so that it could be reduced back to its original neutral form during the reverse voltammetric scans.

Recent in vivo advances in cell-penetrating peptide-assisted drug delivery.

Science.gov (United States)

Kurrikoff, Kaido; Gestin, Maxime; Langel, Ülo

2016-01-01

Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment. In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP-cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA). Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.

Correlation Between Cone Penetration Rate And Measured Cone Penetration Parameters In Silty Soils

DEFF Research Database (Denmark)

Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

2013-01-01

This paper shows, how a change in cone penetration rate affects the cone penetration measurements, hence the cone resistance, pore pressure, and sleeve friction in silty soil. The standard rate of penetration is 20 mm/s, and it is generally accepted that undrained penetration occurs in clay while...... drained penetration occurs in sand. When lowering the penetration rate, the soil pore water starts to dissipate and a change in the drainage condition is seen. In intermediate soils such as silty soils, the standard cone penetration rate may result in a drainage condition that could be undrained......, partially or fully drained. However, lowering the penetration rate in silty soils has a great significance because of the soil permeability, and only a small change in penetration rate will result in changed cone penetration measurements. In this paper, analyses will be done on data from 15 field cone...

Characterization of the cell penetrating properties of a human salivary proline-rich peptide.

Science.gov (United States)

Radicioni, Giorgia; Stringaro, Annarita; Molinari, Agnese; Nocca, Giuseppina; Longhi, Renato; Pirolli, Davide; Scarano, Emanuele; Iavarone, Federica; Manconi, Barbara; Cabras, Tiziana; Messana, Irene; Castagnola, Massimo; Vitali, Alberto

2015-11-01

Saliva contains hundreds of small proline-rich peptides most of which derive from the post-translational and post-secretory processing of the acidic and basic salivary proline-rich proteins. Among these peptides we found that a 20 residue proline-rich peptide (p1932), commonly present in human saliva and patented for its antiviral activity, was internalized within cells of the oral mucosa. The cell-penetrating properties of p1932 have been studied in a primary gingival fibroblast cell line and in a squamous cancer cell line, and compared to its retro-inverso form. We observed by mass-spectrometry, flow cytometry and confocal microscopy that both peptides were internalized in the two cell lines on a time scale of minutes, being the natural form more efficient than the retro-inverso one. The cytosolic localization was dependent on the cell type: both peptide forms were able to localize within nuclei of tumoral cells, but not in the nuclei of gingival fibroblasts. The uptake was shown to be dependent on the culture conditions used: peptide internalization was indeed effective in a complete medium than in a serum-free one allowing the hypothesis that the internalization could be dependent on the cell cycle. Both peptides were internalized likely by a lipid raft-mediated endocytosis mechanism as suggested by the reduced uptake in the presence of methyl-ß-cyclodextrin. These results suggest that the natural peptide may play a role within the cells of the oral mucosa after its secretion and subsequent internalization. Furthermore, lack of cytotoxicity of both peptide forms highlights their possible application as novel drug delivery agents.

Percutaneous penetration of 3H-Huangbai extracts and H3-berberine

International Nuclear Information System (INIS)

Jin Xipeng; Yu Xiaozhong; Zhang Nianbao; Kuang Jianwen

1992-01-01

The percutaneous penetration of 3 H-huangbai extracts and 3 H-berberine through excised guinea pig and human shins was studied using the static diffusion cell technique. The data were treated with mathematical model of skin absorption. The results showed that huangbai extracts and berberine could penetrate the guinea pig and human skins at (above) dose of 8.38 μg/cm 2 and 14.32 μg/cm 2 , respectively. The amount and rate of penetration increased linearly with the time of exposure and dose. The permeability of berberine through guinea pig and human skins in two vehicles (water and glycol) was lower than that of huangbai extracts. When Huangbai extracts and berberine were applied in glycol solution, the vehicle greatly enhanced the penetration of the two penetrant. The lag time of two penetrant through human skin was longer than that through guinea pig skin

Follicular and percutaneous penetration pathways of topically applied minoxidil foam.

Science.gov (United States)

Blume-Peytavi, Ulrike; Massoudy, Lida; Patzelt, Alexa; Lademann, Jürgen; Dietz, Ekkehart; Rasulev, Utkur; Garcia Bartels, Natalie

2010-11-01

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances. This study investigates a selective closure technique of hair follicle orifices in vivo assessing interfollicular and follicular absorption rates of topical minoxidil foam in humans. In delimited skin area, single hair orifices or interfollicular skin were blocked with a microdrop of special varnish-wax-mixture in vivo. Minoxidil foam (5%) was topically applied, and transcutaneous absorption was measured by a new surface ionization mass spectrometry technique in serum. Different settings (open, closed or none of both) enabled to clearly distinguish between interfollicular and follicular penetration of the topically applied minoxidil foam. Five minutes after topical application, minoxidil was detected in blood samples when follicles remained open, whereas with closed follicles 30 min were needed. Highest levels were found first when both pathways were open, followed by open follicles and subsequently by closed follicles. These results demonstrate the high importance of the follicular penetration pathway. Hair follicles are surrounded by a dense network of blood capillaries and dendritic cells and have stem cells in their immediate vicinity, making them ideal targets for drug delivery. Copyright © 2010 Elsevier B.V. All rights reserved.

STYLET PENETRATION BEHAVIOURS OF FOUR Cicadulina ...

African Journals Online (AJOL)

ACSS

Feeding from phloem cells, overall probing and probe mean (the average time per probe) were higher ... Key Words: Cicadulina spp., electrical penetration graph, MSV, Zea mays .... wire and alligator clip clamped to the stem of the .... á All measures are in minutes except for frequency of probing; - Main effect not significant.

Conjugation to the cell-penetrating peptide TAT potentiates the photodynamic effect of carboxytetramethylrhodamine.

Directory of Open Access Journals (Sweden)

Divyamani Srinivasan

2011-03-01

Full Text Available Cell-penetrating peptides (CPPs can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6-carboxytetramethylrhodamine (TMR.We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood cells. These photolytic and photocytotoxic effects were inhibited by hydrophobic singlet oxygen quenchers but not by hydrophilic quenchers.Together, these results suggest that TAT can convert an innocuous fluorophore such as TMR into a potent photolytic agent. This effect involves the targeting of the fluorophore to cellular membranes and the production of singlet oxygen within the hydrophobic environment of the membranes. Our findings may be relevant for the design of reagents with photo-induced endosomolytic activity. The photocytotoxicity exhibited by TMR-TAT also suggests that CPP-chromophore conjugates could aid the development of novel Photodynamic Therapy agents.

Thrombin activatable fibrinolysis inhibitor (TAFI) - A possible link between coagulation and complement activation in the antiphospholipid syndrome (APS).

Science.gov (United States)

Grosso, Giorgia; Vikerfors, Anna; Woodhams, Barry; Adam, Mariette; Bremme, Katarina; Holmström, Margareta; Ågren, Anna; Eelde, Anna; Bruzelius, Maria; Svenungsson, Elisabet; Antovic, Aleksandra

2017-10-01

Thrombosis and complement activation are pathogenic features of antiphospholipid syndrome (APS). Their molecular link is Plasma carboxypeptidase-B, also known as thrombin activatable fibrinolysis inhibitor (TAFIa), which plays a dual role: anti-fibrinolytic, by cleaving carboxyl-terminal lysine residues from partially degraded fibrin, and anti-inflammatory, by downregulating complement anaphylatoxins C3a and C5a. To investigate the levels of TAFI (proenzyme) and TAFIa (active enzyme) in relation to complement activation, fibrin clot permeability and fibrinolytic function in clinical and immunological subsets of 52 APS patients and 15 controls. TAFI (pAPS patients compared to controls. Furthermore, TAFIa was increased (pAPS patients affected by arterial thrombosis compared to other APS-phenotypes. Positive associations were found between TAFI and age, fibrinogen and C5a, and between TAFIa and age, fibrinogen and thrombomodulin. TAFI and TAFIa levels were increased in patients with APS as a potential response to complement activation. Interestingly, TAFI activation was associated with arterial thrombotic APS manifestations. Thus, TAFIa may be considered a novel biomarker for arterial thrombosis in APS. Copyright © 2017 Elsevier Ltd. All rights reserved.

A review of penetration mechanisms and dynamic properties of tungsten and depleted uranium penetrators

International Nuclear Information System (INIS)

Andrew, S.P.; Caligiuri, R.D.; Eiselstein, L.E.

1991-01-01

Kinetic energy penetrators must posses the best possible combination of hardness, stiffness, strength, and fracture toughness characteristics to be effective against modern armor systems. Over the last decade, depleted uranium (DU) and tungsten alloys have been the materials of choice for kinetic energy penetrators. Du and tungsten perform abut the same against semi-infinite targets, and DU outperforms tungsten penetrators in oblique, spaced array targets, but because of environmental and subsequent cost concerns, effort has focused on improving the performance of tungsten penetrators over the last few years. However, despite recent improvements in material properties, the penetration performance of tungsten still lags behind that of DU. One possible reason is the difference in deformation mechanisms at the leading edge of the penetrator during the penetration process-DU alloys tend to shear band and sharpen as they penetrate the target material, whereas tungsten penetrators tend to mushroom and blunt. As a first step to determine whether shear banding is truly the reason for superior DU performance, a review of the fabrication, high strain-rate properties, and penetration phenomena of penetrators manufactured from both tungsten and DU alloys. Specifically, the effects of composition, processing, and heat treatment on material properties and penetration mechanisms of these alloys are discussed

Highly penetrative liposome nanomedicine generated by a biomimetic strategy for enhanced cancer chemotherapy.

Science.gov (United States)

Jia, Yali; Sheng, Zonghai; Hu, Dehong; Yan, Fei; Zhu, Mingting; Gao, Guanhui; Wang, Pan; Liu, Xin; Wang, Xiaobing; Zheng, Hairong

2018-04-25

Liposome nanomedicine has been successfully applied for cancer chemotherapy in patients. However, in general, the therapeutic efficacy is confined by its limited accumulation and penetration in solid tumors. Here, we established a biomimetic strategy for the preparation of highly penetrative liposome nanomedicine for enhanced chemotherapeutic efficacy. By applying this unique type of nanomedicine, membrane proteins on the cancer cells are used as highly penetrative targeting ligands. Biomimetic liposomes are highly stable, exhibiting a superior in vitro homologous targeting ability, and a 2.25-fold deeper penetration in 3D tumor spheroids when compared to conventional liposome nanomedicine. The fluorescence/photoacoustic dual-modal imaging approach demonstrated enhanced tumor accumulation and improved tumor penetration of the biomimetic liposome in C6 glioma tumor-bearing nude mice. Following the intravenous administration of biomimetic liposome nanomedicine, the tumor inhibition rate reached up to 93.3%, which was significantly higher when compared to that of conventional liposome nanomedicine (69.3%). Moreover, histopathological analyses demonstrated that biomimetic liposome nanomedicine has limited side effects. Therefore, these results suggested that a cancer cell membrane-based biomimetic strategy may provide a breakthrough approach for enhancing drug penetration and improving treatment efficacy, holding a great promise for further clinical studies.

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

Science.gov (United States)

Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

How deep can plasma penetrate into a biofilm?

Science.gov (United States)

Xiong, Z.; Du, T.; Lu, X.; Cao, Y.; Pan, Y.

2011-05-01

It is well known that plasma can deactivate various types of microorganisms. However, one fundamental key question has never been addressed, namely, how deep can plasma penetrate into multilayer biofilms. In this letter, Porphyromonas gingivalis (PG) biofilms (10 days growth, which has about 30 layers of PG cells with a thickness of about 15 μm) are treated with a cold plasma plume. It is found that the plasma can penetrate the biofilms and effectively deactivate all the bacteria in the 15 μm thick biofilms. Moreover, it was found that most of the dead cells' structures in the biofilms are not damaged. From the optical emission spectra of the plasma, it can be concluded that it is O and OH, rather than O2-, N2+, or UV emission that play the major role in the deactivation processes.

The Effect of Bacteria Penetration on Chalk Permeability

DEFF Research Database (Denmark)

Halim, Amalia Yunita; Shapiro, Alexander; Nielsen, Sidsel Marie

number of B. licheniformis was detected on the effluent compared with P. putida. However, in the experiment with B. licheniformis mainly spores were detected in the effluent. The core permeability decreased rapidly during injection of bacteria and a starvation period of 12 days did not allow......Bacteria selective plugging is one of the mechanisms through which microorganisms can be applied for enhanced oil recovery. Bacteria can plug the water-bearing zones of a reservoir, thus altering the flow paths and improving sweep efficiency. It is known that the bacteria can penetrate deeply...... into reservoirs, however, a complete understanding of the penetration behavior of bacteria is lacking, especially in chalk formations where the pore throat sizes are almost comparable with the sizes of bacteria vegetative cells. This study investigates the penetration of bacteria into chalk. Two bacteria types...

Estradiol-induced vaginal mucus inhibits antigen penetration and CD8(+) T cell priming in response to intravaginal immunization.

Science.gov (United States)

Seavey, Matthew M; Mosmann, Tim R

2009-04-14

Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8(+) T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APCs) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8(+) T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8(+) T cell priming after insemination or vaginal vaccination.

Estradiol-induced vaginal mucus inhibits antigen penetration and CD8+ T cell priming in response to intravaginal immunization

Science.gov (United States)

Seavey, Matthew M.; Mosmann, Tim R.

2010-01-01

Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8+ T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APC) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8+ T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8+ T cell priming after insemination or vaginal vaccination. PMID:19428849

Translocation of Cell Penetrating Peptide Engrafted Nanoparticles Across Skin Layers

Science.gov (United States)

Patlolla, Ram R; Desai, Pinaki; Belay, Kalayu; Singh, Mandip

2010-01-01

The objective of the current study was to evaluate the ability of cell penetrating peptides (CPP) to translocate the lipid payload into the skin layers. Fluorescent dye (DID-oil) encapsulated nano lipid crystal nanoparticles (FNLCN) were prepared using Compritol, Miglyol and DOGS-NTA-Ni lipids by hot melt homogenization technique. The FNLCN surface was coated with TAT peptide (FNLCNT) or control YKA peptide (FNLCNY) and in vitro rat skin permeation studies were performed using Franz diffusion cells. Observation of lateral skin sections obtained using cryotome with a confocal microscope demonstrated that skin permeation of FNLCNT was time dependent and after 24 h, fluorescence was observed upto a depth of 120 µm which was localized in the hair follicles and epidermis. In case of FNLCN and FNLCNY formulations fluorescence was mainly observed in the hair follicles. This observation was further supported by confocal Raman spectroscopy where higher fluorescence signal intensity was observed at 80 and 120 µm depth with FNLCNT treated skin and intensity of fluorescence peaks was in the ratio of 2:1:1 and 5:3:1 for FNLCNT, FNLCN, and FNLCNY treated skin sections, respectively. Furthermore, replacement of DID-oil with celecoxib (Cxb), a model lipophilic drug showed similar results and after 24 h, the CXBNT formulation increased the Cxb concentration in SC by 3 and 6 fold and in epidermis by 2 and 3 fold as compared to CXBN and CXBNY formulations respectively. Our results strongly suggest that CPP can translocate nanoparticles with their payloads into deeper skin layers. PMID:20413152

Influence of jet thrust on penetrator penetration when studying the structure of space object blanket

Directory of Open Access Journals (Sweden)

N. A. Fedorova

2014-01-01

Full Text Available The article presents the calculation-and-theory-based research results to examine the possibility for using the jet thrust impulse to increase a penetration depth of high-velocity penetrator modules. Such devices can be used for studies of Earth surface layer composition, and in the nearest future for other Solar system bodies too. Research equipment (sensors and different instruments is housed inside a metal body of the penetrator with a sharpened nose that decreases drag force in soil. It was assumed, that this penetrator is additionally equipped with the pulse jet engine, which is fired at a certain stage of penetrator motion into target.The penetrator is considered as a rigid body of variable mass, which is subjected to drag force and reactive force applied at the moment the engine fires. A drag force was represented with a binomial empirical law, and penetrator nose part was considered to be conical. The jet thrust force was supposed to be constant during its application time. It was in accordance with assumption that mass flow and flow rate of solid propellant combustion products were constant. The amount of propellant in the penetrator was characterized by Tsiolkovsky number Z, which specifies the ratio between the fuel mass and the penetrator structure mass with no fuel.The system of equations to describe the penetrator dynamics was given in dimensionless form using the values aligned with penetration of an equivalent inert penetrator as the time and penetration depth scales. Penetration dynamics of penetrator represented in this form allowed to eliminate the influence of penetrator initial mass and its cross-section diameter on the solution results. The lack of such dependency is convenient for comparing the calculation results since they hold for penetrators of various initial masses and cross-sections.To calculate the penetration a lunar regolith was taken as a soil material. Calculations were carried out for initial velocities of

Large-scale preparation of active caspase-3 in E. coli by designing its thrombin-activatable precursors

Directory of Open Access Journals (Sweden)

Park Sung

2008-12-01

Full Text Available Abstract Background Caspase-3, a principal apoptotic effector that cleaves the majority of cellular substrates, is an important medicinal target for the treatment of cancers and neurodegenerative diseases. Large amounts of the protein are required for drug discovery research. However, previous efforts to express the full-length caspase-3 gene in E. coli have been unsuccessful. Results Overproducers of thrombin-activatable full-length caspase-3 precursors were prepared by engineering the auto-activation sites of caspase-3 precursor into a sequence susceptible to thrombin hydrolysis. The engineered precursors were highly expressed as soluble proteins in E. coli and easily purified by affinity chromatography, to levels of 10–15 mg from 1 L of E. coli culture, and readily activated by thrombin digestion. Kinetic evaluation disclosed that thrombin digestion enhanced catalytic activity (kcat/KM of the precursor proteins by two orders of magnitude. Conclusion A novel method for a large-scale preparation of active caspase-3 was developed by a strategic engineering to lack auto-activation during expression with amino acid sequences susceptible to thrombin, facilitating high-level expression in E. coli. The precursor protein was easily purified and activated through specific cleavage at the engineered sites by thrombin, generating active caspase-3 in high yields.

Penetration of equine leukocytes by merozoites of Sarcocystis neurona.

Science.gov (United States)

Lindsay, David S; Mitchell, Sheila M; Yang, Jibing; Dubey, J P; Gogal, Robert M; Witonsky, Sharon G

2006-06-15

Horses are considered accidental hosts for Sarcocystis neurona and they often develop severe neurological disease when infected with this parasite. Schizont stages develop in the central nervous system (CNS) and cause the neurological lesions associated with equine protozoal myeloencephalitis. The present study was done to examine the ability of S. neurona merozoites to penetrate and develop in equine peripheral blood leukocytes. These infected host cells might serve as a possible transport mechanism into the CNS. S. neurona merozoites penetrated equine leukocytes within 5 min of co-culture. Infected leukocytes were usually monocytes. Infected leukocytes were present up to the final day of examination at 3 days. Up to three merozoites were present in an infected monocyte. No development to schizont stages was observed. All stages observed were in the host cell cytoplasm. We postulate that S. neurona merozoites may cross the blood brain barrier hidden inside leukocytes. Once inside the CNS these merozoites can egress and invade additional cells and cause encephalitis.

A review of penetration mechanisms and dynamic properties of tungsten and depleted uranium penetrators

International Nuclear Information System (INIS)

Andrew, S.P.; Caligiuri, R.D.; Eiselstein, L.E.

1991-01-01

Over the last decade, depleted uranium (DU) and tungsten alloys have been the materials of choice for kinetic energy penetrators. However, despite improvements in mechanical properties in recent years, the penetration performance of tungsten still lags behind that of DU. One possible reason is the difference in deformation mechanisms- DU alloys tend to shear band as they penetrate the target material, whereas tungsten penetrators tend to mushroom. As a first step to determining whether shear banding is truly the reason for superior DU performance, a review and summary of the available information was performed. This paper presents a state-of-the-art review of the formulation, high strain- rate properties, and penetration phenomena of penetrators manufactured from both tungsten and DU alloys. Specifically, the effects of composition, processing, and heat treatment on mechanical properties and penetration mechanisms of these alloys are discussed. Penetration data and models for penetration mechanisms (in particular shear banding) are also presented, as well as the applicability of these models and their salient features

Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides.

Science.gov (United States)

Kamei, Noriyasu; Takeda-Morishita, Mariko

2015-01-10

Intranasal administration is considered as an alternative route to enable effective drug delivery to the central nervous system (CNS) by bypassing the blood-brain barrier. Several reports have proved that macromolecules can be transferred directly from the nasal cavity to the brain. However, strategies to enhance the delivery of macromolecules from the nasal cavity to CNS are needed because of their low delivery efficiencies via this route in general. We hypothesized that the delivery of biopharmaceuticals to the brain parenchyma can be facilitated by increasing the uptake of drugs by the nasal epithelium including supporting and neuronal cells to maximize the potentiality of the intranasal pathway. To test this hypothesis, the CNS-related model peptide insulin was intranasally coadministered with the cell-penetrating peptide (CPP) penetratin to mice. As a result, insulin coadministered with l- or d-penetratin reached the distal regions of the brain from the nasal cavity, including the cerebral cortex, cerebellum, and brain stem. In particular, d-penetratin could intranasally deliver insulin to the brain with a reduced risk of systemic insulin exposure. Thus, the results obtained in this study suggested that CPPs are potential tools for the brain delivery of peptide- and protein-based pharmaceuticals via intranasal administration. Copyright © 2014 Elsevier B.V. All rights reserved.

Negligible penetration of incidental amounts of alpha-hydroxy acid from rinse-off personal care products in human skin using an in vitro static diffusion cell model.

Science.gov (United States)

Okuda, M; Donahue, D A; Kaufman, L E; Avalos, J; Simion, F A; Story, D C; Sakaguchi, H; Fautz, R; Fuchs, A

2011-12-01

Alpha-hydroxy acids (AHAs), primarily glycolic and lactic acids, are widely used in cosmetics to alleviate dyspigmentation, photodamage, and other aging skin conditions and as pH adjusters. Glycolic acid reportedly enhances skin damage after repeated ultraviolet light exposure, e.g., increased sunburn cell formation. This study assessed potential in vitro skin penetration of lactic acid and malic acid incorporated into rinse-off personal care products, compared with rinse-off and leave-on exposures to glycolic acid (10%, pH 3.5) in a reference lotion. Radiolabeled AHA-fortified shampoo, conditioner, and lotion were evenly applied as single doses to human epidermal membranes mounted in static diffusion cells (not occluded). Exposures were 1-3 min (rinse-off) or 24 h (leave-on). Epidermal penetration of malic acid and lactic acid from the rinse-off shampoo and conditioner, respectively, was negligible, with >99% removed by rinsing, a negligible portion remaining in the stratum corneum (≤0.15%), and even less penetrating into the viable epidermis (≤0.04%). Glycolic acid penetration from the leave-on reference lotion was 1.42 μg equiv./cm2/h, with total absorbable dose recovery (receptor fluid plus epidermis) of 2.51%, compared to 0.009%, 0.003%, and 0.04% for the rinse-off reference lotion, shampoo (malic acid), and conditioner (lactic acid) exposures, respectively. Dermal penetration of AHAs into human skin is pH-, concentration-, and time-dependent. Alpha-hydroxy acids in rinse-off shampoos and conditioners are almost entirely removed from the skin within minutes by rinsing (resulting in negligible epidermal penetration). This suggests that ultraviolet radiation-induced skin effects of AHA-containing rinse-off products are negligible. Copyright © 2011 Elsevier Ltd. All rights reserved.

Elastic behavior of MFI-type zeolites: Compressibility of H-ZSM-5 in penetrating and non-penetrating media

International Nuclear Information System (INIS)

Quartieri, Simona; Montagna, Gabriele; Arletti, Rossella; Vezzalini, Giovanna

2011-01-01

The elastic behavior of H-ZSM-5 was investigated by in-situ synchrotron X-ray powder diffraction, using both silicone oil (s.o.) and (16:3:1) methanol:ethanol:water (m.e.w.) as 'non-penetrating' and 'penetrating' pressure transmitting media, respectively. From P amb to 6.2 GPa the volume reduction observed in s.o. is 16.6%. This testifies that H-ZSM-5 is one of the most flexible microporous materials up to now compressed in s.o. Volume reduction observed in m.e.w. up to 7.6 GPa is 14.6%. A strong increase in the total electron number of the extraframework system, due to the penetration of water/alcohol molecules in the pores, is observed in m.e.w. This effect is the largest up to now observed in zeolites undergoing this phenomenon without cell volume expansion. The higher compressibility in s.o. than in m.e.w. can be ascribed to the penetration of the extra-water/alcohol molecules, which stiffen the structure and contrast the channel deformations. - Graphical abstract: High-pressure behavior of H-ZSM-5 compressed in (16:3:1) methanol:ethanol:water: (a) projection of the structure along the [0 1 0] direction at P amb , 2 GPa and after pressure release to original ambient conditions (P amb (rev)), and (b) P-dependence of the extraframework content expressed as total number of electrons (gray square represents the number of the extraframework electrons at P amb after decompression). Highlights: → X-ray powder diffraction study of H-ZSM-5 compressibility. → H-ZSM-5 is one of the softest porous material compressed in silicon oil. → Penetration of additional water/alcohol molecules upon compression in m.e.w. → Extra molecules contribute to stiffen the structure and to contrast HP effects.

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

Directory of Open Access Journals (Sweden)

Betty R Liu

Full Text Available Cell-penetrating peptides (CPPs have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW from bovine lactoferricin (LFcin, stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

Percutaneous penetration of [sup 3]H-Huangbai extracts and H[sup 3]-berberine

Energy Technology Data Exchange (ETDEWEB)

Xipeng, Jin; Xiaozhong, Yu [School of Public Health, Shanghai Medical Univ. (China); Nianbao, Zhang; Jianwen, Kuang [Shanghai Inst. of Nuclear Research Acdemic Sinica (China)

1992-02-01

The percutaneous penetration of [sup 3]H-huangbai extracts and [sup 3]H-berberine through excised guinea pig and human shins was studied using the static diffusion cell technique. The data were treated with mathematical model of skin absorption. The results showed that huangbai extracts and berberine could penetrate the guinea pig and human skins at (above) dose of 8.38 [mu]g/cm[sup 2] and 14.32 [mu]g/cm[sup 2], respectively. The amount and rate of penetration increased linearly with the time of exposure and dose. The permeability of berberine through guinea pig and human skins in two vehicles (water and glycol) was lower than that of huangbai extracts. When Huangbai extracts and berberine were applied in glycol solution, the vehicle greatly enhanced the penetration of the two penetrant. The lag time of two penetrant through human skin was longer than that through guinea pig skin.

Independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain.

Science.gov (United States)

Danthi, Pranav; Coffey, Caroline M; Parker, John S L; Abel, Ty W; Dermody, Terence S

2008-12-01

Apoptosis plays an important role in the pathogenesis of reovirus encephalitis. Reovirus outer-capsid protein mu1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. Ectopic expression of full-length and truncated forms of mu1 indicates that the mu1 phi domain is sufficient to elicit a cell death response. To evaluate the contribution of the mu1 phi domain to the induction of apoptosis following reovirus infection, phi mutant viruses were generated by reverse genetics and analyzed for the capacity to penetrate cell membranes and elicit apoptosis. We found that mutations in phi diminish reovirus membrane penetration efficiency by preventing conformational changes that lead to generation of key reovirus entry intermediates. Independent of effects on membrane penetration, amino acid substitutions in phi affect the apoptotic potential of reovirus, suggesting that phi initiates apoptosis subsequent to cytosolic delivery. In comparison to wild-type virus, apoptosis-defective phi mutant viruses display diminished neurovirulence following intracranial inoculation of newborn mice. These results indicate that the phi domain of mu1 plays an important regulatory role in reovirus-induced apoptosis and disease.

Independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain.

Directory of Open Access Journals (Sweden)

Pranav Danthi

2008-12-01

Full Text Available Apoptosis plays an important role in the pathogenesis of reovirus encephalitis. Reovirus outer-capsid protein mu1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. Ectopic expression of full-length and truncated forms of mu1 indicates that the mu1 phi domain is sufficient to elicit a cell death response. To evaluate the contribution of the mu1 phi domain to the induction of apoptosis following reovirus infection, phi mutant viruses were generated by reverse genetics and analyzed for the capacity to penetrate cell membranes and elicit apoptosis. We found that mutations in phi diminish reovirus membrane penetration efficiency by preventing conformational changes that lead to generation of key reovirus entry intermediates. Independent of effects on membrane penetration, amino acid substitutions in phi affect the apoptotic potential of reovirus, suggesting that phi initiates apoptosis subsequent to cytosolic delivery. In comparison to wild-type virus, apoptosis-defective phi mutant viruses display diminished neurovirulence following intracranial inoculation of newborn mice. These results indicate that the phi domain of mu1 plays an important regulatory role in reovirus-induced apoptosis and disease.

High-pressure-induced water penetration into 3-isopropylmalate dehydrogenase

International Nuclear Information System (INIS)

Nagae, Takayuki; Kawamura, Takashi; Chavas, Leonard M. G.; Niwa, Ken; Hasegawa, Masashi; Kato, Chiaki; Watanabe, Nobuhisa

2012-01-01

Structures of 3-isopropylmalate dehydrogenase were determined at pressures ranging from 0.1 to 650 MPa. Comparison of these structures gives a detailed picture of the swelling of a cavity at the dimer interface and the generation of a new cleft on the molecular surface, which are accompanied by water penetration. Hydrostatic pressure induces structural changes in proteins, including denaturation, the mechanism of which has been attributed to water penetration into the protein interior. In this study, structures of 3-isopropylmalate dehydrogenase (IPMDH) from Shewanella oneidensis MR-1 were determined at about 2 Å resolution under pressures ranging from 0.1 to 650 MPa using a diamond anvil cell (DAC). Although most of the protein cavities are monotonically compressed as the pressure increases, the volume of one particular cavity at the dimer interface increases at pressures over 340 MPa. In parallel with this volume increase, water penetration into the cavity could be observed at pressures over 410 MPa. In addition, the generation of a new cleft on the molecular surface accompanied by water penetration could also be observed at pressures over 580 MPa. These water-penetration phenomena are considered to be initial steps in the pressure-denaturation process of IPMDH

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

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Ding Y

2015-10-01

Full Text Available Yuan Ding,1,* Dan Sun,1,* Gui-Ling Wang,1 Hong-Ge Yang,1 Hai-Feng Xu,1 Jian-Hua Chen,2 Ying Xie,1,3 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Medicine, Jianghan University, Wuhan, 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: Cell-penetrating peptides (CPPs as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into

Physical Penetration Testing: A Whole New Story in Penetration Testing

NARCIS (Netherlands)

Dimkov, T.; Pieters, Wolter

2011-01-01

Physical penetration testing plays an important role in assuring a company that the security policies are properly enforced and that the security awareness of the employees is on the appropriate level. In physical penetration tests the tester physically enters restricted locations and directly

Effects of soap-water wash on human epidermal penetration.

Science.gov (United States)

Zhu, Hanjiang; Jung, Eui-Chang; Phuong, Christina; Hui, Xiaoying; Maibach, Howard

2016-08-01

Skin decontamination is a primary interventional method used to decrease dermal absorption of hazardous contaminants, including chemical warfare agents, pesticides and industrial pollutants. Soap and water wash, the most common and readily available decontamination system, may enhance percutaneous absorption through the "wash-in effect." To understand better the effect of soap-water wash on percutaneous penetration, and provide insight to improving skin decontamination methods, in vitro human epidermal penetration rates of four C(14) -labeled model chemicals (hydroquinone, clonidine, benzoic acid and paraoxon) were assayed using flow-through diffusion cells. Stratum corneum (SC) absorption rates of these chemicals at various hydration levels (0-295% of the dry SC weights) were determined and compared with the results of the epidermal penetration study to clarify the effect of SC hydration on skin permeability. Results showed accelerated penetration curves of benzoic acid and paraoxon after surface wash at 30 min postdosing. Thirty minutes after washing (60 min postdosing), penetration rates of hydroquinone and benzoic acid decreased due to reduced amounts of chemical on the skin surface and in the SC. At the end of the experiment (90 min postdosing), a soap-water wash resulted in lower hydroquinone penetration, greater paraoxon penetration and similar levels of benzoic acid and clonidine penetration compared to penetration levels in the non-wash groups. The observed wash-in effect agrees with the enhancement effect of SC hydration on the SC chemical absorption rate. These results suggest SC hydration derived from surface wash to be one cause of the wash-in effect. Further, the occurrence of a wash-in effect is dependent on chemical identity and elapsed time between exposure and onset of decontamination. By reducing chemical residue quantity on skin surface and in the SC reservoir, the soap-water wash may decrease the total quantity of chemical absorbed in the

Cell-penetrating recombinant peptides for potential use in agricultural pest control applications.

Science.gov (United States)

Hughes, Stephen R; Dowd, Patrick F; Johnson, Eric T

2012-09-28

Several important areas of interest intersect in a class of peptides characterized by their highly cationic and partly hydrophobic structure. These molecules have been called cell-penetrating peptides (CPPs) because they possess the ability to translocate across cell membranes. This ability makes these peptides attractive candidates for delivery of therapeutic compounds, especially to the interior of cells. Compounds with characteristics similar to CPPs and that, in addition, have antimicrobial properties are being investigated as antibiotics with a reduced risk of causing resistance. These CPP-like membrane-acting antimicrobial peptides (MAMPs) are α-helical amphipathic peptides that interact with and perturb cell membranes to produce their antimicrobial effects. One source of MAMPs is spider venom. Because these compounds are toxic to insects, they also show promise for development as biological agents for control of insecticide-resistant agricultural pests. Spider venom is a potential source of novel insect-specific peptide toxins. One example is the small amphipathic α-helical peptide lycotoxin-1 (Lyt-1 or LCTX) from the wolf spider (Lycosa carolinensis). One side of the α-helix has mostly hydrophilic and the other mainly hydrophobic amino acid residues. The positive charge of the hydrophilic side interacts with negatively charged prokaryotic membranes and the hydrophobic side associates with the membrane lipid bilayer to permeabilize it. Because the surface of the exoskeleton, or cuticle, of an insect is highly hydrophobic, to repel water and dirt, it would be expected that amphipathic compounds could permeabilize it. Mutagenized lycotoxin 1 peptides were produced and expressed in yeast cultures that were fed to fall armyworm (Spodoptera frugiperda) larvae to identify the most lethal mutants. Transgenic expression of spider venom toxins such as lycotoxin-1 in plants could provide durable insect resistance.

Rapid penetration into granular media visualizing the fundamental physics of rapid earth penetration

CERN Document Server

Iskander, Magued

2015-01-01

Rapid Penetration into Granular Media: Visualizing the Fundamental Physics of Rapid Earth Penetration introduces readers to the variety of methods and techniques used to visualize, observe, and model the rapid penetration of natural and man-made projectiles into earth materials. It provides seasoned practitioners with a standard reference that showcases the topic's most recent developments in research and application. The text compiles the findings of new research developments on the subject, outlines the fundamental physics of rapid penetration into granular media, and assembles a com

Nanocarriers Conjugated with Cell Penetrating Peptides: New Trojan Horses by Modern Ulysses.

Science.gov (United States)

Zappavigna, Silvia; Misso, Gabriella; Falanga, Annarita; Perillo, Emiliana; Novellino, Ettore; Galdiero, Massimiliano; Grieco, Paolo; Caraglia, Michele; Galdiero, Stefania

Nanomedicine has opened the way to the design of more efficient diagnostics and therapeutics. Moreover, recent literature has illustrated the use of short cationic and/or amphipathic peptides, known as cell-penetrating peptides (CPPs), for mediating advanced drug delivery. CPPs exploit their ability to enter cells and enhance the uptake of many cargoes ranging from small molecules to proteins. The distinctive properties of nanocarriers (NC) based systems provide unforeseen benefits over pure drugs for biomedical applications and constitute a challenging research field particularly focused on imaging and delivery; nonetheless, several problems have to be overcome to make them a viable option in clinic. The use of CPPs improves significantly their delivery to specific intracellular targets and thus readily contributes to their use both for effective tumor therapy and gene therapy. A key issue is related to their mechanism of uptake, because although classical CPPs enhance NCs' uptake, the entry mechanism involves the endocytic pathway, which means that the delivered material is sequestered within vesicles and only a small amount will escape from this environment and reach the desired target. In this review, we will summarize recent advances in the use of CPP for enhanced delivery of nanocarriers, nucleic acids, and drugs, we will discuss their uptake mechanisms and we will describe novel approaches to improve endosomal escape of internalized nanosystems.

[Cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy].

Science.gov (United States)

Tan, Jiao; Wang, Ya-Ping; Wang, Hui-Xin; Liang, Jian-Ming; Zhang, Meng; Sun, Xun; Huang, Yong-Zhuo

2014-12-01

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

Intracellular Delivery of Proteins with Cell-Penetrating Peptides for Therapeutic Uses in Human Disease.

Science.gov (United States)

Dinca, Ana; Chien, Wei-Ming; Chin, Michael T

2016-02-22

Protein therapy exhibits several advantages over small molecule drugs and is increasingly being developed for the treatment of disorders ranging from single enzyme deficiencies to cancer. Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered proteins. Although the molecular mechanisms of uptake are not firmly established, CPPs have been empirically shown to promote uptake of various molecules, including large proteins over 100 kiloDaltons (kDa). Recombinant proteins that include a CPP tag to promote intracellular delivery show promise as therapeutic agents with encouraging success rates in both animal and human trials. This review highlights recent advances in protein-CPP therapy and discusses optimization strategies and potential detrimental effects.

Evaluation of nicotinamide microemulsion on the skin penetration enhancement.

Science.gov (United States)

Boonme, Prapaporn; Boonthongchuay, Chalida; Wongpoowarak, Wibul; Amnuaikit, Thanaporn

2016-01-01

This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components. It was determined for its characteristics and stability under various conditions. The skin penetration and retention studies of nicotinamide microemulsion and solution were performed by modified Franz diffusion cells, using newborn pig skin as the membrane. The results showed that nicotinamide microemulsion could be obtained as clear yellowish liquid, was water-in-oil (w/o) type, possessed Newtonian flow, and exhibited physicochemical stability when kept at 4 °C and room temperature (≈30 ± 2 °C) during 3 months. From the skin penetration data, the microemulsion could enhance the skin penetration of nicotinamide comparing with the solution. Additionally, nicotinamide microemulsion could provide much higher amount of skin retention than that of skin penetration, resulting in suitability for a cosmeceutical product.

Cell-penetrating peptide-driven Cre recombination in porcine primary cells and generation of marker-free pigs.

Science.gov (United States)

Kang, Qianqian; Sun, Zhaolin; Zou, Zhiyuan; Wang, Ming; Li, Qiuyan; Hu, Xiaoxiang; Li, Ning

2018-01-01

Cell-penetrating peptides (CPPs) have been increasingly used to deliver various molecules, both in vitro and in vivo. However, there are no reports of CPPs being used in porcine fetal fibroblasts (PFFs). The increased use of transgenic pigs for basic research and biomedical applications depends on the availability of technologies for efficient genetic-modification of PFFs. Here, we report that three CPPs (CPP5, TAT, and R9) can efficiently deliver active Cre recombinase protein into PFFs via an energy-dependent endocytosis pathway. The three CPP-Cre proteins can enter PFFs and subsequently perform recombination with different efficiencies. The recombination efficacy of CPP5-Cre was found to be nearly 90%. The rate-limiting step for CPP-Cre-mediated recombination was the step of endosome escape. HA2 and chloroquine were found to improve the recombination efficiency of TAT-Cre. Furthermore, we successfully obtained marker-free transgenic pigs using TAT-Cre and CPP5-Cre. We provide a framework for the development of CPP-based farm animal transgenic technologies that would be beneficial to agriculture and biomedicine.

Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Science.gov (United States)

Civallero, Monica; Citti, Cinzia; Cosenza, Maria; Baldassarre, Francesca; Cannazza, Giuseppe; Pozzi, Samantha; Sacchi, Stefano

2018-01-01

Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO3 NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration. PMID:29370086

Role of ATP-binding cassette and solute carrier transporters in erlotinib CNS penetration and intracellular accumulation.

Science.gov (United States)

Elmeliegy, Mohamed A; Carcaboso, Angel M; Tagen, Michael; Bai, Feng; Stewart, Clinton F

2011-01-01

To study the role of drug transporters in central nervous system (CNS) penetration and cellular accumulation of erlotinib and its metabolite, OSI-420. After oral erlotinib administration to wild-type and ATP-binding cassette (ABC) transporter-knockout mice (Mdr1a/b(-/-), Abcg2(-/-), Mdr1a/b(-/-)Abcg2(-/-), and Abcc4(-/-)), plasma was collected and brain extracellular fluid (ECF) was sampled using intracerebral microdialysis. A pharmacokinetic model was fit to erlotinib and OSI-420 concentration-time data, and brain penetration (P(Brain)) was estimated by the ratio of ECF-to-unbound plasma area under concentration-time curves. Intracellular accumulation of erlotinib was assessed in cells overexpressing human ABC transporters or SLC22A solute carriers. P(Brain) in wild-type mice was 0.27 ± 0.11 and 0.07 ± 0.02 (mean ± SD) for erlotinib and OSI-420, respectively. Erlotinib and OSI-420 P(Brain) in Abcg2(-/-) and Mdr1a/b(-/-)Abcg2(-/-) mice were significantly higher than in wild-type mice. Mdr1a/b(-/-) mice showed similar brain ECF penetration as wild-type mice (0.49 ± 0.37 and 0.04 ± 0.02 for erlotinib and OSI-420, respectively). In vitro, erlotinib and OSI-420 accumulation was significantly lower in cells overexpressing breast cancer resistance protein (BCRP) than in control cells. Only OSI-420, not erlotinib, showed lower accumulation in cells overexpressing P-glycoprotein (P-gp) than in control cells. The P-gp/BCRP inhibitor elacridar increased erlotinib and OSI-420 accumulation in BCRP-overexpressing cells. Erlotinib uptake was higher in OAT3- and OCT2-transfected cells than in empty vector control cells. Abcg2 is the main efflux transporter preventing erlotinib and OSI-420 penetration in mouse brain. Erlotinib and OSI-420 are substrates for SLC22A family members OAT3 and OCT2. Our findings provide a mechanistic basis for erlotinib CNS penetration, cellular uptake, and efflux mechanisms. ©2010 AACR.

Nanoparticle augmented radiation treatment decreases cancer cell proliferation.

Science.gov (United States)

Townley, Helen E; Rapa, Elizabeth; Wakefield, Gareth; Dobson, Peter J

2012-05-01

We report significant and controlled cell death using novel x-ray-activatable titania nanoparticles (NPs) doped with lanthanides. Preferential incorporation of such materials into tumor tissue can enhance the effect of radiation therapy. Herein, the incorporation of gadolinium into the NPs is designed to optimize localized energy absorption from a conventional medical x-ray. This result is further optimized by the addition of other rare earth elements. Upon irradiation, energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species (ROS). The authors report significant and controlled cell death using x-ray-activated titania nanoparticles doped with lanthanides as enhancers. Upon irradiation X-ray energy is transferred to the titania crystal structure, resulting in the generation of reactive oxygen species. Copyright © 2012 Elsevier Inc. All rights reserved.

Particle-in-cell simulations of fast magnetic field penetration into plasmas due to the Hall electric field

International Nuclear Information System (INIS)

Swanekamp, S.B.; Grossmann, J.M.; Fruchtman, A.; Oliver, B.V.; Ottinger, P.F.

1996-01-01

Particle-in-cell (PIC) simulations are used to study the penetration of magnetic field into plasmas in the electron-magnetohydrodynamic (EMHD) regime. These simulations represent the first definitive verification of EMHD with a PIC code. When ions are immobile, the PIC results reproduce many aspects of fluid treatments of the problem. However, the PIC results show a speed of penetration that is between 10% and 50% slower than predicted by one-dimensional fluid treatments. In addition, the PIC simulations show the formation of vortices in the electron flow behind the EMHD shock front. The size of these vortices is on the order of the collisionless electron skin depth and is closely coupled to the effects of electron inertia. An energy analysis shows that one-half the energy entering the plasma is stored as magnetic field energy while the other half is shared between internal plasma energy (thermal motion and electron vortices) and electron kinetic energy loss from the volume to the boundaries. The amount of internal plasma energy saturates after an initial transient phase so that late in time the rate that magnetic energy increases in the plasma is the same as the rate at which kinetic energy flows out through the boundaries. When ions are mobile it is observed that axial magnetic field penetration is followed by localized thinning in the ion density. The density thinning is produced by the large electrostatic fields that exist inside the electron vortices which act to reduce the space-charge imbalance necessary to support the vortices. This mechanism may play a role during the opening process of a plasma opening switch. copyright 1996 American Institute of Physics

Penetration through the Skin Barrier

DEFF Research Database (Denmark)

Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

2016-01-01

The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates......-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous...

Deep ocean model penetrator experiments

International Nuclear Information System (INIS)

Freeman, T.J.; Burdett, J.R.F.

1986-01-01

Preliminary trials of experimental model penetrators in the deep ocean have been conducted as an international collaborative exercise by participating members (national bodies and the CEC) of the Engineering Studies Task Group of the Nuclear Energy Agency's Seabed Working Group. This report describes and gives the results of these experiments, which were conducted at two deep ocean study areas in the Atlantic: Great Meteor East and the Nares Abyssal Plain. Velocity profiles of penetrators of differing dimensions and weights have been determined as they free-fell through the water column and impacted the sediment. These velocity profiles are used to determine the final embedment depth of the penetrators and the resistance to penetration offered by the sediment. The results are compared with predictions of embedment depth derived from elementary models of a penetrator impacting with a sediment. It is tentatively concluded that once the resistance to penetration offered by a sediment at a particular site has been determined, this quantity can be used to sucessfully predict the embedment that penetrators of differing sizes and weights would achieve at the same site

A novel strategy to improve antigen presentation for active immunotherapy in cancer. Fusion of the human papillomavirus type 16 E7 antigen to a cell penetrating peptide

International Nuclear Information System (INIS)

Granadillo, Milaid; Torrens, Isis; Guerra, Maribel

2012-01-01

Facilitating the delivery of exogenous antigens to antigen-presenting cells, ensuing processing and presentation via the major histocompatibility complex class I and induction of an effective immune response are fundamental for an effective therapeutic cancer vaccine. In this regard, we propose the use of cell-penetrating peptides fused to a tumor antigen. To demonstrate this concept we designed a fusion protein comprising a novel cell-penetrating and immunostimulatory peptide corresponding to residues 32 to 51 of the Limulus anti-lipopolysaccharide factor protein (LALF 32-51 ) linked to human papillomavirus 16 E7 antigen (LALF 32-51 -E7). In this work, we demonstrated that the immunization with LALF 32-51 -E7 using the TC-1 mouse model induces a potent and long-lasting anti-tumor response supported on an effective E7-specific CD8 +T -cell response. The finding that therapeutic immunization with LALF 32-51 or E7 alone, or an admixture of LALF32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF 32-51 and E7 is required for the anti-tumor effect. These results support the use of this novel cell-penetrating peptide as an efficient means for delivering therapeutic targets into cellular compartments with the induction of a cytotoxic CD8 +T lymphocyte immune response. This approach is promissory for the treatment of tumors associated with the human papillomavirus 16, which is responsible for the 50% of cervical cancer cases worldwide and other malignancies. Furthermore, protein-based vaccines can circumvent the major histocompatibility complex specificity limitation associated with peptide vaccines providing a greater extent in their application

One-year follow-up of femtosecond laser-assisted penetrating keratoplasty

Directory of Open Access Journals (Sweden)

Tan JCH

2013-02-01

Full Text Available Johnson Choon-Hwai Tan, Wee-Jin HengNational Healthcare Group Eye Institute, Tan Tock Seng Hospital, SingaporeBackground: The purpose of this report is to describe the initial outcomes of femtosecond laser-assisted penetrating keratoplasty.Methods: This retrospective surgical case series consisted of 10 eyes from 10 patients undergoing penetrating keratoplasty at a tertiary center. Femtosecond laser was used to perform a zig-square incision on the donor cornea with matched dimensions on the recipient cornea. Outcomes measured included: unaided visual acuity and best spectacle-corrected visual acuity preoperatively and at one, 3, 6, and 12 months postoperatively; manifest refractive and topographic astigmatism at 3, 6, and 12 months postoperatively; and endothelial cell density loss, calculated at the end of the one-year follow-up period.Results: At one-year follow-up, there was an improvement in unaided visual acuity from a mean preoperative logMAR of 1.67 to 0.44, and best spectacle-corrected visual acuity from a mean preoperative logMAR of 1.33 to 0.13. By postoperative month 3, mean manifest refractive and topographic astigmatism was 2.31 ± 1.41 D and 2.59 ± 1.57 D, respectively. The mean reduction in endothelial cell density was 20.7% after one year of follow-up.Conclusion: Femtosecond laser-assisted penetrating keratoplasty provided a good visual outcome and early visual rehabilitation due to precise graft-host alignment and reduced astigmatism in the early postoperative months.Keywords: penetrating keratoplasty, femtosecond laser-assisted keratoplasty

The penetrating depth analysis of Lunar Penetrating Radar onboard Chang’e-3 rover

Science.gov (United States)

Xing, Shu-Guo; Su, Yan; Feng, Jian-Qing; Dai, Shun; Xiao, Yuan; Ding, Chun-Yu; Li, Chun-Lai

2017-04-01

Lunar Penetrating Radar (LPR) has successfully been used to acquire a large amount of scientific data during its in-situ detection. The analysis of penetrating depth can help to determine whether the target is within the effective detection range and contribute to distinguishing useful echoes from noise. First, this study introduces two traditional methods, both based on a radar transmission equation, to calculate the penetrating depth. The only difference between the two methods is that the first method adopts system calibration parameters given in the calibration report and the second one uses high-voltage-off radar data. However, some prior knowledge and assumptions are needed in the radar equation and the accuracy of assumptions will directly influence the final results. Therefore, a new method termed the Correlation Coefficient Method (CCM) is provided in this study, which is only based on radar data without any a priori assumptions. The CCM can obtain the penetrating depth according to the different correlation between reflected echoes and noise. To be exact, there is a strong correlation in the useful reflected echoes and a random correlation in the noise between adjacent data traces. In addition, this method can acquire a variable penetrating depth along the profile of the rover, but only one single depth value can be obtained from traditional methods. Through a simulation, the CCM has been verified as an effective method to obtain penetration depth. The comparisons and analysis of the calculation results of these three methods are also implemented in this study. Finally, results show that the ultimate penetrating depth of Channel 1 and the estimated penetrating depth of Channel 2 range from 136.9 m to 165.5 m ({\\varepsilon }r=6.6) and from 13.0 m to 17.5 m ({\\varepsilon }r=2.3), respectively.

In-place HEPA filter penetration test

International Nuclear Information System (INIS)

Bergman, W.; Wilson, K.; Elliott, J.; Bettencourt, B.; Slawski, J.W.

1997-01-01

We have demonstrated the feasibility of conducting penetration tests on high efficiency particulate air (HEPA) filters as installed in nuclear ventilation systems. The in-place penetration test, which is designed to yield equivalent penetration measurements as the standard DOP efficiency test, is based on measuring the aerosol penetration of the filter installation as a function of particle size using a portable laser particle counter. This in-place penetration test is compared to the current in-place leak test using light scattering photometers for single HEPA filter installations and for HEPA filter plenums using the shroud method. Test results show the in-place penetration test is more sensitive than the in-place leak test, has a similar operating procedure, but takes longer to conduct. Additional tests are required to confirm that the in-place penetration test yields identical results as the standard dioctyl phthalate (DOP) penetration test for HEPA filters with controlled leaks in the filter and gasket and duct by-pass leaks. Further development of the procedure is also required to reduce the test time before the in- place penetration test is practical

Visualization of Protease Activity In Vivo Using an Activatable Photo-Acoustic Imaging Probe Based on CuS Nanoparticles

Science.gov (United States)

Yang, Kai; Zhu, Lei; Nie, Liming; Sun, Xiaolian; Cheng, Liang; Wu, Chenxi; Niu, Gang; Chen, Xiaoyuan; Liu, Zhuang

2014-01-01

Herein, we for the first time report a novel activatable photoacoustic (PA) imaging nano-probe for in vivo detection of cancer-related matrix metalloproteinases (MMPs). A black hole quencher 3 (BHQ3) which absorbs red light is conjugated to near-infrared (NIR)-absorbing copper sulfide (CuS) nanoparticles via a MMP-cleavable peptide linker. The obtained CuS-peptide-BHQ3 (CPQ) nano-probe exhibits two distinctive absorption peaks at 630 nm and 930 nm. Inside the tumor microenviorment where MMPs present, the MMP-sensitive peptide would be cleaved, releasing BHQ3 from the CuS nanoparticles, the former of which as a small molecule is then rapidly cleared out from the tumor, whereas the latter of which as large nanoparticles would retain inside the tumor for a much longer period of time. As the result, the PA signal at 680 nm which is contributed by BHQ3 would be quickly diminished while that at 930 nm would be largely retained. The PA signal ratio of 680 nm / 930 nm could thus serve as an in vivo indicator of MMPs activity inside the tumor. Our work presents a novel strategy of in vivo sensing of MMPs based on PA imaging, which should offer remarkably improved detection depth compared with traditional optical imaging techniques. PMID:24465271

Dual Targeting of Intracellular Pathogenic Bacteria with a Cleavable Conjugate of Kanamycin and an Antibacterial Cell-Penetrating Peptide.

Science.gov (United States)

Brezden, Anna; Mohamed, Mohamed F; Nepal, Manish; Harwood, John S; Kuriakose, Jerrin; Seleem, Mohamed N; Chmielewski, Jean

2016-08-31

Bacterial infection caused by intracellular pathogens, such as Mycobacterium, Salmonella, and Brucella, is a burgeoning global health epidemic that necessitates urgent action. However, the therapeutic value of a number of antibiotics, including aminoglycosides, against intracellular pathogenic bacteria is compromised due to their inability to traverse eukaryotic membranes. For this significant problem to be addressed, a cleavable conjugate of the antibiotic kanamycin and a nonmembrane lytic, broad-spectrum antimicrobial peptide with efficient mammalian cell penetration, P14LRR, was prepared. This approach allows kanamycin to enter mammalian cells as a conjugate linked via a tether that breaks down in the reducing environment within cells. Potent antimicrobial activity of the P14KanS conjugate was demonstrated in vitro, and this reducible conjugate effectively cleared intracellular pathogenic bacteria within macrophages more potently than that of a conjugate lacking the disulfide moiety. Notably, successful clearance of Mycobacterium tuberculosis within macrophages was observed with the dual antibiotic conjugate, and Salmonella levels were significantly reduced in an in vivo Caenorhabditis elegans model.

A novel growing device inspired by plant root soil penetration behaviors.

Directory of Open Access Journals (Sweden)

Ali Sadeghi

Full Text Available Moving in an unstructured environment such as soil requires approaches that are constrained by the physics of this complex medium and can ensure energy efficiency and minimize friction while exploring and searching. Among living organisms, plants are the most efficient at soil exploration, and their roots show remarkable abilities that can be exploited in artificial systems. Energy efficiency and friction reduction are assured by a growth process wherein new cells are added at the root apex by mitosis while mature cells of the root remain stationary and in contact with the soil. We propose a new concept of root-like growing robots that is inspired by these plant root features. The device penetrates soil and develops its own structure using an additive layering technique: each layer of new material is deposited adjacent to the tip of the device. This deposition produces both a motive force at the tip and a hollow tubular structure that extends to the surface of the soil and is strongly anchored to the soil. The addition of material at the tip area facilitates soil penetration by omitting peripheral friction and thus decreasing the energy consumption down to 70% comparing with penetration by pushing into the soil from the base of the penetration system. The tubular structure provides a path for delivering materials and energy to the tip of the system and for collecting information for exploratory tasks.

Penetration portion shielding structure

International Nuclear Information System (INIS)

Hayashi, Katsumi; Narita, Hitoshi; Handa, Hiroyuki; Takeuchi, Jun; Tozuka, Fumio.

1994-01-01

Openings of a plurality of shieldings for penetration members are aligned to each other, and penetration members are inserted from the openings. Then, the openings of the plurality of shielding members are slightly displaced with each other to make the penetration portions into a helical configuration, so that leakage of radiation is reduced. Upon removal of the members, reverse operation is conducted. When a flowable shielding material is used, the penetration portions are constituted with two plates having previously formed openings and pipes for connecting the openings with each other and a vessel covering the entire of them. After passing the penetration members such as a cable, the relative position of the two plates is changed by twisting, to form a helical configuration which reduces radiation leakage. Since they are bent into the helical configuration, shielding performance is extremely improved compared with a case that radiation leakage is caused from an opening of a straight pipe. In addition, since they can be returned to straight pipes, attachment, detachment and maintenance can be conducted easily. (N.H.)

In-place HEPA filter penetration test

Energy Technology Data Exchange (ETDEWEB)

Bergman, W.; Wilson, K.; Elliott, J. [Lawrence Livermore National Lab., CA (United States)] [and others

1997-08-01

We have demonstrated the feasibility of conducting penetration tests on high efficiency particulate air (HEPA) filters as installed in nuclear ventilation systems. The in-place penetration test, which is designed to yield equivalent penetration measurements as the standard DOP efficiency test, is based on measuring the aerosol penetration of the filter installation as a function of particle size using a portable laser particle counter. This in-place penetration test is compared to the current in-place leak test using light scattering photometers for single HEPA filter installations and for HEPA filter plenums using the shroud method. Test results show the in-place penetration test is more sensitive than the in-place leak test, has a similar operating procedure, but takes longer to conduct. Additional tests are required to confirm that the in-place penetration test yields identical results as the standard dioctyl phthalate (DOP) penetration test for HEPA filters with controlled leaks in the filter and gasket and duct by-pass leaks. Further development of the procedure is also required to reduce the test time before the in-place penetration test is practical. 14 refs., 14 figs., 3 tabs.

Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

Directory of Open Access Journals (Sweden)

Hamidreza Namazi

2016-01-01

Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

[Professor WU Zhongchao's experience of penetration needling].

Science.gov (United States)

Zhang, Ning; Wang, Bing; Zhou, Yu

2016-08-12

Professor WU Zhongchao has unique application of penetration needling in clinical treatment. Professor WU applies penetration needling along meridians, and the methods of penetration needling include self-meridian penetration, exterior-interior meridian penetration, identical-name meridian penetration, different meridian penetration. The meridian differentiation is performed according to different TCM syndromes, locations and natures of diseases and acupoint nature, so as to make a comprehensive assessment. The qi movement during acupuncture is focused. In addition, attention is paid on anatomy and long-needle penetration; the sequence and direction of acupuncture is essential, and the reinforcing and reducing methods have great originality, presented with holding, waiting, pressing and vibrating. Based on classical acupoint, the acupoint of penetration needling is flexible, forming unique combination of acupoints.

Targeted drug delivery and penetration into solid tumors.

Science.gov (United States)

Corti, Angelo; Pastorino, Fabio; Curnis, Flavio; Arap, Wadih; Ponzoni, Mirco; Pasqualini, Renata

2012-09-01

Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma. © 2011 Wiley Periodicals, Inc.

A novel chimeric cell-penetrating peptide with membrane-disruptive properties for efficient endosomal escape.

Science.gov (United States)

Salomone, Fabrizio; Cardarelli, Francesco; Di Luca, Mariagrazia; Boccardi, Claudia; Nifosì, Riccardo; Bardi, Giuseppe; Di Bari, Lorenzo; Serresi, Michela; Beltram, Fabio

2012-11-10

Efficient endocytosis into a wide range of target cells and low toxicity make the arginine-rich Tat peptide (Tat(11): YGRKKRRQRRR, residues 47-57 of HIV-1 Tat protein) an excellent transporter for delivery purposes. Unfortunately, molecules taken up by endocytosis undergo endosomal entrapment and possible metabolic degradation. Escape from the endosome is therefore actively researched. In this context, antimicrobial peptides (AMPs) provide viable templates for the design of new membrane-disruptive motifs. In particular the Cecropin-A and Melittin hybrids (CMs) are among the smallest and most effective peptides with membrane-perturbing abilities. Here we present a novel chimeric peptide in which the Tat(11) motif is fused to the CM(18) hybrid (KWKLFKKIGAVLKVLTTG, residues 1-7 of Cecropin-A and 2-12 of Melittin). When administered to cells, CM(18)-Tat(11) combines the two desired functionalities: efficient uptake and destabilization of endocytotic-vesicle membranes. We show that this chimeric peptide effectively increases cargo-molecule cytoplasm availability and allows the subsequent intracellular localization of diverse membrane-impermeable molecules (i.e. Tat(11)-EGFP fusion protein, calcein, dextrans, and plasmidic DNA) with no detectable cytotoxicity. The present results open the way to the rational engineering of "modular" cell-penetrating peptides (CPPs) that combine (i) efficient translocation from the extracellular milieu into vesicles and (ii) efficient release of molecules from vesicles into the cytoplasm. Copyright © 2012 Elsevier B.V. All rights reserved.

Design and mechanism of action of a novel bacteria-selective antimicrobial peptide from the cell-penetrating peptide Pep-1

International Nuclear Information System (INIS)

Zhu, W.L.; Lan Hongliang; Park, Il-Seon; Kim, Jae Il; Jin, H.Z.; Hahm, Kyung-Soo; Shin, S.Y.

2006-01-01

Here, we report the successful design of a novel bacteria-selective antimicrobial peptide, Pep-1-K (KKTWWKTWWTKWSQPKKKRKV). Pep-1-K was designed by replacing Glu-2, Glu-6, and Glu-11 in the cell-penetrating peptide Pep-1 with Lys. Pep-1-K showed strong antibacterial activity against reference strains (MIC = 1-2 μM) of Gram-positive and Gram-negative bacteria as well as against clinical isolates (MIC = 1-8 μM) of methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. In contrast, Pep-1-K did not cause hemolysis of human erythrocytes even at 200 μM. These results indicate that Pep-1-K may be a good candidate for antimicrobial drug development, especially as a topical agent against antibiotic-resistant microorganisms. Tryptophan fluorescence studies indicated that the lack of hemolytic activity of Pep-1-K correlated with its weak ability to penetrate zwitterionic phosphatidylcholine/cholesterol (10:1, w/w) vesicles, which mimic eukaryotic membranes. Furthermore, Pep-1-K caused little or no dye leakage from negatively charged phosphatidylethanolamine/phosphatidylglycerol (7:3, w/w) vesicles, which mimic bacterial membranes but had a potent ability to cause depolarization of the cytoplasmic membrane potential of intact S. aureus cells. These results suggested that Pep-1-K kills microorganisms by not the membrane-disrupting mode but the formation of small channels that permit transit of ions or protons but not molecules as large as calcein

Metasploit penetration testing cookbook

CERN Document Server

Agarwal, Monika

2013-01-01

This book follows a Cookbook style with recipes explaining the steps for penetration testing with WLAN, VOIP, and even cloud computing. There is plenty of code and commands used to make your learning curve easy and quick.This book targets both professional penetration testers as well as new users of Metasploit, who wish to gain expertise over the framework and learn an additional skill of penetration testing, not limited to a particular OS. The book requires basic knowledge of scanning, exploitation, and the Ruby language.

Human skin penetration of silver nanoparticles through intact and damaged skin

International Nuclear Information System (INIS)

Larese, Francesca Filon; D'Agostin, Flavia; Crosera, Matteo; Adami, Gianpiero; Renzi, Nadia; Bovenzi, Massimo; Maina, Giovanni

2009-01-01

There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 μg/cm 2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm -2 (range -2 (range 0.43-11.6) were found in the receiving solutions of cells where the nanoparticles solution was applied on intact skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62 ± 0.2 ng cm -2 with a lag time <1 h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very low but detectable, and that in case of damaged skin it was possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system

Modeling of Oblique Penetration into Geologic Targets Using Cavity Expansion Penetrator Loading with Target free-Surface Effects

Energy Technology Data Exchange (ETDEWEB)

Jung, Joe; Longcope, Donald B.; Tabbara, Mazen R.

1999-05-03

A procedure has been developed to represent the loading on a penetrator and its motion during oblique penetration into geologic media. The penetrator is modeled with the explicit dynamics, finite element computer program PRONTO 3D and the coupled pressure on the penetrator is given in a new loading option based on a separate cavity expansion (CE) solution that accounts for the pressure-reduction from a nearby target free surface. The free-surface influ- ence distance is selected in a predictive manner by considering the pressure to expand a spherical cavity in a finite radius sphere of the target material. The CE/PRONTO 3D procedure allows a detailed description of the penetrator for predicting shock environments or structural failure dur- ing the entire penetration event and is sufficiently rapid to be used in design optimization. It has been evaluated by comparing its results with data from two field tests of a full-scale penetrator into frozen soil at an impact angles of 49.6 and 52.5 degrees from the horizontal. The measured penetrator rotations were 24 and 22 degrees, respectively. In the simulation, the rotation was21 degrees and predominately resulted from the pressure reduction of the free surface. Good agree- ment was also found for the penetration depth and axial and lateral acceleration at two locations in the penetrator.

Thrombin activatable fibrinolysis inhibitor and clot lysis time in pregnant patients with antiphospholipid syndrome: relationship with pregnancy outcome and thrombosis.

Science.gov (United States)

Martinez-Zamora, Maria Angeles; Tassies, Dolors; Carmona, Francisco; Espinosa, Gerard; Cervera, Ricard; Reverter, Juan Carlos; Balasch, Juan

2009-12-01

Antiphospholipid syndrome (APS) pregnancies are associated with thrombotic obstetric complications, despite treatment. This study evaluated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) levels, TAFI gene polymorphisms and Clot Lysis Time (CLT) in pregnant patients with APS in relation to pregnancy outcome and thrombosis. Group 1 consisted of 67 pregnant patients with APS. Group 2 included 66 pregnant patients with uneventful term pregnancies and delivery. Patients were sampled during each trimester and at baseline. TAFI antigen and CLT and two polymorphisms of the TAFI gene, Ala147Thr and +1542C/G, were determined. Significantly prolonged CLT was found at baseline in Group 1. Allele distribution of the TAFI gene polymorphisms was similar in both groups. Basal TAFI and CLT in patients with APS having an adverse or a good obstetrical outcome were similar. Comparison of TAFI and CLT baseline levels in patients with APS with or without previous thrombosis showed no statistical differences. Patients with APS have impairment in fibrinolysis evidenced by prolonged CLT at baseline. TAFI and CLT do not seem to be useful as markers of obstetric outcome or risk of thrombosis in patients with APS.

A Mass Loss Penetration Model to Investigate the Dynamic Response of a Projectile Penetrating Concrete considering Mass Abrasion

Directory of Open Access Journals (Sweden)

NianSong Zhang

2015-01-01

Full Text Available A study on the dynamic response of a projectile penetrating concrete is conducted. The evolutional process of projectile mass loss and the effect of mass loss on penetration resistance are investigated using theoretical methods. A projectile penetration model considering projectile mass loss is established in three stages, namely, cratering phase, mass loss penetration phase, and remainder rigid projectile penetration phase.

Promotion of SH-SY5Y Cell Growth by Gold Nanoparticles Modified with 6-Mercaptopurine and a Neuron-Penetrating Peptide

Science.gov (United States)

Xiao, Yaruo; Zhang, Enqi; Fu, Ailing

2017-12-01

Much effort has been devoted to the discovery of effective biomaterials for nerve regeneration. Here, we reported a novel application of gold nanoparticles (AuNPs) modified with 6-mercaptopurine (6MP) and a neuron-penetrating peptide (RDP) as a neurophic agent to promote proliferation and neurite growth of human neuroblastoma (SH-SY5Y) cells. When the cells were treated with 6MP-AuNPs-RDP conjugates, they showed higher metabolic activity than the control. Moreover, SH-SY5Y cells were transplanted onto the surface coated with 6MP-AuNPs-RDP to examine the effect of neurite development. It can be concluded that 6MP-AuNPs-RDP attached to the cell surface and then internalized into cells, leading to a significant increase of neurite growth. Even though 6MP-AuNPs-RDP-treated cells were recovered from frozen storage, the cells still maintained constant growth, indicating that the cells have excellent tolerance to 6MP-AuNPs-RDP. The results suggested that the 6MP-AuNPs-RDP had promising potential to be developed as a neurophic nanomaterial for neuronal growth.

Effects of Sizes and Conformations of Fish-Scale Collagen Peptides on Facial Skin Qualities and Transdermal Penetration Efficiency

OpenAIRE

Chai, Huey-Jine; Li, Jing-Hua; Huang, Han-Ning; Li, Tsung-Lin; Chan, Yi-Lin; Shiau, Chyuan-Yuan; Wu, Chang-Jer

2010-01-01

Fish-scale collagen peptides (FSCPs) were prepared using a given combination of proteases to hydrolyze tilapia (Oreochromis sp.) scales. FSCPs were determined to stimulate fibroblast cells proliferation and procollagen synthesis in a time- and dose-dependent manner. The transdermal penetration capabilities of the fractionationed FSCPs were evaluated using the Franz-type diffusion cell model. The heavier FSCPs, 3500 and 4500?Da, showed higher cumulative penetration capability as opposed to the...

Validation of In Vitro Cell-Based Human Blood-Brain Barrier Model Using Clinical Positron Emission Tomography Radioligands To Predict In Vivo Human Brain Penetration

International Nuclear Information System (INIS)

Mabondzo, A.; Guyot, A.C.; Bottlaender, M.; Deverre, J.R.; Tsaouin, K.; Balimane, P.V.

2010-01-01

We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB) model that could predict in vivo human brain penetration for compounds with different BBB permeabilities using the clinical positron emission tomography (PET) data. Comparison studies were also performed to demonstrate that the in vitro cell-based human BBB model resulted in better predictivity over the traditional permeability model in discovery organizations, Caco-2 cells. We evaluated the in vivo BBB permeability of [ 18 F] and [ 11 C]-compounds in humans by PET imaging. The in vivo plasma-brain exchange parameters used for comparison were determined in humans by PET using a kinetic analysis of the radiotracer binding. For each radiotracer, the parameters were determined by fitting the brain kinetics of the radiotracer using a two-tissue compartment model of the ligand-receptor interaction. Bidirectional transport studies with the same compounds as in in vivo studies were carried out using the in vitro cell-based human BBB model as well as Caco-2 cells. The in vitro cell-based human BBB model has important features of the BBB in vivo and is suitable for discriminating between CNS and non-CNS marketed drugs. A very good correlation (r 2 =0.90; P≤0.001) was demonstrated between in vitro BBB permeability and in vivo permeability coefficient. In contrast, a poor correlation (r 2 = 0.17) was obtained between Caco-2 data and in vivo human brain penetration. This study highlights the potential of this in vitro cell-based human BBB model in drug discovery and shows that it can be an extremely effective screening tool for CNS programs. (authors)

FAA Fluorescent Penetrant Activities - An Update

Energy Technology Data Exchange (ETDEWEB)

Moore, D.G.

1998-10-20

The Federal Aviation Administration's Airworthiness Assurance NDI Validation Center (AANC) is currently characterizing low cycle fatigue specimens that will support the needs of penetrant manufacturers, commercial airline industry and the Federal Aviation Administration. The main focus of this characterization is to maintain and enhance the evaluation of penetrant inspection materials and apply resources to support the aircraft community needs. This paper discusses efforts to-date to document the Wright Laboratory penetrant evaluation process and characterize penetrant brightness readings in the initial set of sample calibration panels using Type 1 penetrant.

Cell Penetrating Polymers Containing Guanidinium Trigger Apoptosis in Human Hepatocellular Carcinoma Cells unless Conjugated to a Targeting N-Acetyl-Galactosamine Block.

Science.gov (United States)

Tan, Zhe; Dhande, Yogesh K; Reineke, Theresa M

2017-12-20

delivery vehicles may be limited by their high cytotoxicity to certain cell types. Thus, the use of cell penetrating structures in polyplex formulations should be used with caution and carefully tailored toward individual cell/tissue types.

Penetration Tester's Open Source Toolkit

CERN Document Server

Faircloth, Jeremy

2011-01-01

Great commercial penetration testing tools can be very expensive and sometimes hard to use or of questionable accuracy. This book helps solve both of these problems. The open source, no-cost penetration testing tools presented do a great job and can be modified by the user for each situation. Many tools, even ones that cost thousands of dollars, do not come with any type of instruction on how and in which situations the penetration tester can best use them. Penetration Tester's Open Source Toolkit, Third Edition, expands upon existing instructions so that a professional can get the most accura

Cyclic Dipeptide Shuttles as a Novel Skin Penetration Enhancement Approach: Preliminary Evaluation with Diclofenac

Science.gov (United States)

Namjoshi, Sarika; Giralt, Ernest; Benson, Heather

2016-01-01

This study demonstrates the effectiveness of a peptide shuttle in delivering diclofenac into and through human epidermis. Diclofenac was conjugated to a novel phenylalanyl-N-methyl-naphthalenylalanine-derived diketopiperazine (DKP) shuttle and to TAT (a classical cell penetrating peptide), and topically applied to human epidermis in vitro. DKP and TAT effectively permeated into and through human epidermis. When conjugated to diclofenac, both DKP and TAT enhanced delivery into and through human epidermis, though DKP was significantly more effective. Penetration of diclofenac through human epidermis (to receptor) was increased by conjugation to the peptide shuttle and cell penetrating peptide with enhancement of 6x by DKP-diclofenac and 3x by TAT-diclofenac. In addition, the amount of diclofenac retained within the epidermis was significantly increased by peptide conjugation. COX-2 inhibition activity of diclofenac was retained when conjugated to DKP. Our study suggests that the peptide shuttle approach may offer a new strategy for targeted delivery of small therapeutic and diagnostic molecules to the skin. PMID:27548780

Effect of compressibility on the hypervelocity penetration

Science.gov (United States)

Song, W. J.; Chen, X. W.; Chen, P.

2018-02-01

We further consider the effect of rod strength by employing the compressible penetration model to study the effect of compressibility on hypervelocity penetration. Meanwhile, we define different instances of penetration efficiency in various modified models and compare these penetration efficiencies to identify the effects of different factors in the compressible model. To systematically discuss the effect of compressibility in different metallic rod-target combinations, we construct three cases, i.e., the penetrations by the more compressible rod into the less compressible target, rod into the analogously compressible target, and the less compressible rod into the more compressible target. The effects of volumetric strain, internal energy, and strength on the penetration efficiency are analyzed simultaneously. It indicates that the compressibility of the rod and target increases the pressure at the rod/target interface. The more compressible rod/target has larger volumetric strain and higher internal energy. Both the larger volumetric strain and higher strength enhance the penetration or anti-penetration ability. On the other hand, the higher internal energy weakens the penetration or anti-penetration ability. The two trends conflict, but the volumetric strain dominates in the variation of the penetration efficiency, which would not approach the hydrodynamic limit if the rod and target are not analogously compressible. However, if the compressibility of the rod and target is analogous, it has little effect on the penetration efficiency.

Web penetration testing with Kali Linux

CERN Document Server

Muniz, Joseph

2013-01-01

Web Penetration Testing with Kali Linux contains various penetration testing methods using BackTrack that will be used by the reader. It contains clear step-by-step instructions with lot of screenshots. It is written in an easy to understand language which will further simplify the understanding for the user.""Web Penetration Testing with Kali Linux"" is ideal for anyone who is interested in learning how to become a penetration tester. It will also help the users who are new to Kali Linux and want to learn the features and differences in Kali versus Backtrack, and seasoned penetration testers

Percutaneous penetration studies for risk assessment

DEFF Research Database (Denmark)

Sartorelli, Vittorio; Andersen, Helle Raun; Angerer, Jürgen

2000-01-01

. In order to predict the systemic risk of dermally absorbed chemicals and to enable agencies to set safety standards, data is needed on the rates of percutaneous penetration of important chemicals. Standardization of in vitro tests and comparison of their results with the in vivo data could produce...... internationally accepted penetration rates and/or absorption percentages very useful for regulatory toxicology. The work of the Percutaneous Penetration Subgroup of EC Dermal Exposure Network has been focussed on the standardization and validation of in vitro experiments, necessary to obtain internationally...... accepted penetration rates for regulatory purposes. The members of the Subgroup analyzed the guidelines on percutaneous penetration in vitro studies presented by various organizations and suggested a standardization of in vitro models for percutaneous penetration taking into account their individual...

Penetration of Photovoltaics in Greece

Directory of Open Access Journals (Sweden)

Eugenia Giannini

2015-06-01

Full Text Available Recently, an interesting experiment was completed in Greece concerning photovoltaic penetration into the electricity production sector. Based on the relevant laws and in accordance to the related European directives, an explosive penetration process was completed in less than three years, resulting in a 7% share of photovoltaics in electricity production instead of the previous negligible share. The legislation was based on licensing simplification and generous feed-in-tariffs. This approach transformed photovoltaic technology from a prohibitively expensive to a competitive one. This work aims to summarize the relevant legislation and illustrate its effect on the resulting penetration. A sigmoid-shape penetration was observed which was explained by a pulse-type driving force. The return on investment indicator was proposed as an appropriate driving force, which incorporates feed-in-tariffs and turnkey-cost. Furthermore, the resulting surcharge on the electricity price due to photovoltaic penetration was also analyzed.

Effects of Sizes and Conformations of Fish-Scale Collagen Peptides on Facial Skin Qualities and Transdermal Penetration Efficiency

Directory of Open Access Journals (Sweden)

Huey-Jine Chai

2010-01-01

Full Text Available Fish-scale collagen peptides (FSCPs were prepared using a given combination of proteases to hydrolyze tilapia (Oreochromis sp. scales. FSCPs were determined to stimulate fibroblast cells proliferation and procollagen synthesis in a time- and dose-dependent manner. The transdermal penetration capabilities of the fractionationed FSCPs were evaluated using the Franz-type diffusion cell model. The heavier FSCPs, 3500 and 4500 Da, showed higher cumulative penetration capability as opposed to the lighter FSCPs, 2000 and 1300 Da. In addition, the heavier seemed to preserve favorable coiled structures comparing to the lighter that presents mainly as linear under confocal scanning laser microscopy. FSCPs, particularly the heavier, were concluded to efficiently penetrate stratum corneum to epidermis and dermis, activate fibroblasts, and accelerate collagen synthesis. The heavier outweighs the lighter in transdermal penetration likely as a result of preserving the given desired structure feature.

Modeling of Oblique Penetration into Geologic Targets Using Cavity Expansion Penetrator Loading with Target free-Surface Effects

Energy Technology Data Exchange (ETDEWEB)

Jung, Joe; Longcope, Donald B.; Tabbara, Mazen R.

1999-06-01

A procedure has been developed to represent the loading on a penetrator and its motion during oblique penetration into geologic media. The penetrator is modeled with the explicit dynamics, finite element computer program PRONTO 3D and the coupled pressure on the penetrator is given in a new loading option based on a separate cavity expansion (CE) solution that accounts for the pressure reduction from a nearby target free surface. The free-surface influence distance is selected in a predictive manner by considering the pressure to expand a spherical cavity in a finite radius sphere of the target material. The CE/PRONTO 3D procedure allows a detailed description of the penetrator for predicting shock environments or structural failure during the entire penetra- tion event and is sufficiently rapid to be used in design optimization. It has been evaluated by comparing its results with data from two field tests of a full-scale penetrator into frozen soil at an impact angles of 49.6 and 52.5 degrees from the horizontal. The measured penetrator rotations were 24 and 22 degrees, respectively. In the simulation, the rotation was 21 degrees and predom- inately resulted from the pressure reduction of the free surface. Good agreement was also found for the penetration depth and axial and lateral acceleration at two locations in the penetrator.

[The construction of cell-penetrating peptide R8 and pH sensitive cleavable polyethylene glycols co-modified liposomes].

Science.gov (United States)

Zhang, Li; Wang, Yang; Gao, Hui-le; He, Qin

2015-06-01

The purpose of the study is to construct R8 peptide (RRRRRRRR) and pH sensitive polyethylene glycols (PEG) co-modified liposomes (Cl-Lip) and utilize them in breast cancer treatment. The co-modified liposomes were prepared with soybean phospholipid, cholesterol, DSPE-PEG2K-R8 and PEG5K-Hz-PE (pH sensitive PEG). The size and zeta potential of Cl-Lip were also characterized. The in vitro experiment demonstrated that the Cl-Lip had high serum stability in 50% fetal bovine serum. The cellular uptake of Cl-Lip under different pre-incubated conditions was evaluated on 4T1 cells. And the endocytosis pathway, lysosome escape ability and tumor spheroid penetration ability were also evaluated. The results showed the particle size of the Cl-Lip was (110.4 ± 5.2) nm, PDI of the Cl-Lip was 0.207 ± 0.039 and zeta potential of the Cl-Lip was (-3.46 ± 0.05) mV. The cellular uptake of Cl-Lip on 4T1 cells was pH sensitive, as the cellular uptake of Cl-Lip pre-incubated in pH 6.0 was higher than that of pH 7.4 under each time point. The main endocytosis pathways of Cl-Lip under pH 6.0 were micropinocytosis and energy-dependent pathway. At the same time, the Cl-Lip with pre-incubation in pH 6.0 had high lysosome escape ability and high tumor spheroid penetration ability. All the above results demonstrated that the Cl-Lip we constructed had high pH sensitivity and is a promising drug delivery system.

Barrier penetration database

International Nuclear Information System (INIS)

Fainberg, A.; Bieber, A.M. Jr.

1978-11-01

This document is intended to supply the NRC and nuclear power plant licensees with basic data on the times required to penetrate forcibly the types of barriers commonly found in nuclear plants. These times are necessary for design and evaluation of the physical protection system required under 10CFR73.55. Each barrier listed is described in detail. Minor variations in basic barrier construction that result in the same penetration time, are also described

Diffusion of radioactively tagged penetrants through rubbery polymers. II. Dependence on molecular length of penetrant

International Nuclear Information System (INIS)

Rhee, C.K.; Ferry, J.D.; Fetters, L.J.

1977-01-01

The diffusion of radioactively tagged n-hexadecane, n-dotriacontane, and a polybutadiene oligomer with molecular weight 1600 has been studied in 12 rubbery polymers. Diffusion coefficients were obtained from the theory for the thin smear method: for n-hexadecane and for n-dotriacontane (with one exception), in the form appropriate for a completely miscible polymer-penetrant pair, and for the oligomer in the form appropriate for slow entry of the pentrant across the penetrant-polymer interface. For the four flexible linear penetrants, n-dodecane, n-hexadecane, n-dotriacontane, and oligomer, the ratios of diffusion coefficients (or translational friction coefficients) are nearly the same in every polymer. It is concluded that these penetrants travel with similar segmentwise motions, although that is not the case with bulkier, more rigid penetrants. For the three normal paraffins, the friction coefficient is approximately proportional to molecular weight, but that for the oligomer is smaller than would be predicted on this basis

Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance.

Science.gov (United States)

Thurber, Greg M; Schmidt, Michael M; Wittrup, K Dane

2008-09-01

Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue.

Kali Linux wireless penetration testing essentials

CERN Document Server

Alamanni, Marco

2015-01-01

This book is targeted at information security professionals, penetration testers and network/system administrators who want to get started with wireless penetration testing. No prior experience with Kali Linux and wireless penetration testing is required, but familiarity with Linux and basic networking concepts is recommended.

Sodium lauryl sulfate enhances nickel penetration through guinea-pig skin. Studies with energy dispersive X-ray microanalysis

International Nuclear Information System (INIS)

Lindberg, M.; Sagstroem, S.R.; Roomans, G.M.; Forslind, B.

1989-01-01

The effect of sodium lauryl sulphate (SLS), a common ingredient of detergents, on the penetration of nickel through the stratum corneum in the guinea-pig skin model was studied with energy dispersive X-ray microanalysis (EDX) to evaluate the barrier-damaging properties of this common detergent. The EDX technique allows a simultaneous determination of physiologically important elements, e.g., Na, Mg, P, Cl, K, Ca and S in addition to Ni at each point of measurement in epidermal cell strata. Our results show that SLS reduces the barrier function to Ni-ion penetration of the stratum corneum. In addition we have shown that EDX allows analysis of the influence of different factors involved in nickel penetration through the skin by giving data on the physiological effects on the epidermal cells caused by the applied substances

Penetration Enhancing Effect of Polysorbate 20 and 80 on the In ...

African Journals Online (AJOL)

Purpose: To investigate the penetration enhancing effect of two polysorbates - polyoxyethylene 20 (POE-20) and polyoxyethylene 80 (POE-80) - on the in vitro percutaneous absorption of ascorbic acid (AA). Methods: For the permeation experiments, Franz diffusion cell covered with aluminum foil providing an effective ...

Domino-Like Intercellular Delivery of Undecylenic Acid-Conjugated Porous Silicon Nanoparticles for Deep Tumor Penetration.

Science.gov (United States)

Yong, Tuying; Hu, Jun; Zhang, Xiaoqiong; Li, Fuying; Yang, Hao; Gan, Lu; Yang, Xiangliang

2016-10-05

Improving the intratumoral distribution of anticancer agents remains the critical challenge for developing efficient cancer chemotherapy. Luminescent porous silicon nanoparticles (PSiNPs) have attracted considerable attention in the biomedical field especially in drug delivery. Here, we described the lysosomal exocytosis-mediated domino-like intercellular delivery of undecylenic acid-conjugated PSiNPs (UA-PSiNPs) for deep tumor penetration. UA-PSiNPs with significantly improved stability in physiological conditions were internalized into tumor cells by macropinocytosis-, caveolae-, and clathrin-mediated endocytosis and mainly colocalized with Golgi apparatus and lysosomes. Substantial evidence showed that UA-PSiNPs was excreted from cells via lysosomal exocytosis after cellular uptake. The exocytosed UA-PSiNPs induced a domino-like infection of adjacent cancer cells and allowed encapsulated doxorubicin (DOX) to deeply penetrate into both three-dimensional tumor spheroids and in vivo tumors. In addition, DOX-loaded UA-PSiNPs exhibited strong antitumor activity and few side effects in vivo. This study demonstrated that UA-PSiNPs as a drug carrier might be applied for deep tumor penetration, offering a new insight into the design of more efficient delivery systems of anticancer drugs.

Market penetration rates of new energy technologies

International Nuclear Information System (INIS)

Lund, Peter

2006-01-01

The market penetration rates of 11 different new energy technologies were studied covering energy production and end-use technologies. The penetration rates were determined by fitting observed market data to an epidemical diffusion model. The analyses show that the exponential penetration rates of new energy technologies may vary from 4 up to over 40%/yr. The corresponding take-over times from a 1% to 50% share of the estimated market potential may vary from less than 10 to 70 years. The lower rate is often associated with larger energy impacts. Short take-over times less than 25 years seem to be mainly associated with end-use technologies. Public policies and subsides have an important effect on the penetration. Some technologies penetrate fast without major support explained by technology maturity and competitive prices, e.g. compact fluorescent lamps show a 24.2%/yr growth rate globally. The penetration rates determined exhibit some uncertainty as penetration has not always proceeded close to saturation. The study indicates a decreasing penetration rate with increasing time or market share. If the market history is short, a temporally decreasing functional form for the penetration rate coefficient could be used to anticipate the probable behavior

Ethical hacking and penetration testing guide

CERN Document Server

Baloch, Rafay

2014-01-01

Requiring no prior hacking experience, Ethical Hacking and Penetration Testing Guide supplies a complete introduction to the steps required to complete a penetration test, or ethical hack, from beginning to end. You will learn how to properly utilize and interpret the results of modern-day hacking tools, which are required to complete a penetration test. The book covers a wide range of tools, including Backtrack Linux, Google reconnaissance, MetaGooFil, dig, Nmap, Nessus, Metasploit, Fast Track Autopwn, Netcat, and Hacker Defender rootkit. Supplying a simple and clean explanation of how to effectively utilize these tools, it details a four-step methodology for conducting an effective penetration test or hack.Providing an accessible introduction to penetration testing and hacking, the book supplies you with a fundamental understanding of offensive security. After completing the book you will be prepared to take on in-depth and advanced topics in hacking and penetration testing. The book walks you through each ...

Projectile penetration into ballistic gelatin.

Science.gov (United States)

Swain, M V; Kieser, D C; Shah, S; Kieser, J A

2014-01-01

Ballistic gelatin is frequently used as a model for soft biological tissues that experience projectile impact. In this paper we investigate the response of a number of gelatin materials to the penetration of spherical steel projectiles (7 to 11mm diameter) with a range of lower impacting velocities (projectile velocity are found to be linear for all systems above a certain threshold velocity required for initiating penetration. The data for a specific material impacted with different diameter spheres were able to be condensed to a single curve when the penetration depth was normalised by the projectile diameter. When the results are compared with a number of predictive relationships available in the literature, it is found that over the range of projectiles and compositions used, the results fit a simple relationship that takes into account the projectile diameter, the threshold velocity for penetration into the gelatin and a value of the shear modulus of the gelatin estimated from the threshold velocity for penetration. The normalised depth is found to fit the elastic Froude number when this is modified to allow for a threshold impact velocity. The normalised penetration data are found to best fit this modified elastic Froude number with a slope of 1/2 instead of 1/3 as suggested by Akers and Belmonte (2006). Possible explanations for this difference are discussed. © 2013 Published by Elsevier Ltd.

Cyclic Dipeptide Shuttles as a Novel Skin Penetration Enhancement Approach: Preliminary Evaluation with Diclofenac.

Directory of Open Access Journals (Sweden)

Yousuf Mohammed

Full Text Available This study demonstrates the effectiveness of a peptide shuttle in delivering diclofenac into and through human epidermis. Diclofenac was conjugated to a novel phenylalanyl-N-methyl-naphthalenylalanine-derived diketopiperazine (DKP shuttle and to TAT (a classical cell penetrating peptide, and topically applied to human epidermis in vitro. DKP and TAT effectively permeated into and through human epidermis. When conjugated to diclofenac, both DKP and TAT enhanced delivery into and through human epidermis, though DKP was significantly more effective. Penetration of diclofenac through human epidermis (to receptor was increased by conjugation to the peptide shuttle and cell penetrating peptide with enhancement of 6x by DKP-diclofenac and 3x by TAT-diclofenac. In addition, the amount of diclofenac retained within the epidermis was significantly increased by peptide conjugation. COX-2 inhibition activity of diclofenac was retained when conjugated to DKP. Our study suggests that the peptide shuttle approach may offer a new strategy for targeted delivery of small therapeutic and diagnostic molecules to the skin.

Penetrating cation/fatty acid anion pair as a mitochondria-targeted protonophore

Science.gov (United States)

Severin, Fedor F.; Severina, Inna I.; Antonenko, Yury N.; Rokitskaya, Tatiana I.; Cherepanov, Dmitry A.; Mokhova, Elena N.; Vyssokikh, Mikhail Yu.; Pustovidko, Antonina V.; Markova, Olga V.; Yaguzhinsky, Lev S.; Korshunova, Galina A.; Sumbatyan, Nataliya V.; Skulachev, Maxim V.; Skulachev, Vladimir P.

2010-01-01

A unique phenomenon of mitochondria-targeted protonophores is described. It consists in a transmembrane H+-conducting fatty acid cycling mediated by penetrating cations such as 10-(6’-plastoquinonyl)decyltriphenylphosphonium (SkQ1) or dodecyltriphenylphosphonium (C12TPP). The phenomenon has been modeled by molecular dynamics and directly proved by experiments on bilayer planar phospholipid membrane, liposomes, isolated mitochondria, and yeast cells. In bilayer planar phospholipid membrane, the concerted action of penetrating cations and fatty acids is found to result in conversion of a pH gradient (ΔpH) to a membrane potential (Δψ) of the Nernstian value (about 60 mV Δψ at ΔpH = 1). A hydrophobic cation with localized charge (cetyltrimethylammonium) failed to substitute for hydrophobic cations with delocalized charge. In isolated mitochondria, SkQ1 and C12TPP, but not cetyltrimethylammonium, potentiated fatty acid-induced (i) uncoupling of respiration and phosphorylation, and (ii) inhibition of H2O2 formation. In intact yeast cells, C12TPP stimulated respiration regardless of the extracellular pH value, whereas a nontargeted protonophorous uncoupler (trifluoromethoxycarbonylcyanide phenylhydrazone) stimulated respiration at pH 5 but not at pH 3. Hydrophobic penetrating cations might be promising to treat obesity, senescence, and some kinds of cancer that require mitochondrial hyperpolarization. PMID:20080732

Penetrating abdominal trauma.

Science.gov (United States)

Henneman, P L

1989-08-01

The management of patients with penetrating abdominal trauma is outlined in Figure 1. Patients with hemodynamic instability, evisceration, significant gastrointestinal bleeding, peritoneal signs, gunshot wounds with peritoneal violation, and type 2 and 3 shotgun wounds should undergo emergency laparotomy. The initial ED management of these patients includes airway management, monitoring of cardiac rhythm and vital signs, history, physical examination, and placement of intravenous lines. Blood should be obtained for initial hematocrit, type and cross-matching, electrolytes, and an alcohol level or drug screen as needed. Initial resuscitation should utilize crystalloid fluid replacement. If more than 2 liters of crystalloid are needed to stabilize an adult (less in a child), blood should be given. Group O Rh-negative packed red blood cells should be immediately available for a patient in impending arrest or massive hemorrhage. Type-specific blood should be available within 15 minutes. A patient with penetrating thoracic and high abdominal trauma should receive a portable chest x-ray, and a hemo- or pneumothorax should be treated with tube thoracostomy. An unstable patient with clinical signs consistent with a pneumothorax, however, should receive a tube thoracostomy prior to obtaining roentgenographic confirmation. If time permits, a nasogastric tube and Foley catheter should be placed, and the urine evaluated for blood (these procedures can be performed in the operating room). If kidney involvement is suspected because of hematuria or penetrating trauma in the area of a kidney or ureter in a patient requiring surgery, a single-shot IVP should be performed either in the ED or the operating room. An ECG is important in patients with possible cardiac involvement and in patients over the age of 40 going to the operating room. Tetanus status should be updated, and appropriate antibiotics covering bowel flora should be given. Operative management should rarely be delayed

A study of the penetration of projectiles into marine sediments

International Nuclear Information System (INIS)

Boisson, J.Y.

1985-01-01

The work described in this document consists of three main parts: - Application, after having reviewed calculation methods and known codes, of a dynamic plasticity model based on the upper bound-method (with dissipated energy calculations by plastic deformations). The soil model used for this calculation is the Cambridge Clay Model. - Carrying out a programme of tests with instrumented small scale penetrators in centrifuge on a consolidated clay-target. The trials are done under 50 g, with projectiles, fired with an airgun at high impact velocity (50 m/s). The penetrators' instrumentation consists of either measuring acceleration, or tip force with strain gauges. - The mounting of a small instrumented penetrator for shallow water depth experimentations, with an accelerometer, and a local cell for tip resistance. A rapid electronic data acquisition system has been developed for these experimentations. The preliminary tests are done in a large tank filled with clay. The geotechnical characteristics of the clay are perfectly controlled. The tests performed under these conditions have shown the following observations: the rapid electronic data acquisition system works perfectly and could be used as a basic component for a deep water instrumentated penetrator; the results, obtained in these particular test conditions, are in a perfect agreement with the predictions of the model developed in the frame of this contract

The Basics of Hacking and Penetration Testing Ethical Hacking and Penetration Testing Made Easy

CERN Document Server

Engebretson, Patrick

2011-01-01

The Basics of Hacking and Penetration Testing serves as an introduction to the steps required to complete a penetration test or perform an ethical hack. You learn how to properly utilize and interpret the results of modern day hacking tools; which are required to complete a penetration test. Tool coverage will include, Backtrack Linux, Google, Whois, Nmap, Nessus, Metasploit, Netcat, Netbus, and more. A simple and clean explanation of how to utilize these tools will allow you  to gain a solid understanding of each of the four phases and prepare them to take on more in-depth texts and topi

Tracheal Penetration and Tracheoesophageal Fistula Caused by an Esophageal Self-Expanding Metallic Stent

Directory of Open Access Journals (Sweden)

Karan Madan

2014-01-01

Full Text Available Tracheal penetration of esophageal self-expanding metallic stents (SEMS with/without tracheoesophageal fistula (TEF formation is a rare occurrence. We report the case of a 66-year-old female patient with advanced esophageal squamous cell carcinoma who had undergone palliative esophageal stenting on three occasions for recurrent esophageal stent obstruction. On evaluation of symptoms of breathing difficulty and aspiration following third esophageal stent placement, tracheal erosion and TEF formation due to the tracheal penetration by esophageal stent were diagnosed. The patient was successfully managed by covered tracheal SEMS placement under flexible bronchoscopy.

The heparin-binding domain of HB-EGF as an efficient cell-penetrating peptide for drug delivery.

Science.gov (United States)

Luo, Zhao; Cao, Xue-Wei; Li, Chen; Wu, Miao-Dan; Yang, Xu-Zhong; Zhao, Jian; Wang, Fu-Jun

2016-11-01

Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30. The intrinsic bioactivities of recombinant MAP30-HBP were well preserved compared to those of free MAP30. Furthermore, HBP conjugated to the C-terminus of MAP30 promoted the cellular uptake of recombinant MAP30-HBP. Moreover, the fusion of HBP to MAP30 gave rise to significantly enhanced cytotoxic effects in all of the tumor cell lines tested. In HeLa cells, this cytotoxicity was mainly caused by the induction of cell apoptosis. Further investigation revealed that HBP enhanced MAP30-induced apoptosis through the activation of the mitochondrial- and death receptor-mediated signaling pathways. In addition, the MAP30-HBP fusion protein caused more HeLa cells to become arrested in S phase compared to MAP30 alone. These results highlight the MAP30-HBP fusion protein as a promising drug candidate for cancer therapy and demonstrate HBP, a novel CPP derived from human HB-EGF, as a new potential vector for antitumor drug delivery. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Electromagnetic modelling of Ground Penetrating Radar responses to complex targets

Science.gov (United States)

Pajewski, Lara; Giannopoulos, Antonis

2014-05-01

This work deals with the electromagnetic modelling of composite structures for Ground Penetrating Radar (GPR) applications. It was developed within the Short-Term Scientific Mission ECOST-STSM-TU1208-211013-035660, funded by COST Action TU1208 "Civil Engineering Applications of Ground Penetrating Radar". The Authors define a set of test concrete structures, hereinafter called cells. The size of each cell is 60 x 100 x 18 cm and the content varies with growing complexity, from a simple cell with few rebars of different diameters embedded in concrete at increasing depths, to a final cell with a quite complicated pattern, including a layer of tendons between two overlying meshes of rebars. Other cells, of intermediate complexity, contain pvc ducts (air filled or hosting rebars), steel objects commonly used in civil engineering (as a pipe, an angle bar, a box section and an u-channel), as well as void and honeycombing defects. One of the cells has a steel mesh embedded in it, overlying two rebars placed diagonally across the comers of the structure. Two cells include a couple of rebars bent into a right angle and placed on top of each other, with a square/round circle lying at the base of the concrete slab. Inspiration for some of these cells is taken from the very interesting experimental work presented in Ref. [1]. For each cell, a subset of models with growing complexity is defined, starting from a simple representation of the cell and ending with a more realistic one. In particular, the model's complexity increases from the geometrical point of view, as well as in terms of how the constitutive parameters of involved media and GPR antennas are described. Some cells can be simulated in both two and three dimensions; the concrete slab can be approximated as a finite-thickness layer having infinite extension on the transverse plane, thus neglecting how edges affect radargrams, or else its finite size can be fully taken into account. The permittivity of concrete can be

Selective imaging of cancer cells with a pH-activatable lysosome-targeting fluorescent probe.

Science.gov (United States)

Shi, Rongguang; Huang, Lu; Duan, Xiaoxue; Sun, Guohao; Yin, Gui; Wang, Ruiyong; Zhu, Jun-Jie

2017-10-02

Fluorescence imaging with tumor-specific fluorescent probe has emerged as a tool to aid surgeons in the identification and removal of tumor tissue. We report here a new lysosome-targeting fluorescent probe (NBOH) with BODIPY fluorephore to distinguish tumor tissue out of normal tissue based on different pH environment. The probe exhibited remarkable pH-dependent fluorescence behavior in a wide pH range from 3.0 to 11.0, especially a sensitive pH-dependent fluorescence change at pH range between 3.5 and 5.5, corresponding well to the acidic microenvironment of tumor cells, in aqueous solution. The response time of NBOH was extremely short and the photostability was proved to be good. Toxicity test and fluorescence cell imaging together with a sub-cellular localization study were carried out revealing its low biotoxicity and good cell membrane permeability. And NBOH was successfully applied to the imaging of tumor tissue in tumor-bearing mice suggesting potential application to surgery as a tumor-specific probe. Copyright © 2017 Elsevier B.V. All rights reserved.

Biofunctionalized nanoparticles with pH-responsive and cell penetrating blocks for gene delivery

International Nuclear Information System (INIS)

Gaspar, V M; Marques, J G; Sousa, F; Queiroz, J A; Correia, I J; Louro, R O

2013-01-01

Bridging the gap between nanoparticulate delivery systems and translational gene therapy is a long sought after requirement in nanomedicine-based applications. However, recent developments regarding nanoparticle functionalization have brought forward the ability to synthesize materials with biofunctional moieties that mimic the evolved features of viral particles. Herein we report the versatile conjugation of both cell penetrating arginine and pH-responsive histidine moieties into the chitosan polymeric backbone, to improve the physicochemical characteristics of the native material. Amino acid coupling was confirmed by 2D TOCSY NMR and Fourier transform infrared spectroscopy. The synthesized chitosan–histidine–arginine (CH–H–R) polymer complexed plasmid DNA biopharmaceuticals, and spontaneously assembled into stable 105 nm nanoparticles with spherical morphology and positive surface charge. The functionalized delivery systems were efficiently internalized into the intracellular compartment, and exhibited remarkably higher transfection efficiency than unmodified chitosan without causing any cytotoxic effect. Additional findings regarding intracellular trafficking events reveal their preferential escape from degradative lysosomal pathways and nuclear localization. Overall, this assembly of nanocarriers with bioinspired moieties provides the foundations for the design of efficient and customizable materials for cancer gene therapy. (paper)

Low Force Penetration of Icy Regolith

Science.gov (United States)

Mantovani, J. G.; Galloway, G. M.; Zacny, K.

2016-01-01

A percussive cone penetrometer measures the strength of granular material by using percussion to deliver mechanical energy into the material. A percussive cone penetrometer was used in this study to penetrate a regolith ice mixture by breaking up ice and decompacting the regolith. As compared to a static cone penetrometer, percussion allows low reaction forces to push a penetrometer probe tip more easily into dry regolith in a low gravity environment from a planetary surface rover or a landed spacecraft. A percussive cone penetrates icy regolith at ice concentrations that a static cone cannot penetrate. In this study, the percussive penetrator was able to penetrate material under 65 N of down-force which could not be penetrated using a static cone under full body weight. This paper discusses using a percussive cone penetrometer to discern changes in the concentration of water-ice in a mixture of lunar regolith simulant and ice to a depth of one meter. The rate of penetration was found to be a function of the ice content and was not significantly affected by the down-force. The test results demonstrate that this method may be ideal for a small platform in a reduced gravity environment. However, there are some cases where the system may not be able to penetrate the icy regolith, and there is some risk of the probe tip becoming stuck so that it cannot be retracted. It is also shown that a percussive cone penetrometer could be used to prospect for water ice in regolith at concentrations as high as 8 by weight.

Ultraviolet and visible light penetration of epidermis

International Nuclear Information System (INIS)

Eggset, G.; Kavli, G.; Volden, G.; Krokan, H.

1984-01-01

Light penetration in untanned skin and skin tanned with UVB (middlewave ultraviolet light) or PUVA (Psoralen photochemotherapy) was compared. Transmission at different wavelengths was measured through sheets of intact epidermis isolated by a suction blister technique. Thick epidermis was collected from a newly formed palmar friction bulla. For these studies a monochromator was used and the range of wavelengths examined was 280-700 nm. The transmission was considerably lower in tanned skin and the difference was most pronounced in the UV range. In the UVB range (290-320 nm), transmission was 13-43% for untanned epidermis, 8-12% for UVB tanned and slightly lower for PUVA tanned epidermis. At wavelengths below 325 nm only a few per cent of light penetrate through thick palmar epidermis. Both UVB and PUVA induce increased melanin content and thickening of the epidermis. Our results indicate that melanin is the most efficient protection against UVA while thickening of epidermis may be as important as the increased melanin content for the protection of living basal cells against the harmful UVB rays. (Auth)

Ground penetrating radar

CERN Document Server

Daniels, David J

2004-01-01

Ground-penetrating radar has come to public attention in recent criminal investigations, but has actually been a developing and maturing remote sensing field for some time. In the light of recent expansion of the technique to a wide range of applications, the need for an up-to-date reference has become pressing. This fully revised and expanded edition of the best-selling Surface-Penetrating Radar (IEE, 1996) presents, for the non-specialist user or engineer, all the key elements of this technique, which span several disciplines including electromagnetics, geophysics and signal processing. The

Long-rod penetration: the transition zone between rigid and hydrodynamic penetration modes

Directory of Open Access Journals (Sweden)

Jian-feng Lou

2014-06-01

Full Text Available Long-rod penetration in a wide range of velocity means that the initial impact velocity varies in a range from tens of meters per second to several kilometers per second. The long rods maintain rigid state when the impact velocity is low, the nose of rod deforms and even is blunted when the velocity gets higher, and the nose erodes and fails to lead to the consumption of long projectile when the velocity is very high due to instantaneous high pressure. That is, from low velocity to high velocity, the projectile undergoes rigid rods, deforming non-erosive rods, and erosive rods. Because of the complicated changes of the projectile, no well-established theoretical model and numerical simulation have been used to study the transition zone. Based on the analysis of penetration behavior in the transition zone, a phenomenological model to describe target resistance and a formula to calculate penetration depth in transition zone are proposed, and a method to obtain the boundary velocity of transition zone is determined. A combined theoretical analysis model for three response regions is built by analyzing the characteristics in these regions. The penetration depth predicted by this combined model is in good agreement with experimental result.

Plutonium in depleted uranium penetrators

International Nuclear Information System (INIS)

McLaughlin, J.P.; Leon-Vintro, L.; Smith, K.; Mitchell, P.I.; Zunic, Z.S.

2002-01-01

Depleted Uranium (DU) penetrators used in the recent Balkan conflicts have been found to be contaminated with trace amounts of transuranic materials such as plutonium. This contamination is usually a consequence of DU fabrication being carried out in facilities also using uranium recycled from spent military and civilian nuclear reactor fuel. Specific activities of 239+240 Plutonium generally in the range 1 to 12 Bq/kg have been found to be present in DU penetrators recovered from the attack sites of the 1999 NATO bombardment of Kosovo. A DU penetrator recovered from a May 1999 attack site at Bratoselce in southern Serbia and analysed by University College Dublin was found to contain 43.7 +/- 1.9 Bq/kg of 239+240 Plutonium. This analysis is described. An account is also given of the general population radiation dose implications arising from both the DU itself and from the presence of plutonium in the penetrators. According to current dosimetric models, in all scenarios considered likely ,the dose from the plutonium is estimated to be much smaller than that due to the uranium isotopes present in the penetrators. (author)

A Novel Method for Preparing Auxetic Foam from Closed-cell Polymer Foam Based on Steam Penetration and Condensation (SPC) Process.

Science.gov (United States)

Fan, Donglei; Li, Minggang; Qiu, Jian; Xing, Haiping; Jiang, Zhiwei; Tang, Tao

2018-05-31

Auxetic materials are a class of materials possessing negative Poisson's ratio. Here we establish a novel method for preparing auxetic foam from closed-cell polymer foam based on steam penetration and condensation (SPC) process. Using polyethylene (PE) closed-cell foam as an example, the resultant foams treated by SPC process present negative Poisson's ratio during stretching and compression testing. The effect of steam-treated temperature and time on the conversion efficiency of negative Poisson's ratio foam is investigated, and the mechanism of SPC method for forming re-entrant structure is discussed. The results indicate that the presence of enough steam within the cells is a critical factor for the negative Poisson's ratio conversion in the SPC process. The pressure difference caused by steam condensation is the driving force for the conversion from conventional closed-cell foam to the negative Poisson's ratio foam. Furthermore, the applicability of SPC process for fabricating auxetic foam is studied by replacing PE foam by polyvinyl chloride (PVC) foam with closed-cell structure or replacing water steam by ethanol steam. The results verify the universality of SPC process for fabricating auxetic foams from conventional foams with closed-cell structure. In addition, we explored potential application of the obtained auxetic foams by SPC process in the fabrication of shape memory polymer materials.

Hemocompatible poly(NIPAm-MBA-AMPS) colloidal nanoparticles as carriers of anti-inflammatory cell penetrating peptides.

Science.gov (United States)

Bartlett, Rush L; Medow, Matthew R; Panitch, Alyssa; Seal, Brandon

2012-04-09

Anionic copolymer systems containing sulfated monomers have great potential for delivery of cationic therapeutics, but N-isopropylacrylamide (NIPAm) 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) copolymer nanoparticles have seen limited characterization to date with regard to physical properties relevant to loading and release of therapeutics. Characterization of polymeric nanoparticles incorporating AMPS showed an increased size and decreased thermodynamic swelling ratios of AMPS containing particles as compared to NIPAm nanoparticles lacking AMPS. Particles with increasing AMPS addition showed an increased propensity for uniformity, intraparticle colloidal stability, and drug loading capacity. Peptide encapsulated in particles was shielded from peptide degradation in serum. Particles were shown not impede blood coagulation or to cause hemolysis. This study has demonstrated that AMPS incorporation into traditional NIPAm nanoparticles presents a tunable parameter for changing particle LCST, size, swelling ratio, ζ potential, and cationic peptide loading potential. This one-pot synthesis results in a thermosensitive anionic nanoparticle system that is a potentially useful platform to deliver cationic cell penetrating peptides.

Ethical Dilemmas and Dimensions in Penetration Testing

OpenAIRE

Faily, Shamal; McAlaney, John; Iacob, C.

2015-01-01

Penetration testers are required to attack systems to evaluate their security, but without engaging in unethical behaviour while doing so. Despite work on hacker values and studies into security practice, there is little literature devoted to the ethical pressures associated with penetration testing. This paper presents several ethical dilemmas and dimensions associated with penetration testing;\\ud these shed light on the ethical positions taken by Penetration testers, and help identify poten...

Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos

Directory of Open Access Journals (Sweden)

Mie Kristensen

2016-01-01

Full Text Available The hydrophilic nature of peptides and proteins renders them impermeable to cell membranes. Thus, in order to successfully deliver peptide and protein-based therapeutics across the plasma membrane or epithelial and endothelial barriers, a permeation enhancing strategy must be employed. Cell-penetrating peptides (CPPs constitute a promising tool and have shown applications for peptide and protein delivery into cells as well as across various epithelia and the blood-brain barrier (BBB. CPP-mediated delivery of peptides and proteins may be pursued via covalent conjugation of the CPP to the cargo peptide or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo. Both approaches have their pros and cons, and which is the better choice likely relates to the physicochemical properties of the CPP and its cargo as well as the route of administration, the specific barrier and the target cell. Besides the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability-enhancing strategies are commonly employed to prolong the CPP half-life. The mechanisms by which CPPs translocate cell membranes are believed to involve both endocytosis and direct translocation, but are still widely investigated and discussed. The fact that multiple factors influence the mechanisms responsible for cellular CPP internalization and the lack of sensitive methods for detection of the CPP, and in some cases the cargo, further complicates the design and conduction of conclusive mechanistic studies.

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.

Science.gov (United States)

de Cogan, Felicity; Hill, Lisa J; Lynch, Aisling; Morgan-Warren, Peter J; Lechner, Judith; Berwick, Matthew R; Peacock, Anna F A; Chen, Mei; Scott, Robert A H; Xu, Heping; Logan, Ann

2017-05-01

To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV. CPPs were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were present in the rat anterior chamber within 6 minutes. A single application of CPP + bevacizumab eye drop delivered clinically relevant concentrations of bevacizumab to the posterior chamber of the rat eye in vivo. Similarly, clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were detected in the porcine vitreous and retina ex vivo. In an established model of CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had significantly reduced areas of CNV when compared with lasered eyes without treatment. CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

Exploring the Possibility of Cryopreservation of Feline and Canine Erythrocytes by Rapid Freezing with Penetrating and Non-Penetrating Cryoprotectants.

Directory of Open Access Journals (Sweden)

Denys Pogozhykh

Full Text Available Efficient application of veterinary blood transfusion approaches for small companion animals requires readily available supply of the donor material. This can be achieved by developing of effective biobanking technologies allowing long-term storage of donor blood components via cryopreservation. Transfusion of an erythrocyte concentrate allows the successful correction of various hematological pathologies, severe bleeding, and etc. While in the past there were several approaches to cryopreserve red blood cells of dogs, to our knowledge there is virtually no data on cryopreservation of feline erythrocytes. In this paper, we performed a comprehensive parameter optimization for low temperature storage of RBCs of both species. Here, the efficiency of single-component and multicomponent cryoprotective media as well as necessary time of pre-incubation with penetrating and non-penetrating cryoprotectants prior to rapid freezing is analyzed. This study showed that glycerol was not sufficient for cryopreservation of red blood cells of the studied species under the investigated conditions. Application of 10% (v/v ME2SO allowed for a significant reduction of canine and feline erythrocytes hemolysis after thawing. 17.5% hydroxyethyl starch demonstrated the highest cryoprotective activity for both species. It was found that dog RBCs should be incubated in cryoprotective media for 30 min at 22°C prior to freezing, while for cat RBCs 20 min is sufficient. Combination of CPAs was less effective. Presented data may be considered in further studies in veterinary transfusion and blood banking optimization.

Experimental Study of Bacterial Penetration into Chalk Rock: Mechanisms and Effect on Permeability

DEFF Research Database (Denmark)

Halim, Amalia Yunita; Shapiro, Alexander; Eliasson Lantz, Anna

2014-01-01

Bacterial selective plugging is one of the mechanisms through which microorganisms can be applied for enhanced oil recovery, as bacteria can plug the water-swept zones of a reservoir, thus altering the flow paths and improving sweep efficiency. However, complete understanding of the penetration...... behavior of bacteria is lacking, especially in chalk formations where characteristic pore throat sizes are comparable with the sizes of bacterial cells. In this study, two bacterial strains, Bacillus licheniformis 421 (spore-forming) and Pseudomonas putida K12 (non-spore forming) were used to investigate...... the penetration of bacteria into chalk and its effect on permeability reduction. The core plugs were produced from Stevns Klint outcrop with low permeability (2–4 mD) and with pore sizes comparable to bacterial sizes. Both types of bacteria were able to penetrate and to be transported through the cores to some...

Design of Fire/Gas Penetration Seals and fire exposure tests for Tokamak Fusion Test Reactor experimental areas

International Nuclear Information System (INIS)

Cavalluzzo, S.

1983-01-01

A Fire/Gas Penetration Seal is required in every penetration through the walls and ceilings into the Test Cell housing the Tokamak Fusion Test Reactor (TFTR), as well as other adjacent areas to protect the TFTR from fire damage. The penetrations are used for field coil lead stems, diagnostics systems, utilities, cables, trays, mechanical devices, electrical conduits, vacuum liner, air conditioning ducts, water pipes, and gas pipes. The function of the Fire/Gas Penetration Seals is to prevent the passage of fire and products of combustion through penetrations for a period of time up to three hours and remain structurally intact during fire exposure. The Penetration Seal must withstand, without rupture, a fire hose water stream directed at the hot surface. There are over 3000 penetrations ranging in size from several square inches to 100 square feet, and classified into 90 different types. The material used to construct the Fire/Gas Penetration Seals consist of a single and a two-component room temperature vulcanizing (RTV) silicone rubber compound. Miscellaneous materials such as alumina silica refractory fibers in board, blanket and fiber forms are also used in the construction and assembly of the Seals. This paper describes some of the penetration seals and the test procedures used to perform the three-hour fire exposure tests to demonstrate the adequacy of the seals

Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation

Energy Technology Data Exchange (ETDEWEB)

Amand, Helene L., E-mail: helene.amand@chalmers.se [Chalmers University of Technology, Department of Chemical and Biological Engineering/Physical Chemistry, SE-412 96 Gothenburg (Sweden); Norden, Bengt, E-mail: norden@chalmers.se [Chalmers University of Technology, Department of Chemical and Biological Engineering/Physical Chemistry, SE-412 96 Gothenburg (Sweden); Fant, Kristina, E-mail: kristina.fant@sp.se [Chalmers University of Technology, Department of Chemical and Biological Engineering/Physical Chemistry, SE-412 96 Gothenburg (Sweden)

2012-02-17

Highlights: Black-Right-Pointing-Pointer Reversible CPP dimerisation is a simple yet efficient strategy to improve delivery. Black-Right-Pointing-Pointer Dimer formation enhances peptiplex stability, resulting in increased transfection. Black-Right-Pointing-Pointer By dimerisation, the CPP EB1 even gain endosomal escape properties while lowering cytotoxicity. -- Abstract: Cell-penetrating peptides have the ability to stimulate uptake of macromolecular cargo in mammalian cells in a non-toxic manner and therefore hold promise as efficient and well tolerated gene delivery vectors. Non-covalent peptide-DNA complexes ('peptiplexes') enter cells via endocytosis, but poor peptiplex stability and endosomal entrapment are considered as main barriers to peptide-mediated delivery. We explore a simple, yet highly efficient, strategy to improve the function of peptide-based vectors, by adding one terminal cysteine residue. This allows the peptide to dimerize by disulfide bond formation, increasing its affinity for nucleic acids by the 'chelate effect' and, when the bond is reduced intracellularly, letting the complex dissociate to deliver the nucleic acid. By introducing a single C-terminal cysteine in the classical CPP penetratin and the penetratin analogs PenArg and EB1, we show that this minor modification greatly enhances the transfection capacity for plasmid DNA in HEK293T cells. We conclude that this effect is mainly due to enhanced thermodynamic stability of the peptiplexes as endosome-disruptive chloroquine is still required for transfection and the effect is more pronounced for peptides with lower inherent DNA condensation capacity. Interestingly, for EB1, addition of one cysteine makes the peptide able to mediate transfection in absence of chloroquine, indicating that dimerisation can also improve endosomal escape properties. Further, the cytotoxicity of EB1 peptiplexes is considerably reduced, possibly due to lower concentration of free peptide

Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation

International Nuclear Information System (INIS)

Åmand, Helene L.; Nordén, Bengt; Fant, Kristina

2012-01-01

Highlights: ► Reversible CPP dimerisation is a simple yet efficient strategy to improve delivery. ► Dimer formation enhances peptiplex stability, resulting in increased transfection. ► By dimerisation, the CPP EB1 even gain endosomal escape properties while lowering cytotoxicity. -- Abstract: Cell-penetrating peptides have the ability to stimulate uptake of macromolecular cargo in mammalian cells in a non-toxic manner and therefore hold promise as efficient and well tolerated gene delivery vectors. Non-covalent peptide-DNA complexes (“peptiplexes”) enter cells via endocytosis, but poor peptiplex stability and endosomal entrapment are considered as main barriers to peptide-mediated delivery. We explore a simple, yet highly efficient, strategy to improve the function of peptide-based vectors, by adding one terminal cysteine residue. This allows the peptide to dimerize by disulfide bond formation, increasing its affinity for nucleic acids by the “chelate effect” and, when the bond is reduced intracellularly, letting the complex dissociate to deliver the nucleic acid. By introducing a single C-terminal cysteine in the classical CPP penetratin and the penetratin analogs PenArg and EB1, we show that this minor modification greatly enhances the transfection capacity for plasmid DNA in HEK293T cells. We conclude that this effect is mainly due to enhanced thermodynamic stability of the peptiplexes as endosome-disruptive chloroquine is still required for transfection and the effect is more pronounced for peptides with lower inherent DNA condensation capacity. Interestingly, for EB1, addition of one cysteine makes the peptide able to mediate transfection in absence of chloroquine, indicating that dimerisation can also improve endosomal escape properties. Further, the cytotoxicity of EB1 peptiplexes is considerably reduced, possibly due to lower concentration of free peptide dimer resulting from its stronger binding to DNA.

Skull penetrating wound

International Nuclear Information System (INIS)

Gonzalez Orlandi, Yvei; Junco Martin, Reinel; Rojas Manresa, Jorge; Duboy Limonta, Victor; Matos Herrera, Omar; Saez Corvo, Yunet

2011-01-01

The cranioencephalic trauma is common in the emergence centers to care for patients with multiple traumata and it becames in a health problem in many countries. Skull penetrating trauma is located in a special place due to its low frequency. In present paper a case of male patient aged 52 severely skull-injured with penetrating wound caused by a cold steel that remained introduced into the left frontotemporal region. After an imaging study the emergence surgical treatment was applied and patient evolves adequately after 25 days of hospitalization. Nowadays, she is under rehabilitation treatment due to a residual right hemiparesis.(author)

MDCT diagnosis of penetrating diaphragm injury

Energy Technology Data Exchange (ETDEWEB)

Bodanapally, Uttam K.; Shanmuganathan, Kathirkamanathan; Mirvis, Stuart E.; Sliker, Clint W.; Fleiter, Thorsten R.; Sarada, Kamal; Miller, Lisa A. [University of Maryland School of Medicine, Department of Diagnostic Radiology, Baltimore, MD (United States); Stein, Deborah M. [University of Maryland, Department of Surgery, Shock Trauma Center, Baltimore, MD (United States); Alexander, Melvin [National Study Center for Trauma and Emergency Medical Systems, Baltimore, MD (United States)

2009-08-15

The purpose of the study was to determine the diagnostic sensitivity and specificity of multidetector CT (MDCT) in detection of diaphragmatic injury following penetrating trauma. Chest and abdominal CT examinations performed preoperatively in 136 patients after penetrating trauma to the torso with injury trajectory in close proximity to the diaphragm were reviewed by radiologists unaware of surgical findings. Signs associated with diaphragmatic injuries in penetrating trauma were noted. These signs were correlated with surgical diagnoses, and their sensitivity and specificity in assisting the diagnosis were calculated. CT confirmed diaphragmatic injury in 41 of 47 injuries (sensitivity, 87.2%), and an intact diaphragm in 71 of 98 patients (specificity, 72.4%). The overall accuracy of MDCT was 77%. The most accurate sign helping the diagnosis was contiguous injury on either side of the diaphragm in single-entry penetrating trauma (sensitivity, 88%; specificity, 82%). Thus MDCT has high sensitivity and good specificity in detecting penetrating diaphragmatic injuries. (orig.)

MDCT diagnosis of penetrating diaphragm injury

International Nuclear Information System (INIS)

Bodanapally, Uttam K.; Shanmuganathan, Kathirkamanathan; Mirvis, Stuart E.; Sliker, Clint W.; Fleiter, Thorsten R.; Sarada, Kamal; Miller, Lisa A.; Stein, Deborah M.; Alexander, Melvin

2009-01-01

The purpose of the study was to determine the diagnostic sensitivity and specificity of multidetector CT (MDCT) in detection of diaphragmatic injury following penetrating trauma. Chest and abdominal CT examinations performed preoperatively in 136 patients after penetrating trauma to the torso with injury trajectory in close proximity to the diaphragm were reviewed by radiologists unaware of surgical findings. Signs associated with diaphragmatic injuries in penetrating trauma were noted. These signs were correlated with surgical diagnoses, and their sensitivity and specificity in assisting the diagnosis were calculated. CT confirmed diaphragmatic injury in 41 of 47 injuries (sensitivity, 87.2%), and an intact diaphragm in 71 of 98 patients (specificity, 72.4%). The overall accuracy of MDCT was 77%. The most accurate sign helping the diagnosis was contiguous injury on either side of the diaphragm in single-entry penetrating trauma (sensitivity, 88%; specificity, 82%). Thus MDCT has high sensitivity and good specificity in detecting penetrating diaphragmatic injuries. (orig.)

DNA-interactive properties of crotamine, a cell-penetrating polypeptide and a potential drug carrier.

Directory of Open Access Journals (Sweden)

Pei-Chun Chen

Full Text Available Crotamine, a 42-residue polypeptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, has been shown to be a cell-penetrating protein that targets chromosomes, carries plasmid DNA into cells, and shows specificity for actively proliferating cells. Given this potential role as a nucleic acid-delivery vector, we have studied in detail the binding of crotamine to single- and double-stranded DNAs of different lengths and base compositions over a range of ionic conditions. Agarose gel electrophoresis and ultraviolet spectrophotometry analysis indicate that complexes of crotamine with long-chain DNAs readily aggregate and precipitate at low ionic strength. This aggregation, which may be important for cellular uptake of DNA, becomes less likely with shorter chain length. 25-mer oligonucleotides do not show any evidence of such aggregation, permitting the determination of affinities and size via fluorescence quenching experiments. The polypeptide binds non-cooperatively to DNA, covering about 5 nucleotide residues when it binds to single (ss or (ds double stranded molecules. The affinities of the protein for ss- vs. ds-DNA are comparable, and inversely proportional to salt levels. Analysis of the dependence of affinity on [NaCl] indicates that there are a maximum of ∼3 ionic interactions between the protein and DNA, with some of the binding affinity attributable to non-ionic interactions. Inspection of the three-dimensional structure of the protein suggests that residues 31 to 35, Arg-Trp-Arg-Trp-Lys, could serve as a potential DNA-binding site. A hexapeptide containing this sequence displayed a lower DNA binding affinity and salt dependence as compared to the full-length protein, likely indicative of a more suitable 3D structure and the presence of accessory binding sites in the native crotamine. Taken together, the data presented here describing crotamine-DNA interactions may lend support to the design of more

Altered Expression of Genes Implicated in Xylan Biosynthesis Affects Penetration Resistance against Powdery Mildew.

Science.gov (United States)

Chowdhury, Jamil; Lück, Stefanie; Rajaraman, Jeyaraman; Douchkov, Dimitar; Shirley, Neil J; Schwerdt, Julian G; Schweizer, Patrick; Fincher, Geoffrey B; Burton, Rachel A; Little, Alan

2017-01-01

Heteroxylan has recently been identified as an important component of papillae, which are formed during powdery mildew infection of barley leaves. Deposition of heteroxylan near the sites of attempted fungal penetration in the epidermal cell wall is believed to enhance the physical resistance to the fungal penetration peg and hence to improve pre-invasion resistance. Several glycosyltransferase (GT) families are implicated in the assembly of heteroxylan in the plant cell wall, and are likely to work together in a multi-enzyme complex. Members of key GT families reported to be involved in heteroxylan biosynthesis are up-regulated in the epidermal layer of barley leaves during powdery mildew infection. Modulation of their expression leads to altered susceptibility levels, suggesting that these genes are important for penetration resistance. The highest level of resistance was achieved when a GT43 gene was co-expressed with a GT47 candidate gene, both of which have been predicted to be involved in xylan backbone biosynthesis. Altering the expression level of several candidate heteroxylan synthesis genes can significantly alter disease susceptibility. This is predicted to occur through changes in the amount and structure of heteroxylan in barley papillae.

FAA Fluorescent Penetrant Laboratory Inspections

Energy Technology Data Exchange (ETDEWEB)

WINDES,CONNOR L.; MOORE,DAVID G.

2000-08-02

The Federal Aviation Administration Airworthiness Assurance NDI Validation Center currently assesses the capability of various non-destructive inspection (NDI) methods used for analyzing aircraft components. The focus of one such exercise is to evaluate the sensitivity of fluorescent liquid penetrant inspection. A baseline procedure using the water-washable fluorescent penetrant method defines a foundation for comparing the brightness of low cycle fatigue cracks in titanium test panels. The analysis of deviations in the baseline procedure will determine an acceptable range of operation for the steps in the inspection process. The data also gives insight into the depth of each crack and which step(s) of the inspection process most affect penetrant sensitivities. A set of six low cycle fatigue cracks produced in 6.35-mm thick Ti-6Al-4V specimens was used to conduct the experiments to produce sensitivity data. The results will document the consistency of the crack readings and compare previous experiments to find the best parameters for water-washable penetrant.

Studies on penetration of antibiotic in bacterial cells in space conditions (7-IML-1)

Science.gov (United States)

Tixador, R.

1992-01-01

The Cytos 2 experiment was performed aboard Salyut 7 in order to test the antibiotic sensitivity of bacteria cultivated in vitro in space. An increase of the Minimal Inhibitory Concentration (MIC) in the inflight cultures (i.e., an increase of the antibiotic resistance) was observed. Complementary studies of the ultrastructure showed a thickening of the cell envelope. In order to confirm the results of the Cytos 2 experiment, we performed the ANTIBIO experiment during the D1 mission to try to differentiate, by means of the 1 g centrifuge in the Biorack, between the biological effects of cosmic rays and those caused by microgravity conditions. The originality of this experiment was in the fact that it was designed to test the antibiotic sensitivity of bacteria cultivated in vitro during the orbital phase of the flight. The results show an increase in resistance to Colistin in in-flight bacteria. The MIC is practically double in the in-flight cultures. A cell count of living bacteria in the cultures containing the different Colistin concentrations showed a significant difference between the cultures developed during space flight and the ground based cultures. The comparison between the 1 g and 0 g in-flight cultures show similar behavior for the two sets. Nevertheless, a small difference between the two sets of ground based control cultures was noted. The cultures developed on the ground centrifuge (1.4 g) present a slight decrease in comparison with the cultures developed in the static rack (1 g). In order to approach the mechanisms of the increase of antibiotic resistance on bacteria cultivated in vitro in space, we have proposed the study on penetration of antibiotics in bacterial cells in space conditions. This experiment was selected for the International Microgravity Laboratory 1 (IML-1) mission.

A SNARE-protein has opposing functions in penetration resistance and defence signalling pathways

DEFF Research Database (Denmark)

Zhang, Ziguo; Feechan, Angela; Pedersen, Carsten

2007-01-01

Penetration resistance is often the first line of defence against fungal pathogens. Subsequently induced defences are mediated by the programmed cell death (PCD) reaction pathway and the salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) signalling pathways. We previously demonstrated...

Penetrating performance and “self-sharpening” behavior of fine-grained tungsten heavy alloy rod penetrators

Energy Technology Data Exchange (ETDEWEB)

Luo, Rongmei, E-mail: luorm_1999@126.com [School of Energy and Power Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu (China); College of Equipment Engineering, Shenyang Ligong University, Shenyang 110159, Liaoning (China); Huang, Dewu; Yang, Mingchuan; Tang, Enling; Wang, Meng; He, Liping [College of Equipment Engineering, Shenyang Ligong University, Shenyang 110159, Liaoning (China)

2016-10-15

Rod penetrators with 95W–3.75Ni–1.25Fe fine-grained tungsten heavy alloy (fine-grained 95W) and conventional tungsten heavy alloy rod penetrators with the same chemical composition (conventional 95W) were subjected to ballistic impact to compare their penetration performance. “Self-sharpening” behavior and an average 10.5% increase in penetration depth compared to conventional 95W penetrators. An acute head remained on the fine-grained 95W rod with SEM results revealing many micro-cracks and small debris on surface layer of the rod head. The stress-strain curves collected in the Split Hopkinson Pressure Bar (SHPB) experiment showed that critical failure strain values of the fine-grained 95W were 0.12 and 0.39 at strain rate of 2×10{sup 3} s{sup −1} and 3.9×10{sup 3} s{sup −1}, respectively, approximately 40% and 10% lower than those of the conventional 95W. The dynamic strength values of fine-grained 95W were 2100 MPa and 2520 MPa, respectively, which were 500 MPa and 520 MPa higher than those of the conventional 95W. The relationship among microstructure, mechanical property and “self-sharpening” behavior of fine-grained 95W is discussed in this work.

Operating methods to remove the excess of penetrant in surface. Preponderant and characteristic part of water for water washable penetrants

International Nuclear Information System (INIS)

Dubosc, P.

1985-01-01

Penetrant use for quality control, although very well known (nuclear, space industries, offshore platforms) is often poorly practiced. This is largely due to a lack of understanding by the users the way that the different components of the system (penetrants, solvents, emulsifiers, and developers) function. In this talk, we shall explain a particular characteristic that the manufacturers of reputable penetrant seek to build into their water washable penetrants. It is a viscosity curve which has the function of keeping water in a well defined form. We show why the form of the curve is crucial, which reaction between water and penetrant it corresponds to, and we deduce the practical consequences of bringing into play procedures for removing excess penetrant with or without water [fr

Market Penetration Simulation of Hydrogen Powered Vehicles in Korea

International Nuclear Information System (INIS)

Eunju Jun; Yong Hoon, Jeong; Soon Heung, Chang

2006-01-01

As oil price being boosted, hydrogen has been considered to be a strong candidate for the future energy carrier along with electricity. Although hydrogen can be produced by many energy sources, carbon-free sources such as nuclear and renewable energy may be ideal ones due to their environmental friendliness. For the analysis of hydrogen economy, the cost and market penetration of various end-use technologies are the most important factors in production and consumer side, respectively. Particularly, hydrogen powered vehicle is getting more interests as fuel cell technologies are developed. In this paper, the hydrogen powered vehicle penetration into the transportation market is simulated. A system dynamic code, Vensim, was utilized to simulate the dynamics in the transportation, assuming various types of vehicle such as gasoline, hybrid electricity and hydrogen powered. Market shares of each vehicle are predicted by using currently available data. The result showed that hydrogen era will not be bright as we think. To reach the era of hydrogen fuel cell cost should be reduced dramatically. And if the hydrogen cost which includes both operating and capital cost reaches to a $0.16 per kilometer, hydrogen portion can be a 50 percent in the transportation sector. However, if strong policy or subsidy can be given, the result will be changed. [1] (authors)

Development of cell-penetrating bispecific antibodies targeting the N-terminal domain of androgen receptor for prostate cancer therapy.

Science.gov (United States)

Goicochea, Nancy L; Garnovskaya, Maria; Blanton, Mary G; Chan, Grace; Weisbart, Richard; Lilly, Michael B

2017-12-01

Castration-resistant prostate cancer cells exhibit continued androgen receptor signaling in spite of low levels of ligand. Current therapies to block androgen receptor signaling act by inhibiting ligand production or binding. We developed bispecific antibodies capable of penetrating cells and binding androgen receptor outside of the ligand-binding domain. Half of the bispecific antibody molecule consists of a single-chain variable fragment of 3E10, an anti-DNA antibody that enters cells. The other half is a single-chain variable fragment version of AR441, an anti-AR antibody. The resulting 3E10-AR441 bispecific antibody enters human LNCaP prostate cells and accumulates in the nucleus. The antibody binds to wild-type, mutant and splice variant androgen receptor. Binding affinity of 3E10-AR441 to androgen receptor (284 nM) was lower than that of the parental AR441 mAb (4.6 nM), but could be improved (45 nM) through alternative placement of the affinity tags, and ordering of the VH and VK domains. The 3E10-AR441 bispecific antibody blocked genomic signaling by wild-type or splice variant androgen receptor in LNCaP cells. It also blocked non-genomic signaling by the wild-type receptor. Furthermore, bispecific antibody inhibited the growth of C4-2 prostate cancer cells under androgen-stimulated conditions. The 3E10-AR441 biAb can enter prostate cancer cells and inhibits androgen receptor function in a ligand-independent manner. It may be an attractive prototype agent for prostate cancer therapy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Varieties of cognitive penetration in visual perception.

Science.gov (United States)

Vetter, Petra; Newen, Albert

2014-07-01

Is our perceptual experience a veridical representation of the world or is it a product of our beliefs and past experiences? Cognitive penetration describes the influence of higher level cognitive factors on perceptual experience and has been a debated topic in philosophy of mind and cognitive science. Here, we focus on visual perception, particularly early vision, and how it is affected by contextual expectations and memorized cognitive contents. We argue for cognitive penetration based on recent empirical evidence demonstrating contextual and top-down influences on early visual processes. On the basis of a perceptual model, we propose different types of cognitive penetration depending on the processing level on which the penetration happens and depending on where the penetrating influence comes from. Our proposal has two consequences: (1) the traditional controversy on whether cognitive penetration occurs or not is ill posed, and (2) a clear-cut perception-cognition boundary cannot be maintained. Copyright © 2014 Elsevier Inc. All rights reserved.

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Science.gov (United States)

Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

2015-01-01

The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

Peptide nucleic acid (PNA) cell penetrating peptide (CPP) conjugates as carriers for cellular delivery of antisense oligomers

DEFF Research Database (Denmark)

Shiraishi, Takehiko; Nielsen, Peter E

2012-01-01

We have explored the merits of a novel delivery strategy for the antisense oligomers based on cell penetrating peptide (CPP) conjugated to a carrier PNA with sequence complementary to part of the antisense oligomer. The effect of these carrier CPP-PNAs was evaluated by using antisense PNA targeting......-PNA (cPNA1(7)-(D-Arg)8) and hexamer carrier decanoyl-CPP-PNA (Deca-cPNA1(6)-(D-Arg)8), respectively, without showing significant additional cellular toxicity. Most interestingly, the activity reached the same level obtained by enhancement with endosomolytic chloroquine (CQ) treatment, suggesting...... that the carrier might facilitate endosomal escape. Furthermore, 50% downregulation of luciferase expression at 60 nM siRNA was obtained using this carrier CPP-PNA delivery strategy (with CQ co-treatment) for a single stranded antisense RNA targeting normal luciferase mRNA. These results indicated that CPP...

Initial response of a rock penetrator

International Nuclear Information System (INIS)

Longcope, D.B.; Grady, D.E.

1977-12-01

An analysis based on elastic rod theory is given for the early-time axisymmetric response of pointed penetrators. Results of measurements by laser interferometry of the back surface particle velocity of laboratory scale penetrators impacted by sandstone targets are presented. Values of the initial pressure on the penetrator tip are determined which give good agreement between the analytical and experimental results. These initial tip pressures are found to be approximated by the stress-particle velocity Hugoniot for the target material

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides

Directory of Open Access Journals (Sweden)

Barbari GR

2017-05-01

Full Text Available Ghullam Reza Barbari,1 Farid Abedin Dorkoosh,1 Mohsen Amini,2 Mohammad Sharifzadeh,3 Fateme Atyabi,1 Saeed Balalaie,4 Niyousha Rafiee Tehrani,5 Morteza Rafiee Tehrani1 1Department of Pharmaceutics, 2Department of Medicinal Chemistry, 3Department of Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, 4Department of Chemistry, Khaje Nasiroddin University, 5Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Abstract: A simple and reproducible water-in-oil (W/O nanoemulsion technique for making ultrasmall (<15 nm, monodispersed and water-dispersible nanoparticles (NPs from chitosan (CS is reported. The nano-sized (50 nm water pools of the W/O nanoemulsion serve as “nano-containers and nano-reactors”. The entrapped polymer chains of CS inside these “nano-reactors” are covalently cross-linked with the chains of polyethylene glycol (PEG, leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%–19% increase, and animal studies are actively under progress and will be published separately. Keywords: ultrasmall, cell-penetrating peptide, chitosan, oral insulin, nanoemulsion, Caco-2 cell

Evaporation Limited Radial Capillary Penetration in Porous Media.

Science.gov (United States)

Liu, Mingchao; Wu, Jian; Gan, Yixiang; Hanaor, Dorian A H; Chen, C Q

2016-09-27

The capillary penetration of fluids in thin porous layers is of fundamental interest in nature and various industrial applications. When capillary flows occur in porous media, the extent of penetration is known to increase with the square root of time following the Lucas-Washburn law. In practice, volatile liquid evaporates at the surface of porous media, which restricts penetration to a limited region. In this work, on the basis of Darcy's law and mass conservation, a general theoretical model is developed for the evaporation-limited radial capillary penetration in porous media. The presented model predicts that evaporation decreases the rate of fluid penetration and limits it to a critical radius. Furthermore, we construct a unified phase diagram that describes the limited penetration in an annular porous medium, in which the boundaries of outward and inward liquid are predicted quantitatively. It is expected that the proposed theoretical model will advance the understanding of penetration dynamics in porous media and facilitate the design of engineered porous architectures.

In vivo SELEX for Identification of Brain-penetrating Aptamers

Directory of Open Access Journals (Sweden)

Congsheng Cheng

2013-01-01

Full Text Available The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating immune cells, where they act as ligand mimics or can be modified to carry payloads. We developed a library of aptamers and an in vivo evolution protocol to determine whether specific aptamers could be identified that would home to the brain after injection into the peripheral vasculature. Unlike biopanning with recombinant bacteriophage libraries, we found that the aptamer library employed here required more than 15 rounds of in vivo selection for convergence to specific sequences. The aptamer species identified through this approach bound to brain capillary endothelia and penetrated into the parenchyma. The methods described may find general utility for targeting various payloads to the brain.

Synthesis and in vitro evaluation of PNA-peptide-DETA conjugates as potential cell penetrating artificial ribonucleases.

Science.gov (United States)

Petersen, Lene; de Koning, Martijn C; van Kuik-Romeijn, Petra; Weterings, Jimmy; Pol, Christine J; Platenburg, Gerard; Overhand, Mark; van der Marel, Gijsbert A; van Boom, Jacques H

2004-01-01

We report the synthesis of novel artificial ribonucleases with potentially improved cellular uptake. The design of trifunctional conjugates 1a and 1b is based on the specific RNA-recognizing properties of PNA, the RNA-cleaving abilities of diethylenetriamine (DETA), and the peptide (KFF)(3)K for potential uptake into E. coli. The conjugates were assembled in a convergent synthetic route involving native chemical ligation of a PNA, containing an N-terminal cysteine, with the C-terminal thioester of the cell-penetrating (KFF)(3)K peptide to give 12a and 12b. These hybrids contained a free cysteine side-chain, which was further functionalized with an RNA-hydrolyzing diethylenetriamine (DETA) moiety. The trifunctional conjugates (1a, 1b) were evaluated for RNA-cleaving properties in vitro and showed efficient degradation of the target RNA at two major cleavage sites. It was also established that the cleavage efficiency strongly depended on the type of spacer connecting the PNA and the peptide.

Real-time monitoring of caspase cascade activation in living cells.

Science.gov (United States)

Zhu, Lei; Huang, Xinglu; Choi, Ki Young; Ma, Ying; Zhang, Fan; Liu, Gang; Lee, Seulki; Chen, Xiaoyuan

2012-10-10

We introduce a simple, versatile and robust one-step technique that enables real-time imaging of multiple intracellular caspase activities in living cells without the need for complicated synthetic protocols. Conventional fluorogenic probes or recently reported activatable probes have been designed to target various proteases but are limited to extracellular molecules. Only a few have been applied to image intracellular proteases in living cells because most of these probes have limited cell-permeability. Our platform does not need complicated synthetic processes; instead it involves a straightforward peptide synthesis and a simple mixing step with a commercial transfection agent. The transfection agent efficiently delivered the highly quenched fluorogenic probes, comprised of distinctive pairs of dyes and quenchers, to the initiator caspase-8 and the effector caspase-3 in MDA-MB-435 cells, allowing dual-imaging of the activities of both caspases during the apoptotic process induced by TNF-related apoptosis induced ligand (TRAIL). With the combination of multiple fluorogenic probes, this simple platform can be applied to multiplexed imaging of selected intracellular proteases to study apoptotic processes in pathologies or for cell-based high throughput screening systems for drug discovery. Published by Elsevier B.V.

The market penetration of energy-efficiency programs

Energy Technology Data Exchange (ETDEWEB)

Berry, L.

1990-04-01

The focus of this report is on one source of resource planning uncertainty: the expected market penetration of DSM (Demand Site Management) programs. Its purpose is to help refine planning assumptions and reduce uncertainty about the market penetration of utility DSM programs by: (1) investigating concepts and definitions of market penetration, (2) reviewing data that characterize patterns of variation (including ranges, averages and maximum levels) in program participation rates, (3) identifying the factors that affect participation, and (4) reviewing the structure and data requirements of models that forecast market penetration. 84 refs., 14 figs., 16 tabs.

Real-Time Penetrating Particle Analyzer (PAN)

Science.gov (United States)

Wu, X.; Ambrosi, G.; Bertucci, B.

2018-02-01

The PAN can measure penetrating particles with great precision to study energetic particles, solar activities, and the origin and propagation of cosmic rays. The real-time monitoring of penetrating particles is crucial for deep space human travel.

Control of penetration zone GMAW

Directory of Open Access Journals (Sweden)

Віталій Петрович Iванов

2016-11-01

Full Text Available Thermal properties of the base metal, shielding medium and the nature of the electrode metal transfer to a great extent determine the penetration area formation in gas-arc welding. It is not always possible to take into account the influence of these factors on penetration front forming within the existing models. The aim of the work was to research the penetration area forming in gas-arc welding. The research of the penetration area forming in gas-arc welding of CrNi austenitic steels was made. The parameters of the regime as well as the kind of the gaseous medium influence on the formation of the penetration zone were studied. The article shows a linear proportional relationship between the electrode feed rate and the size of the base metal plate. The penetration area formation mode for welding in argon and carbon dioxide have been worked out. Diameter, feed rate and the speed of the electrode movement have been chosen as the main input parameters. Multiple regression analysis method was used to make up the modes. The relations of the third order that make it possible to take into account the electrode metal transfer and thermal properties change of the materials to be welded were used. These relationships show quite good agreement with the experimental measurements in the calculation of the fusion zone shape with consumable electrode in argon and carbon dioxide. It was determined that the shape of the melting front curve can be shown as a generalized function in which the front motion parameters depend on feed rate and the diameter of the electrode. Penetration zone growth time is determined by the welding speed and is calculated as a discrete function of the distance from the electrode with the spacing along the movement coordinate. The influence of the mode parameters on the formation of the fusion zone has been investigated and the ways to manage and stabilize the weld pool formation have been identified. The modes can be used to develop

Development of penetrant materials from used oil

International Nuclear Information System (INIS)

Mohamad Pauzi Ismail; Azhar Azmi

2014-01-01

This paper described the results of experiment to produce penetrant for nondestructive testing using used engine oil. The used engine oil was obtained from motor vehicle. It was mixed with kerosene at several mix proportion. The penetrability of these mixing were measured and compared with the penetrant available on the market. The results of measurement were explained and discussed. (author)

Selective Nonoperative Management of Penetrating Abdominal Solid Organ Injuries

Science.gov (United States)

Demetriades, Demetrios; Hadjizacharia, Pantelis; Constantinou, Costas; Brown, Carlos; Inaba, Kenji; Rhee, Peter; Salim, Ali

2006-01-01

Objective: To assess the feasibility and safety of selective nonoperative management in penetrating abdominal solid organ injuries. Background: Nonoperative management of blunt abdominal solid organ injuries has become the standard of care. However, routine surgical exploration remains the standard practice for all penetrating solid organ injuries. The present study examines the role of nonoperative management in selected patients with penetrating injuries to abdominal solid organs. Patients and Methods: Prospective, protocol-driven study, which included all penetrating abdominal solid organ (liver, spleen, kidney) injuries admitted to a level I trauma center, over a 20-month period. Patients with hemodynamic instability, peritonitis, or an unevaluable abdomen underwent an immediate laparotomy. Patients who were hemodynamically stable and had no signs of peritonitis were selected for further CT scan evaluation. In the absence of CT scan findings suggestive of hollow viscus injury, the patients were observed with serial clinical examinations, hemoglobin levels, and white cell counts. Patients with left thoracoabdominal injuries underwent elective laparoscopy to rule out diaphragmatic injury. Outcome parameters included survival, complications, need for delayed laparotomy in observed patients, and length of hospital stay. Results: During the study period, there were 152 patients with 185 penetrating solid organ injuries. Gunshot wounds accounted for 70.4% and stab wounds for 29.6% of injuries. Ninety-one patients (59.9%) met the criteria for immediate operation. The remaining 61 (40.1%) patients were selected for CT scan evaluation. Forty-three patients (28.3% of all patients) with 47 solid organ injuries who had no CT scan findings suspicious of hollow viscus injury were selected for clinical observation and additional laparoscopy in 2. Four patients with a “blush” on CT scan underwent angiographic embolization of the liver. Overall, 41 patients (27

Development of coring, consolidating, subterrene penetrators

International Nuclear Information System (INIS)

Murphy, H.D.; Neudecker, J.W.; Cort, G.E.; Turner, W.C.; McFarland, R.D.; Griggs, J.E.

1976-02-01

Coring penetrators offer two advantages over full face-melting penetrators, i.e., formation of larger boreholes with no increase in power and the production of glass-lined, structurally undisturbed cores which can be recovered with conventional core-retrieval systems. These cores are of significant value in geological exploratory drilling programs. The initial design details and fabrication features of a 114-mm-diam coring penetrator are discussed; significant factors for design optimization are also presented. Results of laboratory testing are reported and compared with performance predictions, and an initial field trial is described

Penetration of lycopsamine from a comfrey ointment through human epidermis.

Science.gov (United States)

Jedlinszki, Nikoletta; Balázs, Boglárka; Csányi, Erzsébet; Csupor, Dezső

2017-02-01

Mutagenic and teratogenic pyrrolizidine alkaloids (PAs) have been identified in several plant species. The industrially most important PA-containing plant is Symphytum officinale (common comfrey). The application of its root is restricted in several countries due to its PA content. In medicines, the daily alkaloid quantity and duration of treatment may be limited even in case of topical application. Due to the confirmed good absorption of PAs from the gastrointestinal tract, the prohibition of oral use is justified, however the limitation of external application is not supported by relevant data. Penetration experiments on human skin are not available to be a rational basis for limitation. The aim of our work was to carry out pharmacokinetic studies on the diffusion and penetration of lycopsamine (a main PA of comfrey) from a Symphytum product through a synthetic membrane and human skin. Investigations were carried out on vertical Franz diffusion cell and lycopsamine was quantified by a validated LC-MS method. The amount of lycopsamine diffused through a synthetic membrane varied between 0.11% and 0.72% (within 24 h). On human epidermis, the rate of penetration was lower (0.04-0.22%). Our results may contribute to the more realistic toxicological assessment of externally applied PA-containing products. Copyright © 2016 Elsevier Inc. All rights reserved.

Two methodologies for physical penetration testing using social engineering

NARCIS (Netherlands)

Dimkov, T.; van Cleeff, A.; Pieters, Wolter; Hartel, Pieter H.

2010-01-01

Penetration tests on IT systems are sometimes coupled with physical penetration tests and social engineering. In physical penetration tests where social engineering is allowed, the penetration tester directly interacts with the employees. These interactions are usually based on deception and if not

Effect of a Fusion Peptide by Covalent Conjugation of a Mitochondrial Cell-Penetrating Peptide and a Glutathione Analog Peptide

Directory of Open Access Journals (Sweden)

Carmine Pasquale Cerrato

2017-06-01

Full Text Available Previously, we designed and synthesized a library of mitochondrial antioxidative cell-penetrating peptides (mtCPPs superior to the parent peptide, SS31, to protect mitochondria from oxidative damage. A library of antioxidative glutathione analogs called glutathione peptides (UPFs, exceptional in hydroxyl radical elimination compared with glutathione, were also designed and synthesized. Here, a follow-up study is described, investigating the effects of the most promising members from both libraries on reactive oxidative species scavenging ability. None of the peptides influenced cell viability at the concentrations used. Fluorescence microscopy studies showed that the fluorescein-mtCPP1-UPF25 (mtgCPP internalized into cells, and spectrofluorometric analysis determined the presence and extent of peptide into different cell compartments. mtgCPP has superior antioxidative activity compared with mtCPP1 and UPF25 against H2O2 insult, preventing ROS formation by 2- and 3-fold, respectively. Moreover, we neither observed effects on mitochondrial membrane potential nor production of ATP. These data indicate that mtgCPP is targeting mitochondria, protecting them from oxidative damage, while also being present in the cytosol. Our hypothesis is based on a synergistic effect resulting from the fused peptide. The mitochondrial peptide segment is targeting mitochondria, whereas the glutathione analog peptide segment is active in the cytosol, resulting in increased scavenging ability.

Assessing the credibility of diverting through containment penetrations

International Nuclear Information System (INIS)

Cooley, J.N.; Swindle, D.W. Jr.

1980-01-01

A viable approach has been developed for identifying those containment penetrations in a nuclear fuel reprocessing plant which are credible diversion routes. The approach is based upon systematic engineering and design analyses and is applied to each type of penetration to determine which penetrations could be utilized to divert nuclear material from a reprocessing facility. The approach is described and the results of an application are discussed. In addition, the concept of credibility is developed and discussed. For a typical reprocessing plant design, the number of penetrations determined to be credible without process or piping modifications was approx. 16% of the penetrations originally identified

Quasi-relativistic effects in barrier-penetration processes

International Nuclear Information System (INIS)

Anchishkin, D.V.

1991-01-01

The problem of a particle tunneling through the potential barrier is solved within quasi-relativistic Schroedinger equation. It is shown that the subbarrier relativistic effects give a significant addition to penetration coefficient when some relations between parameters of the barrier and mass of a tunneling particle are satisfied. For instance an account of these effects for penetration of low energy π + -mesons through Coulomb barrier of the 298 U nuclei would give the increasing of penetration coefficient to 30 percent as compared to the nonrelativistic one. Also we give the criteria under which the contribution of the ''under barrier relativism'' to penetration coefficient becomes essential. 3 refs.; 6 figs. (author)

Impact of location on outcome after penetrating colon injuries.

Science.gov (United States)

Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Zarzaur, Ben L; Shahan, Charles P; Parks, Nancy A; Fabian, Timothy C; Croce, Martin A

2012-12-01

Most studies examining suture line failure after penetrating colon injuries have focused on right- versus left-sided injuries. In our institution, operative decisions (resection plus anastomosis vs. diversion) are based on a defined management algorithm regardless of injury location. The purpose of this study was to evaluate the effect of injury location on outcomes after penetrating colon injuries. Consecutive patients with full thickness penetrating colon injuries for 13 years were stratified by age, injury location and mechanism, and severity of shock. According to the algorithm, patients with nondestructive injuries underwent primary repair. Destructive wounds underwent resection plus anastomosis in the absence of comorbidities or large preoperative or intraoperative transfusion requirements (>6 U of packed red blood cells); otherwise, they were diverted. Injury location was defined as ascending, transverse, descending (including splenic flexure), and sigmoid. Multivariable logistic regression was performed to determine whether injury location was an independent predictor of either morbidity or mortality. Four hundred sixty-nine patients were identified: 314 (67%) underwent primary repair and 155 (33%) underwent resection. Most injuries involved the transverse colon (39%), followed by the ascending colon (26%), the descending colon (21%), and the sigmoid colon (14%). Overall, there were 13 suture line failures (3%) and 72 abscesses (15%). Most suture line failures involved injuries to the descending colon (p = 0.06), whereas most abscesses followed injuries to the ascending colon (p = 0.37). Multivariable logistic regression failed to identify injury location as an independent predictor of either morbidity or mortality after adjusting for 24-hour transfusions, base excess, shock index, injury mechanism, and operative management. Injury location did not affect morbidity or mortality after penetrating colon injuries. Nondestructive injuries should be primarily

Thyroid Emphysema Following Penetrating Neck Trauma

Directory of Open Access Journals (Sweden)

Demet Karadağ

2011-03-01

Full Text Available Although traumatic thyroid gland rupture or hemorrhage is usually seen in goitrous glands, injuries of the normal thyroid gland after neck trauma have rarely been described in the literature. We describe a 44-year-old man who presented with thyroid emphysema and subcutaneous emphysema (SCE that occurred after penetrating neck trauma. CT images showed complete resolution of thyroid emphysema and subcutaneous emphysema at follow-up examination. Neck injuries can be life threatening. After penetrating neck traumas, physicians should consider subtle esophageal or tracheal laceration. Thyroid emphysema can occur as the result of penetrating neck trauma. The mechanism of emphysema of the thyroid parenchyma can be explained by the thyroid gland’s presence in a single visceral compartment that encompasses the larynx, trachea and thyroid gland. We describe an unusual case of thyroid emphysema of a normal thyroid gland following a penetrating neck injury.

Crack growth rates in vessel head penetration materials

International Nuclear Information System (INIS)

Gomez Briceno, D.; Lapena, J.; Blazquez, F.

1994-01-01

The cracks detected in reactor vessel head penetrations in certain European plants have been attributed to Primary Water Stress Corrosion Cracking (PWSCC). The penetrations in question are made from Inconel 600. The susceptibility of this alloy to PWSCC has been widely studied in relation to use of this material for steam generator tubes. When the first reactor vessel head penetration cracks were detected, most of the available data on crack propagation rates were from test specimens made from steam generator tubes and tested under conditions that questioned the validity of these data for assessment of the evolution of cracks in penetrations. For this reason, the scope of the Spanish Research Project on the Inspection and Repair of PWR reactor vessel head penetrations included the acquisition of data on crack propagation rates in Inconel 600, representative of the materials used for vessel head penetrations. (authors). 1 fig., 2 tabs., 6 refs

The potent antimicrobial properties of cell penetrating peptide-conjugated silver nanoparticles with excellent selectivity for gram-positive bacteria over erythrocytes.

Science.gov (United States)

Liu, Lihong; Yang, Jun; Xie, Jianping; Luo, Zhentao; Jiang, Jiang; Yang, Yi Yan; Liu, Shaomin

2013-05-07

Silver nanoparticles are of great interest for use as antimicrobial agents. Studies aimed at producing potent nano-silver biocides have focused on manipulation of particle size, shape, composition and surface charge. Here, we report the cell penetrating peptide catalyzed formation of antimicrobial silver nanoparticles in N,N-dimethylformamide. The novel nano-composite demonstrated a distinctly enhanced biocidal effect toward bacteria (gram-positive Bacillus subtilis, gram-negative Escherichia coli) and pathogenic yeast (Candida albicans), as compared to triangular and extremely small silver nanoparticles. In addition, a satisfactory biocompatibility was verified by a haemolysis test. Our results provide a paradigm in developing strategies that can maximize the silver nanoparticle application potentials while minimizing the toxic effects.

Penetration of Photovoltaics in Greece

OpenAIRE

Eugenia Giannini; Antonia Moropoulou; Zacharias Maroulis; Glykeria Siouti

2015-01-01

Recently, an interesting experiment was completed in Greece concerning photovoltaic penetration into the electricity production sector. Based on the relevant laws and in accordance to the related European directives, an explosive penetration process was completed in less than three years, resulting in a 7% share of photovoltaics in electricity production instead of the previous negligible share. The legislation was based on licensing simplification and generous feed-in-tariffs. This approach ...

Recursive Monte Carlo method for deep-penetration problems

International Nuclear Information System (INIS)

Goldstein, M.; Greenspan, E.

1980-01-01

The Recursive Monte Carlo (RMC) method developed for estimating importance function distributions in deep-penetration problems is described. Unique features of the method, including the ability to infer the importance function distribution pertaining to many detectors from, essentially, a single M.C. run and the ability to use the history tape created for a representative region to calculate the importance function in identical regions, are illustrated. The RMC method is applied to the solution of two realistic deep-penetration problems - a concrete shield problem and a Tokamak major penetration problem. It is found that the RMC method can provide the importance function distributions, required for importance sampling, with accuracy that is suitable for an efficient solution of the deep-penetration problems considered. The use of the RMC method improved, by one to three orders of magnitude, the solution efficiency of the two deep-penetration problems considered: a concrete shield problem and a Tokamak major penetration problem. 8 figures, 4 tables

penetrating abdominal trauma

African Journals Online (AJOL)

gender, mechanism of injury, injury severity scores (ISS), penetrating ... ileus, reduced pulmonary function and loss of muscle mass and function, all of .... pathophysiology and rehabilitation. ... quality of life after surgery for colorectal cancer.

Effect of Different Skin Penetration Promoters in Halobetasol Propionate Permeation and Retention in Human Skin

Directory of Open Access Journals (Sweden)

Paulina Carvajal-Vidal

2017-11-01

Full Text Available Halobetasol propionate (HB is a potent synthetic corticosteroid used against inflammatory skin diseases, such as dermatitis, eczema, and psoriasis, among others. The aim of this study is to define how the presence of different skin penetration enhancers (nonane, menthone, limonene, azone, carene, decanol, linoleic acid and cetiol affects the penetration and retention in skin of HB. To determine drug penetration through skin, 5% of each promoter was used in an ex vivo system with human skin on Franz cells. The results showed that the highest permeation occurs in the presence of menthone, followed by nonane. Permeation parameters were determined. The in vivo test was assessed, and the formulation containing HB-menthone presented better anti-inflammatory efficacy. These results are useful to generate a specific treatment according to each patient’s needs, and the inflammatory characteristics of the disease.

Tumor tissue slice cultures as a platform for analyzing tissue-penetration and biological activities of nanoparticles.

Science.gov (United States)

Merz, Lea; Höbel, Sabrina; Kallendrusch, Sonja; Ewe, Alexander; Bechmann, Ingo; Franke, Heike; Merz, Felicitas; Aigner, Achim

2017-03-01

The success of therapeutic nanoparticles depends, among others, on their ability to penetrate a tissue for actually reaching the target cells, and their efficient cellular uptake in the context of intact tissue and stroma. Various nanoparticle modifications have been implemented for altering physicochemical and biological properties. Their analysis, however, so far mainly relies on cell culture experiments which only poorly reflect the in vivo situation, or is based on in vivo experiments that are often complicated by whole-body pharmacokinetics and are rather tedious especially when analyzing larger nanoparticle sets. For the more precise analysis of nanoparticle properties at their desired site of action, efficient ex vivo systems closely mimicking in vivo tissue properties are needed. In this paper, we describe the setup of organotypic tumor tissue slice cultures for the analysis of tissue-penetrating properties and biological activities of nanoparticles. As a model system, we employ 350μm thick slice cultures from different tumor xenograft tissues, and analyze modified or non-modified polyethylenimine (PEI) complexes as well as their lipopolyplex derivatives for siRNA delivery. The described conditions for tissue slice preparation and culture ensure excellent tissue preservation for at least 14days, thus allowing for prolonged experimentation and analysis. When using fluorescently labeled siRNA for complex visualization, fluorescence microscopy of cryo-sectioned tissue slices reveals different degrees of nanoparticle tissue penetration, dependent on their surface charge. More importantly, the determination of siRNA-mediated knockdown efficacies of an endogenous target gene, the oncogenic survival factor Survivin, reveals the possibility to accurately assess biological nanoparticle activities in situ, i.e. in living cells in their original environment. Taken together, we establish tumor (xenograft) tissue slices for the accurate and facile ex vivo assessment of

Cellular Reprogramming Using Protein and Cell-Penetrating Peptides

Directory of Open Access Journals (Sweden)

Bong Jong Seo

2017-03-01

Full Text Available Recently, stem cells have been suggested as invaluable tools for cell therapy because of their self-renewal and multilineage differentiation potential. Thus, scientists have developed a variety of methods to generate pluripotent stem cells, from nuclear transfer technology to direct reprogramming using defined factors, or induced pluripotent stem cells (iPSCs. Considering the ethical issues and efficiency, iPSCs are thought to be one of the most promising stem cells for cell therapy. Induced pluripotent stem cells can be generated by transduction with a virus, plasmid, RNA, or protein. Herein, we provide an overview of the current technology for iPSC generation and describe protein-based transduction technology in detail.

Characterization of nuclear reactor containment penetrations. Preliminary report

International Nuclear Information System (INIS)

Bump, T.R.; Seidensticker, R.W.; Shackelford, M.A.; Gambhir, V.K.; McLennan, G.L.

1984-06-01

This report summarizes the survey work conducted by Argonne National Laboratory on the design and details of major penetrations in 22 nuclear power plants. The survey includes all containment types and materials in current use. It also includes details of all types of penetrations (except for electrical penetration assemblies and valves) and the seals and gaskets used in them. The report provides a test matrix for testing major penetrations and for testing seals and gaskets in order to evaluate their leakage potential under severe accident conditions

Penetration of UV-B radiation in foliage: evidence that the epidermis behaves as a non-uniform filter

International Nuclear Information System (INIS)

Day, T.A.; Martin, G.; Vogelmann, T.C.

1993-01-01

In some plants, particularly herbaceous species, a considerable proportion of incident ultraviolet-B radiation (UV-B, 280-320 nm) penetrates into the leaf mesophyll where it is potentially damaging to nucleic acids and the photosynthetic machinery. We used optical techniques to look at the spatial variation in UV-B penetration through the epidermis of foliage of two herbaceous species (Chenopodium album and Smilacina stellata) and a conifer (Picea pungens). Measurements of UV-B penetration in intact foliage with a fibre-optic microprobe revealed that 300 nm radiation reached 161±36μm (mean±SD) into leaves of C. album, 154±40μm in S. stellata and 17±2μm in P. pungens, with epidermal transmittance being 39±14%, 55±19% and 0%, respectively. A thin polymer film was developed which fluoresced blue when irradiated by UV-B. Fresh epidermal leaf peels were placed over the film and irradiated with UV-B, and microscopic examination of the film from below allowed us to determine the spatial pattern of UV-B penetration through the epidermis. In herbaceous species, film fluorescence below cell walls, but not epidermal and guard cell protoplasts indicated that UV-B transmittance was much greater through anticlinal cell wall regions than protoplasts. Ultraviolet-B transmittance through large areas of epidermal cells could be induced by plasmolysis. Epidermal transmittance was also relatively high through stomal pores (and what appear to be nuclei in Smilacina), but relatively low through stomatal guard cells. Results from the fluorescing film technique were substantiated by direct measurements of UV-B transmittance through epidermal peels with a fibre-optic microprobe run paradermally along the bottom or inner side of irradiated peels. In Smilacina, we estimate that UV-B epidermal transmittance was up to 90% through anticlinal cell wall regions, but <10% through protoplast areas. In contrast to herbaceous species, we did not detect any UV-B transmittance through the

Sorting white blood cells in microfabricated arrays

Science.gov (United States)

Castelino, Judith Andrea Rose

Fractionating white cells in microfabricated arrays presents the potential for detecting cells with abnormal adhesive or deformation properties. A possible application is separating nucleated fetal red blood cells from maternal blood. Since fetal cells are nucleated, it is possible to extract genetic information about the fetus from them. Separating fetal cells from maternal blood would provide a low cost noninvasive prenatal diagnosis for genetic defects, which is not currently available. We present results showing that fetal cells penetrate further into our microfabricated arrays than adult cells, and that it is possible to enrich the fetal cell fraction using the arrays. We discuss modifications to the array which would result in further enrichment. Fetal cells are less adhesive and more deformable than adult white cells. To determine which properties limit penetration, we compared the penetration of granulocytes and lymphocytes in arrays with different etch depths, constriction size, constriction frequency, and with different amounts of metabolic activity. The penetration of lymphocytes and granulocytes into constrained and unconstrained arrays differed qualitatively. In constrained arrays, the cells were activated by repeated shearing, and the number of cells stuck as a function of distance fell superexponentially. In unconstrained arrays the number of cells stuck fell slower than an exponential. We attribute this result to different subpopulations of cells with different sticking parameters. We determined that penetration in unconstrained arrays was limited by metabolic processes, and that when metabolic activity was reduced penetration was limited by deformability. Fetal cells also contain a different form of hemoglobin with a higher oxygen affinity than adult hemoglobin. Deoxygenated cells are paramagnetic and are attracted to high magnetic field gradients. We describe a device which can separate cells using 10 μm magnetic wires to deflect the paramagnetic

40 CFR 1065.365 - Nonmethane cutter penetration fractions.

Science.gov (United States)

2010-07-01

... fractions. 1065.365 Section 1065.365 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Measurements § 1065.365 Nonmethane cutter penetration fractions. (a) Scope and frequency. If you use a FID... penetration fractions of methane, PFCH4, and ethane, PF C2H6. As detailed in this section, these penetration...

The penetration of aerosols through fine orifices

International Nuclear Information System (INIS)

Marshall, I.A.; Latham, L.J.; Ball, M.H.E.; Mitchell, J.P.

1991-07-01

A novel experimental technique has been extended to study the migration of gas-borne glass microspheres in the size range from about 1 to 15 μm volume equivalent diameter through orifices with bores and thicknesses in the range from 2 to 100 μm and 12.7 to 509 μm respectively. The penetration of these particles was significant with all orifices greater than 10 μm bore at a constant driving pressure of 100 kPa. However, few particles penetrated the 5 μm bore orifice, while virtually no particles penetrated the 2 μm bore orifice. Particle size distributions determined after penetration through the orifices were very similar to that of the upstream aerosol except when significant attenuation occurred. (author)

Temporary fire sealing of penetrations on TFTR

International Nuclear Information System (INIS)

Hondorp, H.L.

1981-02-01

The radiation shielding provided for TFTR for D-D and D-T operation will be penetrated by numerous electrical and mechanical services. Eventually, these penetrations will have to be sealed to provide the required fire resistance, tritium sealability, pressure integrity and radiation attenuation. For the initial hydrogen operation, however, fire sealing of the penetrations in the walls and floor is the primary concern. This report provides a discussion of the required and desirable properties of a temporary seal which can be used to seal these penetrations for the hydrogen operation and then subsequently be removed and replaced as required for the D-D and D-T operations. Several candidate designs are discussed and evaluated and recommendations are made for specific applications

Miniature Ground Penetrating Radar, CRUX GPR

Science.gov (United States)

Kim, Soon Sam; Carnes, Steven R.; Haldemann, Albert F.; Ulmer, Christopher T.; Ng, Eddie; Arcone, Steven A.

2006-01-01

Under NASA instrument development programs (PIDDP 2000-2002, MIPD 2003-2005, ESR and T, 2005) we have been developing miniature ground penetrating radars (GPR) for use in mapping subsurface stratigraphy from planetary rovers for Mars and lunar applications. The Mars GPR is for deeper penetration (up to 50 m depth) into the Martian subsurface at moderate resolution (0.5 m) for a geological characterization. As a part of the CRUX (Construction and Resource Utilization Explorer) instrument suite, the CRUX GPR is optimized for a lunar prospecting application. It will have shallower penetration (5 m depth) with higher resolution (10 cm) for construction operations including ISRU (in-situ resource utilization).

Building virtual pentesting labs for advanced penetration testing

CERN Document Server

Cardwell, Kevin

2014-01-01

Written in an easy-to-follow approach using hands-on examples, this book helps you create virtual environments for advanced penetration testing, enabling you to build a multi-layered architecture to include firewalls, IDS/IPS, web application firewalls, and endpoint protection, which is essential in the penetration testing world. If you are a penetration tester, security consultant, security test engineer, or analyst who wants to practice and perfect penetration testing skills by building virtual pen testing labs in varying industry scenarios, this is the book for you. This book is ideal if yo

Cell penetration to nanofibrous scaffolds

Czech Academy of Sciences Publication Activity Database

Rampichová, Michala; Buzgo, Matej; Chvojka, J.; Prosecká, Eva; Kofroňová, Olga; Amler, Evžen

2014-01-01

Roč. 8, č. 1 (2014), s. 36-41 ISSN 1933-6918 Grant - others:GA UK(CZ) 384311; GA UK(CZ) 626012; GA UK(CZ) 270513; GA UK(CZ) 330611; GA UK(CZ) 648112; GA MZd(CZ) NT12156; GA MŠk(CZ) project IPv6 Institutional support: RVO:68378041 ; RVO:61388971 Keywords : fibrous scaffold * mesenchymal stem cells * Forcespinning (R) Subject RIV: FP - Other Medical Disciplines Impact factor: 4.505, year: 2014

Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

Science.gov (United States)

Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

2014-03-01

The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into

Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.

Science.gov (United States)

Richardson, Adam; Muir, Lewis; Mousdell, Sasha; Sexton, Darren; Jones, Sarah; Howl, John; Ross, Kehinde

2018-01-30

Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis. In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L -1 , MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes.

Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides

KAUST Repository

Rydberg, Hanna A.; Matson, Maria; Å mand, Helene L.; Esbjö rner, Elin K.; Nordé n, Bengt

2012-01-01

Cell-penetrating peptides (CPPs) are able to traverse cellular membranes and deliver macromolecular cargo. Uptake occurs through both endocytotic and nonendocytotic pathways, but the molecular requirements for efficient internalization are not fully understood. Here we investigate how the presence of tryptophans and their position within an oligoarginine influence uptake mechanism and efficiency. Flow cytometry and confocal fluorescence imaging are used to estimate uptake efficiency, intracellular distribution and toxicity in Chinese hamster ovarian cells. Further, membrane leakage and lipid membrane affinity are investigated. The peptides contain eight arginine residues and one to four tryptophans, the tryptophans positioned either at the N-terminus, in the middle, or evenly distributed along the amino acid sequence. Our data show that the intracellular distribution varies among peptides with different tryptophan content and backbone spacing. Uptake efficiency is higher for the peptides with four tryptophans in the middle, or evenly distributed along the peptide sequence, than for the peptide with four tryptophans at the N-terminus. All peptides display low cytotoxicity except for the one with four tryptophans at the N-terminus, which was moderately toxic. This finding is consistent with their inability to induce efficient leakage of dye from lipid vesicles. All peptides have comparable affinities for lipid vesicles, showing that lipid binding is not a decisive parameter for uptake. Our results indicate that tryptophan content and backbone spacing can affect both the CPP uptake efficiency and the CPP uptake mechanism. The low cytotoxicity of these peptides and the possibilities of tuning their uptake mechanism are interesting from a therapeutic point of view. © 2012 American Chemical Society.

Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides

KAUST Repository

Rydberg, Hanna A.

2012-07-10

Cell-penetrating peptides (CPPs) are able to traverse cellular membranes and deliver macromolecular cargo. Uptake occurs through both endocytotic and nonendocytotic pathways, but the molecular requirements for efficient internalization are not fully understood. Here we investigate how the presence of tryptophans and their position within an oligoarginine influence uptake mechanism and efficiency. Flow cytometry and confocal fluorescence imaging are used to estimate uptake efficiency, intracellular distribution and toxicity in Chinese hamster ovarian cells. Further, membrane leakage and lipid membrane affinity are investigated. The peptides contain eight arginine residues and one to four tryptophans, the tryptophans positioned either at the N-terminus, in the middle, or evenly distributed along the amino acid sequence. Our data show that the intracellular distribution varies among peptides with different tryptophan content and backbone spacing. Uptake efficiency is higher for the peptides with four tryptophans in the middle, or evenly distributed along the peptide sequence, than for the peptide with four tryptophans at the N-terminus. All peptides display low cytotoxicity except for the one with four tryptophans at the N-terminus, which was moderately toxic. This finding is consistent with their inability to induce efficient leakage of dye from lipid vesicles. All peptides have comparable affinities for lipid vesicles, showing that lipid binding is not a decisive parameter for uptake. Our results indicate that tryptophan content and backbone spacing can affect both the CPP uptake efficiency and the CPP uptake mechanism. The low cytotoxicity of these peptides and the possibilities of tuning their uptake mechanism are interesting from a therapeutic point of view. © 2012 American Chemical Society.

Lipid peroxidation and water penetration in lipid bilayers

DEFF Research Database (Denmark)

Conte, Elena; Megli, Francesco Maria; Khandelia, Himanshu

2012-01-01

to the hydroperoxide groups to interact with the nitroxide at the methyl-terminal, confirming that the H-bonds experimentally observed are due to increased water penetration in the bilayer. The EPR and MD data on model membranes demonstrate that cell membrane damage by oxidative stress cause alteration of water......(zz) parameters revealed that OHPLPC, but mostly HpPLPC, induced a measurable increase in polarity and H-bonding propensity in the central region of the bilayer. Molecular dynamics simulation performed on 16-DSA in the PLPC-HpPLPC bilayer revealed that water molecules are statistically favored with respect...

Chronic Disease Prevalence and Medicare Advantage Market Penetration

Science.gov (United States)

Bernell, Stephanie Lazarus; Casim, Faizan M.; Wilmott, Jennifer; Pearson, Lindsey; Byler, Caitlin M.; Zhang, Zidong

2015-01-01

By March 2015, 30% of all Medicare beneficiaries were enrolled in Medicare Advantage (MA) plans. Research to date has not explored the impacts of MA market penetration on individual or population health outcomes. The primary objective of this study is to examine the relationships between MA market penetration and the beneficiary’s portfolio of cardiometabolic diagnoses. This study uses 2004 to 2008 Medical Expenditure Panel Survey (MEPS) Household Component data to construct an aggregate index that captures multiple diagnoses in one outcome measure (Chronic Disease Severity Index [CDSI]). The MEPS data for 8089 Medicare beneficiaries are merged with MA market penetration data from Centers for Medicare and Medicaid Services (CMS). Ordinary least squares regressions are run with SAS 9.3 to model the effects of MA market penetration on CDSI. The results suggest that each percentage increase in MA market penetration is associated with a greater than 2-point decline in CDSI (lower burden of cardiometabolic chronic disease). Spill-over effects may be driving improvements in the cardiometabolic health of beneficiary populations in counties with elevated levels of MA market penetration. PMID:28462266

Thermo-chemical Ice Penetrator for Icy Moons

Science.gov (United States)

Arenberg, J. W.; Lee, G.; Harpole, G.; Zamel, J.; Sen, B.; Ross, F.; Retherford, K. D.

2016-12-01

The ability to place sensors or to take samples below the ice surface enables a wide variety of potential scientific investigations. Penetrating an ice cap can be accomplished via a mechanical drill, laser drill, kinetic impactor, or heated penetrator. This poster reports on the development of technology for the latter most option, namely a self-heated probe driven by an exothermic chemical reaction: a Thermo-chemical ice penetrator (TChIP). Our penetrator design employs a eutectic mix of alkali metals that produce an exothermic reaction upon contact with an icy surface. This reaction increases once the ice starts melting, so no external power is required. This technology is inspired by a classified Cold-War era program developed at Northrop Grumman for the US Navy. Terrestrial demonstration of this technology took place in the Arctic; however, this device cannot be considered high TRL for application at the icy moons of the solar system due to the environmental differences between Earth's Arctic and the icy moons. These differences demand a TChIP design specific to these cold, low mass, airless worlds. It is expected that this model of TChIP performance will be complex, incorporating all of the forces on the penetrator, gravity, the thermo-chemistry at the interface between penetrator and ice, and multi-phase heat and mass transport, and hydrodynamics. Our initial efforts are aimed at the development of a validated set of tools and simulations to predict the performance of the penetrator for both the environment found on these icy moons and for a terrestrial environment. The purpose of the inclusion of the terrestrial environment is to aid in model validation. Once developed and validated, our models will allow us to design penetrators for a specific scientific application on a specific body. This poster discusses the range of scientific investigations that are enabled by TChIP. We also introduce the development plan to advance TChIP to the point where it can be

Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides.

Science.gov (United States)

Liu, Betty R; Winiarz, Jeffrey G; Moon, Jong-Sik; Lo, Shih-Yen; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2013-11-01

Semiconductor nanoparticles, also known as quantum dots (QDs), are widely used in biomedical imaging studies and pharmaceutical research. Cell-penetrating peptides (CPPs) are a group of small peptides that are able to traverse cell membrane and deliver a variety of cargoes into living cells. CPPs deliver QDs into cells with minimal nonspecific absorption and toxic effect. In this study, water-soluble, monodisperse, carboxyl-functionalized indium phosphide (InP)/zinc sulfide (ZnS) QDs coated with polyethylene glycol lipids (designated QInP) were synthesized for the first time. The physicochemical properties (optical absorption, fluorescence and charging state) and cellular internalization of QInP and CPP/QInP complexes were characterized. CPPs noncovalently interact with QInP in vitro to form stable CPP/QInP complexes, which can then efficiently deliver QInP into human A549 cells. The introduction of 500nM of CPP/QInP complexes and QInP at concentrations of less than 1μM did not reduce cell viability. These results indicate that carboxylated and polyethylene-glycolylated (PEGylated) bifunctionalized QInP are biocompatible nanoparticles with potential for use in biomedical imaging studies and drug delivery applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Penetration shielding applications of CYLSEC

International Nuclear Information System (INIS)

Dexheimer, D.T.; Hathaway, J.M.

1985-01-01

Evaluation of penetration and discontinuity shielding is necessary to meet 10CFR20 regulations for ensuring personnel exposures are as low as reasonably achievable (ALARA). Historically, those shielding evaluations have been done to some degree on all projects. However, many early plants used conservative methods due to lack of an economical computer code, resulting in costly penetration shielding programs. With the increased industry interest in cost effectively reducing personnel exposures to meet ALARA regulations and with the development of the CYLSEC gamma transport computer code at Bechtel, a comprehensive effort was initiated to reduce penetration and discontinuity shielding but still provide a prudent degree of protection for plant personnel from radiation streaming. This effort was more comprehensive than previous programs due to advances in shielding analysis technology and increased interest in controlling project costs while maintaining personnel exposures ALARA. Methodology and resulting cost savings are discussed

Tretinoin-based formulations - influence of concentration and vehicles on skin penetration

Directory of Open Access Journals (Sweden)

Edileia Bagatin

2015-03-01

Full Text Available Tretinoin is used in the management of acne and it is part of a gold standard treatment for photoaging. It has also been reported as an agent for superficial chemical peeling in highly concentrated formulations with few considerations about skin penetration. The aim of this study was to evaluate the influence of drug concentration and vehicles currently used on skin penetration of tretinoin. In vitro permeation tests were carried out using Franz diffusion cells fitted with porcine ear skin and 10% aqueous methanol in the receptor compartment. Formulations studied, cream or hydroalcoholic dispersion, containing 0.25%, 1% and 5% of tretinoin were placed in the donor compartment for six hours. Tretinoin concentration in skin layers was measured by high performance liquid chromatography. The largest amount of tretinoin from both vehicles was detected in stratum corneum with significant differences among the three concentrations. The hydroalcoholic dispersion was the best vehicle. Significant amounts of tretinoin were found even in deep layers of epidermis. The formulation with 0.25% tretinoin showed better results when considered the amount of tretinoin on skin in terms of percentage. Finally, skin penetration of tretinoin was influenced by vehicle and concentration of this drug used in formulation.

Development Of The Nuclear Optical Penetration

Science.gov (United States)

Inoue, K.; Koike, K.; Imada, Y.

1984-10-01

We have developed the nuclear optical penetration to be incorporated in the wall penetration of the shell to introduce a data transmission system using optical fibers into a nuclear power plant with a pressurized water reactor. Radiation-induced coloration in optical glass seriously affects transmission characteristics of optical fibers, whereas it has been revealed that the pure-silica core optical fiber without any dopant in the core has wide applicability in radiation fields thanks to its very low radiation-induced attenuation. The wall penetration of the shell should have airtightness and resistivity to heat, vibration, and pressure, let alone radiation, excellent enough to be invariable in data transmission efficiency even when subjected to severe environmental tests. The sealing modules of this newly developed nuclear optical penetration are hermetically sealed. The gap between the optical fiber rod (100 pm in core diameter and 5 mm in rod diameter) and stainless steel tube is sealed with lamingted glass layer. As the result of He gas leakage test, high airtightness of less than 10 cc/sec was achieved. No thermal deformation of the core was caused by sealing with laminated glass layer, nor was observed transmission loss. Then the sealiing modules were subjected to the irradiation test using 60 Co gamma ray exposure of 2 x 10 rads. Though silica glass layer supporting the fiber rod and sealing glass portion turned blackish purple, transparency of the fiber was not affected. Only less than 0.5 dB of connecting loss was observed at the connecting point with the optical fiber cable. The sealing modules were also found to have resistivity to vibration and pressure as excellent as that of existing nuclear electric penetrations. We expect the nuclear optical fiber penetration will be much effective in improving reliability of data transmission systems using optical fibers in radiation fields.

Theory of activated penetrant diffusion in viscous fluids and colloidal suspensions

International Nuclear Information System (INIS)

Zhang, Rui; Schweizer, Kenneth S.

2015-01-01

We heuristically formulate a microscopic, force level, self-consistent nonlinear Langevin equation theory for activated barrier hopping and non-hydrodynamic diffusion of a hard sphere penetrant in very dense hard sphere fluid matrices. Penetrant dynamics is controlled by a rich competition between force relaxation due to penetrant self-motion and collective matrix structural (alpha) relaxation. In the absence of penetrant-matrix attraction, three activated dynamical regimes are predicted as a function of penetrant-matrix size ratio which are physically distinguished by penetrant jump distance and the nature of matrix motion required to facilitate its hopping. The penetrant diffusion constant decreases the fastest with size ratio for relatively small penetrants where the matrix effectively acts as a vibrating amorphous solid. Increasing penetrant-matrix attraction strength reduces penetrant diffusivity due to physical bonding. For size ratios approaching unity, a distinct dynamical regime emerges associated with strong slaving of penetrant hopping to matrix structural relaxation. A crossover regime at intermediate penetrant-matrix size ratio connects the two limiting behaviors for hard penetrants, but essentially disappears if there are strong attractions with the matrix. Activated penetrant diffusivity decreases strongly with matrix volume fraction in a manner that intensifies as the size ratio increases. We propose and implement a quasi-universal approach for activated diffusion of a rigid atomic/molecular penetrant in a supercooled liquid based on a mapping between the hard sphere system and thermal liquids. Calculations for specific systems agree reasonably well with experiments over a wide range of temperature, covering more than 10 orders of magnitude of variation of the penetrant diffusion constant

Hacking and penetration testing with low power devices

CERN Document Server

Polstra, Philip

2014-01-01

Hacking and Penetration Testing with Low Power Devices shows you how to perform penetration tests using small, low-powered devices that are easily hidden and may be battery-powered. It shows how to use an army of devices, costing less than you might spend on a laptop, from distances of a mile or more. Hacking and Penetration Testing with Low Power Devices shows how to use devices running a version of The Deck, a full-featured penetration testing and forensics Linux distribution, and can run for days or weeks on batteries due to their low power consumption. Author Philip Polstra shows how to

Penetration, distribution and kinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human skin in vitro

International Nuclear Information System (INIS)

Weber, L.W.D.; Rozman, K.

1991-01-01

The in vitro penetration of 3 H-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into human cadaver skin was studied at concentrations of 65 and 6.5 ng TCDD per cm 2 of skin surface. Vehicles used were acetone to simulate exposure to TCDD as a dry material, and mineral oil to simulate exposure to TCDD in an oily medium. Penetration was performed for 30, 100, 300, and 1000 min in improved Franz cells. Skin was used either intact, or with stripped horny layer. Skin was sectioned along its natural layers and radioactivity determined in epidermis and dermis. TCDD did not readily penetrate into human skin in vitro. The vehicle of exposure to TCDD played an important role in dermal penetration. The rapidly evaporating acetone allowed TCDD to penetrate deeply into the loose surface lamellae of the horny layer, but then appeared to be poorly available for further penetration. Mineral oil as the vehicle showed its penetration even more. The stratum corneum acted as a protective barrier, as its removal increased the amount of TCDD absorbed into layers of the skin. Hourly rates of adsorption of TCDD per unit area of skin were calculated in two ways: a worst case scenario where TCDD absorbed into any layer of skin including the stratum corneum and a physiological approach where only that amount of TCDD was considered absorbed which had penetrated beyond the epidermis. Under worst case scenario conditions the stratum corneum appeared to mediate dermal absorption of TCDD. This was, however, not the case with the physiological approach. There was a consistent relationship between concentration of TCDD applied and concentration of TCDD found in skin. Also, a clear-cut correlation was found between the amount of TCDD that penetrated and the time of exposure. (orig./MG)

Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

Science.gov (United States)

Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

2018-02-01

Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion

International Nuclear Information System (INIS)

Paredes, Angel M.; Ferreira, Davis; Horton, Michelle; Saad, Ali; Tsuruta, Hiro; Johnston, Robert; Klimstra, William; Ryman, Kate; Hernandez, Raquel; Chiu Wah; Brown, Dennis T.

2004-01-01

Alphaviruses have the ability to induce cell-cell fusion after exposure to acid pH. This observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid pH after incorporation into a cell endosome. We have investigated the requirements for the induction of virus-mediated, low pH-induced cell-cell fusion and cell-virus fusion. We have correlated the pH requirements for this process to structural changes they produce in the virus by electron cryo-microscopy. We found that exposure to acid pH was required to establish conditions for membrane fusion but that membrane fusion did not occur until return to neutral pH. Electron cryo-microscopy revealed dramatic changes in the structure of the virion as it was moved to acid pH and then returned to neutral pH. None of these treatments resulted in the disassembly of the virus protein icosahedral shell that is a requisite for the process of virus membrane-cell membrane fusion. The appearance of a prominent protruding structure upon exposure to acid pH and its disappearance upon return to neutral pH suggested that the production of a 'pore'-like structure at the fivefold axis may facilitate cell penetration as has been proposed for polio (J. Virol. 74 (2000) 1342) and human rhino virus (Mol. Cell 10 (2002) 317). This transient structural change also provided an explanation for how membrane fusion occurs after return to neutral pH. Examination of virus-cell complexes at neutral pH supported the contention that infection occurs at the cell surface at neutral pH by the production of a virus structure that breaches the plasma membrane bilayer. These data suggest an alternative route of infection for Sindbis virus that occurs by a process that does not involve membrane fusion and does not require disassembly of the virus protein shell

Enhancement of percutaneous penetration of aniline and o-toluidine in vitro using skin barrier creams.

Science.gov (United States)

Korinth, Gintautas; Lüersen, Lars; Schaller, Karl Heinz; Angerer, Jürgen; Drexler, Hans

2008-04-01

Aniline (ANI) and the human carcinogen o-toluidine (OT) are released at the workplace during the production and processing of rubber. Recently, we showed in rubber industry workers that a frequent use of skin barrier creams (SBC) increased the internal exposure of ANI and OT. In the present study, diffusion cells were used to investigate the effects of two SBC and one skin care cream (SCC) on percutaneous penetration of neat ANI and OT as well as of OT from a mixture with a workplace specific lubricant. The experiments were carried out with untreated and with skin creams treated human skin. A considerable percutaneous penetration enhancement of test compounds was observed for treated skin compared with untreated skin; the highest enhancement (mean factors 6.2-12.3) was found for SBC (based on oil in water emulsion) treated skin. The lowest penetration enhancement showed SCC treated skin (mean factors 4.2-9.7). The in vitro data support our findings in workers that the percutaneous absorption of aromatic amines significantly increases in presence of skin creams. The efficacy of skin creams to protect the percutaneous penetration of aromatic amines is not confirmed by our own experiments.

HMO penetration and the geographic mobility of practicing physicians.

Science.gov (United States)

Polsky, D; Kletke, P R; Wozniak, G D; Escarce, J J

2000-09-01

In this study, we assessed the influence of changes in health maintenance organization (HMO) penetration on the probability that established patient care physicians relocated their practices or left patient care altogether. For physicians who relocated their practices, we also assessed the impact of HMO penetration on their destination choices. We found that larger increases in HMO penetration decreased the probability that medical/surgical specialists in early career stayed in patient care in the same market, but had no impact on generalists, hospital-based specialists, or mid career medical/surgical specialists. We also found that physicians who relocated their practices were much more likely to choose destination markets with the same level of HMO penetration or lower HMO penetration compared with their origin markets than they were to choose destination markets with higher HMO penetration. The largely negligible impact of changes in HMO penetration on established physicians' decisions to relocate their practices or leave patient care is consistent with high relocation and switching costs. Relocating physicians' attraction to destination markets with the same level of HMO penetration as their origin markets suggests that, while physicians' styles of medical practice may adapt to changes in market conditions, learning new practice styles is costly.

Skin Penetration Enhancement by Natural Oils for Dihydroquercetin Delivery.

Science.gov (United States)

Čižinauskas, Vytis; Elie, Nicolas; Brunelle, Alain; Briedis, Vitalis

2017-09-12

Natural oils are commonly used in topical pharmaceutical formulations as emulsifiers, stabilizers or solubility enhancers. They are presented as safe and inert components, mainly used for formulation purposes. It is confirmed that natural oils can affect the skin penetration of various substances. Fatty acids are mainly responsible for this effect. Current understanding lacks reliable scientific data on penetration of natural oils into the skin and their skin penetration enhancement potential. In the current study, fatty acid content analysis was used to determine the principal fatty acids in soybean, olive, avocado, sea-buckthorn pulp, raspberry seed and coconut oils. Time of flight secondary ion mass spectrometry bioimaging was used to determine the distribution of these fatty acids in human skin ex vivo after application of the oils. Skin penetration enhancement ratios were determined for a perspective antioxidant compound dihydroquercetin. The results demonstrated skin penetration of fatty acids from all oils tested. Only soybean and olive oils significantly increased the skin distribution of dihydroquercetin and can be used as skin penetration enhancers. However, no correlation can be determined between the fatty acids' composition and skin penetration enhancement using currently available methodological approaches. This indicates that potential chemical penetration enhancement should be evaluated during formulation of topically applied products containing natural oils.

A Study on Factors Affecting Airborne LiDAR Penetration

Directory of Open Access Journals (Sweden)

Wei-Chen Hsu

2015-01-01

Full Text Available This study uses data from different periods, areas and parameters of airborne LiDAR (light detection and ranging surveys to understand the factors that influence airborne LiDAR penetration rate. A discussion is presented on the relationships between these factors and LiDAR penetration rate. The results show that the flight height above ground level (AGL does not have any relationship with the penetration rate. There are some factors that should have larger influence. For example, the laser is affected by a wet ground surface by reducing the number of return echoes. The field of view (FOV has a slightly negative correlation with the penetration rate, which indicates that the laser incidence angle close to zero should achieve the best penetration. The vegetation cover rate also shows a negative correlation with the penetration rate, thus bare ground and reduced vegetation in the aftermath of a typhoon also cause high penetration rate. More return echoes could be extracted from the full-waveform system, thereby effectively improving the penetration rate. This study shows that full-waveform LiDAR is an effective method for increasing the number of surface reflected echoes. This study suggests avoiding LiDAR survey employment directly following precipitation to prevent laser echo reduction.

Modification of Salmonella Lipopolysaccharides Prevents the Outer Membrane Penetration of Novobiocin

Energy Technology Data Exchange (ETDEWEB)

Nobre, Thatyane M.; Martynowycz, Michael W.; Andreev, Konstantin; Kuzmenko, Ivan; Nikaido, Hiroshi; Gidalevitz, David

2015-12-01

Small hydrophilic antibiotics traverse the outer membrane of Gram-negative bacteria through porin channels. Large lipophilic agents traverse the outer membrane through its bilayer, containing a majority of lipopolysaccharides in its outer leaflet. Genes controlled by the two-component regulatory system PhoPQ modify lipopolysaccharides. We isolate lipopolysaccharides from isogenic mutants of Salmonella sp., one lacking the modification, the other fully modified. These lipopolysaccharides were reconstituted asmonolayers at the air-water interface, and their properties, aswell as their interaction with a large lipophilic drug, novobiocin, was studied. X-ray reflectivity showed that the drug penetrated the monolayer of the unmodified lipopolysaccharides reaching the hydrophobic region,butwas prevented fromthis penetration intothemodified lipopolysaccharides.Results correlatewith behavior of bacterial cells, which become resistant to antibiotics after PhoPQ-regulated modifications. Grazing incidence x-ray diffraction showed that novobiocin produced a striking increase in crystalline coherence length, and the size of the near-crystalline domains.

Penetration Testing Professional Ethics: a conceptual model and taxonomy

Directory of Open Access Journals (Sweden)

Justin Pierce

2006-05-01

Full Text Available In an environment where commercial software is continually patched to correct security flaws, penetration testing can provide organisations with a realistic assessment of their security posture. Penetration testing uses the same principles as criminal hackers to penetrate corporate networks and thereby verify the presence of software vulnerabilities. Network administrators can use the results of a penetration test to correct flaws and improve overall security. The use of hacking techniques, however, raises several ethical questions that centre on the integrity of the tester to maintain professional distance and uphold the profession. This paper discusses the ethics of penetration testing and presents our conceptual model and revised taxonomy.

Contribution to the penetration of radionuclides across the skin

International Nuclear Information System (INIS)

Koprda, V.; Harangozo, M.; Kassai, Z.

2000-01-01

The human skin as well as the skin of animal species represent a strong barrier against the permeation of ionic forms of substances into an organism. Radionuclides of cesium, cobalt and actinides belong to frequent potential contaminants of human body at an accidental radioactive contamination. Regarding the actual composition of contaminating mixture of radionuclides the damage of an organism after internal contamination is proportional to the extent of penetrated amounts of radionuclides across the skin. In this paper: the time dependence of permeation of 137 Cs + , 60 Co 2+ , and 147 Pm 3+ from aqueous solution through animal skin model was studied, the biologic structure mostly responsible for the barrier effect was selected and proved, the relative importance of the main diffusion pathways for 137 Cs + , 60 Co 2+ and 147 Pm 3+ , the diffusion across the intact skin and the diffusion through the hair channels was assessed, the effect of isotopic carrier on the penetration process was studied, and the retarding capacities of different substances were researched. In all experiments the radioactive tracers were used. The experimental arrangement consisted of Franz-type vertical permeation cells. The well standardized animal skin models were chosen: fresh skin from abdominal region of 5 day old rats (5DR) of Wistar strain (Breeding Farm Dobra Voda, SK) and 9 day old rats (9DR), resp.. The skins of 5DR are still hairless, and 9DR are just short haired. The 5DR skin was used intact, and also with decreasing thickness of horny layer after it had been stripped with Scotch type (3M) 5-20 times respectively, or the skin had been splitted in 60degC hot water, whereby the whole epidermis was removed. Ions penetrated in vitro through the skin from donor solution (vehicle water) to receptor solution (phosphate buffered saline), were determined in aliquots sampled in 1,3,5,7 a 24 hours. The penetrated amounts of ions were found proportional to the time at least in the first 7

Chronic Disease Prevalence and Medicare Advantage Market Penetration

Directory of Open Access Journals (Sweden)

Steven W. Howard

2015-10-01

Full Text Available By March 2015, 30% of all Medicare beneficiaries were enrolled in Medicare Advantage (MA plans. Research to date has not explored the impacts of MA market penetration on individual or population health outcomes. The primary objective of this study is to examine the relationships between MA market penetration and the beneficiary’s portfolio of cardiometabolic diagnoses. This study uses 2004 to 2008 Medical Expenditure Panel Survey (MEPS Household Component data to construct an aggregate index that captures multiple diagnoses in one outcome measure (Chronic Disease Severity Index [CDSI]. The MEPS data for 8089 Medicare beneficiaries are merged with MA market penetration data from Centers for Medicare and Medicaid Services (CMS. Ordinary least squares regressions are run with SAS 9.3 to model the effects of MA market penetration on CDSI. The results suggest that each percentage increase in MA market penetration is associated with a greater than 2-point decline in CDSI (lower burden of cardiometabolic chronic disease. Spill-over effects may be driving improvements in the cardiometabolic health of beneficiary populations in counties with elevated levels of MA market penetration.

Radon penetration of concrete slab cracks, joints, pipe penetrations, and sealants

NARCIS (Netherlands)

Nielson, KK; Rogers, VC; Holt, RB; Pugh, TD; Grondzik, WA; deMeijer, RJ

1997-01-01

Radon movement through 12 test slabs with different cracks, pipe penetrations, cold joints, masonry blocks, sealants, and tensile stresses characterized the importance of these anomalous structural domains, Diffusive and advective radon transport were measured with steady-state air pressure

Sphere impact and penetration into wet sand

KAUST Repository

Marston, J. O.

2012-08-07

We present experimental results for the penetration of a solid sphere when released onto wet sand. We show, by measuring the final penetration depth, that the cohesion induced by the water can result in either a deeper or shallower penetration for a given release height compared to dry granular material. Thus the presence of water can either lubricate or stiffen the granular material. By assuming the shear rate is proportional to the impact velocity and using the depth-averaged stopping force in calculating the shear stress, we derive effective viscosities for the wet granular materials.

Sphere impact and penetration into wet sand

KAUST Repository

Marston, J. O.; Vakarelski, Ivan Uriev; Thoroddsen, Sigurdur T

2012-01-01

We present experimental results for the penetration of a solid sphere when released onto wet sand. We show, by measuring the final penetration depth, that the cohesion induced by the water can result in either a deeper or shallower penetration for a given release height compared to dry granular material. Thus the presence of water can either lubricate or stiffen the granular material. By assuming the shear rate is proportional to the impact velocity and using the depth-averaged stopping force in calculating the shear stress, we derive effective viscosities for the wet granular materials.

Penetrating eye injury in war.

Science.gov (United States)

Biehl, J W; Valdez, J; Hemady, R K; Steidl, S M; Bourke, D L

1999-11-01

The percentage of penetrating eye injuries in war has increased significantly in this century compared with the total number of combat injuries. With the increasing use of fragmentation weapons and possibly laser weapons on the battle-field in the future, the rate of eye injuries may exceed the 13% of the total military injuries found in Operations Desert Storm/Shield. During the Iran-Iraq War (1980-1988), eye injuries revealed that retained foreign bodies and posterior segment injuries have an improved prognosis in future military ophthalmic surgery as a result of modern diagnostic and treatment modalities. Compared with the increasing penetrating eye injuries on the battlefield, advances in ophthalmic surgery are insignificant. Eye armor, such as visors that flip up and down and protect the eyes from laser injury, needs to be developed. Similar eye protection is being developed in civilian sportswear. Penetrating eye injury in the civilian sector is becoming much closer to the military model and is now comparable for several reasons.

Cracks on instrumentation penetrations in reactor vessel: a new challenge; Fissuration des penetrations de cuve: un nouveau defi

Energy Technology Data Exchange (ETDEWEB)

Anon

2004-02-01

In august 2003 NRC (nuclear regulatory commission) issued a warning concerning the deposits of boron acid that might accumulate on instrumental penetrations in the bottom of PWR vessels. These deposits were first detected on the David-Besse power plant and more recently on the unit 1 of South Texas Project (STP) during a refueling shutdown. STP contracted with the Areva company in order to perform inspections on all the 58 vessel penetrations of the unit 1 and to propose solutions. For that purpose the Areva company had to design a specific visual inspection tool that combined both ultra-sound method and Foucault current probing. The results of the inspection campaign on the unit 1 showed that only 2 penetration tubes were concerned with axial defects in their walls, that no circumferential defects were detected and that butt welds presented no cracks. The 2 incriminated penetration tubes were repaired: a section of both was replaced by an alloy-690 tube. (A.C.)

Penetration Testing dan Analisis Kemanan Web Paud Dikmas

OpenAIRE

Giffari, Abizar

2018-01-01

Sebuah instansi atau perusahaan tentunya mempunyai data penting yang tersimpan dalam sebuah sistem database yang kuat dan aman untuk menghindari ancaman pencurian data dari pihak luar. Untuk mengukur sejauh mana tingkat keamanan yang dibuat, diperlukan sebuah metode pengetesan yang disebut Penetration Testing. Penetration Testing memungkinkan kita untuk dapat menentukan sejauh mana tingkat keamanan sistem yang di test. Penetration Testing juga memungkinkan kita menyerang sistem layaknya attac...

Quantitative penetration testing with item response theory

NARCIS (Netherlands)

Pieters, W.; Arnold, F.; Stoelinga, M.I.A.

2013-01-01

Existing penetration testing approaches assess the vulnerability of a system by determining whether certain attack paths are possible in practice. Therefore, penetration testing has thus far been used as a qualitative research method. To enable quantitative approaches to security risk management,

Penetrating ureteral trauma

Directory of Open Access Journals (Sweden)

Gustavo P. Fraga

2007-04-01

Full Text Available OBJECTIVE: The purpose of this series is to report our experience in managing ureteral trauma, focusing on the importance of early diagnosis, correct treatment, and the impact of associated injuries on the management and morbid-mortality. MATERIALS AND METHODS: From January 1994 to December 2002, 1487 laparotomies for abdominal trauma were performed and 20 patients with ureteral lesions were identified, all of them secondary to penetrating injury. Medical charts were analyzed as well as information about trauma mechanisms, diagnostic routine, treatment and outcome. RESULTS: All patients were men. Mean age was 27 years. The mechanisms of injury were gunshot wounds in 18 cases (90% and stab wounds in two (10%. All penetrating abdominal injuries had primary indication of laparotomy, and neither excretory urography nor computed tomography were used in any case before surgery. The diagnosis of ureteric injury was made intra-operatively in 17 cases (85%. Two ureteral injuries (10% were initially missed. All patients had associated injuries. The treatment was dictated by the location, extension and time necessary to identify the injury. The overall incidence of complications was 55%. The presence of shock on admission, delayed diagnosis, Abdominal Trauma Index > 25, Injury Severity Score > 25 and colon injuries were associated to a high complication rate, however, there was no statistically significant difference. There were no mortalities in this group. CONCLUSIONS: A high index of suspicion is required for diagnosis of ureteral injuries. A thorough exploration of all retroperitoneal hematoma after penetrating trauma should be an accurate method of diagnosis; even though it failed in 10% of our cases.

Quantitative Penetration Testing with Item Response Theory

NARCIS (Netherlands)

Arnold, Florian; Pieters, Wolter; Stoelinga, Mariëlle Ida Antoinette

2014-01-01

Existing penetration testing approaches assess the vulnerability of a system by determining whether certain attack paths are possible in practice. Thus, penetration testing has so far been used as a qualitative research method. To enable quantitative approaches to security risk management, including

Quantitative penetration testing with item response theory

NARCIS (Netherlands)

Arnold, Florian; Pieters, Wolter; Stoelinga, Mariëlle

2013-01-01

Existing penetration testing approaches assess the vulnerability of a system by determining whether certain attack paths are possible in practice. Thus, penetration testing has so far been used as a qualitative research method. To enable quantitative approaches to security risk management, including

Chemical Penetration Enhancers for Transdermal Drug Delivery ...

African Journals Online (AJOL)

for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

Containment penetration design and analysis by finite element methods

International Nuclear Information System (INIS)

Perry, R.F.; Rigamonti, G.; Dainora, J.

1975-01-01

Containment penetration designs which provide complete support to process piping containing high pressure and high temperature fluids and which do not employ cooling coils, require special provisions to sustain loadings associated with normal/abnormal conditions and to limit maximum temperature transmitted to the containment concrete wall. In order to accomodate piping loads and fluid temperatures within code and regulatory limitations, the containment penetration designs require careful analysis of two critical regions: 1) the portion of the penetration sleeve which is exposed to containment ambient conditions and 2) the portion of the penetration which connects the sleeve to process piping (flued head). Analytical models using finite element representation of process piping, penetration flued head, and exposed sleeve were employed to investigate the penetration assembly design. By application of flexible multi-step analyses, different penetration configurations were evaluated to determine the effects of key design parameters. Among the parameters studied were flued head angles with the process piping, sleeve length and wall thickness. Special designs employing fins welded to the sleeve to further lower the temperature at the concrete wall interface were also investigated and fin geometry effects reported. (Auth.)

Akon - A Penetrator for Europa

Science.gov (United States)

Jones, Geraint

2016-04-01

Jupiter's moon Europa is one of the most intriguing objects in our Solar System. This 2000km-wide body has a geologically young solid water ice crust that is believed to cover a global ocean of liquid water. The presence of this ocean, together with a source of heating through tidal forces, make Europa a conceivable location for extraterrestrial life. The science case for exploring all aspects of this icy world is compelling. NASA has selected the Europa Mission (formerly Europa Clipper) to study Europa in detail in the 2020s through multiple flybys, and ESA's JUICE mission will perform two flybys of the body in the 2030s. The US agency has extended to the European Space Agency an invitation to provide a contribution to their mission. European scientists interested in Europa science and exploration are currently organizing themselves, in the framework of a coordinated Europa M5 Inititative to study concurrently the main options for this ESA contribution, from a simple addition of individual instruments to the NASA spacecraft, to a lander to investigate Europa's surface in situ. A high speed lander - a penetrator - is by far the most promising technology to achieve this latter option within the anticipated mass constraints, and studies of such a hard lander, many funded by ESA, are now at an advanced level. An international team to formally propose an Europa penetrator to ESA in response to the anticipated ESA M5 call is growing. The working title of this proposal is Akon (Άκων), named after the highly accurate javelin gifted to Europa by Zeus in ancient Greek mythology. We present plans for the Akon penetrator, which would impact Europa's surface at several hundred metres per second, and travel up to several metres into the moon's subsurface. To achieve this, the penetrator would be delivered to the surface by a dedicated descent module, to be destroyed on impact following release of the penetrator above the surface. It is planned that the instruments to be

Vehicle effects on human stratum corneum absorption and skin penetration.

Science.gov (United States)

Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

2017-05-01

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Stylet penetration of Cacopsylla pyri; an electrical penetration graph (EPG) study

NARCIS (Netherlands)

Civolani, S.; Leis, M.; Grandi, G.; Garzo, E.; Pasqualini, E.; Musacchi, S.; Chicca, M.; Castaldelli, G.; Rossie, M.; Tjallingii, W.F.

2011-01-01

Detailed information on plant penetration activities by pear psylla Cacopsylla pyri L. (Hemiptera Psyllidae) is essential to study phytoplasma transmission of “Candidatus Phytoplasma pyri” responsible of pear decline disease (PD) and to trace and evaluate resistant traits in new pear tree selections

Prophylactic antibiotics for penetrating abdominal trauma.

Science.gov (United States)

Brand, Martin; Grieve, Andrew

2013-11-18

Penetrating abdominal trauma occurs when the peritoneal cavity is breached. Routine laparotomy for penetrating abdominal injuries began in the 1800s, with antibiotics first being used in World War II to combat septic complications associated with these injuries. This practice was marked with a reduction in sepsis-related mortality and morbidity. Whether prophylactic antibiotics are required in the prevention of infective complications following penetrating abdominal trauma is controversial, however, as no randomised placebo controlled trials have been published to date. There has also been debate about the timing of antibiotic prophylaxis. In 1972 Fullen noted a 7% to 11% post-surgical infection rate with pre-operative antibiotics, a 33% to 57% infection rate with intra-operative antibiotic administration and 30% to 70% infection rate with only post-operative antibiotic administration. Current guidelines state there is sufficient class I evidence to support the use of a single pre-operative broad spectrum antibiotic dose, with aerobic and anaerobic cover, and continuation (up to 24 hours) only in the event of a hollow viscus perforation found at exploratory laparotomy. To assess the benefits and harms of prophylactic antibiotics administered for penetrating abdominal injuries for the reduction of the incidence of septic complications, such as septicaemia, intra-abdominal abscesses and wound infections. Searches were not restricted by date, language or publication status. We searched the following electronic databases: the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library 2013, issue 12 of 12), MEDLINE (OvidSP), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) and PubMed. Searches were last conducted in January 2013. All randomised controlled trials of antibiotic prophylaxis in patients with penetrating abdominal trauma versus no

Deformation analysis of shallow penetration in clay

Science.gov (United States)

Sagaseta, C.; Whittle, A. J.; Santagata, M.

1997-10-01

A new method of analysis is described for estimating the deformations and strains caused by shallow undrained penetration of piles and caissons in clay. The formulation combines previous analyses for steady, deep penetration, with methods used to compute soil deformations due to near-surface ground loss, and is referred to as the Shallow Strain Path Method (SSPM). Complete analytical solutions for the velocity and strain rates are given for a planar wall, an axisymmetric, closed-ended pile and unplugged, open-ended pile geometries. In these examples, the analyses consider a single source penetrating through the soil at a constant rate, generating a family of penetrometers with rounded tips, referred to as simple wall, pile and tube geometries. Soil deformations and strains are obtained by integrating the velocity and strain rates along the particle paths.The transition from shallow to deep penetration is analysed in detail. Shallow penetration causes heave at the ground surface, while settlements occur only in a thin veneer of material adjacent to the shaft and in a bulb-shaped region around the tip. The size of this region increases with the embedment depth. Deformations inside an open-ended pile/caisson are affected significantly by details of the simple tube wall geometry.

Clinical outcomes of trabeculectomy vs. Ahmed glaucoma valve implantation in patients with penetrating keratoplasty : (Trabeculectomy vs. Ahmed galucoma valve in patients with penetrating keratoplasty).

Science.gov (United States)

Akdemir, Mehmet Orcun; Acar, Banu Torun; Kokturk, Furuzan; Acar, Suphi

2016-08-01

The aim of this study was to compare the visual outcomes, intraocular pressure (IOP), and endothelial cell loss caused by trabeculectomy (TRAB) and Ahmed glaucoma valve (AGV) implantation in patients who had previously undergone penetrating keratoplasty (PKP). The data from all patients who underwent surgical treatment of glaucoma after PKP were reviewed at the Cornea Department of Haydarpasa Numune Education and Research Hospital. Eighteen patients who had undergone surgical treatment of glaucoma after PKP were included in this retrospective study. Time between PKP and glaucoma surgeries, visual acuity results, IOP results, endothelial cell counts (ECC) before the surgery, at 1st, 6th, and 12th month of surgery were recorded. Differences between two groups were evaluated. Mean loss of ECC was 315 cells/mm(2) in the AGV group and 197 cells/mm(2) in TRAB group at 12th month of glaucoma surgery. The difference between endothelial cell loss at 12th month of surgery was statistically significant and higher in AGV group (p glaucoma. Ahmed glaucoma valve had a significantly better IOP lowering but higher endothelial cell loss effect.

Air pollutant penetration through airflow leaks into buildings

Energy Technology Data Exchange (ETDEWEB)

Liu, De-Ling [Univ. of California, Berkeley, CA (United States)

2002-01-01

The penetration of ambient air pollutants into the indoor environment is of concern owing to several factors: (1) epidemiological studies have shown a strong association between ambient fine particulate pollution and elevated risk of human mortality; (2) people spend most of their time in indoor environments; and (3) most information about air pollutant concentration is only available from ambient routine monitoring networks. A good understanding of ambient air pollutant transport from source to receptor requires knowledge about pollutant penetration across building envelopes. Therefore, it is essential to gain insight into particle penetration in infiltrating air and the factors that affect it in order to assess human exposure more accurately, and to further prevent adverse human health effects from ambient particulate pollution. In this dissertation, the understanding of air pollutant infiltration across leaks in the building envelope was advanced by performing modeling predictions as well as experimental investigations. The modeling analyses quantified the extent of airborne particle and reactive gas (e.g., ozone) penetration through building cracks and wall cavities using engineering analysis that incorporates existing information on building leakage characteristics, knowledge of pollutant transport processes, as well as pollutant-surface interactions. Particle penetration is primarily governed by particle diameter and by the smallest dimension of the building cracks. Particles of 0.1-1 μm are predicted to have the highest penetration efficiency, nearly unity for crack heights of 0.25 mm or higher, assuming a pressure differential of 4 Pa or greater and a flow path length of 3 cm or less. Supermicron and ultrafine particles (less than 0.1 μm) are readily deposited on crack surfaces by means of gravitational settling and Brownian diffusion, respectively. The fraction of ozone penetration through building leaks could vary widely, depending significantly on its

[Special penetration needling for refractory peripheral facial paralysis].

Science.gov (United States)

Cao, Rongjuan; Qiu, Xiaohu; Xie, Xiaokun

2018-03-12

To observe the clinical effect difference between special penetration needling and conventional penetration needling for the refractory peripheral facial paralysis. A total of 97 patients with intractable facial paralysis were randomized into an observation group (49 cases and 2 dropping) and a control group (48 cases and 4 dropping). In the observation group, special penetration needling at an angle about 45° between the penetration needle and paralysis muscle bundle was used, Yangbai (GB 14) through Touwei (ST 8), Yangbai (GB 14) through Shangxing (GV 23), Sizhukong (TE 23) through Yuyao (EX-HN 4), Qianzhen (Extra) through Yingxiang (LI 20), mutual penetration between Yingxiang (LI 20) and Jiache (ST 6). Conventional penetration needling was applied in the control group, Yangbai (GB 14) through Yuyao (EX-HN 4), Cuanzhu (BL 2) through Yuyao (EX-HN 4), mutual penetration between Dicang (ST 4) and Jiache (ST 6), Qianzheng (Extra) through Dicang (ST 4), Sibai (ST 2) through Yingxiang (LI 20). Three groups of electroacupuncture (discontinuous wave, 1 Hz) with tolerance were connected respectively in the two groups, Yangbai (GB 14) and Sizhukong (TE 23), Yangbai (GB 14) and Qianzheng (Extra), Yingxiang (LI 20) and Jiache (ST 6) in the observation group, Yangbai (GB 14) and Cuanzhu (BL 2), Dicang (ST 4) and Jiache (ST 6), Qianzheng (Extra) and Sibai (ST 2) in the control group. TDP was applied in the two groups at the affected Yifeng (TE 17), Jiache (ST 6) and Qianzheng (Extra), which were around the ear. Perpendicular insertion was used at Yifeng (TE 17) at the affected side and Hegu (LI 4) at the healthy side and bilateral Zusanli (ST 36). The needles were retained for 30 min. The treatment was given for 3 courses, once a day and 10 days as a course, 5 days at the interval. House-Brackmann (H-B) facial nerve grading score was recorded before and after treatment. The clinical effects were compared. The H-B scores after treatment in the two groups were higher than

Opportunities for high wind energy penetration

DEFF Research Database (Denmark)

Tande, J.O.; Hansen, J.C.

1997-01-01

Wind power is today a mature technology, which at windy locations, is economically competitive to conventional power generation technologies. This and growing global environmental concerns have led governments to encourage and plan for wind energy development, a typical aim being 10% of electricity...... consumption. The successful operation of the three major power systems of Cape Verde, with a total wind energy penetration of about 15% since December 1994, demonstrates that power systems can be operated with high penetration of wind energy by adding simple control and monitoring systems only. Thorough...... analyses conclude that expanding to even above 15% wind energy penetration in the Cape Verde power systems is economical. Worldwide, numerous locations with favorable wind conditions and power systems similar to the Capeverdean provide good opportunities for installing wind farms and achieving high wind...

The cluster [Re6Se8I6]3- penetrates biological membranes: drug-like properties for CNS tumor treatment and diagnosis.

Science.gov (United States)

Estrada, Lisbell D; Duran, Elizabeth; Cisterna, Matias; Echeverria, Cesar; Zheng, Zhiping; Borgna, Vincenzo; Arancibia-Miranda, Nicolas; Ramírez-Tagle, Rodrigo

2018-03-24

Tumorigenic cell lines are more susceptible to [Re 6 Se 8 I 6 ] 3- cluster-induced death than normal cells, becoming a novel candidate for cancer treatment. Still, the feasibility of using this type of molecules in human patients remains unclear and further pharmacokinetics analysis is needed. Using coupled plasma optical emission spectroscopy, we determined the Re-cluster tissue content in injected mice, as a biodistribution measurement. Our results show that the Re-cluster successfully reaches different tissues, accumulating mainly in heart and liver. In order to dissect the mechanism underlying cluster biodistribution, we used three different experimental approaches. First, we evaluate the degree of lipophilicity by determining the octanol/water partition coefficient. The cluster mostly remained in the octanol fraction, with a coefficient of 1.86 ± 0.02, which indicates it could potentially cross cell membranes. Then, we measured the biological membrane penetration through a parallel artificial membrane permeability assays (PAMPA) assay. The Re-cluster crosses the artificial membrane, with a coefficient of 122 nm/s that is considered highly permeable. To evaluate a potential application of the Re-cluster in central nervous system (CNS) tumors, we analyzed the cluster's brain penetration by exposing cultured blood-brain-barrier (BBB) cells to increasing concentrations of the cluster. The Re-cluster effectively penetrates the BBB, reaching nearly 30% of the brain side after 24 h. Thus, our results indicate that the Re-cluster penetrates biological membranes reaching different target organs-most probably due to its lipophilic properties-becoming a promising anti-cancer drug with high potential for CNS cancer's diagnosis and treatment.

Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea.

Science.gov (United States)

Chaiyasan, Wanachat; Praputbut, Sakonwun; Kompella, Uday B; Srinivas, Sangly P; Tiyaboonchai, Waree

2017-01-01

Topical application of drugs to the eyes suffers from poor bioavailability at the ocular surface and in the anterior chamber. This is due to rapid clearance of the drug because of tear secretion and outflow. This study has investigated mucoadhesive and penetration characteristics of chitosan-dextran sulfate nanoparticles (CDNs), prepared by polyelectrolyte complexation technique, following topical administration to the ocular surface. Topical FITC-labeled CDNs (FCDNs; mean size of 400nm and a surface charge of +48mV) were retained on the porcine ocular surface for more than 4h. Topical FCDNs were partially endocytosed into porcine corneal epithelial cells via a clathrin-dependent pathway. After 6h of topical FCDNs, particles accumulated in the corneal epithelium but not found in the corneal stroma. When epithelium was removed, FCDNs penetrated the stroma. Thus, CDNs are potentially useful for drug/gene delivery to the ocular surface and to stroma when epithelium is damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of a passive method for determining particle penetration through protective clothing materials.

Science.gov (United States)

Jaques, Peter A; Portnoff, Lee

2017-12-01

The risk of workers' exposure to aerosolized particles has increased with the upsurge in the production of engineered nanomaterials. Currently, a whole-body standard test method for measuring particle penetration through protective clothing ensembles is not available. Those available for respirators neglect the most common challenges to ensembles, because they use active vacuum-based filtration, designed to simulate breathing, rather than the positive forces of wind experienced by workers. Thus, a passive method that measures wind-driven particle penetration through ensemble fabric has been developed and evaluated. The apparatus includes a multidomain magnetic passive aerosol sampler housed in a shrouded penetration cell. Performance evaluation was conducted in a recirculation aerosol wind tunnel using paramagnetic Fe 3 O 4 (i.e., iron (II, III) oxide) particles for the challenge aerosol. The particles were collected on a PVC substrate and quantified using a computer-controlled scanning electron microscope. Particle penetration levels were determined by taking the ratio of the particle number collected on the substrate with a fabric (sample) to that without a fabric (control). Results for each fabric obtained by this passive method were compared to previous results from an automated vacuum-based active fractional efficiency tester (TSI 3160), which used sodium chloride particles as the challenge aerosol. Four nonwoven fabrics with a range of thicknesses, porosities, and air permeabilities were evaluated. Smoke tests and flow modeling showed the passive sampler shroud provided smooth (non-turbulent) air flow along the exterior of the sampler, such that disturbance of flow stream lines and distortion of the particle size distribution were reduced. Differences between the active and passive approaches were as high as 5.5-fold for the fabric with the lowest air permeability (0.00067 m/sec-Pa), suggesting the active method overestimated penetration in dense fabrics

The penetration of aerosols through fine capillaries

International Nuclear Information System (INIS)

Mitchell, J.P.; Edwards, R.T.; Ball, M.H.E.

1989-10-01

A novel experimental technique has been developed to study the penetration of aerosol particles ranging from about 1 to 15 μm aerodynamic diameter through capillaries varying from 20 to 80 μm bore and from 10 to 50 mm in length. When the driving pressure was 100 kPa, the penetration of the airborne particles was considerably smaller than expected from a simple comparison of particle diameter with the bore of the capillary. Particle size distributions determined after penetration through the capillaries were in almost all cases similar to the particle size distribution of the aerosol at the capillary entrance. This lack of size-selectivity can be explained in terms of the capillary behaving as a conventional suction-based sampler from a near still (calm) air environment. The resulting particle penetration data are important in assessing the potential for the leakage of aerosols through seals in containers used to transport radioactive materials. (author)

Application of Uintah-MPM to shaped charge jet penetration of aluminum

International Nuclear Information System (INIS)

Burghardt, J; Leavy, B; Brannon, R; Guilkey, J; Xue, Z

2010-01-01

The capability of the generalized interpolation material point (GIMP) method in simulation of penetration events is investigated. A series of experiments was performed wherein a shaped charge jet penetrates into a stack of aluminum plates. Electronic switches were used to measure the penetration time history. Flash x-ray techniques were used to measure the density, length, radius and velocity of the shaped charge jet. Simulations of the penetration event were performed using the Uintah MPM/GIMP code with several different models of the shaped charge jet being used. The predicted penetration time history for each jet model is compared with the experimentally observed penetration history. It was found that the characteristics of the predicted penetration were dependent on the way that the jet data are translated to a discrete description. The discrete jet descriptions were modified such that the predicted penetration histories fell very close to the range of the experimental data. In comparing the various discrete jet descriptions it was found that the cumulative kinetic energy flux curve represents an important way of characterizing the penetration characteristics of the jet. The GIMP method was found to be well suited for simulation of high rate penetration events.

Fuel cells:

DEFF Research Database (Denmark)

Sørensen, Bent

2013-01-01

A brief overview of the progress in fuel cell applications and basic technology development is presented, as a backdrop for discussing readiness for penetration into the marketplace as a solution to problems of depletion, safety, climate or environmental impact from currently used fossil and nucl......A brief overview of the progress in fuel cell applications and basic technology development is presented, as a backdrop for discussing readiness for penetration into the marketplace as a solution to problems of depletion, safety, climate or environmental impact from currently used fossil...... and nuclear fuel-based energy technologies....

Medicaid HMO penetration and its mix: did increased penetration affect physician participation in urban markets?

Science.gov (United States)

Adams, E Kathleen; Herring, Bradley

2008-02-01

To use changes in Medicaid health maintenance organization (HMO) penetration across markets over time to test for effects on the extent of Medicaid participation among physicians and to test for differences in the effects of increased use of commercial versus Medicaid-dominant plans within the market. The nationally representative Community Tracking Study's Physician Survey for three periods (1996-1997, 1998-1999, and 2000-2001) on 29,866 physicians combined with Centers for Medicare and Medicaid Services (CMS) and InterStudy data. Market-level estimates of Medicaid HMO penetration are used to test for (1) any participation in Medicaid and (2) the degree to which physicians have an "open" (i.e., nonlimited) practice accepting new Medicaid patients. Models account for physician, firm, and local characteristics, Medicaid relative payment levels adjusted for geographic variation in practice costs, and market-level fixed effects. There is a positive effect of increases in commercial Medicaid HMO penetration on the odds of accepting new Medicaid patients among all physicians, and in particular, among office-based physicians. In contrast, there is no effect, positive or negative, from expanding the penetration of Medicaid-dominant HMO plans within the market. Increases in cost-adjusted Medicaid fees, relative to Medicare levels, were associated with increases in the odds of participation and of physicians having an "open" Medicaid practice. Provider characteristics that consistently lower participation among all physicians include being older, board certified, a U.S. graduate and a solo practitioner. The effects of Medicaid HMO penetration on physician participation vary by the type of plan. If states are able to attract and retain commercial plans, participation by office-based physicians is likely to increase in a way that opens existing practices to more new Medicaid patients. Other policy variables that affect participation include the presence of a federally

Penetration enhancer: monoethylether of diethylene glycol

International Nuclear Information System (INIS)

Koprda, V.; Kassai, Z.; Bohacik, L.; Bezek, S.; Hadcrafft, J.; Falson-Rieg, F.

1999-01-01

The monoethylether of diethylene glycol (Transcutol), an excellent solubilising agent, has been suggested as a penetration enhancer compatible with trans-dermal drug delivery systems. Using the abdominal skin of 5 day old rats and Franz-type diffusion cells the following topics were studied in this contribution: (1) Flux of Transcutol, labelled with [Ethyl- 14 C]-ether, across an intact skin model, (2) Changes in properties of the skin barrier after stripping with adhesive tape, and (3) Changes in flux of Transcutol when mixed with different co-solvents. The flux from pure solvent in donor compartment reached around 50 μg cm -2 hr -1 across the intact skin horny layer, whilst after 12 strips the flux increased about 200 times. In the presence of propylene glycol dipelargonate, the flux over 2 mg cm -2 hr -1 across non stripped skin was achieved. (authors)

Natural oils affect the human skin integrity and the percutaneous penetration of benzoic acid dose-dependently

DEFF Research Database (Denmark)

Nielsen, Jesper Bo

2006-01-01

three natural oils (eucalyptus oil, tea tree oil, peppermint oil) would affect the skin integrity and the percutaneous penetration of benzoic acid when applied topically in relevant concentrations. An experimental in vitro model using static diffusion cells mounted with human breast or abdominal skin...

Freezing tolerance of sea urchin embryonic cells: Differentiation commitment and cytoskeletal disturbances in culture.

Science.gov (United States)

Odintsova, Nelly A; Ageenko, Natalya V; Kipryushina, Yulia O; Maiorova, Mariia A; Boroda, Andrey V

2015-08-01

This study focuses on the freezing tolerance of sea urchin embryonic cells. To significantly reduce the loss of physiological activity of these cells that occurs after cryopreservation and to study the effects of ultra-low temperatures on sea urchin embryonic cells, we tested the ability of the cells to differentiate into spiculogenic or pigment directions in culture, including an evaluation of the expression of some genes involved in pigment differentiation. A morphological analysis of cytoskeletal disturbances after freezing in a combination of penetrating (dimethyl sulfoxide and ethylene glycol) and non-penetrating (trehalose and polyvinylpyrrolidone) cryoprotectants revealed that the distribution pattern of filamentous actin and tubulin was similar to that in the control cultures. In contrast, very rare spreading cells and a small number of cells with filamentous actin and tubulin were detected after freezing in the presence of only non-penetrating cryoprotectants. The largest number of pigment cells was found in cultures frozen with trehalose or trehalose and dimethyl sulfoxide. The ability to induce the spicule formation was lost in the cells frozen only with non-penetrating cryoprotectants, while it was maximal in cultures frozen in a cryoprotective mixture containing both non-penetrating and penetrating cryoprotectants (particularly, when ethylene glycol was present). Using different markers for cell state assessment, an effective cryopreservation protocol for sea urchin cells was developed: three-step freezing with a low cooling rate (1-2°C/min) and a combination of non-penetrating and penetrating cryoprotectants made it possible to obtain a high level of cell viability (up to 65-80%). Copyright © 2015 Elsevier Inc. All rights reserved.

Prevention of serious impurity penetration into water-steam circuits

International Nuclear Information System (INIS)

Burgmann, F.; Bursik, A.; Flunkert, F.; Nieder, R.

1977-01-01

In consequence of reports from several power Plants concerning heavy damages due to penetrations of impurities into the water-steam circuit, the VGB Sub-Committee 'Water Chemistry in Thermal Power Plants' has established a working group to check-up how serious impurity penetration can be avoided. The lecture describes possible danger points. Suitable technical arrangements for the avoidance of penetrations, and possibilities for monitoring will be discussed. Penetration of impurities cannot be avoided with absolute reliability, even when the recommended arrangements and usual monitoring are realized. Additional measures for the protection of water steam circuits will be suggested. (orig.) [de

Consistent constitutive modeling of metallic target penetration using empirical, analytical, and numerical penetration models

Directory of Open Access Journals (Sweden)

John (Jack P. Riegel III

2016-04-01

Full Text Available Historically, there has been little correlation between the material properties used in (1 empirical formulae, (2 analytical formulations, and (3 numerical models. The various regressions and models may each provide excellent agreement for the depth of penetration into semi-infinite targets. But the input parameters for the empirically based procedures may have little in common with either the analytical model or the numerical model. This paper builds on previous work by Riegel and Anderson (2014 to show how the Effective Flow Stress (EFS strength model, based on empirical data, can be used as the average flow stress in the analytical Walker–Anderson Penetration model (WAPEN (Anderson and Walker, 1991 and how the same value may be utilized as an effective von Mises yield strength in numerical hydrocode simulations to predict the depth of penetration for eroding projectiles at impact velocities in the mechanical response regime of the materials. The method has the benefit of allowing the three techniques (empirical, analytical, and numerical to work in tandem. The empirical method can be used for many shot line calculations, but more advanced analytical or numerical models can be employed when necessary to address specific geometries such as edge effects or layering that are not treated by the simpler methods. Developing complete constitutive relationships for a material can be costly. If the only concern is depth of penetration, such a level of detail may not be required. The effective flow stress can be determined from a small set of depth of penetration experiments in many cases, especially for long penetrators such as the L/D = 10 ones considered here, making it a very practical approach. In the process of performing this effort, the authors considered numerical simulations by other researchers based on the same set of experimental data that the authors used for their empirical and analytical assessment. The goals were to establish a

Penetration analysis of projectile with inclined concrete target

Directory of Open Access Journals (Sweden)

Kim S.B.

2015-01-01

Full Text Available This paper presents numerical analysis result of projectile penetration with concrete target. We applied dynamic material properties of 4340 steels, aluminium and explosive for projectile body. Dynamic material properties were measured with static tensile testing machine and Hopkinson pressure bar tests. Moreover, we used three concrete damage models included in LS-DYNA 3D, such as SOIL_CONCRETE, CSCM (cap model with smooth interaction and CONCRETE_DAMAGE (K&C concrete models. Strain rate effect for concrete material is important to predict the fracture deformation and shape of concrete, and penetration depth for projectiles. CONCRETE_DAMAGE model with strain rate effect also applied to penetration analysis. Analysis result with CSCM model shows good agreement with penetration experimental data. The projectile trace and fracture shapes of concrete target were compared with experimental data.

Penetration analysis of projectile with inclined concrete target

Science.gov (United States)

Kim, S. B.; Kim, H. W.; Yoo, Y. H.

2015-09-01

This paper presents numerical analysis result of projectile penetration with concrete target. We applied dynamic material properties of 4340 steels, aluminium and explosive for projectile body. Dynamic material properties were measured with static tensile testing machine and Hopkinson pressure bar tests. Moreover, we used three concrete damage models included in LS-DYNA 3D, such as SOIL_CONCRETE, CSCM (cap model with smooth interaction) and CONCRETE_DAMAGE (K&C concrete) models. Strain rate effect for concrete material is important to predict the fracture deformation and shape of concrete, and penetration depth for projectiles. CONCRETE_DAMAGE model with strain rate effect also applied to penetration analysis. Analysis result with CSCM model shows good agreement with penetration experimental data. The projectile trace and fracture shapes of concrete target were compared with experimental data.

Age-related percutaneous penetration part 1: skin factors.

Science.gov (United States)

Konda, S; Meier-Davis, S R; Cayme, B; Shudo, J; Maibach, H I

2012-05-01

Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.

Numerical analysis of impact-penetration problems for nuclear reactor safety

International Nuclear Information System (INIS)

Dubois, J.J.; Chedmail, J.F.; Bianchini, J.C.

1977-01-01

This paper discusses the finite element and finite difference analysis of two impact penetration problems, namely a fuel cask drop on a foundation slab and a missile penetration into a reinforced concrete structure. For a realistic detailed analysis, advanced techniques were required in the following areas: reinforced concrete simulation; remeshing algorithms for penetration induced distortions; boundary condition. The fuel cask drop on a concrete slab generates complex elasto plastic waves which propagate towards the pool where tensile cracks might appear. The problem is analysed in two steps: calculation of the energy absorbed locally around the impacted area; calculation of the three dimensional wave propagation towards the pool. For the analysis of missile penetration problems, two examples are shown: a 3000 kg missile with a velocity of 132 m/s penetrates a 1.2 m thick concrete wall (PAM-GDYNS) and a 3600 kg missile with a velocity of 90 m/s (F.D. Program HEMP-ESI) penetrates a wall at a floor level. For the second case, the computed impact-penetration mechanism is

Water Penetration through a Superhydrophobic Mesh During a Drop Impact

Science.gov (United States)

Ryu, Seunggeol; Sen, Prosenjit; Nam, Youngsuk; Lee, Choongyeop

2017-01-01

When a water drop impacts a mesh having submillimeter pores, a part of the drop penetrates through the mesh if the impact velocity is sufficiently large. Here we show that different surface wettability, i.e., hydrophobicity and superhydrophobicity, leads to different water penetration dynamics on a mesh during drop impact. We show, despite the water repellence of a superhydrophobic surface, that water can penetrate a superhydrophobic mesh more easily (i.e., at a lower impact velocity) over a hydrophobic mesh via a penetration mechanism unique to a superhydrophobic mesh. On a superhydrophobic mesh, the water penetration can occur during the drop recoil stage, which appears at a lower impact velocity than the critical impact velocity for water penetration right upon impact. We propose that this unique water penetration on a superhydrophobic mesh can be attributed to the combination of the hydrodynamic focusing and the momentum transfer from the water drop when it is about to bounce off the surface, at which point the water drop retrieves most of its kinetic energy due to the negligible friction on superhydrophobic surfaces.

Topological properties of the limited penetrable horizontal visibility graph family

Science.gov (United States)

Wang, Minggang; Vilela, André L. M.; Du, Ruijin; Zhao, Longfeng; Dong, Gaogao; Tian, Lixin; Stanley, H. Eugene

2018-05-01

The limited penetrable horizontal visibility graph algorithm was recently introduced to map time series in complex networks. In this work, we extend this algorithm to create a directed-limited penetrable horizontal visibility graph and an image-limited penetrable horizontal visibility graph. We define two algorithms and provide theoretical results on the topological properties of these graphs associated with different types of real-value series. We perform several numerical simulations to check the accuracy of our theoretical results. Finally, we present an application of the directed-limited penetrable horizontal visibility graph to measure real-value time series irreversibility and an application of the image-limited penetrable horizontal visibility graph that discriminates noise from chaos. We also propose a method to measure the systematic risk using the image-limited penetrable horizontal visibility graph, and the empirical results show the effectiveness of our proposed algorithms.

Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

Directory of Open Access Journals (Sweden)

Krista Freimann

2018-03-01

Full Text Available Although advances in genomics and experimental gene therapy have opened new possibilities for treating otherwise incurable diseases, the transduction of nucleic acids into the cells and delivery in vivo remain challenging. The high molecular weight and anionic nature of nucleic acids require their packing into nanoparticles for the delivery. The efficacy of nanoparticle drugs necessitates the high bioactivity of constituents, but their distribution in organisms is mostly governed by the physical properties of nanoparticles, and therefore, generation of stable particles with strictly defined characteristics is highly essential. Using previously designed efficient cell-penetrating peptide NF55, we searched for strategies enabling control over the nanoparticle formation and properties to further improve transfection efficacy. The size of the NF55/pDNA nanoparticles correlates with the concentration of its constituents at the beginning of assembly, but characteristics of nanoparticles measured by DLS do not reliably predict the applicability of particles in in vivo studies. We introduce a new formulation approach called cryo-concentration, where we acquired stable and homogeneous nanoparticles for administration in vivo. The cryo-concentrated NF55/pDNA nanoparticles exhibit several advantages over standard formulation: They have long shelf-life and do not aggregate after reconstitution, have excellent stability against enzymatic degradation, and show significantly higher bioactivity in vivo.

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

Directory of Open Access Journals (Sweden)

Uram Ł

2015-09-01

Full Text Available Łukasz Uram,1 Magdalena Szuster,1 Aleksandra Filipowicz,2 Krzysztof Gargasz,3 Stanisław Wołowiec,3 Elżbieta Wałajtys-Rode4 1Bioorganic Chemistry Laboratory, Faculty of Chemistry, Rzeszow University of Technology, 2Cosmetology Department, University of Information Technology and Management in Rzeszow, 3Institute of Nursery and Health Sciences, Faculty of Medicine, University of Rzeszow, Rzeszow, 4Department of Drug Technology and Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland Abstract: The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM dendrimer and its biotin–pyridoxal (BC-PAMAM bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ and squamous epithelial carcinoma (SCC-15 cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all

Containment penetration design and analysis by finite element methods

International Nuclear Information System (INIS)

Perry, R.F.; Rigamonti, G.; Dainora, J.

1975-01-01

Containment penetration designs which provide complete support to process piping containing high pressure and high temperature fluids and which do not employ cooling coils, require special provisions to sustain loadings associated with normal/abnormal conditions and to limit maximum temperature transmitted to the containment concrete wall. In order to accommodate piping imposed loads and fluid temperatures within code and regulatory limitations, the containment penetration designs require careful analysis of two critical regions: the portion of the penetration sleeve which is exposed to containment ambient conditions and the portion of the penetration which connects the sleeve to process piping (flued head). The length and thickness of the sleeve must be designed to provide maximum heat dissipation to the atmosphere and minimum heat conduction through the sleeve to meet concrete temperature limitations. The sleeve must have the capability to transmit the postulated piping loads to concrete embedments in the containment shell. The penetration flued head design must be strong enough to transfer high mechanical loads and be flexible enough to accommodate the thermal stresses generated by the high temperature fluid. Analytical models using finite element representations of process piping, penetration flued head, and exposed sleeve were employed to investigate the penetration assembly design. By application of flexible multi-step analyses, different penetration configurations were evaluated to determine the effects of key design parameters. Among the parameters studied were flued head profiles, flued head angles with the process piping, sleeve length and wall thickness. Special designs employing fins welded to the sleeve to lower the temperature at the concrete wall interface were investigated and fin geometry effects reported

Network Penetration Testing and Research

Science.gov (United States)

Murphy, Brandon F.

2013-01-01

This paper will focus the on research and testing done on penetrating a network for security purposes. This research will provide the IT security office new methods of attacks across and against a company's network as well as introduce them to new platforms and software that can be used to better assist with protecting against such attacks. Throughout this paper testing and research has been done on two different Linux based operating systems, for attacking and compromising a Windows based host computer. Backtrack 5 and BlackBuntu (Linux based penetration testing operating systems) are two different "attacker'' computers that will attempt to plant viruses and or NASA USRP - Internship Final Report exploits on a host Windows 7 operating system, as well as try to retrieve information from the host. On each Linux OS (Backtrack 5 and BlackBuntu) there is penetration testing software which provides the necessary tools to create exploits that can compromise a windows system as well as other operating systems. This paper will focus on two main methods of deploying exploits 1 onto a host computer in order to retrieve information from a compromised system. One method of deployment for an exploit that was tested is known as a "social engineering" exploit. This type of method requires interaction from unsuspecting user. With this user interaction, a deployed exploit may allow a malicious user to gain access to the unsuspecting user's computer as well as the network that such computer is connected to. Due to more advance security setting and antivirus protection and detection, this method is easily identified and defended against. The second method of exploit deployment is the method mainly focused upon within this paper. This method required extensive research on the best way to compromise a security enabled protected network. Once a network has been compromised, then any and all devices connected to such network has the potential to be compromised as well. With a compromised

Penetrating Brain Injury after Suicide Attempt with Speargun

Directory of Open Access Journals (Sweden)

John Ross Williams

2014-07-01

Full Text Available Penetrating cranial injury by mechanisms other than are exceedingly rare, and so strategies and guidelines for the management of PBI are largely informed by data from higher-velocity penetrating injuries. Here we present a case of penetrating brain injury by the low velocity mechanism of a harpoon from an underwater fishing speargun in an attempted suicide by a 56-year-old Caucasian male. The case raised a number of interesting points in management of lower-velocity penetrating brain injury (LVPBI, including benefit in delaying foreign body removal to allow for tamponade; the importance of history taking in establishing the social/legal significance of the events surrounding the injury; the use of cerebral angiogram in all cases of PBI; advantages of using DECT to reduce artifact when available; and antibiotic prophylaxis in the context of idiosyncratic histories of usage of penetrating objects before coming in contact with the intracranial environment. We present here the management of the case in full along with an extended discussion and review of existing literature regarding key points in management of LVPBI vs. higher velocity forms of intracranial injury.

CNS penetration of ART in HIV-infected children

NARCIS (Netherlands)

van den Hof, Malon; Blokhuis, Charlotte; Cohen, Sophie; Scherpbier, Henriette J.; Wit, Ferdinand W. N. M.; Pistorius, M. C. M.; Kootstra, Neeltje A.; Teunissen, Charlotte E.; Mathot, Ron A. A.; Pajkrt, Dasja

2018-01-01

Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce. Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Patients and methods: Antiretroviral drug levels were measured in paired

Analysis of 178 penetrating stomach and small bowel injuries.

Science.gov (United States)

Salim, Ali; Teixeira, Pedro G R; Inaba, Kenji; Brown, Carlos; Browder, Timothy; Demetriades, Demetrios

2008-03-01

Surgical site infections (SSIs), such as wound infection, fascial dehiscence, and intraabdominal abscess, commonly occur following penetrating abdominal trauma. However, most of the literature involves penetrating colon injuries. There are few reports describing complications following penetrating stomach and small bowel injuries. Based on the hypothesis that SSIs are commonly found following penetrating stomach and small bowel trauma, a prospective observational study was performed at an academic Level I trauma center from March 1, 2004 until August 31, 2006. The subjects were patients who had sustained a penetrating injury to the stomach or small bowel. Patients were followed for the development of an SSI, defined as wound infection, fascial dehiscence, or intraabdominal abscess. A total of 178 patients were admitted with penetrating stomach or small bowel injuries over the 29-month period. There were 121 (68%) gunshot injuries and 57 (32%) stab wounds. Associated intraabdominal injuries occurred in 74% of patients. Overall, SSIs occurred in 20% of cases. Risk factors for SSI included associated duodenal or colon injury, whereas time to operating room, blood loss, and type and duration of antibiotic use were not. When associated colon injuries were excluded, SSIs occurred in 16% of patients with gastric injuries and 13% of those with small bowel injuries. SSIs commonly follow penetrating stomach and small bowel trauma. Risk factors for SSI include associated duodenal or colon injury. Delay to operating room, blood loss, and type and length of antibiotic prophylaxis were not associated with an increased risk of SSI.

NRC Information Notice No. 93-25: Electrical penetration assembly degradation

International Nuclear Information System (INIS)

Grimes, B.K.

1993-01-01

In July 1987 and in October 1989, the licensee for the Trojan Nuclear Plant, the Portland and General Electric Company, reported problems with containment air leakage through its Bunker-Ramo electrical penetration assembly seals. In July and August 1991, the NRC inspected the use of containment electrical penetration assembly seals at Trojan and concluded that the licensee had not established an effective program for trending and evaluating electrical penetration assembly seal leakage. On October 28, 1991, while the plant was in a refueling outage, the licensee reported to the NRC that in the originally installed electrical penetration assemblies, the seal (polyurethane) and lubricant (Celvacen or Glycerin) materials were inappropriate for the application. The licensee concluded that these materials may cause seal degradation and that the seals may become degraded if subjected to design basis accident conditions for moisture or temperature. The licensee replaced the electrical penetration assembly seal with an environmentally qualified ethylene propylene rubber seal and added a silicone rubber backup O-ring to the outer face of each electrical penetration assembly module. The licensee subsequently replaced all the Bunker-Ramo electrical penetration assemblies with Conax assemblies

Penetration testing with Perl

CERN Document Server

Berdeaux, Douglas

2014-01-01

If you are an expert Perl programmer interested in penetration testing or information security, this guide is designed for you. However, it will also be helpful for you even if you have little or no Linux shell experience.

Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury.

Science.gov (United States)

Lee, Stephanie W; Gajavelli, Shyam; Spurlock, Markus S; Andreoni, Cody; de Rivero Vaccari, Juan Pablo; Bullock, M Ross; Keane, Robert W; Dietrich, W Dalton

2018-04-02

Penetrating traumatic brain injury (PTBI) is a significant cause of death and disability in the United States. Inflammasomes are one of the key regulators of the interleukin (IL)-1β mediated inflammatory responses after traumatic brain injury. However, the contribution of inflammasome signaling after PTBI has not been determined. In this study, adult male Sprague-Dawley rats were subjected to sham procedures or penetrating ballistic-like brain injury (PBBI) and sacrificed at various time-points. Tissues were assessed by immunoblot analysis for expression of IL-1β, IL-18, and components of the inflammasome: apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, X-linked inhibitor of apoptosis protein (XIAP), nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3), and gasdermin-D (GSDMD). Specific cell types expressing inflammasome proteins also were evaluated immunohistochemically and assessed quantitatively. After PBBI, expression of IL-1β, IL-18, caspase-1, ASC, XIAP, and NLRP3 peaked around 48 h. Brain protein lysates from PTBI animals showed pyroptosome formation evidenced by ASC laddering, and also contained increased expression of GSDMD at 48 h after injury. ASC-positive immunoreactive neurons within the perilesional cortex were observed at 24 h. At 48 h, ASC expression was concentrated in morphologically activated cortical microglia. This expression of ASC in activated microglia persisted until 12 weeks following PBBI. This is the first report of inflammasome activation after PBBI. Our results demonstrate cell-specific patterns of inflammasome activation and pyroptosis predominantly in microglia, suggesting a sustained pro-inflammatory state following PBBI, thus offering a therapeutic target for this type of brain injury.

The effect of steam curing on chloride penetration in geopolymer concrete

Directory of Open Access Journals (Sweden)

Jaya Ekaputri Januarti

2017-01-01

Full Text Available In this paper, we present the result of our study on the effect of steam curing to chloride ion penetration in geopolymer concrete. Class F fly ash was activated using sodium hydroxide (NaOH and sodium silicate (Na2SiO3. The concrete specimens were then steam-cured at 40°C, 60°C, 80°C and room temperature at 24 hours. The treatment was followed by wet curing for 28 days, and then followed by immersion of all specimens in salt water for the durations of 30, 60, and 90 days. Cylindrical specimens were then prepared for compressive strength, chloride ion penetration, pH, and porosity tests. A 16 mm-steel bar was fixed at the center of the specimen concrete blocks (specimen size: 10cm × 10cm × 15cm. Corrosion probability was determined by conducting Half Cell Potential test. Our result showed that increasing the curing temperature to 80°C induced chloride ion penetration into the concrete’s effective pores, despite improvements in compressive strength. We also found that chloride ingress on the geopolymer concrete increases commensurately with the increase of the curing temperature. The corrosion potential measurement of geopolymer concrete was higher than OPC concrete even if corrosion was not observed in reinforcing. Based on our result, we suggest that the corrosion categorization for geopolymer concretes needs to be adjusted.

Standard practice for liquid penetrant examination for general industry

CERN Document Server

American Society for Testing and Materials. Philadelphia

2009-01-01

1.1 This practice covers procedures for penetrant examination of materials. Penetrant testing is a nondestructive testing method for detecting discontinuities that are open to the surface such as cracks, seams, laps, cold shuts, shrinkage, laminations, through leaks, or lack of fusion and is applicable to in-process, final, and maintenance testing. It can be effectively used in the examination of nonporous, metallic materials, ferrous and nonferrous metals, and of nonmetallic materials such as nonporous glazed or fully densified ceramics, as well as certain nonporous plastics, and glass. 1.2 This practice also provides a reference: 1.2.1 By which a liquid penetrant examination process recommended or required by individual organizations can be reviewed to ascertain its applicability and completeness. 1.2.2 For use in the preparation of process specifications and procedures dealing with the liquid penetrant testing of parts and materials. Agreement by the customer requesting penetrant inspection is strongly rec...

Evaporation and skin penetration characteristics of mosquito repellent formulations

International Nuclear Information System (INIS)

Reifenrath, W.G.; Hawkins, G.S.; Kurtz, M.S.

1989-01-01

Formulations of the mosquito repellent N,N-diethyl-3-methylbenzamide (deet) in combination with a variety of additives were developed to control repellent evaporation and percutaneous penetration. Deet was also formulated with the repellent dimethyl phthalate to study the interaction of the two compounds on the skin. The evaporation and penetration processes were evaluated on whole and split-thickness pig skin using radiolabeled repellents with an in vitro apparatus. Under essentially still air and air flow conditions, one of the deet formulations resulted in significantly reduced total evaporation and percutaneous penetration of deet as compared to unformulated repellent. When deet and dimethyl phthalate were combined, neither repellent affected the total amount of evaporation and penetration of the other compound. However, initial percutaneous penetration and evaporation rates were slightly less and decayed less rapidly than when both chemicals were tested separately at the same dose. These results indicated a degree of competition of the two compounds for the same avenues of loss

Effect of penetration modifiers on the dermal and transdermal delivery of drugs and cosmetic active ingredients.

Science.gov (United States)

Otto, A; Wiechers, J W; Kelly, C L; Hadgraft, J; du Plessis, J

2008-01-01

In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation. Copyright 2008 S. Karger AG, Basel.

Integrated computation model of lithium-ion battery subject to nail penetration

International Nuclear Information System (INIS)

Liu, Binghe; Yin, Sha; Xu, Jun

2016-01-01

Highlights: • A coupling model to predict battery penetration process is established. • Penetration test is designed and validates the computational model. • Governing factors of the penetration induced short-circuit is discussed. • Critical safety battery design guidance is suggested. - Abstract: The nail penetration of lithium-ion batteries (LIBs) has become a standard battery safety evaluation method to mimic the potential penetration of a foreign object into LIB, which can lead to internal short circuit with catastrophic consequences, such as thermal runaway, fire, and explosion. To provide a safe, time-efficient, and cost-effective method for studying the nail penetration problem, an integrated computational method that considers the mechanical, electrochemical, and thermal behaviors of the jellyroll was developed using a coupled 3D mechanical model, a 1D battery model, and a short circuit model. The integrated model, along with the sub-models, was validated to agree reasonably well with experimental test data. In addition, a comprehensive quantitative analysis of governing factors, e.g., shapes, sizes, and displacements of nails, states of charge, and penetration speeds, was conducted. The proposed computational framework for LIB nail penetration was first introduced. This framework can provide an accurate prediction of the time history profile of battery voltage, temperature, and mechanical behavior. The factors that affected the behavior of the jellyroll under nail penetration were discussed systematically. Results provide a solid foundation for future in-depth studies on LIB nail penetration mechanisms and safety design.

Generic penetration in the retail antidepressant market.

Science.gov (United States)

Ventimiglia, Jeffrey; Kalali, Amir H

2010-06-01

In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Quantitative wood–adhesive penetration with X-ray computed tomography

Energy Technology Data Exchange (ETDEWEB)

Paris, Jesse L.; Kamke, Frederick A. (Oregon State U.); (Willamette Valley)

2015-09-01

Micro X-ray computed tomography (XCT) was used to analyze the 3D adhesive penetration behavior of different wood–adhesive bondlines. Three adhesives, a phenol formaldehyde (PF), a polymeric diphenylmethane diisocyanate (pMDI), and a hybrid polyvinyl acetate (PVA), all tagged with iodine for enhanced X-ray attenuation, were used to prepare single-bondline laminates in two softwoods, Douglas-fir and loblolly pine, and one hardwood, a hybrid polar. Adhesive penetration depth was measured with two separate calculations, and results were compared with 2D fluorescent micrographs. A total of 54 XCT scans were collected, representing six replicates of each treatment type; each replicate, however, consisted of approximately 1500 individual, cross-section slices stacked along the specimen length. As these adhesives were highly modified, the presented results do not indicate typical behavior for their broader adhesive classes. Still, clear penetration differences were observed between each adhesive type, and between wood species bonded with both the PF and pMDI adhesives. Furthermore, penetration results depended on the calculation method used. Two adhesive types with noticeably different resin distributions in the cured bondline, showed relatively similar penetration depths when calculated with a traditional effective penetration equation. However, when the same data was calculated with a weighted penetration calculation, which accounts for both adhesive area and depth, the results appeared to better represent the different distributions depicted in the photomicrographs and tomograms. Additionally, individual replicate comparisons showed variation due to specimen anatomy, not easily observed or interpreted from 2D images. Finally, 3D views of segmented 3D adhesive phases offered unique, in-situ views of the cured adhesive structures. In particular, voids formed by CO₂ bubbles generated during pMDI cure were clearly visible in penetrated columns of the solidified

WAPTT - Web Application Penetration Testing Tool

Directory of Open Access Journals (Sweden)

DURIC, Z.

2014-02-01

Full Text Available Web applications vulnerabilities allow attackers to perform malicious actions that range from gaining unauthorized account access to obtaining sensitive data. The number of reported web application vulnerabilities in last decade is increasing dramatically. The most of vulnerabilities result from improper input validation and sanitization. The most important of these vulnerabilities based on improper input validation and sanitization are: SQL injection (SQLI, Cross-Site Scripting (XSS and Buffer Overflow (BOF. In order to address these vulnerabilities we designed and developed the WAPTT (Web Application Penetration Testing Tool tool - web application penetration testing tool. Unlike other web application penetration testing tools, this tool is modular, and can be easily extended by end-user. In order to improve efficiency of SQLI vulnerability detection, WAPTT uses an efficient algorithm for page similarity detection. The proposed tool showed promising results as compared to six well-known web application scanners in detecting various web application vulnerabilities.

Penetrating power of resonant electromagnetic induction imaging

Directory of Open Access Journals (Sweden)

Roberta Guilizzoni

2016-09-01

Full Text Available The possibility of revealing the presence and identifying the nature of conductive targets is of central interest in many fields, including security, medicine, industry, archaeology and geophysics. In many applications, these targets are shielded by external materials and thus cannot be directly accessed. Hence, interrogation techniques are required that allow penetration through the shielding materials, in order for the target to be identified. Electromagnetic interrogation techniques represent a powerful solution to this challenge, as they enable penetration through conductive shields. In this work, we demonstrate the power of resonant electromagnetic induction imaging to penetrate through metallic shields (1.5-mm-thick and image targets (having conductivities σ ranging from 0.54 to 59.77 MSm−1 concealed behind them.

Simple Amides of Oleanolic Acid as Effective Penetration Enhancers

Science.gov (United States)

Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

2015-01-01

Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented. PMID:26010090

Simple amides of oleanolic acid as effective penetration enhancers.

Science.gov (United States)

Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

2015-01-01

Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented.

Safety considerations of laser related penetration in LCTR central power stations

International Nuclear Information System (INIS)

Botts, T.E.; Chan, C.K.; Ullman, A.Z.

1976-01-01

The following topics are briefly described: (1) requirements for optical penetration performance, (2) failure sequences in LCTR optical penetrations, (3) thermal stress in optical penetrations, and (4) nonlinear optical effects

Combined HLA matched limbal stem cells allograft with amniotic membrane transplantation as a prophylactic surgical procedure to prevent corneal graft rejection after penetrating keratoplasty: case report

Directory of Open Access Journals (Sweden)

Paolo Capozzi

2014-09-01

Full Text Available Purpose. To determine if the use of combined HLA matched limbal stem cells allograft with amniotic membrane transplantation (AMT is a safe and effective prophylactic surgical procedure to prevent corneal graft after penetrating keratoplasty (PK. Methods. We report the case of a 17 years old patient with a history of congenital glaucoma, trabeculectomy and multiple corneal graft rejections, presenting total limbal cell deficiency. To reduce the possibility of graft rejection in the left eye after a new PK, a two step procedure was performed. At first the patient underwent a combined HLA matched limbal stem cells allograft (LAT and AMT and then, 10 months later, a new PK. Results. During 12 months of follow-up, the corneal graft remained stable and smooth, with no sign of graft rejection. Conclusions. In our patient, the prophylactic use of LAT from HLA-matched donors and AMT before PK, may result in a better prognosis of corneal graft survival.

Importance Of Penetration Testing For Legacy Operating System

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Poorvi Bhatt

2017-12-01

Full Text Available Penetration testing is very important technique to find vulnerabilities in commercial networks. There are various techniques for ethical hacking via penetration testing. This report explains a white hat hacker approach of penetration testing. I have performed this test on private network where three PCs are connected through LAN via switch and without firewall. This network is not connected with Internet. All the PCs have windows operating system. The attacker host has windows server 2003 with Service Pack1 second host has windows XP with Service Pack 2 and third host has windows 2000 with service pack 4.

Magnetic field penetration into superconductors with sharp edges

International Nuclear Information System (INIS)

Zhilichev, Yuriy N.

2003-01-01

The magnetic field and surface currents induced within a superconductor are calculated assuming the field penetrates in it near sharp corners. Rounding the corners is used to keep the field less than a critical value. Analytical formulas for a corner radius are given for a wire of the rectangular cross-section and a cylinder in the external magnetic field. A boundary integral method is used to calculate the boundary of the Meissner domain when the external field penetrates deep into the superconductor. The effect of degree of penetration on the magnetic moment of superconducting cylinders and wires is discussed

Probing the Penetration of Antimicrobial Polymyxin Lipopeptides into Gram-Negative Bacteria

Science.gov (United States)

2015-01-01

The dry antibiotic development pipeline coupled with the emergence of multidrug resistant Gram-negative ‘superbugs’ has driven the revival of the polymyxin lipopeptide antibiotics. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections. The lack of molecular imaging probes that possess native polymyxin-like antibacterial activity is a barrier to understanding the resistance mechanisms and the development of a new generation of polymyxin lipopeptides. Here we report the regioselective modification of the polymyxin B core scaffold at the N-terminus with the dansyl fluorophore to generate an active probe that mimics polymyxin B pharmacologically. Time-lapse laser scanning confocal microscopy imaging of the penetration of probe (1) into Gram-negative bacterial cells revealed that the probe initially accumulates in the outer membrane and subsequently penetrates into the inner membrane and finally the cytoplasm. The implementation of this polymyxin-mimetic probe will advance the development of platforms for the discovery of novel polymyxin lipopeptides with efficacy against polymyxin-resistant strains. PMID:24635310

An Investigation of Consolidants Penetration in Wood. Part 2: FTIR Spectroscopy

Directory of Open Access Journals (Sweden)

Maria Cristina TIMAR

2011-03-01

Full Text Available FTIR spectroscopy was used in this work for studying the penetration of some consolidants frequentlyused in old wood conservation into test pieces of sound spruce wood (Picea abies wood. Thin microsections(30-60 μm of control and treated wood were analysed in reflectance mode using an ATR system. Theconsolidation products investigated were Paraloid B72, bee wax, a mixture of bee wax / linseed oil and twotypes of paraffins. These products presented FTIR spectra with characteristic common and specific bands,allowing their identification in the treated wood with no impediments coming from their colour, transparencyor the percent of cell lumena filling. The treatment of wood with these products brought about alterations ofthe spectra aspect by the appearance or intensification of some characteristic bands and the modification ofthe ratio between the areas of some characteristic absorption bands so that a qualitative and semiquantitativeevaluation of the presence and penetration depth and distribution of these consolidationproducts in wood was possible, proving the adopted method as valuable and useful for further research inthis field.

Estimating residual life of alloy 600 RPV penetrations

International Nuclear Information System (INIS)

Hunt, E.S.; White, G.A.; Pathania, R.; Arey, M.L.; Whitaker, D.E.

1996-01-01

Primary water stress corrosion cracking (PWSCC) of Alloy 600 penetrations PWR in reactor pressure vessel (RPV) heads has become a significant economic concern worldwide. PWSCC of these penetrations has led to extended maintenance outages, expensive inspections and repairs, and in some cases, replacement of the entire vessel head. This paper describes methodology developed to predict the remaining life of Alloy 600 penetrations in reactor vessel heads. Predictions of remaining life are an important input to planning models used by utilities to select a strategy for responding to the PWSCC issue at the lowest life cycle cost with an acceptably low risk of leakage. The remaining life of RPV penetrations is determined using the results of inspections of penetrations and statistical methods to predict future degradation. The analysis takes into account the effects of material properties, welding residual stresses, and operating temperature on PWSCC initiation and growth. The probability of developing cracks of various depths is assessed using Monte Carlo methods which provide for uncertainties in the input assumptions. For plants which have not yet performed inspections, remaining life predictions are based on inspection results from similar plants which have performed inspections with corrections made for known differences in design details, material properties and operating conditions

Improving Outcomes Following Penetrating Colon Wounds

Science.gov (United States)

Miller, Preston R.; Fabian, Timothy C.; Croce, Martin A.; Magnotti, Louis J.; Elizabeth Pritchard, F.; Minard, Gayle; Stewart, Ronald M.

2002-01-01

Introduction During World War II, failure to treat penetrating colon injuries with diversion could result in court martial. Based on this wartime experience, colostomy for civilian colon wounds became the standard of care for the next 4 decades. Previous work from our institution demonstrated that primary repair was the optimal management for nondestructive colon wounds. Optimal management of destructive wounds requiring resection remains controversial. To address this issue, we performed a study that demonstrated risk factors (pre or intraoperative transfusion requirement of more than 6 units of packed red blood cells, significant comorbid diseases) that were associated with a suture line failure rate of 14%, and of whom 33% died. Based on these outcomes, a clinical pathway for management of destructive colon wounds was developed. The results of the implementation of this pathway are the focus of this report. Methods Patients with penetrating colon injury were identified from the registry of a level I trauma center over a 5-year period. Records were reviewed for demographics, injury characteristics, and outcome. Patients with nondestructive injuries underwent primary repair. Patients with destructive wounds but no comorbidities or large transfusion requirement underwent resection and anastomosis, while patients with destructive wounds and significant medical illness or transfusion requirements of more than 6 units/blood received end colostomy. The current patients (CP) were compared to the previous study (PS) to determine the impact of the clinical pathway. Outcomes examined included colon related mortality and morbidity (suture line leak and abscess). Results Over a 5.5-year period, 231 patients had penetrating colon wounds. 209 survived more 24 hours and comprise the study population. Primary repair was performed on 153 (73%) patients, and 56 patients had destructive injuries (27%). Of these, 40 (71%) had resection and anastomosis and 16 (29%) had diversion

Dynamic hole closure behind a deep ocean sediment penetrator

International Nuclear Information System (INIS)

Dzwilewski, P.T.; Karnes, C.H.

1982-01-01

A freefall or boosted penetrator is one concept being considered to dispose of nuclear waste in the deep ocean seabed. For this technique to be acceptable, the sediment must be an effective barrier to the migration of radioactive nuclides, which means that the hole behind the advancing penetrator must close. One mechanism which can cause the hole to close immediately behind the penetrator is the reduction in water pressure in the wake as water tries to follow the penetrator into the sediment. An approximate solution to this complex problem is presented which analyzes the deformation of the sediment with a nonlinear, large displacement and strain, Lagrangian finite-difference computer code (STEALTH). The water was treated by Bernoulli's Principle for flow in a pipe resulting in a pressure boundary condition applied to the sediment surface along the path after passage of the penetrator. Two one-dimensional and eight two-dimensional calculations were performed with various penetrator velocities (15, 30, and 60 m/s) and sediment shear strengths. In two of the calculations, the dynamic pressure reduction was neglected to see if geostatic stresses alone would close the hole. The results of this study showed that geostatic stresses alone would not close the hole but the dynamic pressure reduction would. The largest uncertainty in the analysis was the pressure conditions in the water behind the penetrator in which frictionless, steady-state flow, in a uniform diameter pipe was assumed. A more sophisticated and realistic pressure condition has been formulated and will be implemented in the computer code in the near future

Effect of water content on the glass transition temperature of mixtures of sugars, polymers, and penetrating cryoprotectants in physiological buffer.

Science.gov (United States)

Drake, Andrew C; Lee, Youngjoo; Burgess, Emma M; Karlsson, Jens O M; Eroglu, Ali; Higgins, Adam Z

2018-01-01

Long-term storage of viable mammalian cells is important for applications ranging from in vitro fertilization to cell therapy. Cryopreservation is currently the most common approach, but storage in liquid nitrogen is relatively costly and the requirement for low temperatures during shipping is inconvenient. Desiccation is an alternative strategy with the potential to enable viable cell preservation at more convenient storage temperatures without the need for liquid nitrogen. To achieve stability during storage in the dried state it is necessary to remove enough water that the remaining matrix forms a non-crystalline glassy solid. Thus, the glass transition temperature is a key parameter for design of cell desiccation procedures. In this study, we have investigated the effects of moisture content on the glass transition temperature (Tg) of mixtures of sugars (trehalose or raffinose), polymers (polyvinylpyrrolidone or Ficoll), penetrating cryoprotectants (ethylene glycol, propylene glycol, or dimethyl sulfoxide), and phosphate buffered saline (PBS) solutes. Aqueous solutions were dried to different moisture contents by equilibration with saturated salt solutions, or by baking at 95°C. The glass transition temperatures of the dehydrated samples were then measured by differential scanning calorimetry. As expected, Tg increased with decreasing moisture content. For example, in a desiccation medium containing 0.1 M trehalose in PBS, Tg ranged from about 360 K for a completely dry sample to about 220 K at a water mass fraction of 0.4. Addition of polymers to the solutions increased Tg, while addition of penetrating cryoprotectants decreased Tg. Our results provide insight into the relationship between relative humidity, moisture content and glass transition temperature for cell desiccation solutions containing sugars, polymers and penetrating cryoprotectants.

Differential Expression of pro-inflammatory and oxidative stress mediators induced by nitrogen dioxide and ozone in primary human bronchial epithelial cells

Science.gov (United States)

CONTEXT: N02 and 03 are ubiquitous air toxicants capable of inducing lung damage to the respiratory epithelium. Due to their oxidizing capabilities, these pollutants have been proposed to target specific biological pathways, but few publications have compared the pathways activat...

Replica scale modelling of long rod tank penetrators

NARCIS (Netherlands)

Diederen, A.M.; Hoeneveld, J.C.

2001-01-01

Experiments and simulations have been conducted using scale size tungsten alloy penetrators at ordnance velocity against an oblique plate array consisting of an inert sandwich and a base armour. The penetrators are made from 2 types of tungsten alloy with different tensile strength. Two scale sizes

The Impact of IPv6 on Penetration Testing

NARCIS (Netherlands)

Ottow, Christiaan; van Vliet, Frank; de Boer, Pieter-Tjerk; Pras, Aiko

In this paper we discuss the impact the use of IPv6 has on remote penetration testing of servers and web applications. Several modifications to the penetration testing process are proposed to accommodate IPv6. Among these modifications are ways of performing fragmentation attacks, host discovery and

Conditions for plasmoid penetration across abrupt magnetic barriers

International Nuclear Information System (INIS)

Brenning, Nils; Hurtig, Tomas; Raadu, Michael A.

2005-01-01

The penetration of plasma clouds, or plasmoids, across abrupt magnetic barriers (of the scale less than a few ion gyro radii, using the plasmoid directed velocity) is studied. The insight gained earlier, from detailed experimental and computer simulation investigations of a case study, is generalized into other parameter regimes. It is concluded for what parameters a plasmoid should be expected to penetrate the magnetic barrier through self-polarization, penetrate through magnetic expulsion, or be rejected from the barrier. The scaling parameters are n e , v 0 , B perpendicular , m i , T i , and the width w of the plasmoid. The scaling is based on a model for strongly driven, nonlinear magnetic field diffusion into a plasma which is a generalization of the earlier laboratory findings. The results are applied to experiments earlier reported in the literature, and also to the proposed application of impulsive penetration of plasmoids from the solar wind into the Earth's magnetosphere

Long-term behavior of aortic intramural hematomas and penetrating ulcers.

Science.gov (United States)

Chou, Alan S; Ziganshin, Bulat A; Charilaou, Paris; Tranquilli, Maryann; Rizzo, John A; Elefteriades, John A

2016-02-01

For intramural hematoma and penetrating atherosclerotic ulcer, long-term behavior and treatment are controversial. This study evaluates the long-term behavior of intramural hematoma and penetrating atherosclerotic ulcer, including radiologic follow-up and survival analysis. Between 1995 and 2014, 108 patients (mean age, 70.8 ± 10 years; 56% female) presented with intramural hematoma or penetrating atherosclerotic ulcer to Yale-New Haven Hospital (New Haven, Conn). We reviewed the medical records, radiology, and online mortality databases. Ten of 55 patients (18%) with intramural hematoma and 17 of 53 patients (32%) with penetrating atherosclerotic ulcer had rupture state symptoms on admission, both greater than type A (8%) or type B dissection (4%) (P hematoma with follow-up imaging, 8 of 14 (57%) worsened (mean follow-up, 9.4 months) and 6 (43%) underwent late surgery. For patients with penetrating atherosclerotic ulcer with follow-up imaging, 6 of 20 (30%) worsened and underwent late surgery, and 11 (55%) showed no change (mean follow-up, 34.3 months). Overall survivals were 77%, 70%, 58%, and 33% at 1, 3, 5, and 10 years, respectively. No operative deaths occurred for patients with nonrupture state. Patients with penetrating atherosclerotic ulcer with initial surgical treatment had better long-term survival than patients treated medically (P = .037). In the intramural hematoma group, no such difference was observed (P = .10). At presentation, the incidence of early rupture of intramural hematoma and penetrating atherosclerotic ulcer was higher than for typical dissection. For branch vessels, intramural hematoma never occludes branch arteries. On imaging follow-up, patients with intramural hematoma and penetrating atherosclerotic ulcer rarely improved, with late surgery commonly needed. Better survival was observed for the initial surgical management of patients with penetrating atherosclerotic ulcer compared with initial medical management. Copyright © 2016

HMO penetration and physicians' earnings.

Science.gov (United States)

Hadley, J; Mitchell, J M

1999-11-01

The goal of this study is to estimate whether cross-sectional variations in enrollment in health maintenance organizations (HMOs) affected physicians' earnings and hourly income in 1990. Using data from a nationally representative sample of 4,577 younger physicians (penetration is endogenous and used the instrumental variables approach to obtain unbiased estimates. HMO penetration had a negative and statistically significant impact on physicians earnings in 1990. A doubling of the average level of HMO penetration in the market is estimated to reduce annual earnings by 7% to 10.7%, and hourly earnings by approximately 6% to 9%. It appears that HMOs were successful in reducing physicians' annual and per hour earnings in 1990, presumably through a combination of fewer visits and lower payment rates for people covered by HMOs. Although these results cannot be generalized to all physicians, the experience of a younger cohort of physicians may still be a good indicator of the future effects of HMOs because younger physicians may be more susceptible to market forces than older and more established physicians. Moreover, these results may be somewhat conservative because they reflect market behavior in 1990, several years before the rapid growth and more aggressive market behavior of HMOs in recent years.

Hybrid treatment of penetrating aortic ulcer

International Nuclear Information System (INIS)

Lara, Juan Antonio Herrero; Martins-Romeo, Daniela de Araujo; Escudero, Carlos Caparros; Falcon, Maria del Carmen Prieto; Batista, Vinicius Bianchi; Vazquez, Rosa Maria Lepe

2015-01-01

Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease. (author)

Hybrid treatment of penetrating aortic ulcer

Energy Technology Data Exchange (ETDEWEB)

Lara, Juan Antonio Herrero; Martins-Romeo, Daniela de Araujo; Escudero, Carlos Caparros; Falcon, Maria del Carmen Prieto; Batista, Vinicius Bianchi, E-mail: jaherrero5@hotmail.com [Unidade de Gestao Clinica (UGC) de Diagnostico por Imagem - Hosppital Universitario Virgen Macarena, Sevilha (Spain); Vazquez, Rosa Maria Lepe [Unit of Radiodiagnosis - Hospital Nuestra Senora de la Merced, Osuna, Sevilha (Spain)

2015-05-15

Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease. (author)

Methane penetration in DIII-D ELMing H-mode plasmas

International Nuclear Information System (INIS)

West, W.P.; Lasnier, C.J.; Whyte, D.G.; Isler, R.C.; Evans, T.E.; Jackson, G.L.; Rudakov, D.; Wade, M.R.; Strachan, J.

2003-01-01

Carbon penetration into the core plasma during midplane and divertor methane puffing has been measured for DIII-D ELMing H-mode plasmas. The methane puffs are adjusted to a measurable signal, but global plasma parameters are only weakly affected (line average density, e > increases by E , drops by 6+ density profiles in the core measured as a function of time using charge exchange recombination spectroscopy. The methane penetration factor is defined as the difference in the core content with the puff on and puff off, divided by the carbon confinement time and the methane puffing rate. In ELMing H-mode discharges with ion ∇B drift direction into the X-point, increasing the line averaged density from 5 to 8x10 19 m -3 dropped the penetration factor from 6.6% to 4.6% for main chamber puffing. The penetration factor for divertor puffing was below the detection limit (<1%). Changing the ion ∇B drift to away from the X-point decreased the penetration factor by more than a factor of five for main chamber puffing

Double ionization chamber survey meter for the separate measurement of penetrating and non-penetrating dose

International Nuclear Information System (INIS)

Lucas, A.C.

1987-01-01

The full capabilities of an advanced 8-bit microprocessor have been utilized in construction of a wide range, multiplexing survey meter based on dual electrometers and ionization chambers. The ionization chambers are constructed of modular conducting and non-conducting parts in such a way that the angular dependence for measurement of beta radiation is controlled by design. Display functions for the high range instrument include logarithmic or linear analog display, digital display of rate or dose, SI or English units, optionally for either total, penetrating, or non-penetrating dose. The instrument is presently configured to operate in the range 0.1 R/hr to 50,000 R/hr in support of the requirements of Regulatory Guide 19.7

Videofluoroscopic Predictors of Penetration-Aspiration in Parkinson's Disease Patients.

Science.gov (United States)

Argolo, Natalie; Sampaio, Marília; Pinho, Patrícia; Melo, Ailton; Nóbrega, Ana Caline

2015-12-01

Parkinson's disease (PD) patients show a high prevalence of swallowing disorders and tracheal aspiration of food. The videofluoroscopic study of swallowing (VFSS) allows clinicians to visualize the visuoperceptual and temporal parameters associated with swallowing disorders in an attempt to predict aspiration risk. However, this subject remains understudied in PD populations. Our aim was to identify the predictors of penetration-aspiration in PD patients using the VFSS. Consecutive patients were evaluated using VFSS with different consistencies and volumes of food. A speech-language pathologist measured the type of intra-oral bolus organization, loss of bolus control, bolus location at the initiation of the pharyngeal swallow, the presence of multiple swallows, piecemeal deglutition, bolus residue in the pharyngeal recesses and temporal measures. Scores ≥3 on the penetration-aspiration scale (PAS) indicated the occurrence of penetration-aspiration. Using logistic marginal regression, we found that residue in the vallecula, residue in the upper esophageal sphincter and piecemeal deglutition were associated with penetration-aspiration (odds ratio (OR) = 4.09, 2.87 and 3.83; P = 0.0040, 0.0071 and 0.0009, respectively). Penetration/aspiration occurred only with fluids (both of thin and thick consistency), and no significant differences were observed between fluid types or food volumes. The mechanisms underlying dysphagia and penetration/aspiration in PD patients and indications for further studies are discussed.

Penetration of nanoparticles in flax (Linum usitatissimum L.) calli and regenerants.

Science.gov (United States)

Kokina, Inese; Gerbreders, Vjačeslavs; Sledevskis, Eriks; Bulanovs, Andrejs

2013-05-20

We demonstrate a method for direct delivery of metal nanoparticles to flax calli and regenerant cells by vacuum deposition of metal nanolayers on powdered hormone followed by dispersal of the combined hormone-metal in medium. The penetration and location of the gold (AuNPs) and silver (AgNPs) nanoparticles in calli and in plant regenerants were confirmed by optical absorption spectroscopy and scanning electron microscopy. We detected a significant effect of the AuNPs and AgNPs on the regeneration type of flax calli. Copyright © 2013 Elsevier B.V. All rights reserved.

The cytosolic domain of T-cell receptor ζ associates with membranes in a dynamic equilibrium and deeply penetrates the bilayer.

Science.gov (United States)

Zimmermann, Kerstin; Eells, Rebecca; Heinrich, Frank; Rintoul, Stefanie; Josey, Brian; Shekhar, Prabhanshu; Lösche, Mathias; Stern, Lawrence J

2017-10-27

Interactions between lipid bilayers and the membrane-proximal regions of membrane-associated proteins play important roles in regulating membrane protein structure and function. The T-cell antigen receptor is an assembly of eight single-pass membrane-spanning subunits on the surface of T lymphocytes that initiates cytosolic signaling cascades upon binding antigens presented by MHC-family proteins on antigen-presenting cells. Its ζ-subunit contains multiple cytosolic immunoreceptor tyrosine-based activation motifs involved in signal transduction, and this subunit by itself is sufficient to couple extracellular stimuli to intracellular signaling events. Interactions of the cytosolic domain of ζ (ζ cyt ) with acidic lipids have been implicated in the initiation and regulation of transmembrane signaling. ζ cyt is unstructured in solution. Interaction with acidic phospholipids induces structure, but its disposition when bound to lipid bilayers is controversial. Here, using surface plasmon resonance and neutron reflection, we characterized the interaction of ζ cyt with planar lipid bilayers containing mixtures of acidic and neutral lipids. We observed two binding modes of ζ cyt to the bilayers in dynamic equilibrium: one in which ζ cyt is peripherally associated with lipid headgroups and one in which it penetrates deeply into the bilayer. Such an equilibrium between the peripherally bound and embedded forms of ζ cyt apparently controls accessibility of the immunoreceptor tyrosine-based activation signal transduction pathway. Our results reconcile conflicting findings of the ζ structure reported in previous studies and provide a framework for understanding how lipid interactions regulate motifs to tyrosine kinases and may regulate the T-cell antigen receptor biological activities for this cell-surface receptor system.

Penetrating Cardiac and Hepatic Injury; Polytrauma of a Child After Bombing

Directory of Open Access Journals (Sweden)

Baris Akca

2013-10-01

Full Text Available After a bombing attack, patients were brought into hospital suffering from a combination of injuries caused by the blast, penetrating injuries and burns which as a case of polytrauma. In penetrating thoracoabdominal injuries due to bombing possibility of cardiac injury should be kept in mind. Penetrating cardiac injuries in children are rare but has a high mortality and morbidity. In some cases there may be difficulty in diagnosis of penetrating cardiac injury. In this case we want to share the diagnosis, treatment and follow-up processes of penetrating cardiac and hepatic injury with burns of a politrauma child due to bombing.

Birch pollen influence the severity of atopic eczema – prospective clinical cohort pilot study and ex vivo penetration study

Directory of Open Access Journals (Sweden)

Fölster-Holst R

2015-10-01

Full Text Available Regina Fölster-Holst,1 Jagoda Galecka,1 Sigo Weißmantel,1 Ute Dickschat,2 Frank Rippke,3 Kerstin Bohnsack,3 Thomas Werfel,4 Katja Wichmann,4 Matthias Buchner,1 Thomas Schwarz,1 Annika Vogt,5 Jürgen Lademann,5 Martina C Meinke5 1Department of Dermatology, Venerology and Allergy, University of Kiel, 2Wörth, 3Beiersdorf AG, Hamburg, 4Department of Dermatology, Venerology and Allergy, Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, 5Department of Dermatology, Venerology and Allergology, Charité – Universitätsmedizin Berlin, Berlin, Germany Abstract: There is little clinical evidence for a correlation between the severity of atopic eczema (AE and pollen exposition. To obtain more data, we performed a clinical cohort pilot study about the influence of pollen on AE between sensitized and nonsensitized subjects and an experimental study addressing the cutaneous penetration of pollen into the skin. Fifty-five patients were monitored during birch pollen season. To study the cutaneous penetration, grass pollen allergens were applied on excised skin and the uptake in CD1c-expressing dendritic cells was investigated. The correlation between environmental pollen load and severity of the Scoring Atopic Dermatitis (SCORAD score and pruritus was observed, regardless of the status of sensitization. The sensitized group recovered significantly worse after the birch pollen season. Remarkably higher amounts of pollen allergens taken up by CD1c cells were detected in epidermal cells derived from skin explants with a disturbed epidermal barrier. These findings suggest an exacerbating role of pollen in AE utilizing the epidermal route. Keywords: aeroallergens, atopic eczema, seasonality, skin antigen-presenting cells, skin barrier penetration

Update on the Management of High-Risk Penetrating Keratoplasty.

Science.gov (United States)

Jabbehdari, Sayena; Rafii, Alireza Baradaran; Yazdanpanah, Ghasem; Hamrah, Pedram; Holland, Edward J; Djalilian, Ali R

2017-03-01

In this article, we review the indications and latest management of high-risk penetrating keratoplasty. Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed. Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.

Cutaneous mucormycosis secondary to penetrative trauma.

Science.gov (United States)

Zahoor, Bilal; Kent, Stephen; Wall, Daryl

2016-07-01

Mucormycosis is a rare but serious sequelae of penetrating trauma [1-5]. In spite of aggressive management, mortality remains high due to dissemination of infection. We completed a review of literature to determine the most optimal treatment of cutaneous mucormycosis which occurs secondary to penetrating trauma. We completed a review regarding the management of mucormycosis in trauma patients. We selected a total of 36 reports, of which 18 were case-based, for review. Surgical debridement is a primary predictor of improved outcomes in the treatment of mucormycosis [3,6,7]. Anti-fungal therapy, especially lipid soluble formulation of Amphotericin B, is helpful as an adjunct or when surgical debridement has been maximally achieved. Further research is needed to fully evaluate the impact of topical dressings; negative pressure wound therapy is helpful. An aggressive and early surgical approach, even at the expense of disfigurement, is necessary to reduce mortality in the setting of cutaneous mucormycosis that results from penetrating trauma [4,8,9]. Anti-fungal therapy and negative pressure wound therapy are formidable adjuncts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Wireless Network Penetration Testing and Security Auditing

Directory of Open Access Journals (Sweden)

Wang Shao-Long

2016-01-01

Full Text Available IEEE802.11 wireless wireless networks have security issues that are vulnerable to a variety of attacks. Due to using radio to transport data, attackers can bypass firewalls, sniff sensitive information, intercept packets and send malicious packets. Security auditing and penetration testing is expected to ensure wireless networks security. The contributions of this work are analyzed the vulnerability and types of attacks pertaining to IEEE 802.11 WLAN, performed well known attacks in a laboratory environment to conduct penetration tests to confirm whether our wireless network is hackable or not. WAIDPS is configured as auditing tool to view wireless attacks, such as WEP/WPA/WPA2 cracking, rouge access points, denial of service attack. WAIDPS is designed to detect wireless intrusion with additional features. Penetration testing and auditing will mitigate the risk and threatening to protect WALN.

Penetrating chest injury: A miraculous life salvage

Directory of Open Access Journals (Sweden)

Santosh B Dalavi

2013-01-01

Full Text Available An unusual penetrating chest injury was caused by high velocity road traffic accident. An 18-year-old had a four wheeler accident and was brought in emergency department with a ′bamboo′ stick on the left side chest exiting through back. After the stabilization of vital parameters, an inter-costal tube drainage was done on the left side. Except the minor brochopleural fistula which healed by 10 th day, his recovery was uneventful. The outcome was consistent with current aggressive management of penetrating chest injuries. Management of penetrating chest injury involving pulmonary trauma is based on three principles. One is stabilization of hemodynamics of patient with proper clinical evaluation. Second, a mere intercostal tube drainage sufficient for majority of the cases. Third, post-operative active as well as passive physiotherapy is necessary for speedy recovery.

Characteristics of rain penetration through a gravity ventilator used for natural ventilation.

Science.gov (United States)

Kim, Taehyeung; Lee, Dong Ho; Ahn, Kwangseog; Ha, Hyunchul; Park, Heechang; Piao, Cheng Xu; Li, Xiaoyu; Seo, Jeoungyoon

2008-01-01

Gravity ventilators rely simply on air buoyancy to extract air and are widely used to exhaust air contaminants and heat from workplaces using minimal energy. They are designed to maximize the exhaust flow rate, but the rain penetration sometimes causes malfunctioning. In this study, the characteristics of rain penetration through a ventilator were examined as a preliminary study to develop a ventilator with the maximum exhaust capacity while minimizing rain penetration. A model ventilator was built and exposed to artificial rain and wind. The paths, intensities and amounts of penetration through the ventilator were observed and measured in qualitative and quantitative fashions. In the first phase, the pathways and intensities of rain penetration were visually observed. In the second phase, the amounts of rain penetration were quantitatively measured under the different configurations of ventilator components that were installed based on the information obtained in the first-phase experiment. The effects of wind speed, grill direction, rain drainage width, outer wall height, neck height and leaning angle of the outer wall from the vertical position were analyzed. Wind speed significantly affected rain penetration. Under the low crosswind conditions, the rain penetration intensities were under the limit of detection. Under the high crosswind conditions, grill direction and neck height were the most significant factors in reducing rain penetration. The installation of rain drainage was also important in reducing rain penetration. The experimental results suggest that, with proper configurations of its components, a gravity ventilator can be used for natural ventilation without significant rain penetration problems.

Barbs facilitate the helical penetration of honeybee (Apis mellifera ligustica) stingers.

Science.gov (United States)

Wu, Jianing; Yan, Shaoze; Zhao, Jieliang; Ye, Yuying

2014-01-01

The stinger is a very small and efficient device that allows honeybees to perform two main physiological activities: repelling enemies and laying eggs for reproduction. In this study, we explored the specific characteristics of stinger penetration, where we focused on its movements and the effects of it microstructure. The stingers of Italian honeybees (Apis mellifera ligustica) were grouped and fixed onto four types of cubic substrates, before pressing into different substrates. The morphological characteristics of the stinger cross-sections were analyzed before and after penetration by microscopy. Our findings suggest that the honeybee stinger undergoes helical and clockwise rotation during penetration. We also found that the helical penetration of the stinger is associated directly with the spiral distribution of the barbs, thereby confirming that stinger penetration involves an advanced microstructure rather than a simple needle-like apparatus. These results provide new insights into the mechanism of honeybee stinger penetration.

Conducting network penetration and espionage in a global environment

CERN Document Server

Middleton, Bruce

2014-01-01

When it's all said and done, penetration testing remains the most effective way to identify security vulnerabilities in computer networks. Conducting Network Penetration and Espionage in a Global Environment provides detailed guidance on how to perform effective penetration testing of computer networks-using free, open source, and commercially available tools, including Backtrack, Metasploit, Wireshark, Nmap, Netcat, and Nessus. It also considers exploits and other programs using Python, PERL, BASH, PHP, Ruby, and Windows PowerShell.The book taps into Bruce Middleton's decades of experience wi

The Effect and Mechanism of Transdermal Penetration Enhancement of Fu's Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics.

Science.gov (United States)

Xie, Wei-Jie; Zhang, Yong-Ping; Xu, Jian; Sun, Xiao-Bo; Yang, Fang-Fang

2017-03-27

In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC 0-t , AUMC 0-t ), area under the zero and first moment curves from 0 to infinity (AUC 0-∞ , AUMC 0-∞ ), maximum plasma concentration (C max ) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3 K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with

Field Test Evaluation of Effect on Cone Resistance Caused by Change in Penetration Rate

DEFF Research Database (Denmark)

Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

2012-01-01

in the laboratory. A change in the measured cone resistance occurs by lowering the penetration rate. This is caused by the changes in drainage conditions. Compared to the normal penetration rate of 20 mm/s, this paper illustrates that lowering the penetration rate leads to an increase in the cone resistance from 1......This paper presents how a change in cone penetration rate affects the measured cone resistance during cone penetration testing in silty soils. Regardless of soil, type the standard rate of penetration is 20 mm/s and it is generally accepted that undrained penetration occurs in clay while drained...... penetration occurs in sand. In intermediate soils such as silty soils, the standard cone penetration rate may result in drainage conditions varying from undrained to partially or fully drained conditions. Field cone penetrations tests have been conducted with different penetration rates on a test site...

Graft failure: III. Glaucoma escalation after penetrating keratoplasty.

Science.gov (United States)

Greenlee, Emily C; Kwon, Young H

2008-06-01

Glaucoma after penetrating keratoplasty is a frequently observed post-operative complication and is a risk factor for graft failure. Penetrating keratoplasty performed for aphakic and pseudophakic bullous keratopathy and inflammatory conditions are more likely to cause postoperative glaucoma compared with keratoconus and Fuchs' endothelial dystrophy. The intraocular pressure elevation may occur immediately after surgery or in the early to late postoperative period. Early postoperative causes of glaucoma include pre-existing glaucoma, retained viscoelastic, hyphema, inflammation, pupillary block, aqueous misdirection, or suprachoroidal hemorrhage. Late causes include pre-existing glaucoma, angle-closure glaucoma, ghost cell glaucoma, suprachoroidal hemorrhage, and steroid-induced glaucoma. Determining the cause of IOP elevation can help guide therapeutic intervention. Treatments for refractory glaucoma include topical anti-glaucoma medications such as beta-adrenergic blockers. Topical carbonic anhydrase inhibitors, miotic agents, adrenergic agonists, and prostaglandin analogs should be used with caution in the post-keratoplasty patient, because of the possibility of corneal decompensation, cystoid macular edema, or persistent inflammation. Various glaucoma surgical treatments have reported success in post-keratoplasty glaucoma. Trabeculectomy with mitomycin C can be successful in controlling IOP without the corneal toxicity noted with 5-fluorouracil. Glaucoma drainage devices have successfully controlled intraocular pressure in postkeratoplasty glaucoma; this is, however, associated with increased risk of graft failure. Placement of the tube through the pars plana may improve graft success compared with implantation within the anterior chamber. In addition, cyclophotocoagulation remains a useful procedure for eyes that have refractory glaucoma despite multiple surgical interventions.

Experience With The Management Of unusual Penetrating Chest ...

African Journals Online (AJOL)

The presentation shows how a victim of fall from height in the bush can sustain a penetrating chest injury on a dry stick of a shrub. Applications on the principles of management of penetrating chest injury is needed despite the grotesque clinical appearance. [Jnl College of Medicine Vol.7(1) 2002: 40-42] ...

An explosive acoustic telemetry system for seabed penetrators

Energy Technology Data Exchange (ETDEWEB)

Hauser, G.C.; Hickerson, J.

1988-04-01

This report discusses the design and past applications of an explosive acoustic telemetry system (EATS) for gathering and transmitting data from seabed penetrators. The system was first fielded in 1982 and has since been used to measure penetrator performance on three other occasions. Descriptions are given of the mechanical hardware, system electronics, and software.

Operational experience of extreme wind penetrations

Energy Technology Data Exchange (ETDEWEB)

Estanqueiro, Ana [INETI/LNEG - National Laboratory for Energy and Geology, Lisbon (Portugal); Mateus, Carlos B. [Instituto de Meteorologia, Lisboa (Portugal); Pestana, Rui [Redes Energeticas Nacionais (REN), Lisboa (Portugal)

2010-07-01

This paper reports the operational experience from the Portuguese Power System during the 2009/2010 winter months when record wind penerations were observed: the instantaneous wind power penetration peaked at 70% of consumption during no-load periods and the wind energy accounted for more than 50% of the energy consumed for a large period. The regulation measures taken by the TSO are presented in the paper, together with the additional reserves operated for added system security. Information on the overall power system behavior under such extreme long-term wind power penetrations will also be addressed. (org.)

Generic Penetration of the SSRI Market.

Science.gov (United States)

Cascade, Elisa F; Kalali, Amir H

2008-04-01

In this article, we investigate the penetration of generic selective serotonin reuptake inhibitors (SSRIs) in the US market and the implications for patient out-of-pocket expense. The data suggest that generic penetration into the SSRI market has grown from approximately nine percent in 2000, the year that the patent for Prozac((R)) expired, to 72 percent in 2007. For December, 2007, the difference in patient out-of-pocket expense for branded vs. generic agents was, on average, $55.42 for patients paying by cash (i.e., they had no prescription drug insurance) and $22.39 for patients with insurance coverage.

Penetrating ocular trauma from trampoline spring.

Science.gov (United States)

Spokes, David; Siddiqui, Salina; Vize, Colin

2010-02-01

The case is presented of a 12-year old boy who sustained severe penetrating ocular trauma while playing on a domestic trampoline. A main spring broke under tension and the hook had struck the eye at high velocity and penetrated the sclera. Primary repair was undertaken but on review it became apparent the eye could not be salvaged. Evisceration was carried out and an orbital implant was placed. Post-operative cosmesis is acceptable. This type of injury has not been reported before. Adult supervision of children on trampolines is recommended to minimise the chance of serious injury.

Fire barrier penetration seals in nuclear power plants

International Nuclear Information System (INIS)

Bajwa, C.S.; West, K.S.

1996-07-01

NNPs are divided into separated fire areas by fire-rated structural barriers. Fire-rated penetration seals are installed to seal certain openings in these barriers, in order to provide reasonable assurance that a fire will be confined to the area where it started. The staff of the Fire Protection Engineering Section, Office of Nuclear Reactor Regulation, US NRC, conducted a comprehensive technical assessment of penetration seals to address reports of potential problems, to determine if there were any problems of safety significance, and to determine if NRC requirements, review guidance, and inspection procedures are adequate. It was concluded that the general condition of penetration seal programs in industry is satisfactory, and that the actions taken in 1988 and 1994 had increased industry awareness of potential problems and resulted in more thorough surveillances, maintenance, and corrective actions. These previous staff actions, together with continued licensee upkeep of existing penetration seal programs and continued NRC inspections, are adequate to maintain public health and safety. Several minor revisions to the NRC fire protection regulation and review guidance are recommended

Determining Hermeticity of Electron Devices by Dye Penetration

CERN Document Server

American Society for Testing and Materials. Philadelphia

1972-01-01

1.1 These practices cover procedures that will normally detect and locate the sites of gross leaks in electron devices. 1.2 These procedures are suitable for use on selected parts during receiving inspection or to verify and locate leakage sites for production control. They are not quantitative; no indication of leak size can be inferred from the test. 1.3 These procedures are most suitable for use on transparent glass-encased devices; all methods are applicable to transparent parts with an internal cavity. Method A, Penetrant-Capillary, is also applicable to parts, such as terminals, end seals or base assemblies, without an internal cavity, and Method C, Penetrant-Pressure Followed by Vacuum, can be used on opaque parts with an internal cavity. Method B, Penetrant-Pressure, can also be used on opaque parts with an internal cavity if the part is opened after dye penetration and before inspection. Parts that have an internal cavity may either contain gas (such as air, nitrogen, nitrogen-helium mixture, etc.) o...

Primary repair of penetrating colon injuries: a systematic review.

Science.gov (United States)

Singer, Marc A; Nelson, Richard L

2002-12-01

Primary repair of penetrating colon injuries is an appealing management option; however, uncertainty about its safety persists. This study was conducted to compare the morbidity and mortality of primary repair with fecal diversion in the management of penetrating colon injuries by use of a meta-analysis of randomized, prospective trials. We searched for prospective, randomized trials in MEDLINE (1966 to November 2001), the Cochrane Library, and EMBase using the terms colon, penetrating, injury, colostomy, prospective, and randomized. Studies were included if they were randomized, controlled trials that compared the outcomes of primary repair with fecal diversion in the management of penetrating colon injuries. Five studies were included. Reviewers performed data extraction independently. Outcomes evaluated from each trial included mortality, total complications, infectious complications, intra-abdominal infections, wound complications, penetrating abdominal trauma index, and length of stay. Peto odds ratios for combined effect were calculated with a 95 percent confidence interval for each outcome. Heterogeneity was also assessed for each outcome. The penetrating abdominal trauma index of included subjects did not differ significantly between studies. Mortality was not significantly different between groups (odds ratio, 1.70; 95 percent confidence interval, 0.51-5.66). However, total complications (odds ratio, 0.28; 95 percent confidence interval, 0.18-0.42), total infectious complications (odds ratio, 0.41; 95 percent confidence interval, 0.27-0.63), abdominal infections including dehiscence (odds ratio, 0.59; 95 percent confidence interval, 0.38-0.94), abdominal infections excluding dehiscence (odds ratio, 0.52; 95 percent confidence interval, 0.31-0.86), wound complications including dehiscence (odds ratio, 0.55; 95 percent confidence interval, 0.34-0.89), and wound complications excluding dehiscence (odds ratio, 0.43; 95 percent confidence interval, 0

Orientation dependence of deformation and penetration behavior of tungsten single-crystal rods

International Nuclear Information System (INIS)

Bruchey, W.J.; Horwath, E.J.; Kingman, P.W.

1991-01-01

This paper reports on the performance of tungsten single crystals as kinetic energy penetrator materials that was investigated in a high length-to-diameter (L/D) rod geometry at sub-scale (1/4 geometric scale). The [111]. [110], and [100] crystal orientations were tested in this 74-g LD = 15 geometry penetrator (6.90-mm diameter x 102.5-mm length). Several 93% tungsten alloy and uranium 3/4 titanium rod geometries were also tested to baseline expected performance of typical penetrator material/geometry combinations. Performance was determined for semi-infinite penetration into RHA steel and finite penetration into 76.20-mm RHA steel. Of the orientation tested, the [100] orientation provided the best ballistic results, with superior performance to mass and geometric equivalent 93% tungsten alloy rods. The [100] orientation also provided similar performance to geometric equivalent uranium 3/4 titanium rods. Favorable slip/cleavage during the compressive loading of the penetration process to allow penetrator material flow without large scale plastic deformation, and final shear localization at a favorable angle for easy material flow away from the penetration interface, contribute to the [100] orientation crystals' excellent performance. The net result was less energy expenditure during penetrator flow and, therefore, more energy for deformation of RHA

UO2/magnetite concrete interaction and penetration study

International Nuclear Information System (INIS)

Farhadieh, R.; Purviance, R.; Carlson, N.

1983-01-01

The concrete structure represents a line of defense in safety assessment of containment integrity and possible minimization of radiological releases following a reactor accident. The penetration study of hot UO 2 particles into limestone concrete and basalt concrete highlighted some major differences between the two concretes. These included penetration rate, melting and dissolution phenomena, released gases, pressurization of the UO 2 chamber, and characteristics of post-test concrete. The present study focuses on the phenomena associated with core debris interaction with and penetration into magnetite type concrete. The real material experiment was carried out with UO 2 particles and magnetite concrete in a test apparatus similar to the one utilized in the UO 2 /limestone experiment

Variance reduction methods applied to deep-penetration problems

International Nuclear Information System (INIS)

Cramer, S.N.

1984-01-01

All deep-penetration Monte Carlo calculations require variance reduction methods. Before beginning with a detailed approach to these methods, several general comments concerning deep-penetration calculations by Monte Carlo, the associated variance reduction, and the similarities and differences of these with regard to non-deep-penetration problems will be addressed. The experienced practitioner of Monte Carlo methods will easily find exceptions to any of these generalities, but it is felt that these comments will aid the novice in understanding some of the basic ideas and nomenclature. Also, from a practical point of view, the discussions and developments presented are oriented toward use of the computer codes which are presented in segments of this Monte Carlo course

A Study of Crystalline Mechanism of Penetration Sealer Materials.

Science.gov (United States)

Teng, Li-Wei; Huang, Ran; Chen, Jie; Cheng, An; Hsu, Hui-Mi

2014-01-14

It is quite common to dispense a topping material like crystalline penetration sealer materials (CPSM) onto the surface of a plastic substance such as concrete to extend its service life span by surface protections from outside breakthrough. The CPSM can penetrate into the existing pores or possible cracks in such a way that it may form crystals to block the potential paths which provide breakthrough for any unknown materials. This study investigated the crystalline mechanism formed in the part of concrete penetrated by the CPSM. We analyzed the chemical composites, in order to identify the mechanism of CPSM and to evaluate the penetrated depth. As shown in the results, SEM observes the acicular-structured crystals filling capillary pores for mortar substrate of the internal microstructure beneath the concrete surface; meanwhile, XRD and FT-IR showed the main hydration products of CPSM to be C-S-H gel and CaCO₃. Besides, MIP also shows CPSM with the ability to clog capillary pores of mortar substrate; thus, it reduces porosity, and appears to benefit in sealing pores or cracks. The depth of CPSM penetration capability indicated by TGA shows 0-10 mm of sealer layer beneath the concrete surface.

Penetration, Post-penetration Development, and Reproduction of Meloidogyne incognita on Cucumis melo var. texanus.

Science.gov (United States)

Faske, T R

2013-03-01

Cucumis melo var. texanus, a wild melon commonly found in the southern United States and two accessions, Burleson Co. and MX 1230, expressed resistance to Meloidogyne incognita in preliminary experiments. To characterize the mechanism of resistance, we evaluated root penetration, post-penetration development, reproduction, and emigration of M. incognita on these two accessions of C. melo var. texanus. Additionally, we evaluated 22 accessions of C. melo var. texanus for their reaction against M. incognita in a greenhouse experiment. Fewer (P ≤ 0.05) J2 penetrated the root system of C. melo var. texanus accessions (Burleson Co. and MX 1230) and C. metuliferus (PI 482452) (resistant control), 7 days after inoculation (DAI) than in C. melo 'Hales Best Jumbo' (susceptible control). A delayed (P ≤ 0.05) rate of nematode development was observed at 7, 14, and 21 DAI that contributed to lower (P ≤ 0.05) egg production on both accessions and C. metuliferus compared with C. melo. Though J2 emigration was observed on all Cucumis genotypes a higher (P ≤ 0.05) rate of J2 emigration was observed from 3 to 6 DAI on accession Burleson Co. and C. metuliferus than on C. melo. The 22 accessions of C. melo var. texanus varied relative to their reaction to M. incognita with eight supporting similar levels of nematode reproduction to that of C. metuliferus. Cucumis melo var. texanus may be a useful source of resistance against root-knot nematode in melon.

Spatiotemporal Dynamics of Soil Penetration Resistance of Recultivated Soil

Directory of Open Access Journals (Sweden)

Zadorozhnaya Galina

2018-03-01

Full Text Available This article examines changes in the spatial distribution of soil penetration resistance in ordinary chernozem (Calcic Chernozem and in the recultivated soil in 2012 and 2014. The measurements were carried out in the field using an Eijkelkamp penetrometer on a regular grid. The depth of measurement was 50 cm, the interval was 5 cm. The indices of variation of soil penetration resistance in space and time have been determined. The degree of spatial dependence of soil penetration resistance has been determined layer by layer. The nature of temporal dynamics of soil penetration resistance of chernozem and technical soil has been described. A significant positive relationship of the structure of chernozem in the two years of the research has been shown. Significant correlations between the data of different years in the technical soil were found to be mostly negative.

The contemporary management of penetrating splenic injury.

Science.gov (United States)

Berg, Regan J; Inaba, Kenji; Okoye, Obi; Pasley, Jason; Teixeira, Pedro G; Esparza, Michael; Demetriades, Demetrios

2014-09-01

Selective non-operative management (NOM) is standard of care for clinically stable patients with blunt splenic trauma and expectant management approaches are increasingly utilised in penetrating abdominal trauma, including in the setting of solid organ injury. Despite this evolution of clinical practice, little is known about the safety and efficacy of NOM in penetrating splenic injury. Trauma registry and medical record review identified all consecutive patients presenting to LAC+USC Medical Center with penetrating splenic injury between January 2001 and December 2011. Associated injuries, incidence and nature of operative intervention, local and systemic complications and mortality were determined. During the study period, 225 patients experienced penetrating splenic trauma. The majority (187/225, 83%) underwent emergent laparotomy. Thirty-eight clinically stable patients underwent a deliberate trial of NOM and 24/38 (63%) were ultimately managed without laparotomy. Amongst patients failing NOM, 3/14 (21%) underwent splenectomy while an additional 6/14 (42%) had splenorrhaphy. Hollow viscus injury (HVI) occurred in 21% of all patients failing NOM. Forty percent of all NOM patients had diaphragmatic injury (DI). All patients undergoing delayed laparotomy for HVI or a splenic procedure presented symptomatically within 24h of the initial injury. No deaths occurred in patients undergoing NOM. Although the vast majority of penetrating splenic trauma requires urgent operative management, a group of patients does present without haemodynamic instability, peritonitis or radiologic evidence of hollow viscus injury. Management of these patients is complicated as over half may remain clinically stable and can avoid laparotomy, making them potential candidates for a trial of NOM. HVI is responsible for NOM failure in up to a fifth of these cases and typically presents within 24h of injury. Delayed laparotomy, within this limited time period, did not appear to increase

The Current Status of the Japanese Penetrator Mission: LUNAR-A

Science.gov (United States)

Tanaka, S.; Shiraishi, H.; Fujimura, A.; Hayakawa, H.

The scientific objective of the LUNAR-A, Japanese Penetrator Mission, is to explore the lunar interior by seismic and heat-flow experiments. Two penetrators containing two seismometers (horizontal and vertical components) and heat-flow probes will be deployed from a spacecraft onto the lunar surface, one on the nearside and the other on the farside of the moon. The final impact velocity of the penetrator will be about 300m/sec; it will encounter a shock of about 8000 G at impact on the lunar surface. According to numerous experimental impact tests using model penetrators and a lunar regolith analog target, each penetrator is predicted to penetrate to a depth of 1 to 3 m. The data obtained by the penetrators will be transmitted to the earth station via the LUNAR-A mother spacecraft orbiting at an altitude of about 200 km. The penetrator is a missile-shaped instrument carrier, which is about 14cm in diameter, 75cm in length, and about 14kg in weight without attitude control system. It contains a two-component seismometer and heat flow probes together with other supporting instruments such as a tilt meter and an accelerometer. The seismic observations are expected to provide key data on the size of the lunar core, as well as data on deep lunar mantle structure. The heat flow measurements at two penetrator deployment sites will also provide important data on the thermal structure and bulk concentrations of heat-generating elements in the Moon. These data will provide much stronger geophysical constraints on the origin and evolution of the Moon than has been obtained so far. The LUNAR-A spacecraft was supposed to be launched in the summer of 2004, but it was postponed due to the necessity of a replacement of the valves used in the RCS propulsion system of the spacecraft, following a recall issued by the manufacturer who found a malfunction of similar valves. Then, the technological review boards by ISAS and JAXA recommended that both the more robustness of the

Ink Penetration of Uncoated Inkjet Paper and Impact on Printing Quality

Directory of Open Access Journals (Sweden)

Ren'ai Li

2015-10-01

Full Text Available This study investigated ink penetration through imaging technology, first by gray and contour mapping and then calculating the ink penetration depth by programing. Next, a series of further analyses were carried out, including average ink permeability, ink distributions, and printability of different uncoated inkjet paper with different parameters. The impact on ink penetration of the microstructure and hydrophilicity of the uncoated paper was also studied. The experimental results indicated that paper specimens with sizing agent were resistant to the ink, resulting in a slow and shallow ink penetration. Paper containing filler had a more hydrophilic surface and porous structure, leading to a faster and deeper ink penetration. However, the calendering operation could make the paper structure more compact and reduce the porosity and penetration depth. When an appropriate combination of sizing agent, filler content, and the calendering process was utilized, a more stable hue could be produced with improvements in optical density, saturation, and color.

Barbs facilitate the helical penetration of honeybee (Apis mellifera ligustica stingers.

Directory of Open Access Journals (Sweden)

Jianing Wu

Full Text Available The stinger is a very small and efficient device that allows honeybees to perform two main physiological activities: repelling enemies and laying eggs for reproduction. In this study, we explored the specific characteristics of stinger penetration, where we focused on its movements and the effects of it microstructure. The stingers of Italian honeybees (Apis mellifera ligustica were grouped and fixed onto four types of cubic substrates, before pressing into different substrates. The morphological characteristics of the stinger cross-sections were analyzed before and after penetration by microscopy. Our findings suggest that the honeybee stinger undergoes helical and clockwise rotation during penetration. We also found that the helical penetration of the stinger is associated directly with the spiral distribution of the barbs, thereby confirming that stinger penetration involves an advanced microstructure rather than a simple needle-like apparatus. These results provide new insights into the mechanism of honeybee stinger penetration.

A state of the art on penetration failure estimation under external vessel cooling

International Nuclear Information System (INIS)

Min, B. T.; Park, R. J.; Kang, K. H.; Cho, Y. R.; Kim, J. W.; Kim, S. B.; Park, S. Y.; Lee, K. Y.

2000-04-01

A state of the art on penetration failure was reviewed and analyzed to establish the direction of the experimental program in the KNGR and to decide the test section design. The interaction between the corium and the reactor vessel and the corium behavior in the lower plenum of the reactor vessel were analyzed to investigate the penetration effect on severe accident progression, and the TMI-2 accident was investigated in the point of penetration failure. Theoretical model and experiment results on penetration failure under the severe accident were investigated and reviewed to establish the direction of the experimental program on the estimation of the penetration failure in the KNGR. These results were compared with the TMI-2 results. The existing test facilities on penetration failure were investigated and reviewed to decide the test section design. It can be said from the state of the art review that penetration in the lower plenum of the reactor vessel is a week point in the reactor vessel failure under the severe accident, but the reactor vessel may not be failed by penetration failure in condition with the coolant supply to the penetration. Since the penetration is different with reactor types and there is no study on estimation of the penetration welding, it is necessary to investigate failure or not of the penetration in condition with external vessel cooling to maintain the reactor vessel integrity in KNGR. In the present experimental program on the integrity estimation of the KNGR penetration, the aluminum oxide melt by thermite reaction and the test section with one penetration of the real size and real material were selected. The melt mass, the pressure of the system, and the vessel geometry were selected as an experimental parameter. (author)

Quantitative penetration testing with item response theory (extended version)

NARCIS (Netherlands)

Arnold, Florian; Pieters, Wolter; Stoelinga, Mariëlle Ida Antoinette

2013-01-01

Existing penetration testing approaches assess the vulnerability of a system by determining whether certain attack paths are possible in practice. Therefore, penetration testing has thus far been used as a qualitative research method. To enable quantitative approaches to security risk management,

Penetration and fusion of phospholipid vesicles by lysozyme

International Nuclear Information System (INIS)

Kim, J.; Kim, H.

1989-01-01

The lysozyme-induced fusion of phosphatidylserine/phosphatidylethanolamine vesicles as studied at a wide range of pH is found to correlate well with the binding of this protein to the vesicles. An identical 6000 molecular weight segment of lysozyme at the N-terminal region is found to be protected from tryptic digestion when initially incubated with vesicles at several pH values. Only this segment is labeled by dansyl chloride, which is partitioned into the bilayer. These results suggest the penetration of one segment of lysozyme into the bilayer. Photoactivated labeling of the membrane-penetrating segment of lysozyme with 3-(trifluoromethyl)-3-([ 125 I]iodophenyl)diazirine ([ 125 I]TID) and subsequent identification of the labeled residues by Edman degradation and gamma-ray counting indicate that four amino acids from the N-terminal are located outside the hydrophobic core of the bilayer. Although treatment of the membrane-embedded segment with aminopeptidase failed to cleave any amino acids from the N-terminal, it appears that a loop of lysozyme segment near the N-terminal penetrates into the bilayer at acidic pH. A helical wheel diagram shows that the labeling is done mainly on one surface of the alpha-helix. The penetration kinetics as studied by time-dependent [ 125 I]TID labeling coincide with the fusion kinetics, strongly suggesting that the penetration of the lysozyme segment into the vesicles is the cause of the fusion

Penetration and fusion of phospholipid vesicles by lysozyme

Energy Technology Data Exchange (ETDEWEB)

Kim, J.; Kim, H. (Korea Advanced Institute of Science and Technology, Seoul)

1989-10-01

The lysozyme-induced fusion of phosphatidylserine/phosphatidylethanolamine vesicles as studied at a wide range of pH is found to correlate well with the binding of this protein to the vesicles. An identical 6000 molecular weight segment of lysozyme at the N-terminal region is found to be protected from tryptic digestion when initially incubated with vesicles at several pH values. Only this segment is labeled by dansyl chloride, which is partitioned into the bilayer. These results suggest the penetration of one segment of lysozyme into the bilayer. Photoactivated labeling of the membrane-penetrating segment of lysozyme with 3-(trifluoromethyl)-3-(({sup 125}I)iodophenyl)diazirine (({sup 125}I)TID) and subsequent identification of the labeled residues by Edman degradation and gamma-ray counting indicate that four amino acids from the N-terminal are located outside the hydrophobic core of the bilayer. Although treatment of the membrane-embedded segment with aminopeptidase failed to cleave any amino acids from the N-terminal, it appears that a loop of lysozyme segment near the N-terminal penetrates into the bilayer at acidic pH. A helical wheel diagram shows that the labeling is done mainly on one surface of the alpha-helix. The penetration kinetics as studied by time-dependent ({sup 125}I)TID labeling coincide with the fusion kinetics, strongly suggesting that the penetration of the lysozyme segment into the vesicles is the cause of the fusion.

Effect of Drainage Conditions on Cone Penetration Testing in Silty Soils

DEFF Research Database (Denmark)

Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

2011-01-01

This paper discusses the challenges that occur when performing Cone Penetration Tests (CPT) in silty soil due to changes in drainage conditions. In this paper, CPT results from various papers and researchers are collected and interpreted. Results from cone penetrations tests with various penetrat......This paper discusses the challenges that occur when performing Cone Penetration Tests (CPT) in silty soil due to changes in drainage conditions. In this paper, CPT results from various papers and researchers are collected and interpreted. Results from cone penetrations tests with various...

Effects of magnetic shear on current penetration in a tokamak

International Nuclear Information System (INIS)

Zhang Pengyun; Wang Long

2001-01-01

The penetrations of the parallel and perpendicular components of plasma currents are interrelated to each other due to the existence of magnetic shear in a tokamak configuration. Effects of the shear on the penetration of Fourier components of toroidal plasma current are analysed in a cylindrical column model. The current penetration is obviously strengthened by the shear for a bell-bike conductivity profile and low safety factor and low aspect ratio

Europa Kinetic Ice Penetrator (EKIP)

Data.gov (United States)

National Aeronautics and Space Administration — The goal of the proposed work is to validate an initial design for a Europa penetrator that can withstand the high g load associated with the expected hypervelocity...

In vitro penetration of bleaching agents into the pulp chamber

DEFF Research Database (Denmark)

Benetti, Ana Raquel; Valera, M C; Mancini, M N G

2004-01-01

To investigate pulp chamber penetration of bleaching agents in teeth following restorative procedures.......To investigate pulp chamber penetration of bleaching agents in teeth following restorative procedures....

Nanodiamond internalization in cells and the cell uptake mechanism

Energy Technology Data Exchange (ETDEWEB)

Perevedentseva, E. [National Dong Hwa University, Department of Physics (China); Hong, S.-F.; Huang, K.-J. [National Dong Hwa University, Department of Life Sciences (China); Chiang, I.-T.; Lee, C.-Y. [National Dong Hwa University, Department of Physics (China); Tseng, Y.-T. [National Dong Hwa University, Department of Life Sciences (China); Cheng, C.-L., E-mail: clcheng@mail.ndhu.edu.tw [National Dong Hwa University, Department of Physics (China)

2013-08-15

Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.

Nanodiamond internalization in cells and the cell uptake mechanism

International Nuclear Information System (INIS)

Perevedentseva, E.; Hong, S.-F.; Huang, K.-J.; Chiang, I.-T.; Lee, C.-Y.; Tseng, Y.-T.; Cheng, C.-L.

2013-01-01

Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed

Orientation dependence of deformation and penetration behavior of tungsten single crystal rods

International Nuclear Information System (INIS)

Bruchey, W.J. Jr.; Horwath, E.J.; Kingman, P.W.

1991-01-01

This paper reports on deformation and flow at a target/penetrator interface that occurs under conditions of high hydrostatic pressure and associated heat generation. To further elucidate the role of material structure in the penetration process, oriented single crystals of tungsten have been launched into steel targets and the residual penetrators recovered and analyzed. Both the penetration depth and the deformation characteristics were strongly influenced by the crystallographic orientation. Deformation modes for the left-angle 100 right-angle rod, which exhibited the best performance, appeared to involve considerable localized slip/cleavage and relatively less plastic working; the residual penetrator was extensively cracked and the eroded penetrator material was extruded in a smooth tube lined with an oriented array of discrete particle exhibiting cleavage fractures. Deformation appeared to be much less localized and to involve more extensive plastic working in the left-angle 011 right-angle rod, which exhibited the poorest penetration, while the left-angle 111 right-angle behaved in an intermediate fashion

Penetration of stimuli of fish skin for Acanthostomum brauni cercariae.

Science.gov (United States)

Ostrowski de Nuñez, M; Haas, W

1991-02-01

The cercaria of Acanthostomum brauni penetrates the skin of its fish host in response to a combination of two chemical signals from the fish skin surface: free fatty acids and a macro-molecular mucus component. The latter seems to be a protein, as the penetration-stimulating activity of fish skin surface mucus is eliminated by digestion with proteinase, but not by digestion with glycosidases, nor by a removal of glycosaminoglycans. These penetration-stimulating host signals differ from the glycoproteins that stimulate the attachment of A. brauni cercariae to the host and also from the macromolecular fish host signals which have been found to stimulate the attachment and penetration by Opisthorchis viverrini cercariae.

Use of track-end alpha particles from 241Am to study radiosensitive sites in CHO cells

International Nuclear Information System (INIS)

Datta, R.; Cole, A.; Robinson, S.

1976-01-01

Monolayers of CHO cells placed on membrane filters were irradiated with alpha particles from a 241 Am source. Particle penetration into the cells was controlled by placing the cell sample at various distances from the source. Dosimetric and spectrometric measurements were performed at comparable positions using a parallel plate ionization chamber and a scintillation crystal spectrometer. Cell survival, as measured by conventional cloning techniques, was single hit in form. A pronounced minimum in mean lethal dose of 29 rad was observed for alpha particle beams that penetrated only about 3 μm into the cell. A pronounced maximum in inactivation cross section of 90 μm 2 , equal to about half the projected area of the nucleus, occurred for beams that penetrated only 5 to 7 μm into the cell. Thus, a single alpha particle penetration several micrometers within the cell nucleus was effective in killing the cell, while fully penetrating beams were actually less efficient; the latter beams required multiple particle traversals and about three times the cell dose to achieve the same effect. These results support the proposal that radiosensitive sites are located in a thin peripheral region of the nucleus

Impact of adult atopic dermatitis on topical drug penetration

DEFF Research Database (Denmark)

Garcia Ortiz, Patricia; Hansen, Steen H; Shah, Vinod P

2009-01-01

Appropriate methodologies for the determination of drug penetration in diseased skin have not yet been established. The aim of this study was to determine the cutaneous penetration of a metronidazole cream formulation in atopic dermatitis, employing dermal microdialysis and tape strip sampling...

Measurements of current penetration during PDX discharge start-up

International Nuclear Information System (INIS)

Meyerhofer, D.D.; Goldston, R.J.; Kaita, R.; Cavallo, A.; Grek, B.; Johnson, D.; McCune, D.C.; McGuire, K.; White, R.B.

1984-11-01

The current penetration phase of PDX discharges is examined. The Fast Ion Diagnostic Experiment has been used to measure the temporal evolution of the central q (r/a < 0.4), and to show the effect of magnetic perturbations on fast ions. During plasma current penetration, a series of magnetic perturbations was observed in the plasma. If the current was rising rapidly, the perturbations were accompanied by increases in β/sub theta/ + l/sub i//2 and decreases in the loop voltage, suggesting a rapid penetration of the plasma current. When the plasma current was rising slowly, a series of minor disruptions occurred. These were accompanied by decreases in β/sub theta/ + l/sub i//2 and the loop voltage, and increases in the plasma current. During this phase, current penetration may be enhanced by the change in the resistivity profile which accompanies the disruption

Endodontic sealers: Intratubular penetration and permeability to Enterococcus faecalis

Directory of Open Access Journals (Sweden)

Bortolini Maria Cecilia

2010-01-01

Full Text Available Aim : Evaluate in vitro the intratubular penetration and permeability of endodontic sealers in teeth contaminated with Enterococcus faecalis. Materials and Methods : Human canines were filled with AHPlus ® , Endo CPM-sealer ® or EndoRez ® sealers. To evaluate permeability, the coronary portion of each tooth was contaminated with E. faecalis, then the apical portion was immersed in brain heart infusion (BHI broth, and medium turbidity was observed for thirty days. Scanning electron microscope (SEM was used to evaluate the intratubular penetration of each sealer at the cervical, middle, and apical thirds of the tooth. Results : Only one tooth from the Endo CPM-sealer ® group presented broth contamination. EndoRez ® showed increased intratubular penetration compared to AHPlus ® and Endo CPM-sealer ® . Conclusions : Endo CPM-sealer ® showed greater permeability to E. faecalis and EndoRez ® showed increased intratubular penetration.

Factors Controlling the Pharmacokinetics, Biodistribution and Intratumoral Penetration of Nanoparticles

Science.gov (United States)

Ernsting, Mark J.; Murakami, Mami; Roy, Aniruddha; Li, Shyh-Dar

2014-01-01

Nanoparticle drug delivery to the tumor is impacted by multiple factors: nanoparticles must evade clearance by renal filtration and the reticuloendothelial system, extravasate through the enlarged endothelial gaps in tumors, penetrate through dense stroma in the tumor microenvironment to reach the tumor cells, remain in the tumor tissue for a prolonged period of time, and finally release the active agent to induce pharmacological effect. The physicochemical properties of nanoparticles such as size, shape, surface charge, surface chemistry (PEGylation, ligand conjugation) and composition affect the pharmacokinetics, biodistribution, intratumoral penetration and tumor bioavailability. On the other hand, tumor biology (blood flow, perfusion, permeability, interstitial fluid pressure and stroma content) and patient characteristics (age, gender, tumor type, tumor location, body composition and prior treatments) also have impact on drug delivery by nanoparticles. It is now believed that both nanoparticles and the tumor microenvironment have to be optimized or adjusted for optimal delivery. This review provides a comprehensive summary of how these nanoparticle and biological factors impact nanoparticle delivery to tumors, with discussion on how the tumor microenvironment can be adjusted and how patients can be stratified by imaging methods to receive the maximal benefit of nanomedicine. Perspectives and future directions are also provided. PMID:24075927

Penetrating spinal injuries and their management

Directory of Open Access Journals (Sweden)

A Kumar

2011-01-01

Full Text Available Penetrating spinal trauma due to missile/gunshot injuries has been well reported in the literature and has remained the domain of military warfare more often. Civic society′s recent upsurge in gunshot injuries has created a dilemma for the treating neurosurgeon in many ways as their management has always involved certain debatable and controversial issues. Both conservative and surgical management of penetrating spinal injuries (PSI have been practiced widely. The chief neurosurgical concern in these types of firearm injuries is the degree of damage sustained during the bullet traversing through the neural tissue and the after-effects of the same in long term. We had an interesting case of a penetrating bullet injury to cervical spine at C2 vertebral level. He was operated and the bullets were removed from posterior midline approach. Usually, the management of such cases differs from region to region depending on the preference of the surgeon but still certain common principles are followed world over. Thus, we realized the need to review the literature regarding spinal injuries with special emphasis on PSI and to study the recent guidelines for their treatment in light of our case.

Roentgenologic image of penetrating duodenal bulb ulcer

International Nuclear Information System (INIS)

Strunin, A.E.

1986-01-01

When studying a series of aimed roentgenograms in patients with peptic ulcer a gas bubble of irregular spherical configuration or two-layer niche were determined near the bulb medial contour. Gas bubble was from 0.5-0.7 to 3.5 cm in diameter. In such cases penetrating ulcers were determined in operations. Along with other signs gas bubble symptom, sometimes two-layer signs may be used for timely and exact roentgenological diagnosis of penetrating duodenal bulb ulcer in peptic ulcer disease

Study on penetration-induced initiation of energetic fragment

Science.gov (United States)

Qiao, Xiangxin; Xu, Heyang

2017-09-01

In order to investigate penetration-induced initiation of energetic fragment penetrating target, PTFE/Al (mass ratio 73.5/26.5) pressed and sintered into a Ф8mm × 8mm cylinder. To form energetic fragment, the cylinder was put into a closed container made by 35CrMnSiA. The container is 12mm long, 2mm thick. Energetic fragments were launched by a 14.5mm ballistic gun with a series of velocities and the penetrate process was simulated by AUTODYN-3D. The results show that the stress peak of energetic material exceed the initiation threshold, and energetic material will deflagrate, when energetic fragments impact velocity more than 800 m/s. The research results can provide reference for designs of energetic warhead.

A case of an intrahepatic fish bone penetration

International Nuclear Information System (INIS)

Tsuboi, Kazuhiko; Nakajima, Yoshiro; Yamamoto, Shunji; Nagao, Masatoshi; Nishimura, Kazumasa.

1981-01-01

A 56-year-old man was admitted to our hospital because of epigastric discomfort, appetite loss and body weight loss. A gallstone, signs of chronic inflammation and CEA-Z: 12.5 ng/ml were found. Abdominal CT scan revealed an intrahepatic low density nodule and an intra-and-extrahepatic high-dense, needle-like foreign body. By laparotomy a fish bone penetrating into the left lateral segment of the liver from the anterior wall of the prepyloric region of the stomach was found. Cholecystectomy was performed. The penetrating fish bone was withdrawn from the liver easily. The Postoperative course was smooth. The possibility of the definitive preoperative diagnosis of the intestinal fish bone penetration by abdominal CT scan was suggested. (author)

Preparation and characterization of mucus-penetrating papain/poly(acrylic acid) nanoparticles for oral drug delivery applications

International Nuclear Information System (INIS)

Müller, Christiane; Leithner, Katharina; Hauptstein, Sabine; Hintzen, Fabian; Salvenmoser, Willi; Bernkop-Schnürch, Andreas

2013-01-01

Particle diffusion through the intestinal mucosal barrier is restricted by the viscoelastic and adhesive properties of the mucus gel layer, preventing their penetration to the underlying absorptive endothelial cells. To overcome this natural barrier, we developed nanoparticles which have a remarkable ability to cleave mucoglycoprotein substructures responsible for the structural and rheological properties of mucus. After rheological screening of various mucolytic proteases, nanoparticles composed of poly(acrylic acid) and papain were prepared and characterized regarding particle size and zeta potential. Analysis of nanoparticles showed mean diameters sub-200 nm (162.8–198.5 nm) and negative zeta potentials advancing the mobility in mucus gel. Using diffusion chamber studies and the rotating diffusion tubes method, we compared the transport rates of papain modified (PAPC) and unaltered poly(acrylic acid) (PAA) particles through freshly excised intestinal porcine mucus. Results of the diffusion assays demonstrated strongly enhanced permeation behavior of PAPC particles owing to local mucus disruption by papain. Improved transport rates, reduction in mucus viscosity and the retarded release of hydrophilic macromolecular compounds make proteolytic enzyme functionalized nanoparticles of substantial interest for improved targeted drug delivery at mucosal surfaces. Although cytotoxicity tests of the nanoparticles could not be performed, safety of papain and PAA was already verified making PAPC particles a promising candidate in the pharmaceutical field of research. The focus of the present study was the development of particles which penetrate the mucus barrier to approach the underlying epithelium. Improvements of particles that penetrate the mucus followed by cell uptake in this direction are ongoing.

Preparation and characterization of mucus-penetrating papain/poly(acrylic acid) nanoparticles for oral drug delivery applications

Science.gov (United States)

Müller, Christiane; Leithner, Katharina; Hauptstein, Sabine; Hintzen, Fabian; Salvenmoser, Willi; Bernkop-Schnürch, Andreas

2013-01-01

Particle diffusion through the intestinal mucosal barrier is restricted by the viscoelastic and adhesive properties of the mucus gel layer, preventing their penetration to the underlying absorptive endothelial cells. To overcome this natural barrier, we developed nanoparticles which have a remarkable ability to cleave mucoglycoprotein substructures responsible for the structural and rheological properties of mucus. After rheological screening of various mucolytic proteases, nanoparticles composed of poly(acrylic acid) and papain were prepared and characterized regarding particle size and zeta potential. Analysis of nanoparticles showed mean diameters sub-200 nm (162.8-198.5 nm) and negative zeta potentials advancing the mobility in mucus gel. Using diffusion chamber studies and the rotating diffusion tubes method, we compared the transport rates of papain modified (PAPC) and unaltered poly(acrylic acid) (PAA) particles through freshly excised intestinal porcine mucus. Results of the diffusion assays demonstrated strongly enhanced permeation behavior of PAPC particles owing to local mucus disruption by papain. Improved transport rates, reduction in mucus viscosity and the retarded release of hydrophilic macromolecular compounds make proteolytic enzyme functionalized nanoparticles of substantial interest for improved targeted drug delivery at mucosal surfaces. Although cytotoxicity tests of the nanoparticles could not be performed, safety of papain and PAA was already verified making PAPC particles a promising candidate in the pharmaceutical field of research. The focus of the present study was the development of particles which penetrate the mucus barrier to approach the underlying epithelium. Improvements of particles that penetrate the mucus followed by cell uptake in this direction are ongoing.

Interpretation of Cone Penetration Testing in Silty Soils Conducted under Partially Drained Conditions

DEFF Research Database (Denmark)

Holmsgaard, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

2016-01-01

The standard penetration rate used in cone penetration tests (CPTs) is 20 mm=s, regardless of soil type, which yields fully drained penetration in sand and fully undrained penetration in clay. However, for silty soils that represent an intermediate grain size composition and unique characteristic...

Microstructural observations on the terminal penetration of long rod projectile

OpenAIRE

Krushna Kumbhar; P. Ponguru Senthil; A.K. Gogia

2017-01-01

Present study focuses on the terminal penetration of tungsten heavy alloy (WHA) long rod penetrator impacted against armour steel at an impact velocity of 1600 m/s. The residual penetrator and armour steel target recovered after the ballistic test have been characterized using optical microscope, scanning electron microscope (SEM) and electron probe micro analyzer (EPMA). Metallurgical changes in target steel and WHA remnant have been analysed. Large shear stresses and shear localization have...

A single-cell technique for the measurement of membrane potential, membrane conductance, and the efflux of rapidly penetrating solutes in Amphiuma erythrocytes.

Science.gov (United States)

Stoner, L C; Kregenow, F M

1980-10-01

We describe a single-cell technique for measuring membrane potential, membrane resistance, and the efflux of rapidly penetrating solutes such as Cl and H2O. Erythrocytes from Amphiuma means were aspirated into a Sylgard (Dow Corning Corp.)-coated capillary. The aspirated cell separated a solution within the capillary from a solution in the bath. Each of these two solutions was contiguous with approximately 5% of the total membrane surface. Microelectrodes placed concentrically within the capillary permit the measurement of intracellular voltage, specific membrane resistance, and the electrical seal between the two solutions. The intracellular voltage averaged -17.7 mV (pH 7.6) and changed as either intra- or extracellular chloride was varied. The average specific membrane resistance measured by passing current across the exposed membrane surface was 110 ohm-cm2. 36Cl and tritiated H2O fluxes (0.84 +/- 0.05 x 10(-6) M . cm-2 . min-1 and 6.4 +/- 1.5 x 10(-3) M . cm-2 . min-1, respectively) were determined by noting the rate at which isotope leaves the cell and crosses the membrane exposed to the bath. Our measured values for the flux of 36Cl and tritiated H2O approximate reported values for free-floating cells. 36Cl efflux, in addition, is inhibited by 4-acetamido-4'-isothiocyano-stilbene 2,2'-disulfonic acid (SITS) and furosemide, known inhibitors of the anion exchange mechanism responsible for the rapid anion fluxes of red blood cells. One can also demonstrate directly that > 89% of 36Cl efflux is "electrically silent" by analyzing the flux in the presence of an imposed transcellular voltage.

Two methodologies for physical penetration testing using social engineering

NARCIS (Netherlands)

Dimkov, T.; Pieters, Wolter; Hartel, Pieter H.

2009-01-01

During a penetration test on the physical security of an organization, if social engineering is used, the penetration tester directly interacts with the employees. These interactions are usually based on deception and if not done properly can upset the employees, violate their privacy or damage

Penetration of varnishes into demineralized root dentine in vitro

NARCIS (Netherlands)

Arends, J; Duschner, H; Ruben, JL

1997-01-01

In this paper the penetration of three different varnishes employed in caries prevention (Duraphat(R), Fluor Protector(R) and Cervitec(R)) into demineralized dentine is quantified using confocal laser scanning microscopy. The results show that the varnish penetration into lesions about 85 mu m in

Development of a market penetration forecasting model for Hydrogen Fuel Cell Vehicles considering infrastructure and cost reduction effects

International Nuclear Information System (INIS)

Park, Sang Yong; Kim, Jong Wook; Lee, Duk Hee

2011-01-01

In order to cope with climate change, the development and deployment of Hydrogen Fuel Cell Vehicles (HFCVs) is becoming more important. In this study, we developed a forecasting model for HFCVs based on the generalized Bass diffusion model and a simulation model using system dynamics. Through the developed model, we could forecast that the saturation of HFCVs in Korea can be moved up 12 years compared with the US. A sensitivity analysis on external variables such as price reduction rates of HFCVs and number of hydrogen refueling stations is also conducted. The results of this study can give insights on the effects of external variables on the market penetration of HFCVs, and the developed model can also be applied to other studies in analyzing the diffusion effects of HFCVs. - Highlights: → A forecasting model for HFCVs was developed using the generalized Bass diffusion model. → A simulation model using system dynamics was also developed. → The empirical study shows that the infrastructure is an important factor to the initial purchase. → The results of this study can promote research related to the diffusion of innovation.

A Study of Crystalline Mechanism of Penetration Sealer Materials

Directory of Open Access Journals (Sweden)

Li-Wei Teng

2014-01-01

Full Text Available It is quite common to dispense a topping material like crystalline penetration sealer materials (CPSM onto the surface of a plastic substance such as concrete to extend its service life span by surface protections from outside breakthrough. The CPSM can penetrate into the existing pores or possible cracks in such a way that it may form crystals to block the potential paths which provide breakthrough for any unknown materials. This study investigated the crystalline mechanism formed in the part of concrete penetrated by the CPSM. We analyzed the chemical composites, in order to identify the mechanism of CPSM and to evaluate the penetrated depth. As shown in the results, SEM observes the acicular-structured crystals filling capillary pores for mortar substrate of the internal microstructure beneath the concrete surface; meanwhile, XRD and FT-IR showed the main hydration products of CPSM to be C-S-H gel and CaCO3. Besides, MIP also shows CPSM with the ability to clog capillary pores of mortar substrate; thus, it reduces porosity, and appears to benefit in sealing pores or cracks. The depth of CPSM penetration capability indicated by TGA shows 0–10 mm of sealer layer beneath the concrete surface.

An integrated approach to fire penetration seal program management

International Nuclear Information System (INIS)

Rispoli, R.D.

1996-01-01

This paper discusses the utilization of a P.C. based program to facilitate the management of Entergy Operations Arkansas Nuclear One (ANO) fire barrier penetration seal program. The computer program was developed as part of a streamlining process to consolidate all aspects of the ANO Penetration Seal Program under one system. The program tracks historical information related to each seal such as maintenance activities, design modifications and evaluations. The program is integrated with approved penetration seal design details which have been substantiated by full scale fire tests. This control feature is intended to prevent the inadvertent utilization of an unacceptable penetration detail in a field application which may exceed the parameters tested. The system is also capable of controlling the scope of the periodic surveillance of penetration seals by randomly selecting the inspection population and generating associated inspection forms. Inputs to the data base are required throughout the modification and maintenance process to ensure configuration control and maintain accurate data base information. These inputs are verified and procedurally controlled by Fire Protection Engineering (FPE) personnel. The implementation of this system has resulted in significant cost savings and has minimized the allocation of resources necessary to ensure long term program viability

Interaction between Orobanche crenata and its host legumes: unsuccessful haustorial penetration and necrosis of the developing parasite.

Science.gov (United States)

Pérez-DE-Luque, A; Rubiales, D; Cubero, J I; Press, M C; Scholes, J; Yoneyama, K; Takeuchi, Y; Plakhine, D; Joel, D M

2005-05-01

Orobanche species represent major constraints to crop production in many parts of the world as they reduce yield and alter root/shoot allometry. Although much is known about the histology and effect of Orobanche spp. on susceptible hosts, less is known about the basis of host resistance to these parasites. In this work, histological aspects related to the resistance of some legumes to Orobanche crenata have been investigated in order to determine which types of resistance responses are involved in the unsuccessful penetration of O. crenata. Samples of resistance reactions against O. crenata on different genotypes of resistant legumes were collected. The samples were fixed, sectioned and stained using different procedures. Sections were observed using a transmission light microscope and by epi-fluorescence. Lignification of endodermal and pericycle host cells seems to prevent parasite intrusion into the root vascular cylinder at early infection stages. But in other cases, established tubercles became necrotic and died. Contrary to some previous studies, it was found that darkening at the infection site in these latter cases does not correspond to death of host tissues, but to the secretion of substances that fill the apoplast in the host-parasite interface and in much of the infected host tissues. The secretions block neighbouring host vessels. This may interfere with the nutrient flux between host and parasite, and may lead to necrosis and death of the developing parasite. The unsuccessful penetration of O. crenata seedlings into legume roots cannot be attributed to cell death in the host. It seems to be associated with lignification of host endodermis and pericycle cells at the penetration site. The accumulation of secretions at the infection site, may lead to the activation of xylem occlusion, another defence mechanism, which may cause further necrosis of established tubercles.

Study of the disorder by means of the superconducting penetration depth

International Nuclear Information System (INIS)

Arce, R.D.

1982-11-01

Measurements of the weak magnetic field penetration depth in the amorphous superconducting systems Lasub(1-x) Msub(x), being M = Cu, Al, Ga and Au, and in the Zr 70 Cu 30 system are presented. Measurements of the sample geometrical factors and the flux expulsion between the lowest temperature reached and the critical temperature, allows the determination of zero temperature penetration depth. The measurement of the flux expulsion as a function of temperature is used to determine the temperature dependence of penetration depth, used to evaluate the temperature dependence superconducting gap. The magnetization measurements have been made using an rf-SQUID. The evolution of the penetration depth with annealing is studied in the La 70 Cu 30 and Zr 70 Cu 30 systems. Measurements of the electrical resistivity and the critical temperature are used to verify the Gorkov equations in these materials. The variation of the penetration depth with annealing suggests that a metallurgical phase separation occurs within the submicrometer range. Penetration depth measurement is a tool to detect this type of phase separation in high kappa materials. (M.E.L.) [es

Market penetration of ethanol

International Nuclear Information System (INIS)

Szulczyk, Kenneth R.; McCarl, Bruce A.; Cornforth, Gerald

2010-01-01

This research examines in detail the technology and economics of substituting ethanol for gasoline. This endeavor examines three issues. First, the benefits of ethanol/gasoline blends are examined, and then the technical problems of large-scale implementation of ethanol. Second, ethanol production possibilities are examined in detail from a variety of feedstocks and technologies. The feedstocks are the starch/sugar crops and crop residues, while the technologies are corn wet mill, dry grind, and lignocellulosic fermentation. Examining in detail the production possibilities allows the researchers to identity the extent of technological change, production costs, byproducts, and GHG emissions. Finally, a U.S. agricultural model, FASOMGHG, is updated which predicts the market penetration of ethanol given technological progress, variety of technologies and feedstocks, market interactions, energy prices, and GHG prices. FASOMGHG has several interesting results. First, gasoline prices have a small expansionary impact on the U.S. ethanol industry. Both agricultural producers' income and cost both increase with higher energy prices. If wholesale gasoline is $4 per gallon, the predicted ethanol market penetration attains 53% of U.S. gasoline consumption in 2030. Second, the corn wet mill remains an important industry for ethanol production, because this industry also produces corn oil, which could be converted to biodiesel. Third, GHG prices expand the ethanol industry. However, the GHG price expands the corn wet mill, but has an ambiguous impact on lignocellulosic ethanol. Feedstocks for lignocellulosic fermentation can also be burned with coal to generate electricity. Both industries are quite GHG efficient. Finally, U.S. government subsidies on biofuels have an expansionary impact on ethanol production, but may only increase market penetration by an additional 1% in 2030, which is approximately 6 billion gallons. (author)